Immunology Flashcards Preview

FDN3 By Nathan and Minnie > Immunology > Flashcards

Flashcards in Immunology Deck (866)
Loading flashcards...
1
Q

What are the characteristics of innate immunity?

A
  • Present at birth
  • Rapid
  • Relies on pattern recognition
  • Not specific
  • No memory
  • Primarily mediated by neutrophils
2
Q

What are the characteristics of adaptive immunity?

A
  • Slow (on first exposure)
  • Diverse
  • Adapts to antigen (not pre-formed)
  • Highly specific
  • Generates memory and improved immunity w/ repeated antigen exposure
3
Q

What is specificity?

A

The ability to distinguish between different substances

4
Q

Describe specificity with regards to innate immunity

A

Proteins that recognize common patterns of infectious organisms

Not very specific

5
Q

Describe specificity with regards to adaptive immunity

A

Surface protein recognizes unique molecules

Highly specific

6
Q

What is passive immunity?

Describe the characteristics of passive immunity

A

Transfer of pre-formed antibody from one person or animal to another

Rapid

Short-lived

7
Q

What are examples of passive immunity?

A
  • Antitoxins for botulinum toxins
  • Antibodies to rabies virus
  • Maternal IgG antibodies crossing the placenta
  • Maternal IgA antibodies in breast milk
8
Q

What is active immunity?

Describe the characteristics of active immunity

A

Induction of an immune response (exposure to antigen)

Slow

Memory (long-lived)

9
Q

What is an example of active immunity?

A

An immunization

10
Q

Patient AJ is planning to travel internationally in 3 days to a region endemic for Hepatitis A. She will be there for one year. What is the best type of immunity-based therapy to offer her to prevent infection?

A

Immunization against Hepatitis A with Ig and the inactivated virus

11
Q

Which immunoglobulin do nursing infants have?

A

Maternal IgA

12
Q

Which immunoglobulin do all very young infants (under 6 weeks) have?

A

Maternal IgG

(And Maternal IgA if they are nursing)

13
Q

Which sort of immune response are infants under the age unable to generate?

A

Infants under 2 years old cannot generate an effective T-cell independent B cell response

(such as to a polysaccharide capsule)

14
Q

Which sort of immune response do older adults have a decreased ability to generate?

A

T-cell independent B cell response

15
Q

Which two groups cannot generate / generated reduced T-cell independent B cell responses?

A
  • Infants under age of two
  • Older adults

Struggle w/ encapsulated bacteria

Have greater frequency and severity of infections

16
Q

Why are encapsulated bacteria particularly dangerous to infants under the age of two?

A

Infants under two cannot generate an effective T-cell independent B cell response

17
Q

Why are encapsulated bacteria particularly dangerous to older adults?

A

Older adults have decreased ability to generate an effective T-cell independent B cell response

18
Q

What must pneumoccal vaccines consisting of polysaccharides be conjugated to in order for children under the age of 2 to allow for a protective immune response?

A

Proteins

19
Q

What are cytokines?

A

Small proteins that are produced by cells and have effects on cells

Include chemokines, interleukins, lymphokines, tumor necrosis factors, interferons

20
Q

What is the function of IL-2?

A

Promotes T cell growth and activation

21
Q

What is “clusters of differentiation”?

A

Nomenclature system for the proteins used to identify cells

22
Q

What does a CD refer to?

A

A protein expressed by cells

23
Q

On which cells is CD3 expressed?

A

All T cells

24
Q

On which cells is CD4 expressed?

What does CD4 bind to?

A

Helper T cells

Binds to MHC class II

25
Q

On which cells is CD8 expressed?

What does CD8 bind to?

A

Cytotoxic T cells

Binds to MHC class I

26
Q

On which cells is CD19 expressed?

A

All B cells

27
Q

On which cells is CD56 expressed?

A

NK cells

28
Q

What is CD28?

What does it bind to?

A

Co-stimulatory protein on T cells (2nd signal)

Binds to B7 on APCs

29
Q

A 33 year old woman is planning to travel internationally in 3 days to a region endemic for Hepatitis A. What is the best type of immunity-based therapy to offer her to prevent infection?

A

Due to short time before her potential exposure to Hepatitis A, she should receive immune globulin (Ig), which is passive immunization, since the antibody is preformed and the protection is rapid.

This protection is short-lived, so she should also receive inactive Hepatitis A vaccine, which provides longer protection.
Ideally, she would also have a booster in 6 months for much longer protection.

30
Q

What protein must antigen-presenting cells express on their surface to present a peptide to CD4+ T helper cells?

A

MHC II

31
Q

Would exposure to only the polysaccharide capsule of bacteria lead to a T cell mediated immune response?

Could there still be an immune response?

A

No, if there is no protein present, there will not be a T cell-mediated immune response

There could be a T cell independent immune response driven by B cells

32
Q

How do pathogens prevent being destroyed by innate immunity?

A
  • Evade immune system
  • Use elements of immune system for their own advantage
33
Q

How does Bordetella pertusis evade the immune system?

A

Has proteins that bind to ciliated respiratory cells to enable infection

34
Q

What is innate immunity?

A

Part of immune response that exists at birth and is present in all multicellular organisms

Rapid, relies on pattern recognition to identify pathogens, has no specificity, shows no memory or improvement in immunity with time or repeated antigen exposure

35
Q

Which white blood cells are involved in the innate immune response?

A
  • Neutrophils
  • Monocytes/macrophages
  • Basophils
  • Mast cells
  • NK cells
36
Q

What is the role of neutrophils in innate immunity?

A

Neutrophils (granulocytes, PMNs)

  • First responders
  • Rapidly migrate from bone marrow to blood to tissue (peripheral blood neutrophilia)
  • Engulf/kill pathogens
  • Release additional pro-inflammatory cytokines
  • Major cell of acute inflammatory response
  • Do not present antigen on MHC class II
37
Q

What is neutropenia?

What causes it?

What does it lead to?

A

Too few neutrophils

Often caused by chemotherapy

Leads to significantly increased susceptibility to infection

38
Q

What is the role of monocytes in the blood / tissue macrophages in innate immunity?

A

Tissue macrophages

  • Recognize pathogens through pattern recognition
  • Release cytokines to recruit neutrophils
  • Macrophages phagocytose organisms
  • Antigen-presenting cells (express MHC class II)
39
Q

Where are mast cells present?

What are mast cells activated by?

What do mast cells release?

A

Mast cells

  • Present throughout connective tissue
  • Activated by trauma, complement proteins (C3a and CD5a), and cross-linking of IgE (which is bound by IgE Fc freceptor)
  • Express-tole like receptors that recognize bacteria and viruses
  • Release histamine and other mediators of inflammation
40
Q

Where are basophils present?

What are basophils activated by?

What do basophils release?

A

Basophils

  • Present in blood
  • Activated by trauma, complement proteins (C3a and CD5a), and cross-linking of IgE (which is bound by IgE Fc freceptor)
  • Express-tole like receptors that recognize bacteria and viruses
  • Release histamine and other mediators of inflammation
41
Q

What is the role of NK cells in innate immunity?

A

NK cells (CD56+ and CD16+)

  • Directly kill infected cells
  • Recognize virus-infected cells and tumor cells via lack of MHC class I on those cells and by binding Fc (constant region) of antibody bound to those cells (antibody-dependent cellular cytotoxicity)
  • Produce and secrete cytotoxic granules such as perforin and granzyme B
  • Do not express specific antigen receptors
42
Q

What are complement proteins?

A

>20 plasma proteins that augment inflammation

43
Q

What do complement proteins circulate as?

A

Inactive precursors

44
Q

How are complement proteins activated?

A

Activated in a cascade of cleavage reactions that allow proteins and immune complexes to be destroyed or eliminated

45
Q

What are the functions of complement?

A
  • Direct lysis of cells
  • Generation of mediators of inflammation
  • Opsonization (enhancement of phagocytosis)
46
Q

Why is regulation of complement essential?

A

To prevent tissue damage

47
Q

What do the three mechanisms of complement activation converge on?

A

C3 convertase

48
Q

What does C3 convertase do?

A

Acts on C3 to make C3a and C3b

49
Q

What does C3b do?

A

Acts on C5 to make C5a and C5b

50
Q

What does C5b do?

A

Inserts into cell membrane of pathogen and is bound by C6, C7, C8, and C9 to make the membrane attack complex

51
Q

What does the membrane attack complex do?

Which bacteria are particularly susceptible?

A

Forms a hole in the membrane causing the pathogen to lyse

Gram-negative bacteria are particularly susceptible

52
Q

Describe the classic pathway of complement activation

A

C1 binds to the constant fragment of IgG or IgM (antigen-antibody complex)

53
Q

Describe the alternative pathway of complement activation

A

Microbial products directly activate complement

54
Q

Describe the lectin pathway of complement activation

A

Mannose-binding lectin (serum protein) binds carbohydrate antigens on the surface of micro-organisms (such as encapsulated bacteria)

55
Q

What is the function of C1?

A

Recognizes antigen-antibody complexes in the classical pathway of complement activation

56
Q

What is the function of C3 convertase?

A

Associates with pathogen cell membrane and cleaves/activates other complement proteins

57
Q

What is the function of C3a?

A

Triggers mast cells to degranulate and release histamine (anaphylatoxins)

58
Q

What are the functions of C5a?

A
  • Triggers mast cells to degranulate and release histamine (anaphylatoxins)
  • Chemotactic for neutrophils
59
Q

What is the function of C3b?

A

Opsonin for phagocytosis (iC3b and C3d are breakdown products of C3b)

60
Q

What do C5b, C6, C7, C8, and C9 form?

A

The membrane attack complex

61
Q

What is the function of C1 esterase inhibitor?

A

Inhibits the formation of C3

62
Q

What is the function of decay accelerating factor (CD55)?

A

Inhibits the formation of C3

63
Q

What condition does a deficiency in C1 esterase inhibitor cause?

What is the biomolecular cause of the condition?

What are the symptoms?

A

Hereditary angiodema

Uncontrolled generation of bradykinins

Persistent swelling in extremities, face, lips, genitals, and GI tract

64
Q

What do deficiencies in the membrane attack complex (C5b, C6, C7, C8, C9) lead to?

A

Predispose to infections with Neisseria

65
Q

What does C1 bind to initiate the classical complement pathway?

A

IgG bound to antigen

66
Q

What are defensins?

Where are defensins found?

A

Small cationic peptides that bind to and create pores in microbes

Alpha definsins are in the GI tract

Beta defensins are in the respiratory tract

67
Q

What are interferons (alpha and beta)?

A

Anti-viral proteins that bind to the cell surface and induce an anti-viral state in cells

Inhibit viral replication

Produced by lymphocytes and macrophages

68
Q

How do bacterial capsules reduce the effectiveness of the complement system?

A
  • Prevents complement activation
  • Decreases C3b binding

(Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae)

69
Q

How are monocytes/macrophages involved in inflammation?

A
  1. Monocytes and macrophages express pattern recognition proteins
  2. Recognize PAMPs (ex: CD14/TLR4 recognizes LPS)
  3. Release pro-inflammatory cytokines/mediators and stimulate acute phase reponse

Macrophages also release anti-inflammatory cytokines to control immune response

70
Q

What do pro-inflammatory cytokines trigger?

What occurs?

A

Acute phase response

Increased synthesis of plasma proteins by the liver, including C-reactive protein, mannose-binding lectin, Factor XII

Contributes to sepsis

71
Q

What is IL-1?

A
  • Pro-inflammatory cytokine
  • Endogenous pyrogen
  • Induces acute phase response
72
Q

What is IL-6?

A
  • Pro-inflammatory cytokine
  • Endogenous pyrogen
  • Induces acute phase response
73
Q

What is IL-8?

A
  • Pro-inflammatory cytokine
  • Recruits neutrophils (chemokine)

Clean up in aisle 8 (IL-8)

74
Q

What is tumor necrosis factor alpha (TNFa)?

A
  • Pro-inflammatory cytokine
  • Numerous pro-inflammatory effects
  • Stimulates cell growth and proliferation
  • Recruits neutrophils
  • Increases cyclooxygenase
75
Q

What is the function of cyclooxygenase?

A

Acts on arachidonic acid from cell membrane to produce prostaglandins

Prostaglandins mediate vasodilation and increased vascular permeability, pain, and fever

76
Q

What is IL-10?

A
  • Anti-inflammatory cytokine
  • Turns off immune response
77
Q

What is transforming growth factor beta (TGFb)?

A
  • Anti-inflammatory cytokine
  • Turns off immune response
78
Q

On which cells is CD14 expressed?

What is the function of CD14?

A

Monocytes/macrophages

Co-receptor for TLR4 that recognizes LPS

79
Q

What elements of innate immunity might defend against infection by bacteria in the GI tract?

A
  • Intact mucosal epithelium
  • Mucous
  • pH
  • Microbial molecules such as defensins
  • Macrophages
  • Dendritic cells
80
Q

The classic complement pathway is initiated by interaction of C1 with what?

A

IgG or IgM

81
Q

What is the role of pattern recogniton in triggering inflammation?

