Immune System Flashcards Preview

► Med 11 - USMLE 1 > Immune System > Flashcards

Flashcards in Immune System Deck (172):
1

Innate Immunity
Receptor coding?
Response to pathogens is
Memory?
Cells involved?
Molecules involved?

Receptors that recognize pathogens are germline encoded
Response to pathogens is fast and nonspecific
No Memory
Neutrophils, Macs, Dendritic Cells, Natural Killer Cells (lymphoid origin)
Complement

2

Adaptive Immunity
Innate Immunity
Receptor coding?
Response to pathogens is
Memory?
Cells involved?
Molecules involved?

Receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development
Response is slow on first exposure. Memory response is faster and more robust.
T and B cells
Antibodies

3

MHC
Stands for
Encoded by what gene?
Function
What does it bind?

Major Histocompatibility Complex
Human Leukocyte Antigen (HLA) gene
Presents antigen fragments to T cells and binds TCR

4

MHC I
Genes encoding it?
Binds what receptors
Which cells express it?
Where is antigen loaded
What kind of antigens?
What kind of immunity does it mediate?
What does it pair with and why?
Where is peptide groove?

HLA A, B and C
Binds TCR and CD8
All nucleated cells (not RBCs)
Antigen loaded in RER with mostly intracellular peptides
Mediates viral immunity
Pairs with β2 microglobins (aids in transport to cell surface)
Peptide groove in α chain

5

MHC II
Genes encoding it?
Binds what receptors
Which cells express it?
When is antigen loaded
What does it look like?

HLA DR, DP and DQ
Binds TCR and CD4
Expressed only on APCs
Antigen is loaded following release of invariant chain in an acidified endosome
α and β chains pair with peptide groove in between

6

Association with HLA A3

Hemochromatosis

7

Association with HLA B27

"PAIR"
Psoriasis, Ankylosing Spondylitis, IBDm Reiter's syndrome

8

Association with HLA DQ2/DQ8

Celiac

9

Association with HLA DR2

Multiple Sclerosis, Hay Fever, SLE, Goodpastures

10

Association with HLA DR3

DM type 1, Graves' Disease

11

Association with HLA DR4

RA, DM type 1

12

Association with HLA DR5

Pernicious anemia (B12 deficiency), Hashimoto's thyroiditis

13

Natural Killer Cells
What do they do?
What do they use to do it?
How are they unique?
What molecules enhance their activity?
When are they induced to kill?

Induce apoptosis in virally infected cells or tumor cells
Use perforin and granzymes
Only lymphocyte member of innate immune system
"#2, get #12, tell him the boss needs to take out α and β"
Activity is enhanced by IL2, IL12, INFα, INFβ
Induced to kill when exposed to a nonspecific activation signal on target cell +/or to an absence of MHCI on target cell surface

14

B cells functions

Make Abs: opsonize bacteria, neutralize viruses (IgG), Activate complement (IgM and IgG), Sensitize mast cells (IgE)
Allergy (Type I hypersensitivity): IgE
Cytotoxic (Type II hypersensitivity): IgG
Immune Complex (Type III hypersensitivity): IgG
Hyperacute and humorally mediated acute and chronic organ rejection

15

T cell functions
Generally
CD4
CD8

Delayed cell mediated hypersensitivity reaction (IV)
Acute and chronic cellular organ rejection
CD4+ cells help B cells make Ab and produce cytokines to activate other cells of the immune system
CD8+ cells kill virus infected cells directly

16

Differentiation of T cells
In Bone Marrow
In Thymus
In Lymph Node

In BM: T cell precursor
In T: expresses TCR, CD4 and CD8 and then will switch to only expressing one of the CDs and a TCR
In LN: CD8+ --> cytotoxic T cells
CD4+: if exposed to IL12 --> Th1
if exposed to IL4 --> Th2

17

Where is there Positive selection in T cell differentiation?

In the Thymic Cortex where T cells expressing TCR capable of binding self MHC survive

18

Where is there Negative selection in T cell differentiation?

Medulla where T cells expressing TCR with high affinity for self antigens undergo apoptosis

19

APCs
# of signals needed for what?

