Week 5 Immunology Flashcards

1
Q

What cell types are part of adaptive immunity ?

A

B cells

T cells

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2
Q

what cell types are part of innate immunity?

A

Natural killer cells
Dendritic cells
Monocytes
Granulocytes

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3
Q

What cells come from common lymphoid progenitors ?

A

B cells
T cells
Natural killer cells

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4
Q

What cells come from a common myeloid progenitor ?

A

Monocytes

Granulocytes

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5
Q

What cells produce antibodies

A

B cells and plasma cells

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6
Q

What role do complement proteins play in the immune system ?

A

Plasma proteins that cleave and active each other to kill extra cellular pathogens
Bind directly to pathogens or to antibodies coating pathogens

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7
Q

What role do cytokines play in immune response

A

They act on nearby or distant cells to influence innate and adaptive immunity

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8
Q

What are chemokines and what role do they play in immune response ?

A

Cytokines that attract other cells to the site of infections

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9
Q

What are primary lymphoid organs ?

A

Organs where lymphocytes develop from progenitor cells
Bone marrow: B cells and T cell progenitors
Thymus: T cells

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10
Q

What are secondary lymphoid organs ?

A

Where lymphocytes interact with each other and nonlymphoid cells
Initiate adaptive immune responses
Lymph nodes and spleen

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11
Q

What are the roles of neutrophils ?

A

Phagocytosis
Kill pathogens
Major white blood cell
Identify pathogens using receptors that recognize common patterns found in microbes

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12
Q

What are the roles of macrophages ?

A

Phagocytosis
Kill pathogens
Antigen presenting cells
Identify pathogens using receptors that recognize common patterns found in microbes

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13
Q

What are the roles of dendritic cells ?

A

Phagocytosis
Best antigen presenting cell
Identify pathogens using receptors that recognize common patterns found in microbes

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14
Q

How do innate cells recognize microbes ?

A

PAMPs derived from microbes bind to PRRs on innate immune cells

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15
Q

What roles do eosinophils and mast cells have ?

A

Protect against helminth infections

Implicated in allergic responses

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16
Q

What role do basophils have in innate immune reponse ?

A

Implicated in allergic responses

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17
Q

What function do natural killer cells have in innate immunity ?

A

Destroy infected or cancerous cells

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18
Q

What are the 3 classical antigen presenting cells ?

A

B cells
Macrophages
Dendritic cells

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19
Q

How many different B cell receptors are there ?

A

Each B cell generates a unique cell-surface bound antibody (B celll receptor) that recognizes a specific antigen

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20
Q

What do T cell receptors recognize ?

A

Peptide antigens that are presented on the surface of cells in an MHC molecule

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21
Q

What is the role of CD4+ T helper cells ?

A

Help activate other immune cells

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22
Q

What type of pathogens do TH1 cells protect against

A

Intracellular (cell-mediated immunity)

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23
Q

What type of pathogens do TH2 cells protect against

A

Extra cellular (humoral immunity)

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24
Q

What is the role of CD8+ cytotoxic T cells ?

A

Defend against cytosolic pathogens
Kill cells infected with intracellular pathogens
Protection against neoplasms

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25
Q

MHC class I molecules location and importance

A

On all nucleated cells
Bind to CD8+
Allow cytotoxic T cells to recognize virally infected or cancerous cells

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26
Q

MHC class II molecules location and importance

A

On the 3 classic antigen presenting cells
Binds to CD4+
Initiates adaptive immune response

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27
Q

What is the primary cell type that is recruited to sites of infection ?

A

Neutrophils

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28
Q

What do dendritic cells do once they take up antigens?

A

Bring to nearest lymph node —> present to T cell —> initiate adaptive immune response

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29
Q

Once in lymph nodes during immune reponses what do dendritic cells do ?

A

Present antigen to CD4+ T cell on MHC II molecule —> produce costimulatory molecules and cytokines —> antigen recognized —> activated T cell differentiates into TH2 cell

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30
Q

How do activated TH2 cells provide help to B cells during active immune response ?

A

Helps form cytokines and co-stimulation
—> activated B cells proliferate —> antibody-secreting plasma cells
—> some B and T cells —> long lived memory cells

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31
Q

Length of AA sequence on MHC I and MHC II molecules respectively

A

8-11

10-30

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32
Q

What is often needed for cell activation ?

A

2 signals, cross linking

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33
Q

What do proteases do ?