A

Pattern recognition receptors (PRRs) such as TLRs on monocytes/macrophages, mast cells, and other cells of the immune system recognize the pathogen-associated molecular patterns (PAMPs)

The signal leads the cell to release pro-inflammatory cytokines

82
Q

In a patient with a chronic inflammatory disease mediated by the release of pro-inflammatory cytokines, which cytokines could oppose the inflammation and tissue damage?

A

Anti-inflammatory cytokines such as IL-10 and TGF-beta

(However, anti-inflammatory cytokines can also contribute to tissue damage under certain circumstances)

83
Q

What is acute inflammation? What are the cells involved?

A

Predominantly an innate immune response (rapid, not specific) mediated by fluid in the tissues (edema) and neutrophil migration into tissues

Macrophages arrive after neutrophils and release further cytokines

Can resolve (such as fibrosis or scar tissue) or progress to chronic inflammation

84
Q

What is the role of neutrophils in acute inflammation?

A
  • Drawn towards inflammatory mediators from macrophages and mast cells
  • Phagocytose and destroy organisms
  • Release further cytokines to draw additional neutrophils
85
Q

What is chronic inflammation? Which cells are involved?

A

Predominantly an adaptive immune response (delayed, specific) mediated by lymphocytes, plasma cells, and monocytes/macrophages

86
Q

What are the causes of chronic inflammation?

A

Persistent infection, prolonged exposure to a toxic agent, or autoimmunity

87
Q

What is granulomatous inflammation?

What is a granuloma?

A

A subtype of chronic inflammation characterized by granuloma formation

A granuloma is a collection of macrophages, sometimes with giant cells (large macrophages with multiple nuclei) and surrounding lymphocytes

88
Q

What is the difference between a caseating and non-caseating granuloma?

A

A caseating granuloma has central necrosis (TB, fungal infection)

A non-caseating granuloma lacks central necrosis (foreign material reaction, sarcoidosis, cat scratch disease)

89
Q

What type of response to extracellular pathogens tend to give rise to?

Which cells/molecules are involved?

A

Pyogen (pus-producing) response

Neutrophils, antibodies, complement

90
Q

What type of response do intracellular pathogens tend to give rise to?

Which cells/substances are involved?

A

Granulomatous response

Macrophages, CD4+ T cells

91
Q

What are the basic steps in inflammation produced by the innate immune system?

A
  1. Cells of the innate immune system recognize pathogens through PAMPs
  2. These cells release pro-inflammatory cytokines
  3. Cytokines acute phase response and releazse of numerous mediators of inflammation
92
Q

What releases TNFa?

What is the function of TNFa?

A

Macrophages

Pro-inflammatory effects including increased cyclooxygenase

93
Q

What does cyclooxygenase do?

A

Acts on arachidonic acid from the cell membrane to produce prostaglandins which mediate vasodilation and increased vascular permeability, pain, and fever

94
Q

What does 5-lipooxygenase do?

A

Acts on arachidonic acid to produce leukotrienes (LTB4, LTC4, LTD4, LTE4) which attrachts neutrophuls and causes bronchospasm and increased vascular permeability

(contributes to anaphylaxis but is slower acting than histamine)

95
Q

What are bradykinins produced from?

What do bradykinins do?

A

Bradykinins are produced from the kinin system (cleavage of high molecular weight kinogen/kalikrein)

Mediate vasodilation, increased vascular permeability, and pain

Hint: Tom Brady = Brady-kinin

  • Dilates the defense and creates holes in it
  • Causes pain to opponents
96
Q

Which cell releases IL-1, IL-6, and IL-8?

A

Macrophage

97
Q

Which cell releases histamine?

What does histamine do?

A

Mast cells (stimulated by binding of C3a and C5a complement)

Leads to vasodilation, endothelial cell contraction, and increased vascular permeability

98
Q

What are the vascular components of inflammation?

A
  • Vasodilation
  • Increased vascular permeability
99
Q

What does vasodilation lead to?

A

Increased blood flow

100
Q

What causes increased vascular permeability?

What is the function of increased vascular permeability?

A

Caused by endothelial cell contraction and damage

Allows fluid and cells to reach areas of infection

101
Q

Which molecules mediate vessel changes?

A

Histamine, prostaglandins, and leukotrienes

102
Q

What are the basic stages of phagocytosis?

A
  1. Recognitin and attachment
  2. Engulfment
  3. Destruction
  4. Resolution
103
Q

Describe the recognition and attachment stage of phagocytosis

A

Binding of IgG antibody or C3b complement to the bacteria improves recognition and attachment of the bacteria for engulfment by neutrophils (opsonization)

104
Q

Which receptors are involved in the recognition and attachment stage of phagocytosis?

A
  • Pattern recongnitionr receptors for PAMPs: TLRs, NOD, RIG-I
  • Receptors for opsonins: complement C3b, IgG, IgM
105
Q

What molecular compounds that neutrophils have allow them to opsonize bacteria in the recognition and attachment stage of phagocytosis?

A

Receptors for the IgG Fc (constant region) fragment and for C3b

106
Q

What sort of bacteria is opsonization a critical part of phagocytosis for?

A

Encapsulated bacteria

107
Q

cWhat effect do bacterial capsules have on phagocytosis?

A

Capsules decrease ability of neutrophils to phagocytose bacteria

108
Q

What compounds are key to immunity against encapsulated bacteria?

A

Antibodies and complement

109
Q

Describe the engulfment stage of phagocytosis

A

Neutrophils ingest bacteria by invagination of the cell membrane around the bacteria to form a vacuole (phagosome)

110
Q

Describe the destruction phase of phagocytosis

A

Phagosomes containing bacteria merge with lysosomes (containing myeloperoxidase, lysozyme, and other degradative enzymes) to form phagolysosomes, where killing occurs

111
Q

Is oxygen-dependent killing or oxygen-independent killing more effective?

A

Oxygen-dependent

112
Q

What occurs in oxygen-dependent killing by neutrophils?

A
  1. In the respiratory burst, NADPH oxidase forms the superoxide radical
  2. Superoxide dismutase forms hydrogen peroxide
  3. Myeloperoxidase in neutrophils catalyzes production of hypochlorite io
113
Q

Which sort of bacteria is hydrogen peroxide not effective against?

A

Catalase-producing organisms (staphylococci)

114
Q

What is the most effective mediator of the pathogen destruction?

A

Hypochlorite ion

115
Q

Describe oxygen-independent killing

A

Involves other numerous enzymes and is not as effective as oxygen-dependent killing

116
Q

Describe the resolution phase of phagocytosis

A

Neutrophils undergo rapid apoptosis after the inflammatory stimulus is removed

117
Q

What is the cause of chronic granulomatous disease?

What do patients suffer from?

A

Caused by a defect in NAPDH oxidase and failure to produce hydrogen peroxide and kill bacteria

Patients have recurrent infections from catalase-producing organisms

118
Q

What causes Chediak-Higashi syndrome?

What are its symptoms?

A

Caused by failure to form phagolysosomes

Leads to neutropenia, giant granules in the neutrophils and monocytes, albinism, and increased risk of pyogenic infections

119
Q

What may occur if a patient has low numbers or suppressed neutrophils and monocytes/macrophages?

A

Patient may not show the same signs and symptoms of infection with pathogens as quickly as someone that has an intact immune system, masking a serious illness

120
Q

What processes does inflammation resolution involve?

A
  • Some tissues can regenerate
  • Macrophages release anti-inflammatory TGF-beta
  • Macrophages recruit fibroblasts and release vascularization factors (granulation tissue)
  • If tissue architecture is lost, fibroblasts deposit collagen and ECM to form scars
121
Q

What are the two types of healing of cutaneous wounds?

A
  • Healing by first intention (primary union)
  • Healing by second intention (secondary union)
122
Q

When does healing by first intention (primary union) occur?

A

When the injury involves only the epithelial layer and the wound edges are approximated (i.e. clean surgical incision approximated by sutures)

123
Q

What is the principal mechanism of repair in healing by first intention?

A

Epithelial regeneration

124
Q

What are the stages of repair in healing by first intention?

A
  1. Hemorrhage and formation of a blood clot
  2. Acute inflammation
  3. Proliferation of the epithelial cells
  4. Organization of the wound
  5. A scar composed of connective tissue w/ scant inflammatory cells
125
Q

What occurs in the first stage of healing by first intention?

A

Hemorrhage and formation of a blood clot involving activation of the coagulation cascade, platelets, and fibrin

126
Q

What occurs in the second stage of healing by first intention?

A

Acute inflamamtion occurs initially with neutrophils and then macrophages (24-48) hours

The tissue is edematous with increased fluid and necrotic debris

Dehydration of the external surface of the clot and the overlying necrotic material forms a scab over the wound

127
Q

What occurs in the third stage of healing by first intention?

A

Proliferation of the epithelial cells where the basal cells at the edge of the epidermis proliferate and migrate along the dermis

The epithelial cells meet in the middle to close the wound and form and intact layer under the scab

Neutrophils regress and granulation tissue invades the wound space with macrophages, fibroblasts, and new blood vessels

128
Q

What occurs in the fourth stage of healing by first intention?

A

Organization of the wound occurs over weeks to months and involves collagen accumulation and fibroblast proliferation with decreased inflammation and regression of the vessels

129
Q

What occurs in the fifth stage of healing by first intention?

A

A scar composed of connective tissue with scant inflammatory cells

The epidermis is fairly normal and dermal appendeges are absent

Maximum strength slowly increases but never reaches the same level as before the wound

130
Q

When does healing by secondary intention (secondary union) occur?

A

When tissue loss is extensive and the wound edges cannot be brought together (e.g. ulcer)

131
Q

What are the similarities and differences between healing by secondary intention to healing by first intention?

A

In healing by secondary intention,

  • The clot is larger
  • Inflammation is more intense
  • There is more granulation tissue with greater likelihood of complications
  • Wound contraction occurs due to myofibroblasts
132
Q

Which cells are involved in wound contraction in healing by secondary intention?

A

Myofibroblasts

133
Q

What is fibrosis?

A

A similar process to wound healing that occurs in parenchymal organs with excessive deposition of collagen and other extracellular matrix components in the tissue in response to injurious stimuli

134
Q

What can continued/extensive fibrosis lead to?

A

Loss of organ function

135
Q

What is the major cytokine involved in fibrosis?

A

TGF-beta

136
Q

Why does a child with leukocyte adhesion deficiency, a defect in integrin (CD18 subunit) have increased peripheral blood neutrophils?

A

Integrins are required for adhesion of the neutrophils to the endothelium

Without adhesion to endothelium, neutrophils cannot cross the endothelium to exit in peripheral blood and other tissues

The number of neutrophils in peripheral blood will increase because the neutrophils cannot leave the peripheral blood

137
Q

What is the role of myeloperoxidase in neutrophils?

A

Myeloperoxidase catalyzes formation of hypochlorite ion, which is the most effective mediator of pathogen destruction

138
Q

What type of infections occur in patients with neutropenia?

A

Severe bacterial and fungal infections

Organisms that are typically not harmful or have low virulence can be fatal (opportunistic infections)

The bacterial infections include a wide range of bacteria (such as coagulase negative staph, other Gram positive, and Gram negative bacteria)

Sepsis is a major concern

Fungal infections can be invasive (Candida and Aspergillus) and can also involve the blood

139
Q

What is the function of prostaglandins?

A

Mediate vasodilation and icnreased vasculafr permeability, pain, and fever

140
Q

What do leukotrienes do?

A

Attrach neutrophils, mediate bronchospasm, and increased vascular permeability

141
Q

What is the function of the vascular component of inflammation?

A

Allows fluid, proteins, and cells to reach pathogen or tissue damage

142
Q

What are the mediators of endothelial cell contraction?

A
  • Prostaglandins
  • Leukotrienes
  • Bradykinins
  • Histamines
  • Others
143
Q

What are the soluble mediators of inflammation?

A
  • Proinflammatory cytokines
  • Arachidonic acid products
  • Bradykinins
  • Histamines
144
Q

What are the cellular mediators of inflammation?

A
  • Neutrophils and monocytes first
  • Then monocytes, lymphocytes, and plasma cells
145
Q

How do catalase producing organisms such as Staphylococci evade oxygen-dependent destruction?

A

Catalase breaks down hydrogen peroxide

This decreases the formation of hypochlorite by myeloperoxidase

146
Q

A 4 yo pt has recurrent infections, currently with Staph aureus pneumonia. Her peripheral blood neutrophil count is low and testing shows neutrophil NADPH oxidase function is normal. Which disease does she likely have?

A

Chediak-Higashi syndrome

147
Q

What are antibodies?

A

Proteins produced by B-cells and plasma cells that are composed of two heavy chains and two light chains

They play a major role in providing protection against infection

Antibody = immunoglobulin

148
Q

A light chain of an antibody can have which components?

A

Lambda

Kappa

149
Q

A heavy chain of an antibody can have which components?

A

Mu (IgM)

Delta (IgD)

Gamma (IgG)

Alpha (IgA)

Epsilon (IgE)

150
Q

What two parts do each heavy chain and light chain have?