Dendritic cell (Only APC that can activate naive T cell)
Macrophage
B cell
2 signals needed for T cell activation, B cell activation, and class switching

20

Steps of naive T cell activation

1. Foreign body is phagocytosed by dendritic cell
2. Foreign antigen presented on MHCII
3. MHCII + antigen recognized by TCR on Th cell or MHCI + antigen recognized by TCR on Tc cell
4. Costimulatory signal given by interaction of B7 (DC) and CD28 (T cell)
5. T cell activated: Th produced cytokines, Tc kills virus infected cells

21

Steps of B cell activation and class switching

1. Th cell activated
2. B cell receptor mediated endocytosis
3. Foreign antigen presented on MHCII
4. MHCII + antigen recognized by TCR on Th cell
5. CD40 receptor on B cell binds CD40 ligand on Th cell
6. Th cell secretes cytokines that determine Ig class switching of B cell
7. B cell activates and undergoes class switching, affinity maturation, and Ab production

22

Th1
What do they secrete
What do they activate
What inhibits them

Secretes INFγ
Activates Macs
Inhibited by IL4 and IL10 from Th2

23

Macrophage-Lymphocyte interaction

Activated lymphocyte --> INFγ --> Macs --> IL1 and TNFα --> lymphocytes

24

Th2
What do they secrete
What do they activate
What inhibits them

Secrete IL4, IL5, IL10, IL13
Recruit eosinophils for parasite defense, promote IgE production by B cells
Inhibited by INFγ from Th1

25

Lymph Node
What is it?
Afferents?
Efferents?
Encapsulated?
Function

Secondary Lymphoid Organ
Many afferents
1 or more efferents
Encapsulated w/ trabeculae
Filtration by Macs, storage, activation of B and T cells, Ab production

26

Lymph Node Follicle
Location
Function
Primary vs Secondary

Outer cortex
B cell localization and proliferation
Primary: dense and dormant
Secondary: pale central germinal centers and are active

27

Lymph Node Medulla
What does it consist of?

Medullary cords: closely packed lymphocytes and plasma cells
Medullary sinuses: Communicate with efferent lymphatics and contain reticular cells and Macs

28

Paracortex
Location
What does it house?
What does it contain?
What happens in an extreme cellular response?
Disease?

Between follicles and medulla
T cells
High endothelial venules through which T and B cells enter from blood
In extreme celular response, becomes enlarged
Not well developed in DiGeorge Syndrome

29

Lymph Drainage of Upper limb and lateral breast

Axillary

30

Lymph Drainage of Stomach

Celiac

31

Lymph Drainage of Duodenum and Jejunum

Superior Mesenteric

32

Lymph Drainage of Sigmoid Colon

Colic --> Inferior Mesenteric

33

Lymph Drainage of lower rectum and anal canal above pectinate line

Internal Iliac

34

Lymph Drainage of Anal Canal Below Pectinate Line

Superficial Inguinal

35

Lymph Drainage of Testes

Superficial and Deep Plexuses --> Para-Aortic

36

Lymph Drainage of Scrotum

Superficial Inguinal

37

Lymph Drainage of Thigh

Superficial Inguinal

38

Lymph Drainage of Lateral Side of Dorsum of the foot

Popliteal

39

What does Right Lymphatic Duct drain?
What does Thoracic Duct drain?

Right arm, right chest, Right half of head
Everything else

40

Sinusoids of the Spleen
What are they?
What are found nearby

Long Vascular Channels in red pulp with fenestrated "barrel hoop" basement membrane
Macrophages found nearby

41

Where are T cells in the spleen?

Periarterial lymphatic sheath (PALS) w/in white pulp

42

Where are B cells in the spleen?

Follicles w/in white pulp

43

What do macrophages do in the spleen?

Remove encapsulated bacteria

44

Splenic Dysfunction
Pathway
What are pts susceptible to?