A

Chop antigens into small AA fragments

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34
Q

Activating signal for neutrophils/macrophages/dendritic cells

A

DAMPs and PAMPs cross link TLRs

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35
Q

Activating signal for B cells

A

3D antigen binding to and crosslinking surface mounted Ig molecules (BCR)

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36
Q

Activating signal for CD4+ T helper cells

A

Linear AA sequence mounted on specific MHCII molecule which cross links TCR

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37
Q

Activating signal for CD8+ cytotoxic T cell

A

Linear AA sequence mounted on specific MHCI molecule which cross links TCR

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38
Q

Response to antigen intake in dendritic cell

A

Naive T cell activation:

Clonal expansion and differentiation into effector T cells

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39
Q

Response to antigen uptake bu macrophage

A

Effector T cell response:

Macrophage activation

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40
Q

Response to antigen intake by B cell

A

Effector T cell response:

B cell activation and antibody production

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41
Q

Where are T precursor cells produced ?

A

Bone marrow

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42
Q

Where do T cells mature ?

A

Thymus

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43
Q

Where are T cells activated ?

A

Secondary lymphoid organs

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44
Q

What is the variable region of a T cell composed of ?

A

V,D and J segments

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45
Q

How is the variable region of a T cell synthesized ?

A
  1. Synapsis
  2. Cleavage
  3. Hairpin opening and end-processing
  4. Joining
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46
Q

How can the number of T cells someone has generated be measured ?

A

Measure # of T cell receptor excision circles (TRECs)

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47
Q

What is positive selection

A

T cells must interact with MHC (-90%)

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48
Q

What is negative selection ?

A

T cells must not activate too strongly to self peptide (-5%)

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49
Q

What is required for 2 factor authentication of T cells ?

A

Co-stimulation

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50
Q

When does T cell anergy occur and what is it’s effect?

A

When there is antigen specific signal alone without stimulation from APC.
Cell can no longer respond to antigen —> incapable of being activated

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51
Q

What treatment are molecules that block co-stimulation or enhance inhibition being used in ?

A

Treatment of autoimmune and allergic diseases

52
Q

What are molecules that enhance co-stimulation or block inhibition recently being used to treat ?

A

Cancer

53
Q

3 key events during B cell maturation

A
  1. Rearrangement and expression of immunoglobulin genes in a precise order
  2. Selection and proliferation of developing B cells at the pre-antigen checkpoint
  3. Selection of the mature B cell repertoire
54
Q

What process is the RAG gene involved in ?

A

VDJ recombination in both B and T cells

55
Q

What is VDJ recombination ?

A

Random combo of germline gene segments being brought together and by the random addition or deletion sequences at the junctions between segments before they are united.

56
Q

What results when there are defects in RAG, Artemis or DNA ligand IV ?

A

Severe combined immunodeficiency (SCID)

57
Q

What is another word for negative selection

A

Central tolerance

58
Q

What happens to mature B cells that migrate back to the bone marrow following antigen exposure ?

A

Called plasma cells and they secrete antibodies

59
Q

B cell response to T-dependent antigens

A

Initiated by binding of the protein antigen to specific Ig receptors of naive B cells —> recruit T and B cells into germinal centres of spleen/nodes

60
Q

B cell response to T-independent antigen

A

Initiated by recognition of non-protein antigens by specific Ig receptors of naive B cells —>
Induction of B cell clonal expansion and IgM secretion

61
Q

What type of B cell activation can occur in the mucosal tissues and peritoneal cavity ?

A

T- independent, Short lived plasma cells

62
Q

What is the co-stimulation interaction that is needed for B cell proliferation and differentiation?

A

CD40-CD40L interaction

63
Q

What are the two types of antibodies produced by B cells ?

A

Membrane bound

Secreted

64
Q

Function of membrane bound anti-bodies vs secreted anti-bodies

A

Antigen receptors

Neutralize toxins

65
Q

What is the core structure of an antibody ?

A

2 identical lambda or kappa light chains
2 identical heavy chains

Each chain has amino-terminal variable region (V)
And a carboxyl terminal constant region (C)

66
Q

What are the 5 different classes of antibodies ?