A

Constant region

Variable region

151
Q

Which isotype/cass of antibody is a B cell receptor?

A

B cell receptor is surface IgM or IgD

152
Q

Which region of a chain on an antibody determines class/isotype?

A

Constant region

153
Q

What is the B cell receptor?

A

An antibody (IgM and IgD in naive B cells) on the surface of B cells that has a transmembrane domain and is associated with Ig-alpha (CD79a) and Ig-beta (CD79b)

Also has CD19

154
Q

Describe the specificity of a BCR on a B cell

A

Each B cell has a BCR specific for one antigen

155
Q

Which two genes are involved in the VJD recombinase?

A

RAG1
RAG2

156
Q

Which segments does a variable region of heavy chain have?

A

V, J, and D

157
Q

Which segments does a light chain of a variable region have?

A

V and J segments

158
Q

Apart from VDJ recombinase, what are RAG 1 and RAG 2 involved in?

A

TCR gene rearrangement

159
Q

Mutations in RAG1 or RAG2 can cause which immune disorder?

A

SCID

160
Q

What two types of diversity do B cell receptors have?

A

Combinatorial diversity

Junctional diversity

161
Q

What is combinatorial diversity?

A

Somatic recombination of the V and J gene regions occurs for antibody light chain variable regions and V, D, and J antibody regions for the heavy chain variable regions

Mediated by VDJ recombinase

162
Q

What are the characteristics of junctional diversity?

A
  • Nucleotides are added and removed during recombination
  • Occurs at the joining ends of the gene segments
  • Significantly increases diversity of the VDJ and VJ regions
  • Known as hypervariable regions
163
Q

What regions does junctional diversity affect?

A

Hypervariable regions

164
Q

Describe the “steps” in isotype determination of an antibody

A

Isotype of antibody is determined by constant region of heavy chain

  • Constant region genes join to variable region genes
  • IgM is produced first
  • Successful gene rearrangement and protein production leads to B cell development
165
Q

What are the stages in B cell development with regards to the B cell receptor?

A
  1. Pro-B cell has no heavy chains
  2. Pre-B cell has cytoplasmic mu heavy chains and is pre-BCR, successful gene rearrangement of mu heavy chain
  3. Immature B cell has IgM surface BCR, successful gene rearrangement of the light chain (kappa or lambda)
  4. Naive B cell has IgM, IgD surface BCR
166
Q

How does the pro-B cell to pre-B cell transition occur?

A

Successful gene rearrangement of the mu heavy chain

167
Q

How does the pre-B cell to immature B cell transition occur?

A

Successful gene rearrangement of the light chain (kappa or lambda) which allows for expression of an IgM BCR

168
Q

What is Bruton’s tyrosine kinase?

A

A signal transduction protein required for pre-B cells to differentiate to B cells

169
Q

What causes X-linked agammaglobulinemia?

What does a patient with X-linked agammaglobulinemia experience?

A

Mutation in Bruton’s tyrosine kinase (cannot go from pre-B cell to immature B cell)

Markedly decreased B cells, low antibodies of all types, no tonsils

170
Q

What type of infections would patients with X-linked agammaglobulinemia be most susceptible to?

A

Pyogenic infections

(No antibodies -> decreased opsonization -> trouble w/ extracellular bacteria especially ones with capsules -> get a neutrophil pus-producing response)

171
Q

What two things are critical for increased antibody affinity for antigen?

A
  • Germinal centers
  • CD40L: CD40 interactions
172
Q

What are the steps of antigen recognition and B cell activation?

A
  1. Antibody variable region of the IgM component of the BCR recognizes and binds a specific antigen
  2. Binding leads to receptor cross-linking in association with Ig-alpha/Ig-beta (CD79a/CD79b) and phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs)
  3. ITAM phosphorylation triggers downstream signaling pathways
173
Q

What does binding antigen signal through?

A

ITAMs

174
Q

What is CD21 (CR2)?

A

A complement receptor expressed with CD19 on the B cell surface

175
Q

How does CD21 serve as a second signal for B cells?

A

CD21 interacts with the C3d complement component bound to antigen (alternative complement pathway)

Enhances B cell activation ~1000 fold

176
Q

Where does the B cell migrate after antigen binding?

Why?

A

Secondary lymphoid tissues

To interact with T cells, antigen-presenting cells, and follicular dendritic cells

177
Q

What occurs in the germinal center of the lymphoid tissues to antigen activated B cells?

A
  • Rapidly divide
  • Antigen-specific B cells express antigenic peptides on MHC class II to CD4+ T helper cells
  • Interact with antigen-specific T cells, APCs, and follicular dendritic cells
  • Undergo isotype switching, somatic hypermutation, and affinity maturation
178
Q

How do B7 and CD40 act as a second signal for B cells?

A

After binding of antigen, B cell upregulates costimulatory molecules (B7 and CD40)

CD40 interacts with CD40L on T cell

B7 interacts with CD28 on T cell

BCR takes up the antigen and expresses protein antigens on MHC class II protein

179
Q

What does T cell express to provide a second signal?

A

T cell expresses CD40L which binds to CD40 on the B cell to provide a second signal

(also B7 of B cell which interacts with CD28 of T cell)

180
Q

Production of which molecules leads to isotype/class switching?

A

Production of cytokines by the CD4+ T cells in the presence of CD40:CD40L interaction

181
Q

What signal triggers B-cell isotype switching?

A

Certain cytokines in the setting of CD40 binding by CD40L

182
Q

What occurs in B cell isotype switching?

A

B cells switch the heavy chain constant region from the IgM constant region to a downstream isotype (IgG, IgA, or IgE)

Antigen specificity (VJD) is not altered by isotype switching

183
Q

Why do B cells undergo isotype switching?

A

Different antibody isotypes are specialized for different protective responses

Note: isotype switching does not alter antigen binding specificity

184
Q

What is deleted during B cell isotype switching?

A

Intervening heavy chain DNA

B cells cannot revert back to expressing IgM antibodies after isotype switching

185
Q

Describe the succession of isotype switching in B-Cells

Can the order ever change?

A

IgM -> IgG -> IgA -> IgE

The order can never change; in order to switch isotypes, DNA is deleted (this is irreversible)

186
Q

What are the functions of follicular dendritic cells?

A
  • Capture complement/antigen complexes on the cell surface
  • Present antigen complexes to B cells and allow selection for B cells with higher affinity/avidity antibodies
187
Q

What does T cell co-stimulation cause B cells to undergo?

What occurs in this process?

A

Somatic hypermutation in the germinal center

Antibody variable regions are subject to random point mutations (activation-induced cytidine deaminase [AID])

Some of the mutations give rise to higher affinity/avidity antibodies which are selected for by FDCs and T cell interactions

188
Q

What is affinity maturation?

A

The process of selection for increased affinity/avidity in B cells in the germinal center

This occurs after B cells have undergone somatic hypermutation in the germinal center

189
Q

What do B cells undergo in the germinal center?

A

B cells are antigen-selected

  • Antigen-specific B cells interact with antigen-specific CD4+ T cells, antigen-presenting cells, and follicular dendritic cells
  • B cells mutate the antibody genes to improve binding to antigen
  • B cells that are highly antigen-specific differentiate into plasma cells and memory B cells
190
Q

In the germinal center, what is the fate of B cells that are highly specific for antigen??

A
  • They differentiate into Antibody-producing plasma cells
    • Some may become long-lived memory B cells
191
Q

Describe the antibodies that plasma cells produce

A

Antibodies are highly specific for an antigen

This makes sense, because these plasma cells came from the B-cells with the highest affinity for a specific antigen (they were selected in affinity maturation)

192
Q

What proteins do plasma cells express?

A

CD38, CD138, and cytoplasmic immunoglobulins

193
Q

Where is CD19 expressed?

A

Expressed on B cell surface

Component of BCR

194
Q

What are CD79a and CD79b?

A

B cell receptor associated proteins (Ig-alpha, Ig-beta) involved in signal transduction after antigen crosslinking

Their activation leads to phosphorylation of ITAMs to trigger downstream signaling pathways

195
Q

Where is CD20 expressed?

A

B cell surface

196
Q

What is CD21?

A

CD21 = Complement receptor (CR2)

It binds to the complement component C3d (on the antigen) when the antigen binds to the antibody on the B-cell.

This dramatically enhances the B-cell response

197
Q

What is CD40?

A

CCD40 is a co-stimulatory molecule expressed on B cell surface. It binds to CD40L on helper T cells to provide a second signal to B cells.

Critical for class switching, affinity maturation, and differentiation

198
Q

Where are CD38 and CD138 expressed?

A

Plasma cell surface

199
Q

On an individual naive B cell expressing both IgM and IgD surface antibody, which regions of the surface IgM antibodies are identical to the surface IgD antibody?

A

Variable regions of both heavy and light chains are identical between the IgM and IgD antibody

B cells only express one heavy chain variable region and one light chain variable region, even when the constant regions differ

200
Q

On an individual naive B cell expressing both IgM and IgD surface antibody…

which regions of the surface IgM antibodies are different from the surface IgD antibody?

A

The constant region of the heavy chain

IgM has a Mu heavy chain

IgD has a Delta heavy chain

201
Q

What is the role of follicular dendritic cells in the adaptive immune response?

A

FDCs are present in the germinal center and trap complement/antigen complexes on their surface to present to B cells

B cells recognize and bind to the antigen on the surface of FDC

FDCs select for the B cells with antibodies on their surface (BCRs) that bind with high affinity/avidity to the antigen on the surface of the FDCs

202
Q

Can class switching occur in the absence of T cells?

Why?

A

Yes, but it is very limited

T cells express CD40L, which binds to CD40 on B cells. This is critical in the formation of an effective germinal center response which gives rise to isotype switching and somatic hypermutation

203
Q

What might happen if the immune system cannot recognize “self” component?

A

Autoimmunity

204
Q

What might happen if the immune system fails to recognize “non-self”?

A

No protection from infection

205
Q

What is humoral immunity?

What does it protect us from?

What mediates it?

A

Part of adaptive immunity

  • Antibody-mediated
  • Protects us from extracellular bacteria, viruses, toxins
  • Mediated by B-cells and plasma cells
206
Q

What are the roles of B-cells and plasma cells in adaptive immunity?

A

Mediate humoral immunity

  • Neutralize toxins and viruses
  • Opsonize pathogens
    • Makes them tastier to macrophages :)
207
Q

What is cell-mediated immunity?

What does it protect us from?

What mediates it?

A
  • The cell-mediated arm of adaptive immunity
  • Protects us from intracellular bacteria, viruses, fungi, parasites
  • Mediated by T-cells and macrophages
208
Q

What are the roles of T-cells and macrophages in adaptive immunity?

A

Mediate cell-mediated immunity

  • Directly kill virus-infected cells
209
Q

Which immune cells would respond to the presence of a bacterial polysaccharide capsule in the body?

A

B-Cells; B-cell receptors can recognize and respond to almost anything, including proteins, carbohydrates, drugs, etc.

(T-cells can only recognize peptides in the context of MHC)

210
Q

What is the difference between an antibody and a B-cell receptor?

A
  • An antibody is secreted by B-cells
  • A B-cell receptor remains attached to the B-cell membrane

Antibodies and B-cells have similar structures and can bind similar molecules

211
Q

T-Cell independent immune response

  1. Which type of immunity?
  2. What mediates it?
  3. What does it do?
A

T-Cell independent immune response

  1. Highly specific, humoral (antibody-mediated) arm of adaptive immunity
  2. Mediated by B-cells
  3. Produces IgM in response to multivalent non-proteins (ex: polysaccharide capsule)
212
Q

What kinds of molecules would activate the T-cell independent response?

A

Multivalent non-proteins

Example: polysaccharide capsule, other non-protein non-self molecules

213
Q

Antibody-driven immune response

  1. Which type of immunity?
  2. What mediates it?
  3. What does it do?
A

Antibody-driven immune response

  1. Highly specific, humoral arm of adaptive immunity
  2. Mediated by CD 4+ helper T-cells and B-Cells
  3. MHC II presents peptides to CD4+ helper T-cells
    • The helper T-cells help out by secreting molecules that activate B-cells to produce antibodies
    • The antibodies activate CD8+ cytotoxic T-cells to attack and destroy virus-infected cells
214
Q

What is the difference between an immunogen and an antigen?

A
  • An antigen is any molecule that reacts with an antibody
    • Almost anything can react with an antibody
  • An immunogen is any molecule that induces an immune response
    • Not all antigens are immunogens
215
Q

What do antibodies do?

A
  • Neutralize toxins and viruses
  • Opsonize bacteria (enhance phagocytosis)
216
Q

What kinds of molecules will T-Cell receptors recognize?

A

T-cell receptors (TCRs) will ony recognize proteins

All T-cells require the activation of the TCR and co-receptor: CD4+ and CD 8+ co-receptors only recognize linear peptides presented by MHC

  • CD4+ Helper T-cells recognize peptides presented by MHC II
  • CD8+ Cytotoxic T-cells recognize peptides presented by MHC I
217
Q

Which cells express MHC Class I?