↓ IgM --> ↓ Complement activation --> ↓ C3b opsonization --> ↑ susceptibility to encapsulated organisms
"SHiNE SKiS"
Strep pneumoniae, Haemophilis influenza type B, Neisseria meningitidis, Salmonella, Klebsiella pneumoniae, Group B Strep, E coli

45

Blood of pt post Splenectomy

Howell Jolly Bodies, Target Cells, Thrombocytosis

46

Thymus
Function
Encapsulated
Development
Origin of lymphocytes

Site of T cell differentiation and maturation
Encapsulated
From epithelium of 3rd Branchial pouches
Lymphocytes of mesenchymal origin

47

Thymus Cortex
Appearance
Kind of T cells there?
Kind of selection

Dense
Immature T cells
Positive selection (MHC restriction)

48

Thymus Medulla
Appearance
Kind of T cells there?
Histo
Kind of selection

Pale
Mature T cells
Epithelial Reticular cells containing Hassall's Corpuscles
Negative Selection (nonreactive to self)

49

Cytotoxic T cells
Function
What doe they release
Markers

Kill virus-infected cells, Neoplastic, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (Perforin, Granzyme, Granulysin)
CD8

50

Perforin
Granzyme
Granulysin

Perforin: Helps deliver the content of granules to target cells
Granzyme: Serine Protease activates apoptosis inside target cells
Granulysin: Antimicrobial, induces apoptosis

51

Regulator T cells
Function
Markers
What doe they produce?

Help maintain specific immune tolerance by suppressing CD4 and CD8 T cells
CD3, CD4, CD25 (α-chain of IL2 receptor)
IL10 and TGFβ

52

What part of Ab recognizes Ag

Variable portion of L and H chains

53

Function of Fc portion of IgM and IgG

Fix complement

54

Composition of Fc and Fab fractions Re H and L chains

H contributes to both Fc and Fab
L contributes only to Fab

55

Fab functions

Ag binding fragment

56

Fc portion
What is it?
Which end of the protein?
Function
Side chains
What does it determine?

Constant portion
Carboxy terminal
Complement binding @ CH2 (IgM and IgG only)
Carbohydrate side chains
Determine isotype (IgM, IgD...)

57

How is Ab diversity generated?

Light chain undergoes random VJ recombination
H undergoes random VDJ recombination
Random combination of H and L chains
Somatic Hypermutation following Ag stimulation (AID)
Addition of NTs to DNA during recombination by Terminal Deoxynucleotidyl Transferase

58

Mature B lymphocytes express what on their surface?

IgM and IgD

59

What mediates Isotype switching

Cytokines and CD40 ligand

60

IgG
Main Ab of what?
Abundance?
Function

Secondary Delayed Response
Most abundant type
Fixes complement, Crosses Placenta, Opsonizes bacteria, Neutralizes bacterial toxins and viruses

61

IgA
Function
Complement?
Single or group?
How does it cross epithelial cells
Where is it found?

Prevents attachement of bacteria and viruses to mucous membrane
Doesn't fix complement
Monomer in circulation, Dimer when secreted
Transcytosis where it picks up secretory component
Secretions (tears, saliva, mucus) and early breast milk (colostrum )

62

IgM
When is it produced?
Function
Placenta?
Single or group?

Primary immediate response to Ag
Fixes complement
Does not cross placenta
Monomer on B cells or Pentamer

63

IgD
Location
Function

Surface of B cells and in serum
Unclear function

64

IgE
Mediates what kind of Immunity?
Function
Abundance

Mediates immediate (type I) hypersensitivity through release of inflammatory mediators (histamine). Mediates immunity to worms by activating eosinophils
Binds mast cells and basophils. Cross links when exposed to allergen
Lowest concentration

65

Thymus Independent Antigens
What is it?
What do they stimulate
Memory?

Ags lacking peptide component and thus cannot be presented on MHC to T cells
Stimulate release of Ab
Do not result in memory

66

Thymus Dependent Antigens
What is it?
What do they stimulate
Memory?