A

IgE, IgG, IgA, IgD, IgM

67
Q

Effector functions of IgG antibodies

A

Opsonization of antigens for phagocytosis
Activation of the classical pathway of complement
Antibody dependent cell-mediated cytotoxicity
Neonatal immunity
Feedback inhibition of B cell activation

68
Q

Effector functions of IgM antibodies

A

Activation of classical pathway of complement

Antigen receptor of naive B lymphocytes

69
Q

Effector functions of IgA antibodies

A

Mucosal immunity

70
Q

Effector functions of IgE antibodies

A

Mast cell degranulation: immediate hypersensitivity reactions

71
Q

Effector functions of IgD antibodies

A

Antigen receptor of naive B lymphocytes

72
Q

What antibody isotype makes up almost 80% of circulating antibodies

A

IgG

73
Q

What is somatic hypermutation ?

A

Process that introduces random mutation in the variable region of the BCR Ig heavy and light chains at a high rate during B cell proliferation.

74
Q

What is the effect of hypermutation ?

A

Increased affinity of antibodies for antigen impart selective survival advantage to B cells producing those antibodies and lead to affinity maturation of the humoral response

75
Q

Somatic hypermutation is only seen in T-___________ protein antigens ?

A

Dependent

76
Q

What is affinity maturation ?

A

Process that leads to increased affinity of antibodies for a particular antigen, is result of hypermutation followed by selective survival of B cells

77
Q

What cells make antibodies

A

B cells only !

78
Q

What structures does the innate immune system look for ?

A

Structures that are unique to pathogens and injured self:

PAMPs and DAMPs

79
Q

Would do TLRs recognize and where are they located ?

A

Bacteria, viruses, fungi

Plasma and endosomal membranes

80
Q

What do NOD-like receptors recognize and where are they located ?

A

Bacteria, cell membrane damage

Cytosol

81
Q

What do RIG-like receptors recognize and where are they located ?

A

Viruses

Cytosol

82
Q

What do natural antibodies recognize and where are they located ?

A

Bacteria, fungi, injured self

Plasma

83
Q

What does complement recognize and where is it located ?

A

Bacteria

Plasma

84
Q

What 2 major groups opsonize ?

A
  1. Antibodies

2. Complement system

85
Q

What does the cell signaling from PRR activation result in ?

A
  1. Increased vascular permeability
  2. Influx of important proteins (complement, antibodies, clotting factors)
  3. Influx of cells (innate and adaptive)
86
Q

Result of PRR activation

A
  1. Cytokines
  2. Chemokines
  3. Cell adhesion molecules
  4. Microbe specific responses
87
Q

What cell type bridges the innate and adaptive immune systems ?

A

Dendritic cells

88
Q

Complement floats around inactive in the blood until it has contact with either a ___ or an ______

A

Pathogen, antibody

89
Q

What is C3 convertase composed of and what is it’s role ?

A

C4b+C2a or alternatively C3b + Bb

Cleaves C3

90
Q

What is C5 convertase composed of and what is its role ?

A

C4b + C2a + C3b or (C3b + Bb +C3b)

Cleaves C3 and C5

91
Q

Actions of complement

A

Opsonization
Call for help
Augment immune response
Punching holes in cells

92
Q

Membrane Attack Complex (MAC) formation steps (5)

A
  1. C5b binds C6 and C7
  2. C5b67 complexes bind to membrane via C7
  3. C8 binds to the complex and inserts into the membrane
  4. C9 molecules bind to the complex and polymerize
  5. 10-16 molecules of C9 bind to form a pore in the membrane
93
Q

Complement activation: lectin pathway

A
Ficolin/MBL + MASPs bind carbohydrates —> activate C4 and C2
C4–> C4a+C4b 
C2 —> C2a + C2b 
C4b+C2a= C3 convertase 
C3 convertase + C3b = C5 convertase
94
Q

Complement activation: classical pathway

A
C1q, C1r and C1s bind antibodies —> activate C4 and C2 
C4–> C4a+C4b
C2–> C2a+C2b 
C4b+C2a = C3 convertase 
C3 convertase + C3b = C5 convertase
95
Q

Complement activation alternative pathway

A
C3 activation —> C3a + C3b 
Factor B is cleaved by factor D —> Bb 
C3b binds to Bb —> C3bBb = C3 convertase 
C3bBb is stabilized by Factor P 
C3bBb + C3b = C5 convertase
96
Q

Why is fast clearance of self-antigens important ?

A

Prevents autoimmunity

97
Q

What happens in terminal complement deficiency ?

A

No MAC can be formed

98
Q

What pathogenesis accompanies C1q deficiency ?