A

All nucleated cells in the human body have MHC class I and can present antigen to CD8+ Cytotoxic T-Cells

218
Q

Which cells express MHC class II?

A

Professional antigen-presenting cells have MHC class II. They present antigen to CD4+ Helper T-cells

219
Q

In the most general sense, what is required for B-cell and T-cell activation?

A

2 signals

  1. Recognition of antigen
  2. Costimulatory signal
220
Q

In general, what is required for B-cell activation?

A

2 signals

  1. Antigen recognition by a surface antibody (B-cell receptor)
  2. From T cells through…
    a) Costimulatory molecules in T-cell dependent immune response
    b) complement in T-cell indepenent immune response
221
Q

In general, what is required for CD4+ Helper T-cell activation?

A

2 signals

  1. TCR and co-receptor CD4 recognize and bind the peptide bound to MHC II on the APC
  2. The APC also expresses B7, a protein that binds to CD28 on the T-cell

Activation -> Cytokine production

222
Q

In general, what is required for CD8+ cytotoxic T-cell activation?

A

2 signals

  1. TCR and coreceptor CD8 recognize and bind to the peptide bound to MHC I, presented by an APC
  2. Cytokines secreted from CD4+ cells
223
Q

How do CD8+ Cytotoxic T-cells kill their prey?

A

2 methods

  1. Production of cytotoxic molecules like perforin or granzyme
  2. Expresion of FasL (induces apoptosis when binding to the Fas protein)
224
Q

Which cytokine promotes T-cells growth and differentiation?

A

IL-2

225
Q

List the physical and physiological barriers that prevent infection

A
  1. Skin and mucous membranes
  2. Ciliated cells in the respiratory tract
  3. Enzymes in saliva, other secretions
  4. Low pH of skin and mucous
  5. Defensins in GI tract and respiratory tract
  6. Normal fluid flow
  7. Normal flora
226
Q

What physical/physiological barriers protect against bacterial infection in the respiratory tract?

A

Ciliated cells (The ciliary elevator)

Beta-defensin

227
Q

What might cause damage to the ciliary elevator?

A

Alcohol, cigarettes, viral infections

228
Q

Why are individuals with heart valve defects more susceptible to infection?

A

Stagnant fluid allows for infection by bacteria

(normally, fluid flow prevents colonization and infection)

229
Q

Why are patients with extensive burns at increased risk of infection?

A

Skin is the first line of defense against invasion by pathogens

Multiple holes/defects in this defense leave the body susceptible to infection

230
Q

How do normal flora protect us from infection by harmful bacteria?

A

Normal flora prevent pathogen invasion

Nobody really knows exactly how this works, but it it hypothesized that the normal flora occupies receptors that could be used by a pathogen to enter the body

Note: Normal flora in the wrong palce can be pathogenic

231
Q

Which complement protein first recognizes antigen-antibody complexes in the classic pathway?

A

C1

(C1 = the #1 antigen-antibody recognizing protein)

232
Q

Which complement proteins trigger mast cells to degranulate and release histamine?

A

C3a, C5a

233
Q

Which complement protein is chemotactic to neutrophils?

What does this mean?

A

C5a

Chemotactic = ~attractive~

C5a recruits neutrophils

234
Q

Which complement protein opsonizes bacteria?

A

C3b

235
Q

Which complement proteins form the membrane attack complex?

A

C5a, C6, C7, C8, C9

-> Direct microbe killing

236
Q

Which complement proteins inhibit the formation of C3 convertase?

A

C1 esterase inhibitor

Decay accelarating factor (CD55)

237
Q

What is a PAMP?

A

PAMP = Pathogen-associated molecular pattern

Not present on eukaryotic cells

Basically, a PAMP is the pattern that the innate immune system uses to recognize non-self and initiate an immune response

238
Q

What is the pattern on pathogens that cells of our innate immune system recognize?

A

PAMPs (pathogen-associated molecular patterns)

239
Q

What components of our immune system recognize extracellular pathogenic patterns?

A

Toll-Like Receptors (TLRs)

Mannose Receptors

240
Q
  1. What are TLRs?
  2. Where are they found?
  3. What do they do?
A
  1. TLRs = Toll Like Receptors
    - A family of 10 receptors
  2. TLRs are found on the surfaces of macrophages, dendritic cells, mast cells, and B cells
    - Cells that help connect the innate and adaptive immune systems
  3. TLRs recognize microbial components (like PAMPs) and initiate the synthesis of cytokines
241
Q

What is TLR4?

What does it do?

A

TLR4 = Toll-like receptor 4

Recognizes LPS on the surface of gram negative bacteria

(Works together with CD14 expressed by monocytes and macrophages to recognize LPS)

242
Q

Which receptors participate in the recognition of LPS?

A

TLR 4

CD14

Both are expressed by monocytes and macrophages

243
Q
  1. What are Mannose receptors?
  2. Where are they found?
  3. What do they do?
A
  1. Mannose receptors recognize mannose, a polysaccharide commonly found on the surface of bacterial and yeast cells
  2. Mannose receptors are found on the surfaces of dendritic cells and macrophages
  3. When the mannose receptor binds mannose on the bacterial cell, it induces phagocytosis
244
Q

What components of our immune system recognize intracellular pathogens?

A

NOD receptors

RIG-1 helicase

245
Q
  1. What are NOD receptors?
  2. Where are they found?
  3. What do they do?
A
  1. NOD receptors are pattern-recognition receptors that regognize pathogens within our cells
  2. In the cytosol of immune-competent cells
  3. NOD receptors recognize peptidoglycan
246
Q
  1. What is RIG-1 helicaase
  2. Where is it found?
  3. What does it do?
A
  1. RIG-1 helicase is a pattern recognition protein that recognizes intracellular pathogens
  2. RIG-1 helicase is found in cytoplasm of immune-competent cells
  3. RIG-1 helicase recognizes nucleic acids of viruses
247
Q

Which receptor is especially important in fighting a listeria infection in our bodies?

A

NOD receptors

Listeria is an intracellular pathogen; NOD receptors in the cytoplasm of immune-competent cells can recognize the pathogen and help mount an immune response

248
Q

Which cytokine recruits neutrophils?

A

IL-8

A pro-inflammatory cytokine

249
Q

Which cells link innate and adaptive immunity?

A

Antigen presenting cells (APCs): Macrophages and dendritic cells

250
Q

How do antigen-presenting cells connect adaptive and innate immunity?

A

Innate

  • APCs use pattern recognition to recognize pathogens

Link

  • APCs digest pathogens and turn them into antigens that they present to T-cells
  • APS produce cytokines that activate the adaptive immune response of T-Cells, B-Cells, and plasms cells

Adaptive

  • activated T-Cells, B-Cells, and plasma cells carry out the adaptive immune response
251
Q

Pattern recognition is part of the innate immune response.

Why then, do cells of the adaptive immune response also express TLRs?

A

TLRs are used to recognize patterns of invader cells; pattern recognition is the driver of the innate immune system

Macrophages are the mediators of the adaptive immune response, but they are also important for connecting the innate and adaptive immune systems

They use TLRs to recognize patterns of invader pathogens so they can initate the adaptive immune response

252
Q

Define inflammation

A

The body’s response to infection or tissue necrosis.

Inflammation allows inflammatory cells, plasma proteins, and fluid to enter the interstitial space.

253
Q

Inflammation can cause extensive damage to our tissues.

Why then, does our body produce an inflammatory response?

A

The goal of inflammation is to eliminate pathogens and clear debris.

The process is not easy on our body, but failure to eliminate pathogens can lead to disease progression and death

254
Q

Which mediators of inflammation mediate pain?

A

Prostaglandins

Bradykinin

255
Q

What mediates a pyogenic response of our immune system?

A

Pyogenic (pus-forming) immune responses are due to the action of neutrophils, antibodies, and complement during accute inflammation.

Often triggered by extracellular pathogens

256
Q

What is a giant cell?

Where can we find them?

A

A giant cell is a large macrophage with multiple nuclei

We typically find them surrounding granulomas

257
Q

What kinds of pathogens are often associated with chronic inflammation?

A

Intracellular pathogens

Often triggers granulomatous response mediated by macrophages, CD4+ (helper) T cells

258
Q

Which mediators of inflammation promote mediate vasodilation?

A

Prostaglandins

Bradykinins

Histamines

259
Q

Which mediators of inflammation increase vascular permeability?

A

Prostaglandins

Leukotreines

Bradykinins

Histamines

260
Q

Which interleukins are pyrogenic?

A

Pyrogenic = causes fever

IL-1, IL-6

261
Q

In phagocytic cell recruitment and migration, what molecules direct neutrophils to the site of inflammation?

A

IL-8, C5a

These molecules are chemokines; they are chemotactic for neutrophils

This occurs after diapedesis (neutrophil escape from the blood vessel), when the neutrophil is in the tissue

262
Q

Which cytokine increases cyclooxygenase?

A

TNF-alpha

263
Q

What are the steps of phagocytic cell recruitment and migration into sites of inflammation?

A
  1. Margination
  2. Rolling
  3. Adhesion
  4. Diapedesis and Chemotaxis
264
Q

Describe the margination step of phagocytic cell recruitment and migration

A

Margination includes…

  • Vasodilation
  • Increased vascular permeability
  • Slowing of blood flow
  • White blood cells moving to the periphery of flow
265
Q

Describe the rolling step of phagocytic cell recruitment and migration

A

Sialyl Lewis X on neutrophils binds to P-selectin and E-selectin. This causes the neutrophil to roll slowly along the endothelium

Sialyl Lewis X is expressed constituitively on neutrophils

P-selectin and E selectin are induced by histamine, IL-1, and TNF-alpha

266
Q

What is Sialyl Lewis X?

What process is it involved in?

A

Sialyl Lewis X is a protein expressed constituitively on the surface of neutrophils

It binds to P-selectin in E-selectin in the “rolling” step of phagocytic cell recruitment and migration

267
Q

Which molecules induce P-selectin and E-selectin?

Where are P-selectin and E-selectin expressed?

Why is this important?

A

Histamine, IL-1, and TNF-alpha induce P-selectin and E-selectin expression on the inner walls of blood vessel endothelium

They are induced in response to inflammation; they are important in the rolling step of phagocytic cell recruitment and migration. Without P-selectin and E-selectin, neutrophils cannot reach the site of inflammation

268
Q

Describe the adhesion step of phagocytic cell recruitment and migration

A

Integrins expressed on neutrophils bind to ICAM and VCAM, causing firm adhesion of the neutrophil to the endothelium

  • Integrin expression is induced by C5a and leukotrine
  • ICAM and VCAM are cellular adhesion molecules induced by TNF-alpha and IL-1
269
Q

Which molecules induce integrin expression on neutrophils?

Why is this important?

A

C5a, leukotrine

Integrins are important because they bind to ICAM and VCAM in the ahesion step of phagocytic cell recruitment and migration.

Without integrins (and C5a and leukotrine), neutrophils would not be able to reach the site of inflammation

270
Q

Which molecules induce ICAM and VCAM?

Where are ICAM and VCAM expressed?

Why is this important?

A

ICAM and VCAM are induced by TNF-alpha and IL-1

ICAM and VCAM are cellular adhesion molecules expressed on the inner endothelium of blood vessels

ICAM and VCAM bind to integrins on neutrophils in the adhesion step of phagocytic cell recruitment and migration; without ICAM and VCAM, neutrophils would not reach the site of inflammation

271
Q

Describe the diapedesis and chemotaxis step of phagocytic cell recruitment and migration

A

Diapedesis = neutrophil migrates through endothelium to escape from the blood vessel

Chemotaxis = neutrophil migrates through tissue toward chemokines IL-8 and C5a

272
Q

S. pyogenes secretes C5a peptidase

Describe the effect of C5a peptidase on phagocytic cell recruitment and migration

A

C5a peptidase destroys C5a, which is a chemokine for neutrophils

Without C5a, neutrophils chemotaxis will be decreased; they won’t be able to effectively move toward the site of inflammation

273
Q

A patient has had multiple, recurrent bacterial infections without appropriate pus formation.

What might be the problem?

What evidence would support your diagnosis?

A

This patient might have Leukocyte Adhesion Deficeincy (LAD), due to a defect in the CD18 subunit of integrins. As a result, neutrophils cannot escape from blood vessels to get ot the tissue (Neutrophils can’t adhere to endothelium = they can’t undergo diapedesis)

Normal to high neutrophil count in the peripheral blood would support your diagnosis

274
Q

A defect in the CD18 subunit if integrins causes…

A

Leukocyt adhesion deficiency (LAD)

Neutrophils can’t adhere to the endothelium, which means they cannot migrate to the site of inflammation

275
Q

A defect in NADPH oxidase leads to…

A

Chronic granulomatous disease

  • Defective NADPH oxidase
    • -> Failure to produce hydrogen peroxide
      • -> Cannot make hypochlorite ion
        • Cannot kill bacteria effectively
276
Q

What destructive enzymes are contained in the lysosome?