Ags containing protein component
Stimulate class switching
Memory results of direct contact of B cells w/ Th cells (CD40-CD40 Ligand interaction)

67

C3b

Opsonization

68

C3a and C5a

Anaphylaxis

69

C5a

Neutrophil Chemotaxis

70

C5b-9

Cytolysis by MAC

71

Complement Pathways

Classic: IgG and IgM
Alternative: Microbe Surface Molecule
Lectin: Mannose or other sugars on microbe surface

72

Opsonins

IgG and C3b

73

Inhibitors of Complement pathway

Decay-Accelerating Factor (DAF) and C1 esterase inhibitor

74

Alternative Complement Pathway

Spontaneous and Microbal Surfaces turn C3 into C3b
B --> [D] --> Bb
C3 --> [C3bBb (C3 Convertase)] --> C3a + C3b

75

Classic Complement Pathway

Ab --> C1
C2 --> [C1] --> C2a and C2b
C4 --> [C1] --> C4a and C4b
C3 --> [C4bC2a (C3 convertase)] --> C3a + C3b

76

Lectin Complement Pathway

Mannose Binding Lectin --> [MASP] --> C1-like Complex
C4 --> [C1LC] --> C4a + C4b
C3 --> [C4b2a] --> C3a + C3b

77

Common Complement Pathway

C3bBb3b (C5 convertase)
C4b2a3b (C5 convertase)
C5 --> [C5 convertase] --> C5a + C5b
C5b + C6 through C9) = MAC

78

C1 Esterase Inhibitor Deficiency
Presentation
Contraindications

Hereditary Angioedema
ACE inhibitors Contraindicated

79

C3 Deficiency Presentation

Severe, recurrent pyogenic sinus and respiratory tract infections
Susceptibility to Type III hypersensitivity reactions

80

C5-C9 Deficiency

Recurrent Neisseria Bacteremia

81

DAF (GPI anchored enzyme) deficiency

Complement mediated lysis of RBCs and Paroxysmal Nocturnal Hemoglobinuria

82

IL1
Secreted by what cell?
Function

Macrophages
Endogenous pyrogen. Causes fever, acute inflammation, activates endothelium to express adhesion molecules, Induces chemokine secretion to recruit leukocytes

83

IL6
Secreted by what cell?
Function

Macrophages and TH2
Endogenous pyrogen. Fever and Production of acute phase proteins

84

IL8
Secreted by what cell?
Function

Macrophages
Neutrophil chemotactic

85

IL12
Secreted by what cell?
Function

Macrophages and B cells
Induces differentiation of Th1 cells
Activate NK cells

86

TNFα
Secreted by what cell?
What does it mediate?
Function

Macrophages
Mediates septic shock
Activates endothelium, Leukocyte recruitment, Vascular leak

87

Interleukin Mnemonic

"Hot T-Bone stEAk"
IL1: Hot (fever)
2: stimulate T cells
3: Stimulates Bone marrow
4: IgE
5: IgA

88

Cytokines secreted by all T cells w/ function

IL2: Stimulates growth of Th, Tc, and Treg cells
IL3: Supports growth and differentiation of bone marrow stem cells (like GM CSF)

89

Interferon-γ
What kind of cells secrete it?
Function

Th1 cells
Activate Macrophages and Th1 cells
Suppresses Th2 cells
Antiviral and antitumor properties (upregulates MHCI and MHCII and Ag presentation in all cells)

90

Cytokines secreted by Macrophages

1, 6, 8, 12, TNFα

91

Cytokines secreted by Th2 cells

4, 5, 6, 10

92

IL4
What kind of cells secrete it?
Function

Th2
Induces differentiation into Th2 cells
Promotes growth of B cells
Enhances class switching to IgE and IgG

93

IL5
What kind of cells secrete it?
Function

Th2
Promotes differentiation of B cells
Enhances class switching to IgA
Stimulates Eosinophils

94

IL10
What kind of cells secrete it?
Function
Like what other molecule

Th2 and Treg
Modulates immune response
Inhibits actions of activated T cells and Th1
Similar to TGFβ in that it inhibits inflammation

95

Interferon
Kinds
Function

α, β, γ
Place uninfected cells in an antiviral state
Induce production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA
Activate NK cells

96

IFNα and IFNβ function

Inhibit viral protein synthesis

97

T cell surface markers
Th
Tc

T: TCR, CD3 (associated with TCR), CD28 (binds B7 on APC)
Th: CD4, CD40 lingand
Tc: CD8

98

B cell surface markers

"Drink Beer at the Bar when you're 21"
Ig, CD19, CD20, CD21 (EBV receptor), CD40, MHCII, B7