A

Cannot clear apoptotic cells and 90% of patients will develop SLE

99
Q

Why are C4 and C3 low in patients with SLE?

A

Presence of self antibody —> activation of classical pathway —> C4 and C3 undergo constant activation —> low levels

100
Q

3 causes of hypersensitivity diseases

A

Reactions against:
Self
Microbes
Environmental agents

101
Q

Definition of allergy or atopy

A

Combination of immediate hypersensitivity and late phase reaction

102
Q

Allergen definition

A

Antigens that ellicit immediate hypersensitivity

103
Q

Type I immediate hypersensitivity antigen isotype

A

IgE

104
Q

Type II antibody-mediated hypersensitivity antibody isotype

A

IgM and IgG

105
Q

Type III immune complex mediated hypersensitivity antibody isotype

A

IgM and IgG

106
Q

Type IV T cell mediated hypersensitivity T cells involved ?

A

CD4+: inflammation —> delayed type hypersensitivity

CD8+: directly kill target cell —> granulomatous inflammation seen in TB infection

107
Q

IgE antibody production in Type I hypersensitivity is dependent on what ?

A

Activation of CD4+ effector T cells that produce IL-4

108
Q

Broad outline of how type I hypersensitivities develop

A
  1. First exposure to allergen
  2. Activation of T cells and stimulation of IgE class switching
  3. Production of IgE
  4. Binding of IgE on mast cells
  5. Repeated allergen exposure
  6. Activation of mast cell —> release of mediators
  7. Immediate and late phase reaction
109
Q

What causes allergy symptoms ?

A

Mediators from mast cells

110
Q

Common signs and symptoms of IgE mediated reactions

A
Urticaria 
Laryngeal 
Flush 
Wheeze
Dizziness
Nausea/vomiting 
Rhinitis 
Headache
111
Q

Two main functions of TD4+ effector T cells

A

Recruit and activate phagocytes

Help B lymphocytes to produce antibodies

112
Q

Characteristics of urticaria

A
Raised 
Erythematous 
Central cleaning 
Irregular border
Often migratory
113
Q

Characteristics of Angioedema

A

Localized to subcutaneous or sub mucosal tissues
Never involves gravity-dependent areas
Onset 2-3 hours as part of IgE mediated reaction
Usually asymmetric

114
Q

How do IgG and IgM antibodies cause tissue injury ?

A

Activate complement system
Recruiting inflammatory cells
Interfering with normal cellular functions

115
Q

Anaphylaxis is likely when

  1. Acute onset of illness with skin/mucosal involvement AND at least one of:
A
  • respiratory symptoms

- reduced BP or signs of end-organ dysfunction

116
Q

Anaphylaxis is likely when:

  1. If there is a likely allergen for that patient, 2 of the following:
A
  • skin-mucosal involvement
  • respiratory compromise
  • reduced BP
  • persistent GI symptoms
117
Q

Anaphylaxis is likely when:

3. Reduced BP after:

A

Exposure to known allergen for that patient

118
Q

Alpha-1 adrenergic receptor effects of epinephrine

A
  • vasoconstrictor effect in most body organ systems

- ability to prevent and relieve airway obstruction caused by mucosal edema

119
Q

Beta-1 adrenergic receptor effects from epinephrine

A

Increases cardiac contractility and HR

Ability to prevent and relieve hypotension and shock

120
Q

Beta-2 adrenergic receptor effects from epinephrine

A
  • decreases mediator release from mast cells, basophils
    Increases bronchodilation
    Vasodilator effect on skeletal muscle
121
Q

Second line treatments for anaphylaxis

A

H1 antihistamine
Glucocorticoids
Inhaled B-2 adrenergic agonists

122
Q

Treatment options for primary immunodeficiences

A

Passive administration of antibodies by monthly IV infusion or weekly subcutaneous injection
Continuous prophylactic antibiotics
Hematopoietic stem cell transplantation
Gene therapy to replace the defective gene

123
Q

Most common causes of immunodeficiency:

A

HIV
Malnutrition
Iatrogenic immunosuppression

124
Q

Anti-IgE Antibody mechanism

A

Binds to free IgE —> reduce cell bound IgE — > reduce high affinity receptors —> reduces mediator release

125
Q

Benefits of adjuvants in vaccines

A

Increase immunogenicity of vaccines
Reduce the dose of antigen required for effectiveness
Broaden repertoire of antibody responses
Modulate the phenotype of T cell responses