A

Myeloperoxidase

Lysozyme

Other degradative enzymes

277
Q

A patient has a history of recurrent infections from catalase (+) bacteria with the formaiton of multiple granulomas

What might be the problem?

A

Chronic granulomatous disease;

A defect in NADPH oxidase results in downstream failure to produce the hypochlorite ion from hydrogen peroxide;

Hydrogen peroxide alone is not effective at killing catalase (+) bacteria, because these bacteria can break down hydrogen peroxide.

278
Q

Which inherited immune disorder prevents the formation of phagolysosomes?

What is the clinical presentation?

A

Chediak-higashi syndrome; a defect of organelle trafficking

The patient may also have:

  • Neutropenia
  • Giant granules in neutrophils and monocytes
  • Albinism
  • Increased risk of pyogenic and opportunistic infection
279
Q

How might chronic inflammation cause cancer?

A
  • Chronic inflammation means chronic complement activation
  • This causes activated neutrophils to release free oxygen radicals in a nonspecific manner
    • This is great for killing bacteria, but not great for our cells
  • Persistent exposure to free oxygen radicals can cause cell proliferation and DNA damage
    • This increases the risk of dysplastic or neoplastic changes in tissue
280
Q

What type of infections occur in patients with neutropenia?

A

Neutropenia = fewer neutrophils than normal. The body is misisng the “first responders” to infection, which can result in more innocuous organisms taking hold and causing disease

  • Infection by opportunistic pathogens
  • Bacterial and fungal infections
    • Even organisms with typically low virulence can cause disease
    • Example: catalase (-) organisms
    • Fungal infections may be invasive
  • Increased risk for sepsis
281
Q

What conditions might result in weakened accute inflammation?

A

Any condition that prevents an adequate number of neutrophils from reaching the site of infection/injury

Examples:

  • Neutropenia (Chediak-higashi syndrome, chemotherapy)
  • Failure of neutrophils to migrate to the site of infection (Leukocyte Adhesion deficiency)
282
Q

What two chains are present in an antibody?

A

Heavy chain

Light chain

283
Q

Which chain and region of an antibody determines the isotype?

A

Heavy chain constant region

284
Q

What are the possibilities for the constant region of a heavy chain?

A
  • Mu (IgM)
  • Delta (IgD)
  • Gamma (IgG)
  • Alpha (IgA)
  • Epsilon (IgE)
285
Q

What are the possibilities for the constant region of a light chain?

A
  • Kappa
  • Lambda
286
Q

What is light chain restriction?

A

All antibodies on a B cell must be either all kappa or all lambda

Cannot have two different light chains expressed on B cell or plasma cell

(light chain can be used to identify clonal B cells)

287
Q

What does the Fc portion of an antibody for?

A

Fragment, crystallizable

288
Q

Where is the complement binding region (IgM and IgG) of an antibody found?

A

Fc portion

289
Q

When does the complement binding region become accessible?

Why?

A

When antigen binds

Only want complement active when immune response is necessary

290
Q

What are the two parts of the Fc region of an antibody?

A

Complement binding region

Phagocyte binding region

291
Q

What region does the Fc portion of the antibody contain?

A

Constant region

292
Q

What sorts of cells have receptors that bind the Fc portion of antibodies?

A

Phagocytes

293
Q

What are the two main functions of the Fc portion of an antibody?

A
  • Enhances phagocytosis (opsonization)
  • Mediates many effector functions
294
Q

What does the Fab portion of an antibody stand for?

A

Fragment, antigen-binding

295
Q

What two regions does the Fab portion of an antibody contain?

A
  • Variable regions
  • Complementarity-determining regions (CDRs)
296
Q

Each B cell makes an antibody with a ____ variable region that binds to ____ antigen(s)

A

Each B cell makes an antibody with a unique variable region that binds to one antigen

297
Q

What are the main points about the T cell dependent immune response?

A
  • Surface IgM BCR recognizes a protein antigen
  • B cells express peptides on MHC class II
  • T cell-B cell interaction of CD40/CD40L leads to germinal center formation, class switching, and somatic hypermutation
  • Antibodies produced are of high affinity
298
Q

In the T cell dependent immune response, surface ____ BCR recognizes _____

A

In the T cell dependent immune response, surface IgM BCR recognizes a protein antigen

299
Q

In the T cell dependent immune response, B cells express _____ on _____

A

In the T cell dependent immune response, B cells express peptides on MHC class II

300
Q

In the T cell dependent immune response, T cell-B cell interaction of ___ leads to ___, _____, and _____

A

In the T cell dependent immune response, T cell-B cell interaction of CD40/CD40L leads to germinal center formation, class switching, and somatic hypermutation

301
Q

In the T cell dependent immune response, antibodies produced have ____ affinity

A

In the T cell dependent immune response, antibodies produced have high affinity

302
Q

What are the main points about the T cell independent immune response?

A
  • B cells recognize a non-protein antigen (e.g. polysaccharide cell wall) which can crosslink surface IgM and activate the B cell
  • Antigens often have repeated identical antigenic epitopes that cause crosslinking of the BCR complex
  • This leads to production of secreted IgM (sometimes IgG and IgA) which is specific for the antigen
  • Complement (through CD21) and TLR are involved in B cell activation
  • Affinity generally lower
  • Splenic B cells (marginal zone) and mucosal B cells (B1) are involved
303
Q

In the T cell independent immune response, B cells recognize _____ antigen (e.g. polysaccharide cell wall) which can crosslink surface _____ and active the _____ cell

A

In the T cell independent immune response, B cells recognize a non-protein antigen (e.g. polysaccharide cell wall) which can crosslink surface IgM and activate the B cell

304
Q

In the T cell independent immune response, antigens often have _____ ______ antigenic epitopes that causes crosslinking of the BCR complex

A

In the T cell independent immune response, TI antigens often have repeated identical antigenic epitopes that causes crosslinking of the BCR complex

305
Q

In the T cell independent immune response, ____ (sometimes IgG and IgA) that is ____ for the antigen is secreted

A

In the T cell independent immune response, IgM (sometimes IgG and IgA) that is specific for the antigen is secreted

306
Q

In the T cell independent antigen response, ____ (through CD21) and ___ are involved in B cell activation

A

In the T cell independent antigen response, complement (through CD21) and TLR are involved in B cell activation

307
Q

In the T cell independent antigen response, antibodies have ____ affinity

A

In the T cell independent antigen response, antibodies have lower affinity

308
Q

_____ B cells (marginal zone B cells) and ____ B cells (B1 B cells are involved in the T cell independent antigen response

A

Splenic B cells (marginal zone B cells) and mucosal B cells (B1 B cells) are involved in the T1 antigen response

309
Q

Compare and contrast the T cell dependent and T cell independent responses in terms of chemical nature, isotype switching, affinity maturation, memory, and location

A
310
Q

What is the chemical nature of the antigen for the T cell dependent immune response?

A

Protein

311
Q

What is the chemical nature of the antigen for the T cell independent immune response?

A

Repetitive polymeric antigen (polysaccharide, glycolipid)

312
Q

Describe isotype switching in T cell dependent immune response

A

IgG, IgE, and IgA

313
Q

Describe isotype switching in T cell independent immune response

A

Limited (some IgG and IgA)

314
Q

Does affinity maturation occur in the T cell dependent immune response?

A

Yes

315
Q

Does affinity maturation occur in the T cell independent immune response?

A

No

316
Q

Is there memory in the T cell dependent immune response?

A

Yes

317
Q

Is there memory in the T cell independent immune response?

A

Limited

318
Q

Where does the T cell dependent immune response occur?

A

Germinal center

319
Q

Where does the T cell independent immune response occur?

A

Splenic marginal zone and mucosal regions

320
Q

What are natural antibodies?

A

Some antibodies (namely IgM) present prior to exposure

321
Q

What sort of response to natural antibodies promote? To what antigens?

A

T cell independent B cell response to environmental antigens

322
Q

What is notable about cross-reactivity with regards to natural antibodies?

A

Some degree of cross-reactivity between similar antigen

323
Q

What is the most clinically significant example of natural antibodies?

A

Natural antibodies against ABO glycoproteins on patient’s RBCs that lack the A or B antigen

Antibodies present w/o prior exposure to foreign RBCs

324
Q

An 82 yo male comes in to get a pneumoccocal vaccination. You explain he needs the vaccine that contains the diphtheria toxoid attached to pneumoccocal polysaccharide capsule (PCV13). For an effective antibody immune response to the capsule, what is essential?

A

Helper T cells recognize the diphtheria toxoid

325
Q

There are ____ receptors on neutrophils that bind the IgG ___ portion

A

There are IgG receptors on neutrophils that bind the IgG Fc portion

326
Q
A
327
Q

A 3 yo boy has had multiple recurrent bacterial infections (pneumonia and ear infections) and diagnostic studies show his T cells do not express CD40L after activation. What finding would you expect upon evaluation of serum immunoglobulins?

A

Increased IgM and decreased IgG and IgA (hyper IgM syndrome)

328
Q

What class of antibody is most effective at blocking bacteria from attaching to the mucosa in the stomach?

A

IgA antibodies

329
Q

How can an effective vaccine be developed against a hapten (a molecule that does not elicit an immune response)?

A

Attaching a hapten to a protein will drive a B and T cell immune response, leading to the development of antibodies against the hapten

330
Q

What is an example of an antigen that can induce a T cell independent immune response?

A

Polysaccharide capsule vaccine against pneumococcus (Pneumovax 23)

331
Q

What three types of cells does the T cell dependent immune response involve?

A
  • Antigen presenting cells (presenting antigen and producing cytokines)
  • CD4+ helper T cells
  • B cells
332
Q

Which cell type does the T cell independent immune response involve?

A

B cells

333
Q

Describe the antibody response to a T cell independent antigen in the marginal zone or mucosa

A
  • Naive B cells (marginal zone, mucosal) recognize antigen through IgM BCR
  • Co-stimulation occurs through complement receptors (CD21) and/or TLRs
  • Antigen-specific B cells differentiate to short-lived plasma cells and produce predominantly IgM
    • Limited isotype switch can occur (IgG, IgA)
    • No effective affinity maturation
    • Limited memory
334
Q

Where are the naive B cells located that are involved in the antibody response to a T cell independent antigen?

A
  • Marginal zone
  • Mucosa
335
Q

In the antibody response to a T cell independent antigen, naive B cells (marginal zone, mucosal) recognize _____ through ____ BCR

A

In the T cell indendent immune response, naive B cells (marginal zone, mucosal) recognize antigen through the IgM BCR

336
Q

In the antibody response to a T cell independent antigen, ____ occurs through ____ (e.g. CD21) and/or ____

A

In the antibody response to a T cell indepdent antigen, co-stimulation occurs through complement receptors (e.g. CD21) and/or TLRs

337
Q

In the antibody response to a T cell independent antigen, antigen-specific B cells differentiate to short-lived ____ cells and produce predominantly ____

A

In the antibody response to a T cell independent antigen, antigen-specific B cells differentiate to short-lived plasma cells and produce predominantly IgM

338
Q

In the antibody response to a T cell independent antigen, there is ____ isotype switching (IgG, IgA), _____ affinity maturation, _____ memory

A

In the antibody response to T cell independent antigen, there is limited isotype switching (IgG, IgA), no effective affinity maturation, and limited memory

339
Q

Describe the steps of the antibody response to a T cell depdent antigen for naive B cells outside of the germinal centers

A
  • Recognize antigen through IgM BCR
  • Internalize antigen on the IgM
  • Degrade antigen to peptides to present on MHC class II
  • Express CD40 and B7 (CD80/86)
  • Can receive additional signals from complement, TLR, CD4+ T cells, and/or cytokines
  • After binding antigen and activation, B cells migrate towards B cell-T cell zone border (secondary lymphoid tissues)
340
Q

Where are the naive B cells in a T cell dependent antigen response located?

A

Outside of the germinal centers

341
Q

In the antibody response to a T cell dependent antigen, naive B cells recognize ____ through the ____ BCR

A

In the antibody response to a T cell dependent antigen, naive B cells recognize antigen through the IgM BCR

342
Q

In the antibody response to a T cell dependent antigen, naive B cells ____ the antigen on the IgM

A

In the antibody response to a T cell dependent antigen, naive B cells internalize the antigen on the IgM

343
Q

In the antibody response to a T cell dependent antigen, naive B cells degrade antigen to peptides to present on ________

A

In the antibody response to a T cell dependent antigen, naive B cells degrade antigen to peptides to present on MHC class II

344
Q

In the antibody response to a T cell dependent antigen, naive B cells express _____ and _____

A

In the antibody response to a T cell dependent antigen, naive B cells express CD40 and B7 (CD80/86)

345
Q

In the antibody response to a T cell dependent antigen, naive B cells can receive additional signals from _____, _____, _____, and/or ____

A

In the antibody response to a T cell dependent antigen, naive B cells can receive additional signals from complement, TLR, CD4+ T cells, and/or cytokines

346
Q

In the antibody response to a T cell dependent antigen, naive B cells migrate _______ (secondary lymphoid tissue) after binding ____ and ____

A

In the antibody response to a T cell dependent antigen, naive B cells migrate towards B cell-T cell zone border (secondary lymphoid tissue) after binding antigen and activartion

347
Q

Describe the steps of the antibody response to a T cell dependent antigen for antigen-activated B cells in the B cell-T cell zone border outside germinal center

A
  • Interact with antigen-activated CD4+ T helper cells
  • Differentiate to short-lived plasma cells (plasmablasts)
    • Produce and secrete IgM antibody
    • Antibody is low affinity for antigen
348
Q

Where does antibody response to a T cell dependent antigen by antigen-activated B cells occur?