99

Macrophage surface markers

CD14, CD40, MHCII, B7, Fc receptor, C3b receptor

100

NK cell surface markers

CD16 (binds Fc of IgG), CD56

101

Anergy
What is it?
B vs T

Self-reactive T cells become non reactive without costimulatory molecule
B cells also become anergic but tolerance is less complete than in T cells

102

Superantigen
Produced by what?
Mechanism

S Pyogenes and S aureus
Cross link β region of T cell receptor to MHCII on APC activating T cell and producing massive release of cytokines

103

Endotoxin
AKA
Made by what?
Receptor?
Other cells involved?

Lipopolysaccharide
Gram neg
Directly stimulate Macrophages by binding to CD14
Th not involved

104

Classic Antigen Variation in Bacteria

Salmonella (2 flagellar variants), Borrelia (relapsing fever), Neisseria gonorrhoeae (pilus protein)

105

Classic Antigen Variation in Viruses

Influenza
Major = Shift
Minor = Drift

106

Classic Antigen Variation in Parasites

Trypanosomes (programmed rearrangement)

107

Passive Immunity
Means of acquisition
Onset
Duration
Examples

Receiving preformed Abs
Rapid
Short (Ab half life is 3 weeks)
IgA in breast milk, Antitoxin, Humanized monoclonal Abs

108

Diseases in which patients are given preformed Abs as treatment?

"To Be Healed Rapidly"
Tetanus toxin, Botulinum toxin, HBV, Rabies virus

109

Active Immunity
Means of acquisition
Onset
Duration
Examples

Exposure to foreign Ag
Slow
Long lasting
Natural infection, vaccines, toxoid

110

Combined passive and active immunization can be given in the case of...

HBV or Rabies

111

Live Attenuated Vaccine
What kind of response does it generate?
Examples

Cellular response
Measles, Mumps, Rubella, Varicella, Yellow Fever, Polio (Sabin)

112

Inactivated or Killed Vaccine
What kind of response does it generate?
Examples

Humoral Immunity
Cholera, HAV, Rabies, Polio (Salk)

113

Hypersensitivity Reactions that are Ab mediated?

I, II, and III

114

Type I Hypersensitivity Reaction
Description
Process
Onset
Test

Anaphylactic and Atopic
Free Ag cross-links IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at post-capillary venules (histamine)
Rapid because of preformed Ab
Skin test for specific IgE

115

Type II Hypersensitivity Reaction
Description
Process
Mechanisms
Test

Cytotoxic. Ab mediated
IgM, IgG bind to fixed Ag on "enemy" cell leading to cellular destruction
Opsonization, Complement activation, Ab-Dependent Cell-Mediated cytotoxicity (ADCC) due to NK cells
Direct and Indirect Coombs' Test

116

Type III Hypersensitivity Reaction
Description
Process

Immune Complex
Ag-Ab (IgG) complex activates complement which attracts Neutrophils which release lysosomal enzymes

117

Serum Sickness
What is it?
PathoPhys
Timeframe
Frequency
What causes it?
Presentation

Immune Complex Disease
ICs are deposited in membranes where they fix complement leading to tissue damage
5-10 days after exposure
More common than Arthus
Drugs acting as haptens
Fever, Urticaria, Arthralgias, Proteinuria, Lymphadenopathy

118

Arthus Reaction
What is it?
PathoPhys
Presentation
Test
Frequency

Local Subacute Ab mediated hypersensitivity type III reaction
Intradermal injection of Ag induces Abs which form Ag-Ab complexes in the skin which activate complement
Edema, Necrosis
Immunofluorescent staining
Less common than serum sickness

119

Type IV Hypersensitivity Reaction
Description
Process
Transferable?
Mnemonic
Test

Delayed T cell mediated reaction
Sensitized T lymphocytes encounter Ag and release lymphokines leading to macrophage activation. No Ab involvement
Not transferable in serum
"4Ts: Tcells, Transplant rejection, TB skin test, Touching (contact dermatitis)"
Patch test, PPD

120

Hypersensitivity Reactions

"ACID"
I: Anaphylactic and Atopic
II: Cytotoxic
III: Immune Complex
IV: Delayed (cell mediated)

121

Examples of Type I Hypersensitivity Reactions

Anaphylaxis (allergy)
Allergic and Atopic disorders (Rhinitis, Hay Fever, Eczema, Hives, Asthma)

122

Examples of Type II Hypersensitivity Reactions

"Go PIE TRAP"
Goodpasture's Syndrome
Pernicious Anemia
Idiopathic Thrombocytopenic Purpura
Erythroblastosis Fetalis
Acute Hemolytic Transfusion Reaction
Rheumatic Fever
Autoimmune Hemolytic Anemia
Bullous Pemphigoid, Pemphigus Vulgaris

123

Examples of Type III Hypersensitivity Reactions

"LAPPS"
SLE
Arthus
Polyarteritis nodosa
PSGN
Serum Sickness

124

Examples of Type IV Hypersensitivity Reactions

"Ms PuGG's CD"
MS
PPD test for TB
Gullian Barre
Graft vs Host
Contact Dermatitis (Poison Ivy, Nickel allergy)

125

Allergic Reaction to blood transfusion
Type
Presentation
Treatment

Type I
Urticaria, Pruritus, Wheezing, Fever
Antihistamines

126

Anaphylactic Reaction to blood transfusion
Severity
Precaution
Presentation

Severe
IgA deficient individuals must receive blood that lacks IgA
Dyspnea, Bronchoconstriction, Hypotension, Respiratory Arrest, Shock

127

Febrile NonHemolytic Transfusion Reaction (FNHTR)
Type
Mechanism
Presentation

II
Host Ab against donor HLA Ags and leukocytes
Fever, Headaches, Chills, Flushing

128

Acute Hemolytic Transfusion Reaction (AHTR)
Type
Mechanism
Presentation

II
Intravascular hemolysis (ABO blood group incompatibility) or Extravascular hemolysis (host Ab reaction against foreign Ag or donor RBC)
Fever, Hypotension, Tachycardia, Flank Pain, Hemoglobinemia (intravascular), Jaundice (extravascular)

129

ANA
Anti dsDNA, Anti Smith
Anti-Histone
RF, CCP
Anti centromere
Anti Scl70 (topoisomerase)

SLE, nonspecific
SLE
Drug induced SLE
RA
CREST
Scleroderma (diffuse)

130

Anti-Mitochondiral
IgA anti endomysial, IgA anti Tissue Transglutaminase
Anti BM
Anit Desmoglein

Primary Biliary Cirrhosis
Celiac Disease
Goodpasture's Syndrome
Pemphigus vulgaris

131

Anti-Microsomal, Anti-Thyroglobulin
Anti Jo1, Anti SRP, Anti Mi2
Anti SSA, Anti SSB
Anti U1 RNP

Hashimoto's Thyroiditis
Polymyositis, Dermatomyositis
Sjogren's
Mixed connective tissue disease

132

Anti Smooth Muscle
Anti Glutamate Decarboxylase
cANCA
pANCA

Autoimmune hepatitis
DM1
Wegeners
Microscopic polyangiitis, Churg Strauss syndrome

133

No T cells
Bacteria
Virus
Fungi/Parasites

Sepsis
CMV, EBV, VZV, Chronic Respiratory and GI viruses
Candida, PCP

134

No B cells
Bacteria
Virus
Fungi/Parasites

Encapsulated bacteria "SHiN SKiS"
Enteroviral Encephalitis, Poliovirus
GI Giardiasis (no IgA)

135

No Granulocytes
Bacteria
Virus
Fungi/Parasites

Staph, Burkholderia cepacia, Serratia, Nocardia
N/A
Candida, Aspergillus

136

No Complement
Bacteria
Virus
Fungi/Parasites

Neisseria
N/A
N/A

137

X linked (Burton's) Agammaglobinemia
PathoPhys
Inheritance
Presentation
Findings

Defect in BTK (a tyrosine kinase gene) --> no B cell maturation
Recurrent bacterial infections (bacteria, enterovirus, Giardia- get these 3 whenever defect in immunoglobulins) after 6 months of age
Norma pro-B cells, ↓ # of B cells, ↓ Immunoglobulins of all classes