A

B cell-T cell zone border outside germinal center then inside germinal center

349
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the B cell-T cell zone border outside the germinal center interact with ______

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the B cell-T cell zone border outside the germinal center interact with antigen-activated CD4+ T helper cells

350
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the B cell-T cell zone border outside the germinal center differentiate into _____ cells that secrete _____ which has ___ affinity for antigen

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the B cell-T cell zone border outside the germinal center differentiate into short-lived plasma cells (plasmablasts) that secrete IgM antibody which has low affinity for antigen

351
Q

Describe the steps of the antibody response to a T cell dependent antigen by antigen-activated B cells inside the germinal centers

A
  • Further interact with antigen-specific activated CD4+ T helper cells (mainly through CD40:CD40L)
  • Rapidly proliferate
  • Undergo isotype switching and somatic hypermutation
    • Suppurted by IL-4 and IL-5 (TH2 CD4+ T helper cells)
  • Interact with follicular dendritic cells and antigen-presenting cells to select for high affinity antibody
  • Late germinal center
    • B cells with high affinity antibodies differentiate into memory B cells or plasma cells
352
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers further interact with ______, particularly through ____

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers further interact with antigen-specific activated CD4+ T helper cells, particularly through CD40:CD40L

353
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers rapidly _____

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers rapidly proliferate

354
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers undergo ____ and _____

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers undergo isotype switching and somatic hypermutation

355
Q

In the antibody response to a T cell dependent antigen, what molecules support isotype switching and somatic hypermutation of antigen-activated B cells inside germinal centers?

A

IL-4 and IL-5 (TH2 CD4+ T helper cells)

356
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers interact with _____ and _____ to select for ____ antibody

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells inside the germinal centers interact with follicular dendritic cells and antigen-presenting cells to select for high affinity antibody

357
Q

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the late germinal center with ____ antibodies differentiate into _____ cells or _____ cells

A

In the antibody response to a T cell dependent antigen, antigen-activated B cells in the late germinal center with high affinity antibodies differentiate into memory B cells or plasma cells

358
Q

What is critical for generating a germinal center response?

A

CD40L and MHC class II

359
Q

What do successive exposures to a T cell dependent antigen lead to?

A

Successive exposure to a T cell dependent antigen leads to increased affinity of the B cell receptor/antibody

360
Q

After repeat T cell dependent antigen exposure, what two things occur?

A
  • Antigen-specific memory B cells interact with the antigen-specific T cells in the germinal center
  • Somatic mutations and selection lead to increasingly more specific antibodies
361
Q

What do somatic mutations of Ig V genes lead to?

A

Selection of high-affinity B cells (high-affinity antibodies)

362
Q

What is the purpose of a booster vaccine?

A

Increase affinity of antibodies against pathogens

(multiple T cell dependent antigen exposures increase affinity of the B cell receptor/antibody)

363
Q

Why is feedback inhibition of humoral immunity necessary?

A

Antigen-antibody complexes can have harmful effects

364
Q

Through which pathway do antigen-antibody complexes activate complement?

A

Classical pathway

365
Q

Feedback inhibition is caused by the production of which antibody?

A

IgG

366
Q

Describe the steps involved in feedback inhibition of humoral immunity

A

IgG production leads to feedback inhibition

  • FcyRIIB on surface of B cells
  • Binds Fc portion of IgG
  • Signals through immunomodulatory tyrosine-based inhibition motif (ITIM)
  • Terminates B cell response to antigen
367
Q

What binds to the Fc portion of IgG for feedback inhibition of humoral immunity?

A

FcyRIIB on surface of B cells

368
Q

What is used to signal after FcyRIIB binds the Fc portion of IgG in feedback inhibition of humoral immunity?

A

Immunomodulatory tyrosine-based inhibition motif (ITIM)

369
Q

What is the major class of antibody produced after first exposure to antigen?

Can that class of antibody activate complement?

A

IgM is the first antibody produced afrer exposure to antigen in the primary immune response

IgM can activate complement

370
Q

Does a T cell independent antigen (such as polysaccharide capsule of bacteria) give rise to a secondary immune response to second antigen exposure?

A

T cell independent antigens generate no memory or only very limited memory B cells

Typically no secondary immune response

Second antigen exposure would lead to immune response similar to the first exposure

371
Q

A male patient presents with present but low levels of all classes of immunoglobulins at age 15. What types of infections is he at risk for?

Is it possible he has SCID?

A

He has CVID, so he is at risk for bacterial infections, Giardia, and enterovirus

He does not have SCID. SCID presents in infancy and is life-threatening without therapy. SCID involves an almost complete absence of the adaptive immune response and no immunoglobulins (and almost no B cells, no T cells +/- NK cells)

372
Q

What does IL-7 do?

A

Enhances B-cell development

373
Q

How are T cells selected in MHC restriction?

A

For their ability to bind weakly to self-MHC molecules

374
Q

Which T cells survive MHC restriction?

A

T cells that bind MHC weakly survive

375
Q

What do T cells recognize?

A

Peptide bound to a self-MHC molecule

376
Q

What is the key factor in self vs. non-self discrimination and transplant tolerance?

A

MHC

377
Q

What are the major proteins recognized as foreign in transplant rejection?

A

MHC

378
Q

Where do T cells mature?

A

Thymus

379
Q

What is the CD4/CD8 state of T cells in the cortex?

A

CD4-CD8- to CD4+CD8+

380
Q

What kind of selection occurs on T cells in the cortex of the thymus?

A

Positive selection

381
Q

What is the CD4/CD8 state of T cells in the medulla?

A

CD4+ or CD8+

382
Q

What kind of selection occurs on T cells in the medulla of the thymus?

A

Negative selection

383
Q

What sort of thymocyte exists in the cortex?

A

Double negative thymocyte

384
Q

What are early T cell precursors called?

A

Thymocytes

385
Q

When the T cell precursor transits from the bone marrow to the thymus, what is the state of CD3, CD4, and CD8 on its surface?

A

Negative for surface CD3, CD4, and CD8 molecules

386
Q

What increases as thymocytes develop?

A

Surface CD3 expression

387
Q

Where does the first step of thymic T cell selection occur?

A

Thymic cortex

388
Q

What is the first stage of thymic T cell selection?

What is not expressed?

A

CD4-CD8- (double negative) stage

Does not express TCR

389
Q

What does a TCR have on each chain?

A

A variable region and a constant region

390
Q

What allows for TCR gene rearrangement?

A

RAG1/RAG2 gene expression

391
Q

What does RAG1/RAG2 gene expression lead to in the beta chain of the TCR?

A

VDJ gene rearrangement

392
Q

Which chain of the TCR does VDJ rearrangment occur in?

A

Beta chain

393
Q

What does RAG1/RAG2 gene expression lead to in the alpha chain of the TCR?

A

VJ gene rearrangement

394
Q

Which chain of the TCR does VJ rearrangment occur in?

A

Alpha chain

395
Q

Does isotype switching occur in the TCR?

A

No

396
Q

What does the expression of RAG1/RAG2 genes produce?

A

TCR with unique antigen specificity

397
Q

Where does the second stage of thymic T cell selection occur?

A

Thymic cortex

398
Q

What is the second stage of thymic T cell selection?

What is expressed with the TCR?

A

CD4+CD8+ (double positive) stage

Surface CD3 expressed with the TCR

399
Q

What sort of selection occurs in the double positive stage of thymic T cell selection?

A

Positive selection

400
Q

Describe positive selection in the double positive stage of thymic T cell selection

A

Cortical epithelial cells express MHC class I and class II molecules

A T cell will survive if the TCR with CD4 or CD8 binds weakly to the self-MHC molecules

(Occurs in cortex)

401
Q

Where does the third stage of thymic T cell selection occur?

A

Thymic medulla

402
Q

What is the third stage of thymic T cell selection?

A

CD4+ or CD8+ (single positive) stage

403
Q

What sort of selection occurs in the single positive stage of thymic T cell selection?

A

Negative selection

404
Q

Describe negative selection in the single positive stage of thymic T cell selection

A
  • Cortical epithelial cells express MHC class I and II molecules
  • Autoimmune regulator (AIRE) transcription factor synthesizes self proteins to be expressed in the MHC molecules
  • Strong binding of the TCR to self-antigen/MHC molecules -> cell death or becomes regulatory T cell
  • Weak/no binding of the TCR to self-antigen/MHC molecule -> survive and go to the periphery
405
Q

In the single positive stage of thymic T cell selection, what occurs if the TCR binds strongly to the self-antigen/MHC molecule?

A

T cell death or becomes regulatory T cell

406
Q

In the single positive stage of thymic T cell selection, what occurs if the TCR binds weakly/not at all to the self-antigen/MHC molecule?

A

T cell survives and goes to the periphery

407
Q

Diagram the steps in T cell development

A
408
Q

What tissue is this?

What are the correct labels for the two arrows?

A

Thymus

409
Q

What is positive selection in thymic T cell selection?

A

Inclusive type of selection which checks all thymocytes for ability to recognize peptides on self-MHC

410
Q

What is negative selection in thymic T cell selection?

A

Exclusive type of selection which eliminates potentially autoreactive T cells

411
Q

What occurs in the negative selection portion in thymic selection of T cells?

A
  • Positively selected thymocytes migrate into medulla of thymus
  • Those that react w/ high affinity to self-peptides/MHC complexes will undergo apoptosis or become regulatory T cells
  • Those that react with lower affinity are allowed to survive and leave the thymus as mature T cells
412
Q

What produces self-peptides that are used in negative selection during thymic selection of T cells?

A

Autoimmune regulator (AIRE)

413
Q

What organ fails to form normally in DiGeorge syndrome?

A

Thymus

(thymic aplasia due to developmental defect in third and fourth pharyngeal pouches)

414
Q

What is deficient in people with DiGeorge syndrome?

A

Marked deficiency in T cells

415
Q

What infections are people with DiGeorge syndrome susceptible to?

A

Severe viral, fungal, and protozoal infections

Some also have pyogenic infections

416
Q

What lab finding do people with DiGeorge syndrome exhibit besides low T cell count?

Why?

A

Hypocalcemia

Due to lack of parathyroid glands

417
Q

Some patients with DiGeorge syndrome (thymic aplasia) have decreased serum antibodies and recurrent pyogenic infections. Why might this occur if the B cells develop normally?

A

Lack of CD4+ T cells to support B cell antibody production

418
Q

What do patients with mutations that eliminate the expression of RAG1 or RAG2 genes have?

A

Severe combined immunodeficiency

419
Q

People with severe combined immunodeficiency have no expression of which genes?

A

RAG1 or RAG2

420
Q

What cells do people with RAG deficiency lack?

Which cells do they have?

A

No B or T cells

Normal NK cells

421
Q

Why do people with RAG deficiency lack B cells and T cells?

A

RAG1/RAG2 are required for VDJ recombination and successful development of both B cells and T cells

422
Q

What syndrome do mutations that cause lower than normal but not eliminated RAG expression cause?

How does this syndrome present?

A

Ommen Syndrome

Autoimmune manifestations and immunodeficiency

423
Q

What will occur to T cells that leave the thymus and react with antigen in the absence of co-stimulation?

A

These T cells will become anergic (non-responsive)

424
Q

What is T cell anergy specific to?

A

Antigen-specific

425
Q

What occurs when T cells repeatedly encounter high levels of self-antigen in the periphery?

A

Clonal deletion through apoptosis

(Tregs also participate in suppressing self-reactive T cells)

426
Q

When does clonal deletion through apoptosis of T cells occur?

A

When T cells repeatedly encounter high levels of self-antigen in the periphery

427
Q

How many signals does T cell activation require?

A

2

428
Q

What is the first signal for CD4+ T cell activation?

A

Antigen recognition by the TCR via the MHC class II

429
Q

Describe the steps involved in the first signal for CD4+ T cell activation

A
  1. Antigen recognition in the context of the MHC by the TCR
  2. Binding of antigen by TCR
  3. ITAMs are phosphorylated
  4. ZAP70 tyrosine kinase is recruited and activated
  5. ZAP70 initiates a cascade of signaling
  6. Increased expression of cytokines, cytokine receptors, and cell proliferation genes

The longer the antigen is bound, the more the ITAMs are phosphorylated

430
Q

With regards to the first signal of CD4+ T cell activation, what does longer duration of antigen binding lead to?