138

Selective IgA Deficiency
Frequency
Presentation
Labs

Most common primary immunodeficiency
Majority Asymptomatic. Sino-Pulmonary Infections, GI infections, Autoimmune disease, Anaphylaxis to IgA containing blood products
Low IgA with normal IgM and IgG. False positive βhCG test due to heterophile Ab

139

Common Variable Immunodeficiency (CVID)
PathoPhys
Epidemiology
Risks
Labs

Defect in B cell maturation by many causes
Acquired in 20s-30s
Infections with bacteria, enterovirus, Giardia- get these 3 whenever defect in immunoglobulins
Autoimmune disease**, Lymphoma**, Sinopulmonary infections
Normal # of B cells with ↓ Plasma cells and Immunoglobulin

140

Thymic Aplasia
Name
PathoPhys
Genetics
Presentation
Labs
XR

DiGeorge Syndrome
Failure to develop 3rd and 4th Pharyngeal Pouches
22q11 deletion
Tetany (hypocalcemia), Recurrent viral/fungal infections (T cell deficiency), Congenital Heart and Great Vessel Defect
↓ T cells, ↓ PTH, ↓ Ca
Absent Thymic Shadow on CXR

141

IL12 Receptor Deficiency
PathoPhys
Presentation
Labs

↓ Th1 response
Disseminated Mycobacterial Infections
↓ IFNγ

142

Hyper IgE Syndrome
Name
PathoPhys
Presentation
Labs

Job's Syndrome
Th1 cells fail to produce IFNγ leading to inability to attract neutrophils
"FATED"
course Facies, cold (non inflamed) staphylococcal, Abscesses, retained primary Teeth, ↑IgE, Dermatologic problems (eczema)
↑IgE

143

Chronic Mucocutaneous Candidiasis
PathoPhys
Presentation

T cell dysfunction --> Candida albicans infection of skin and mucous membrane

144

Severe Combined Immunodeficiency
Kind of disorder
PathoPhys
Presentation
XR
Histo
Blood
Treatment

Combined B and T cell disorder
Defective IL2 receptor (most common, X linked) or Adenosine Deaminase deficiency
Failure to thrive, Chronic Diarrhea, Thrush. Recurrent viral, bacterial, fungal, and protozoal infections
No Thymic shadow
No Germinal centers on lymph node biopsy, ↓ T cell recombinant Excision Circles (TREC)
No B or T cells in peripheral blood
Bone Marrow Transplant

145

Ataxia Telangiectasia
PathoPhys
Presentation
Labs

Defect in ATM gene coding for DNA repair enzyme
Cerebellar defects (ataxia), Spider angiomas (Telangiectasia), IgA deficiency
↑AFP

146

Hyper IgM Syndrome
PathoPhys
Presentation
Antibodies

Defective CD40L on Th cells = inability to class switch
Severe pyogenic infections in early life
↑IgM, ↓ IgG, IgA, and IgE

147

Wiskott-Aldrich Syndrom
Inheritance
PathoPhys
Presentation
Labs

XL
WASP gene mutation = T cells unable to reorganize actin cytoskeleton
"TIE"
Thrombocytopenic Purpura, Infections, Eczema
↑IgE, ↑IgA, ↓IgM, Thrombocytopenia

148

Leukocyte Adhesion Deficiency Type 1
Dysfunction of what?
PathoPhys
Presentation
Findings

Phagocyte Dysfunction
Defect in LFA1 integrin (CD18) protein on phagocytes
Recurrent bacterial infections, absent pus formation, Delayed separation of umbilical cord
Neutrophilia

149

Chediak Higashi Syndrome
Dysfunction of what?
Inheritance
PathoPhys
Presentations
Histo

Phagocyte dysfunction
AR
Defect in lysosomal trafficking regulator gene --> MT dysfunction in phagosome-lysosome fusion
Recurrent pyogenic infections by Staph and Strep, Partial Albinism, Peripheral Neuropathy
Giant Granules in Neutrophils

150

Chronic Granulomatous Disease
Dysfunction of what?
PathoPhys
Presentation
Diagnostic test