A

More phosphorylation of ITAMs

431
Q

What are the major components involved in the first signal of CD4+ T cell activation?

A

Antigen, TCR (MHC), ITAMs, ZAP70 tyrosine kinase

432
Q

What is the second signal in CD4+ T cell activation?

A

Binding of activating co-stimulatory molecules (to CD28) or cytokines

433
Q

What is the usual co-stimulatory receptor in the second signal of CD4+ T cell activation?

A

CD28

(cytokines binding to cytokine receptors can also provide second signal)

434
Q

What is the first signal in activation of CD8+ cytotoxic T cells?

A

TCR and co-receptor CD8 recognize and bind the peptide in MHC class I

435
Q

What is the second signal in activation of CD8+ cytotoxic T cells?

A

Cytokines (IL-2) secreted from CD4+ cells or co-stimulatory molecule engagement

436
Q

When T cells are activated, what do T cells upregulate expression of?

A
  • IL-2 (T cell growth factor)
  • IL-2R

(Autocrine effect of IL-2 binding to IL-2 receptor allows clonal growth and proliferation of antigen-specific activated T cells)

437
Q

What does the upregulation of IL-2 and IL-2R by activated T cells lead to?

A

Autocrine effect of IL-2 binding to IL-2 receptor allows clonal growth and proliferation of antigen-specific activated T cells

438
Q

What is CD28?

A

Co-stimulatory molecule

439
Q

What does co-stimulatory molecule CD28 expressed on T cells bind to?

A

B7 (CD80/CD86) on antigen-presenting cells

440
Q

What occurs if a second signal is received after CD28 expressed on T cells binds B7 on the antigen-presenting cells?

A

T cell is activated

441
Q

What occurs if a second signal is not received after CD28 expressed on T cells binds B7 on the antigen-presenting cells?

A

T cell becomes anergic

442
Q

What are CTLA-4 and PD1?

A

Inhibitory molecules expressed on the surface of T cells that help control and downregulate the immune response

443
Q

Where are CTLA-4 and PD1 expressed?

A

Surface of T cells

444
Q

What are the inhibitory molecules expressed on the surface of T cells that help control and downregulate the immune response?

A

CTLA-4 and PD1

445
Q

When are the T cell inhibitory molecules upregulated?

A

48-96 hours after initial T cell activation

446
Q

How does CTLA-4 inhibit T cells?

A

Binds to B7 -> blocks binding of B7 to CD28 -> inhibits IL-2 synthesis

447
Q

How does PD1 inhibit T cells?

A

PD1 interacts with its receptor PDL1 on APCs (macrophages and dendritic cells) -> inhibits immune response

448
Q

Why is PD1 a target for chemotherapy in cancer treatment?

A

Some cancer cells express PD1

449
Q

How do superantigens evade the immune system?

A

Bind directly to TCR and MHC class II protein without internal processing

450
Q

What are two examples of superantigens?

A

Staphylococcal enterotoxins

Toxic shock syndrome toxins

451
Q

What is the effect of superantigen binding directly to TCR and MHC class II protein without internal processing?

A

Activates multiple T cells at once regardless of TCR antigen specificity

Uncontrolled release of cytokines from T cell and APC (IL-2, IL-1, and TNF)

Contributes to illness

452
Q

What does superantigen activation of multiple T cells at once regardless of TCR antigen specificity lead to?

A

Uncontrolled release of cytokines from T cell and APC (IL-2, IL-1, and TNF)

453
Q

What bacteria produces toxic shock syndrome toxin 1 ?

In what part of the body / when might this occur?

Why does not toxicity require bacteria in the blood?

A

Staphylococcus aureus

Vagina in menstruation

Toxin is produced and reaches blood (the toxin is what causes the effects)

454
Q

What are memory T cells?

A

Antigen-specific T cells that have gone through a first primary immune response to antigen

(numerous subsets, live for years)

455
Q

What occurs when memory T cells have a subsequent recognition of antigen?

A
  • Activation with a lower level of co-stimulation
  • Rapid and more robust production of cytokines
456
Q

What is the function of IL-2?

A

Promotes T cell growth and activation, can act in an autocrine fashion

457
Q

What are the functions of IL-4?

A
  • Promotes B cell growth
  • Promotes class switching to IgE and IgG
  • Promotes differentiation of TH2 CD4+ T cells
  • Inhibits differentiation of TH1 CD4+ T cells
458
Q

What are the functions of IL-5?

A
  • Differentiation/activation of eosinophils
  • Class switching to IgA
459
Q

What is the function of IL-10?

A

Turns off immune response (anti-inflammatory)

460
Q

What is the function of IL-12?

A
  • T cell growth factor
  • Stimulates TH1 subset of CD4+ T cells
461
Q

What is the function of IL-13?

A

Activates eosinophils

462
Q

What is the function of IL-17?

A

Promotes neutrophilic inflammation

463
Q

What are the functions of INF-gamma?

A
  • Stimulates phagocytosis by macrophages
  • Increases expression of MHC class I and II
  • Promotes TH1 T cell response
  • Inhibits TH2 CD4+ T cell response
464
Q

In most cases of hypersensitivity, what is true?

A

Immune system has seen the antigen (or closely related antigen) before

465
Q

How does sensitization to an antigen occur?

A

Primary antigen exposure gives rise to immune response with production of antibodies and/or memory T cells

Hypersensitivity response typically occurs on a subsequent exposure

466
Q

AJ goes on a camping trip and develops a rash one day after she returns. You diagnose poison ivy reaction, a form of contact hypersensitivity to organic chemicals called urushiols produced by the poison ivy plants. What is true about the cause of her rash?

A

Her rash is caused by activation of memory CD4+ and CD8+ T cells specific for peptides of urushiol-modified self proteins

467
Q

Which type(s) of hypersensitivity is/are antibody mediated?

A

Types I, II, and III

468
Q

Which type(s) of hypersensitivity is/are T cell mediated?

A

Type IV

469
Q

What is Type I hypersensitivity also known as?

A

Immediate/anaphylactic

470
Q

What is the timescale of Type I hypersensitivity?

A

Very fast, develops in minutes

471
Q

What cells and antibodies are involved in Type I hypersensitivity?

A
  • Mast cells and basophils
  • Preformed IgE (prior B cell response driven by TH2 helper T cells)
472
Q

What is the mechanism of Type I hypersensitivity?

A
  • First exposure sensitization to form IgE antibodies
  • Subsequent exposure: IgE binds antigen and crosslinks mast cell Fc receptors
  • Mast cells release preformed mediators and produce additional mediators
473
Q

In Type I hypersensitivity, what does IgE do upon subsequent exposure?

A

IgE binds antigen and crosslinks mast cell Fc receptor

474
Q

In Type I hypersensitivity, what do mast cells release?

A

Preformed mediators

475
Q

What are examples of Type I hypersensitivity?

A
  • Anaphylaxis
  • Allergic rhinitis
  • Asthma
  • Hives
476
Q

What do mast cells promote in Type I hypersensitivty?

A

Vasodilation and edema

477
Q

What is Type II hypersensitivity also known as?

A

Cytotoxic/antibody-mediated

478
Q

What is the timescale of Type II hypersensitivity?

A

Minutes to hours

479
Q

What cells and antibodies are involved in Type II hypersensitivity?

A
  • CD8+ cytotoxic T cells
  • NK cells
  • Neutrophils
  • Preformed IgG/IgM (produced by B cells, driven by TH2 CD4+ helper T cells or naturally occurring)
480
Q

What is the mechanism of Type II hypersensitivity?

A
  • Preformed IgG or IgM antibody binds to fixed cell surface or extracellular matrix antigens
  • Binding leads to complement activation and opsonization/phagocytosis and/or antibody-dependent cell-mediated cytotoxicity (ADCC) by NK or CD8+ cytotoxic T cells
481
Q

Where do preformed IgG or IgM antibodies bind in Type II hypersensitivity?

A

Fixed cell surface or extracellular matrix antigens

482
Q

What does binding of preformed IgG or IgM antibody to a fixed cell surface or extracelluilar matrix antigens lead to in Type II hypersensitivity?

A
  • Complement activation and opsonization/phagocytosis
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK or CD8+ cytotoxic T cells
483
Q

What is the complement activation mechanism in Type II hypersensitivity?

A
  1. Complement activated
  2. Complement byproducts C5a and C3a act on neutrophils
  3. Neutrophils release enzymes and reactive oxygen intermmediates
484
Q

What is the antibody-dependent cell-mediated cytotoxicity mechanism in Type II hypersensitivity?

A
  1. Antigen specific IgG antibody interacts with target antigen
  2. Release of cytotoxic molecules
485
Q

What are examples of type II hypersensitivity?

A
  • Some drug allergies
  • Incompatible blood transfusions
  • Rh hemolytic disease of newborn
  • Rheumatic fever
  • Goodpasture’s syndrome (antibody against basement membrane)
486
Q

What is Type III hypersensitivity also known as?

A

Immune complex-mediated

487
Q

What is the timescale of Type III hypersensitivity?

A

Hours to days

488
Q

What cells and antibodies are involved in Type III hypersensitivity?

A
  • Antigen and antibody complex (typically IgG)
  • Neutrophils
489
Q

What is the mechanism of Type III hypersensitivity?

A
  • When antigen is abundant, soluble immune complexes (antigen bound to antibody) form and deposit in tissues (particularly in vessels)
  • Immune complex deposition can activate complement and lead to inflammation (chemotaxis of neutrophils, vessel leakage, and vessel damage)
490
Q

In Type III hypersensitivity, what forms and deposits in tissues?

A

Soluble immune complex (antigen bound to antibody)

491
Q

In Type III hypersensitivity, what does immune complex deposition lead to?

A

Complement activation

492
Q

Which types of hypersensitivities involve the activation of complement?

A

Type II and Type III

493
Q

What are examples of Type III hypersensitivity?

A
  • Serum sickness (e.g. drugs)
  • Systemic lupus erythematosus
  • Arthus reaction: local injection of antigen that reacts with preformed IgG
494
Q

What is the Arthus reaction?

A

Local injection of antigen that reacts with preformed IgG

495
Q

Which type of hypersensitivity is the Arthus reaction?

A

Type III hypersensitivity

496
Q

What can be used to visualize immune complex deposition from a Type III hypersensitivitt?

A

Anti-IgG immunofluorescence

497
Q

What is Type IV hypersensitivity also known as?

A

Delayed-type hypersensitivity

498
Q

What is the timescale of Type IV hypersensitivity?

A

Days to weeks to months

499
Q

What cells are involved in Type IV hypersensitivity?

A
  • Antigen-presenting cells
  • TH1 CD4+ helper T cells
  • Sometimes CD8+ cytotoxic T cells

(no antibodies involved)

500
Q

What is the mechanism of Type IV hypersensitivity?

A
  • Antigen-presenting cells prime T cells to response to antigen and drive a TH1 CD4+ helper T cell response
  • On subsequent response to the antigen, previously primed T cells (memory cells) proliferate rapidly and activate a macrophage response and cytokine release
501
Q

In Type IV hypersensitivity, what sort of response do antigen-presenting cells drive?

A

TH1 CD4+ helper T cell response

502
Q

In Type IV hypersensitivity, what do memory T cells activate upon subsequent response to the antigen?

A

Macrophage response and cytokine release

503
Q

Which type hypersensitivity is involved in granuloma formation?

A

Type IV hypersensitivity

504
Q

What are examples of Type IV hypersensitivity?

A
  • Mycobacterium tuberculosis and PPD
  • Graft vs. host disease
  • Contact dermatitis
505
Q

What type of hypersensitivity are M. tuberculosis and PPD?

In M. tuberculosis and PPD, what do the T cells recognize?

A

Type IV hypersensitivity

T cells recognize microbial peptides

506
Q

What type of hypersensitivity is contact dermatitis?

In contact dermatitis, what do the T cells recognize?

A

Type IV hypersensitivity

T cells recognize chemically modified self proteins

507
Q

What is the PPD assay used for?

A

Evaluate for a cell-mediated immune response to M. tuberculosis suggestive of infection or prior vaccination

(type IV hypersensitivity)

508
Q

What occurs in the PPD test?

A
  • Protein derivatives from M. tuberculosis are injected intradermally
  • TH1 CD4+ T helper cells specific to M. tuberculosis antigens produce cytokines
  • Leads to an increase in the permeability of local blood vessels, recruitment of T cells and macrophages, and local tissue destruction
  • Produces swelling/induration of the skin ~48 hours after injection
509
Q

What does a positive PPD test indicate?

A

TB infection or prior BCG vaccine

510
Q

What cells does M. tuberculosis / PPD involve?

A

CD4+ T helper cells and macrophages

511
Q

What type of hypersensitivity is this?

How do you know?

A

Type IV hypersensitivity

This is predominantly a lymphocyte response (type IV hypersensitivity is cell-mediated)

512
Q

List the stages of B-cell development

A
  1. Early hematopoietic stem cell
  2. Lymphocyte progenitor
  3. Pro B-Cell
  4. Pre B-Cell
  5. Immature B-Cell
  6. Naïve B-Cell
513
Q

Which protein stimulates the formation of T-cell and B-cell precursors from lymphoid progenitor cells?

A

IL-7

514
Q

Which protein stimulates the formation of lymphoid progenitor cells from early hematopoietic stem cells?

A

IL-7

515
Q

How would decreased IL-7 expression affect white blood cell development?

A

Decreased IL-7 might cause…

  • Decreased lympoid progenitor cell formation (from early hematopoietic stem cells)
  • Decreased B-cell and T-cell formation from lymphoid progenitor cels
  • May eventually lead to impaired adaptive immune response
516
Q

What components are expressed by a Pro B-cell?

A

None

Pro B-cells do not express heavy chains, light chains, or surface antibodies

517
Q

What components are expressed by a Pre B-Cell?

A
  • Mu heavy chain in cytoplasm (not as a surface receptor)
  • No rearranged light chain
518
Q

What components are expressed by an immature B-cell?

A
  • Mu heavy chain and light chain = a fully formed IgM BCR
519
Q

What components are expressed by a Naïve B-cell?

A

IgM and IgD

(Both sets of antibodies on an individual B-cell have the same antigen binding specificity)

520
Q

What must happen in the transition from pro B-cell to pre B-cell?

A

Successful rearrangement of the Ig Mu heavy chain

521
Q

What must happen in the transition from pre B-Cell to immature B-cell?

A

Successful rearrangement of the light-chain (kappa or lambda)

Together, the light chain and heavy chain combine to express IgM in the BCR

522
Q

What must happen in the transition from immature B-cell to Naïve B-cell?

A

Clonal deletion

  • Immature B-cells with IgM that does not bind to self-antigen begin expressing IgD with the same light chain specificity as IgM, and they are released from the bone marrow
  • Immature B-cells with IgM that does bind to self-antigen have two fates…
    • 1) undergo apoptosis
    • 2) undergo receptor editing; VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a second type of light chain, which combines with the original heavy chain. If this second type of receptor does not bind to self it begins expressing IgD and is released from the bone marrow
523
Q

What is clonal deletion?

A

The process by which immature B-cells become naive B-cells

B-cells that bind self-antigen must be eliminated or edited so that they do not mount an autoimmune response

  • Immature B-cells with IgM that does not bind to self-antigen begin expressing IgD with the same light chain specificity as IgM, and they are released from the bone marrow
  • Immature B-cells with IgM that does bind to self-antigen have two fates…
    • 1) undergo apoptosis
    • 2) undergo receptor editing; VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a second type of light chain, which combines with the original heavy chain.
      • If this second type of receptor does not bind to self it begins expressing IgD and is released from the bone marrow
      • If this second type of receptor does bind to self, the B-cell undergoes apoptosis
524
Q

What is receptor editing?

When does it occur?

A

Receptor editing occurs in the bone marrow during clonal deltion. When a B-cell expresses IgM that binds to self-antigen, it must be altered to prevent that cell from being released and initiating an autoimmune response

Receptor editing: VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a second type of light chain, which combines with the original heavy chain. If this second type of receptor does not bind to self it begins expressing IgD and is released from the bone marrow

If the second type of of receptor continues to bind to self, the B-cell undergoes apoptosis

525
Q

Which part of IgM is altered in receptor editing?

A

The light chain variable region

526
Q

Why is B cell clonal deletion and receptor editing important?

A
  • Clonal deletion is necessary to promote the apoptosis of immature B-cells with IgM that binds to self-antigen
    • This is important in preventing B-cells from initiating an autoimmune response
  • Receptor editing rearranges the light chain of a self-reactive IgM to basically give it a “second chance” to not bind to self-antigen
    • If successful, the immature B-cell will begin expressing IgD and continue maturation
527
Q

What is the major cytokine produced by APCs that drives a TH1 CD4+ T cell response?

A

IL-12

528
Q

What would be a major risk if a patient with DiGeorge’s syndrome received a thymus transplant from an adult?

A

Mature T cells present in an adult thymus may recognize the recipient’s tissues as foreign and cause damage to many different organs in the recipient (graft vs host)

529
Q

Production of which interleukins promote class switching of IgE and leads to an increased risk for allergy and anaphylaxis?

A

IL-4 is the predominant interleukin that drives class switching to IgE

IL-4 is produced by TH2 CD4+ T cells

530
Q

What is MHC restriction?

A

TCR and co-receptor can only recognize peptides in the context of self-MHC molecule

531
Q

What are the three subsets of T cells?

A
  • CD4+ helper T cells
  • CD8+ cytotoxic T cells
  • Regulatory T cells
532
Q

Which MHC class do CD4+ helper T cells express?

A

MHC class II

533
Q

What is the function of CD4+ helper T cells?

A

Secrete cytokines to support other cells

534
Q

What are the three types of CD4+ helper T cells?

A
  • TH1
  • TH2
  • TH17
535
Q

Which MHC class do CD8+ cytotoxic T cells express?

A

MHC class I

536
Q

What are the functions of CD8+ cytotoxic T cells?

A
  • Directly kill infected target cells
  • Participate in macrophage activation
  • Releases perforin and granzymes
537
Q

What do TH1 CD4+ T helper cells produce?

A

IFN-gamma

538
Q

What are the functions of TH1 CD4+ T helper cells?

A
  • Promote cellular activity
  • Participate in macrophage activation
539
Q

What do TH2 CD4+ T helper cells produce?

A

IL-4, IL-5, and IL-13

540
Q

What are the functions of TH2 CD4+ T helper cells?

A
  • Promote humoral immunity
  • Promotes antihelminth responses
541
Q

What do TH17 CD4+ T helper cells produce?

A

IL-17

542
Q

What are the functions of TH17 CD4+ T helper cells?

A
  • Host defense
  • Pathogenesis of autoimmune disease
543
Q

Which two T cell subsets are involved in cell-mediated immunity?

A

CD8+ cytotoxic T cells and TH1 CD4+ T helper cells

544
Q

How do CD8+ cytotoxic T cells mediate direct cellular killing?

A
  • Perforins and granzymes are present in granules and released
  • Activate caspases
  • FasL is expressed on cytotoxic T cells that bind to Fas
545
Q

What is the function of perforins released by CD8+ cytotoxic T cells?

A

Insert into the cell membrane and form a channel

546
Q

What is the function of granzymes released by CD8+ cytotoxic T cells?

A

Granzymes are proteases that degrade proteins in the cell membrane

547
Q

What does the activation of caspases by CD8+ cytotoxic T cells lead to?

A

Apoptosis

548
Q

What does the expression of FasL on CD8+ cytotoxic T cells lead to?

A

Apoptosis after binding Fas on the target cell

549
Q

Where do mycobacteria survive inside cells?

How?

A

Mycobacteria survive within a phagosome by preventing fusion with the lysosome and acidification

(infection is controlled by a cell-mediated immune response but not always eradicated)

550
Q

What are the functions of mycolic acids and lipids for mycobacteria?

A
  • Essential for survival in host
  • May alter host immune response
551
Q

What occurs when intracellular pathogens persist?

A

Pathologic immune response

552
Q

What is the classic example of cell-mediated immunity that leads to persistent inflammation?

A

Granulomatous response to M. tuberculosis

553
Q

Describe the steps involved in granuloma formation due to Mycobacterium tuberculosis infection

A
  1. Chronic antigen stimulation of the organism drives CD4+ TH1 T cell responses (production of IL-2 and IFN-gamma)
  2. IFN-gamma drives macrophages to secrete IL-12 and the cycle of activation continues
  3. Macrophages secrete hydrolytic enzymes and form granulomas which often have central necrosis
  4. These pathways lead to tissue damage but can keep the organism dormant
554
Q

What does the chronic antigen stimulation of Mycobacterium tuberculosis drive?

A

CD4+ TH1 T cell responses (production of IL-2 and IFN-gamma)

555
Q

What does IFN-gamma produced by CD4+ TH1 T cell responses lead?

A

Macrophage secretion of IL-12

556
Q

What does macrophage secretion of IL-12 in the granulomatous response to Mycobacterium tuberculosis lead to?

A

Macrophage secretion of hydrolytic enzymes

(leads to formation of granulomas which often have central necrosis)

557
Q

What does granuloma formation do to Mycobacterium tuberculosis?

A

Keeps Mycobacterium tuberculosis dormant

558
Q

Which viruses can suppress cell-mediated immunity?

A

Measles and CMV

559
Q

What can suppression of cell-mediated immunity by measles and CMV lead to?

A

Reactivation of M. tuberculosis infection

560
Q

Infection with which bacterium clearly demonstrates the TH1 versus TH2 response?

A

Mycobacterium leprae (cause of leprosy)

561
Q

Describe the T cell response in tuberculoid leprosy

A
  • TH1 driven
  • Intense cell-mediated response
  • Few bacteria
  • Non-caseating granulomas
562
Q

Which type of CD4+ T helper cell drives tuberculoid leprosy?

A

TH1

563
Q

Describe the T cell response in lepromatous leprosy

A
  • TH2 driven response
  • No cellular immune response
  • Many bacteria
564
Q

In which form of leprosy is there an intense cell-mediated response?

A

Tuberculoid leprosy

565
Q

In which form of leprosy are there few bacteria?

A

Tuberculoid leprosy

566
Q

In which form of leprosy do non-caseating granulomas form?

A

Tuberculoid leprosy

567
Q

Which type of CD4+ T helper cell drives lepromatous leprosy?

A

TH2

568
Q

In which form of leprosy is there no cellular immune response?

A

Lepromatous leprosy

569
Q

In which form of leprosy are there many bacteria?

A

Lepromatous leprosy

570
Q

What response to mycobacteria would you expect in a patient with IFN-gamma receptor deficiency?

A

Disseminated mycobacterial infection

(need IFN-gamma for granuloma formation)

(latent mycobacterial infection requires intact cell-mediated immunity)

571
Q

What occurs in IL-12 receptor deficiency?

A
  • Decreased TH1 response
  • Disseminated mycobacterial infections
  • Decreased IFN-gamma
572
Q

How can cross-presentaiton by APCs impact the response to immunization?

A

Cross-presentation is when APCs, particularly dendritic cells, can present extracellular antigens on the MHC class I molecules to initiate a CD8+ T cell response

Cross-presentation involves a transfer of extracellular antigens from the endosomes into the cytosol of the APC

This can impact immunization design because an antigen that is extracellular (i.e. cannot infect the cell) can still elicit a CD8+ T cell memory response through cross-presentation after uptake by APCs

573
Q

In HIV/AIDS, the CD4+ T cells are decreased. What types of pathogens would patients with HIV/AIDS be particularly susceptible to?

A

Wide array of all types of infections (bacterial, fungal, viral)

Particularly susceptible to opportunistic infections (infections by organisms that typically do not cause disease)

574
Q

What is an antigen?

A

Anything that can bind to an anitobdy

We can form antibodies to almost anything

575
Q

What is an immunogen?

A

An antigen that induces and immune response

Can be a

  • Protein
  • Large multivalent non-protein
    • Immunogenicity depends on size, repetition
576
Q

What is a hapten?

A

An antigen that does not induce an immune response on its own

Ex: A small chemical

577
Q

How can a hapten induce an immune reasponse?

Describe teh process

A

If multiple haptens are bound to a carrier protein, the hapten/protein complex can elicit a T-cell response

  • B-cell binds to haptens attached to carrier proteins
  • BCR endocytosis; the receptor bound to the haptens + protein is internalized
  • The protein is degraded to peptides
  • The B-cell presents the peptides on MHC Class II to CD4+ helper T-cells
  • The T-cell is activated and makes antibodies
578
Q

What is the likely outcome of impaired activation-induced citidine deaminase (AID)?

A
  • Imparied isotype switching
  • Imparied somatic hypermutaiton

This can result in increased risk of infection, decrease antigen binding specificity

579
Q

What processes are mediated by activation-indiced citidine deaminase?

A

Somatic hypermutation

Isotype/class switching

580
Q

What are the functions of IgM?

A
  • Fix complement
  • Important in primary response
    • 1st antibody produced upon exosure
  • Main antibody in a T-cell independent response
581
Q

Which antibody can cross the placenta?

Why is this important?

A

IgG

This is important in the maternal immune response to fetal red blood cells

582
Q

What are the functions of IgD?

A

Expresses only on naive B-cells

Not secreted

Honestly, not much is known about their function

583
Q

Which antibodies can fix complement?

Which pathway do they use?

A

IgM and IgG fix complement via the classic pathway

584
Q

Which antibodies most effectivly opsonizes bacteria?

A

IgG

585
Q

What are the functions of IgG?

A
  • Fixes complement; activates the classic pathway
  • Opsonizes bacteria
    • The most effective opsonizer!
  • Neutralizes bacterial toxins and viruses
  • Most abundant antibody in the secondary immune response
  • Can cross the placenta
  • Most abundant circulating antibody
  • Most effective antibody in many infections
586
Q

Which antibody is most abundant in a primary immune response?

A

IgM

587
Q

Which antibody is most abundant in a secondary immune response?

A

IgG