Phagocyte dysfunction
Lack of NADPH oxidase --> ↓ ROS and absent respiratory burst in neutrophils
Susceptibility to catalase + organisms (S aureus, E coli, Aspergillus)
Abnormal dihydrorhodamine (DHR) flow cytometry test
Nitroblue Tetrazolium due reduction test no longer preferred

151

Synteneic Graft

Graft from Identical Twin or Clone

152

Hyperacute Transplant rejection
Onset after transplantation
PathoPhys
Presentation

Minutes
Type II: Preformed antidonor Ab
Occludes graft vessels causing ischemia and necrosis

153

Acute Transplant rejection
Onset after transplantation
PathoPhys
Reversible?
Histo

Weeks
Cell mediated reaction: CTLs react against foreign MHC
Reversible with immunosuppression
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate

154

Chronic Transplant rejection
Onset after transplantation
PathoPhys
Reversible?
Histo

Months to years
Non-self MHCI recognized as self and presents non-self Ag
Irreversible
T cell and Ab mediated vascular damage (obliterative vascular fibrosis), Fibrosis of graft tissue and blood vessels

155

Graft Vs Host Disease
Onset after transplantation
PathoPhys
Presentation
What kind of transplants
When can it be potentially beneficial?

Varies
Grafted T cells attack host
Maculopapular rash, Jaundice, HSM, Diarrhea
Usually in Bone Marrow and Liver Transplants
Potentialy beneficial in Bone Marrow Transplant

156

Cyclosporine
MoA
Use
Tox

Binds Cyclophilins. Complex blocks differentiation and activatino of T cells by inhibiting Calcineurin thereby preventing production of IL2 and its receptor
Suppress organ rejection. Autoimmune disorders
Nephrotoxicity, HTN, Hyperlipidemia, Hyperglycemia, Tremor, Gingival Hyperplasia, Hirsutism

157

Tacrolimus
AKA
MoA
Use
Tox

FK506
Binds FK binding protein thereby inhibiting calcineurin and secretion of IL2 and other cytokines
Organ transplant
Nephrotoxicity, HTN, Hyperlipidemia, Hyperglycemia, Tremor

158

Sirolimus
AKA
MoA
Use
Tox

Rapamycin
Inhibits mTOR thereby inhibiting T cell proliferation in response to IL2
Kidney transplant w/ cyclosporine and corticosteroids. Drug Eluting Stents
Hyperlipidemia, Thrombocytopenia, Leukopenia

159

Azathioprine
MoA
Use
Tox

Antimetabolite precursor to 6MP that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes
Kidney transplantation, Autoimmune disorders (including glomerulonephritis and hemolytic anemia)
Bone Marrow Suppression

160

Muromonab CD3
AKA
MoA
Use
Tox

OKT3
Ab that binds CD3 on T cell surface. Blocks cellular interaction with CD3 protein responsible for T cell signal transduction
Kidney Transplant
Cytokine release syndrome, Hypersensitivity Reaction

161

Recombinant IL2
Name
Use

Aldesleukin
Renal Cell Carcinoma, Metastatic Melanoma

162

Recombinant EPO
Name
Use

Epoetic Alfa
Anemias (especially renal failure)

163

Recombinant Granulocyte CSF
Name
Use

Filgrastim
Recovery of bone marrow

164

Recombinant Granulocyte Macrophage CSF
Name
Use

Sargramostim
Recovery of Bone Marrow

165

Recombinant IFNα Use

HBV, HCV, Kaposi Sarcoma, Leukemias, Malignant Melanoma

166

Recombinant IFNβ Use

MS

167

Recombinant IFNγ Use

Chronic Granulomatous Disease

168

Recombinant IL11
Name
Use

Oprelvekin
Thrombocytopenia

169

Recombinant Thrombopoietin Use

Thrombocytopenia

170

Omalizumab

anti IgE Ab used in asthma

171

Rituximab

Anti CD20 Ab used in B cell Non-Hodgkin's Lymphoma

172

Abciximab

Anti GP IIb/IIIa Ab used to prevent cardiac ischemia in unstable angina and in pts treated with percutaneous coronary intervention