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ACVIM General Exam > Immunology > Flashcards

Immunology Flashcards

1
Q

What are the functions of the complement system?

A
  1. Kills pathogens immediately when they enter the body
  2. Alerts the immune system to the presence of invaders
  3. Regulates inflammation
  4. Removes damaged or altered cells
  5. Regulates adaptive immune responses
  6. Clearance of antigen-antibody complexes
  7. Blood vessel formation
  8. Tissue regeneration
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2
Q

What is the function of IFN-γ?

A
  1. Upregulates MHC I and MHC II expression

2. Activates macrophages

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3
Q

How are macrophages activated?

A
  1. IFNγ
  2. TNFα
  3. IL-2
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4
Q

What are the adverse effects of chlorambucil

A
  1. GI upset
  2. Myelosuppression (delayed 1 month)
  3. Alopecia
  4. Fanconi like syndrome in cats
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5
Q

Which portions of the complement system are involved in cell lysis?

A
  1. Membrane attack complex

* Ruptures bacterial cell wall

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6
Q

Which portions of the complement system are involved in chemotaxis?

A
  1. C3a → attracts eosinophils
  2. C5a → attracts neutrophils and macrophages to where antigen is present
  3. C567 → attracts neutrophils and eosinophils
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7
Q

What is the effector mechanisms for type I hypersensitivity reactions?

A
  1. Mast cell activation → release of vasoactive mediators
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8
Q

What expresses CD8?

A

Cytotoxic T cell

*Receptors for MHC I

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9
Q

What is detected by a gel agglutination test?

A
  1. Antibody
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10
Q

Describe neutrophil emigration

A
  1. PAMPs and DAMPs detected → endothelial cells express P-selectin
  2. L-selectin on neutrophils binds to P-selectin
  3. Nearby chemokine and leukotrienes trigger neutrophils to express leukocyte associated antigen 1 (LFA-1)
  4. LFA-1 binds intercellular adhesion molecule 1 (ICAM-1) on endothelial cells → causes firm adhesion to the endothelium
  5. Neutrophils can then undergo diapedesis
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11
Q

How is cytokine signaling regulated?

A
  1. Changes in receptor expression
  2. Presence of specific binding proteins
  3. Cytokines that exert opposing effects
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12
Q

What are the adverse effects of azathioprine?

A
  1. GI
  2. Myelosuppression
  3. Hepatotoxicosis (idiosyncratic)
  4. Pancreatitis
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13
Q

What do PRRs recognize for acid fast bacteria?

A

Glycolipids

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14
Q

What are contraindications for leflunomide?

A
  1. Pregnancy → teratogenic
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15
Q

What is the effector mechanisms for type IV hypersensitivity reactions?

A

Sensitized Th1 cells release cytokines that activate macrophages (IFN-γ or TNF) or cytotoxic t lymphocytes that mediate direct cellular damage

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16
Q

Name the hypersensitivity reaction:

- Leishmania

A

Type III

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17
Q

What cytokines produce Th2 cells?

A
  1. IL-4

2. IL-1

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18
Q

What cytokines produce Th17 cells?

A
  1. IL-6

2. TGF-β

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19
Q

What expresses CD3?

A

T lymphocytes

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20
Q

Rank the immunoglobulins from largest to smallest

A
  1. IgM
  2. IgA
  3. IgE (think mast cells)
  4. IgG
  5. IgD (not in cats)
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21
Q

What is detected by TLR-4?

A

LPS

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22
Q

What are 3 ways that antibodies can participate in host defense?

A
  1. Opsinization
  2. Complement
  3. Neutralization
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23
Q

What are interleukins?

A

Signal between lymphocytes and other leukocytes

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24
Q

What are drug interactions for azathioprine?

A
  1. Allopurinol → xanthine oxidase inhibitor → need to reduce the azathioprine dose
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25
What are type 2 interferons?
2. Produced by macrophages, lymphocytes, and fibroblasts - γ - Promotes a cytotoxic T cell response → immunomodulatory when used for treatment
26
Name the hypersensitivity reaction: | - Anaphylaxis
Type I
27
What do PRRs recognize for virus?
Nucleic acids - dsRNA = TLR-3 - ssRNA = TLR-7, TLR-8 - dsDNA = TLR-9 *When you see virus, think 3, 7, 8, 9
28
What are the 3 mechanisms for central self tolerance?
1. Clonal deletion (apoptosis) 2. Clonal anergy (inability to respond) 3. Suppression (inhibition of reactivity)
29
What is significant about IgA?
It cannot activate complement
30
What are contraindications for azathioprine?
1. DO NOT GIVE TO CATS | - Cats do not have the enzyme needed for the detoxification pathway (TPMT)
31
What is the function of IL-8?
1. Chemotaxis and activation → especially neutrophils
32
What is produced by Th17 cells?
1. IL-17
33
What lab findings would be associated with X-linked SCID?
1. Low lymphocyte counts 2. Low IgG, IgA 3. Normal IgM
34
How do macrophages act as sentinel cells?
1. Produce many cytokines: IL-1, IL-6, IL-12, IL-18, TNF-α | 2. Produce chemokines: CXCL8 (IL-8) → recruits and attracts neutrophils
35
What are the major cytokines released by sentinel cell promoting inflammation?
1. TNF-α 2. IL-1 3. IL-6
36
MHC class II pathway involves (exogenous/endogenous) antigens
Exogenous
37
Th1 cells are primarily involved in (cell mediated/humoral) immunity
Cell mediated
38
What is produced by Tregs?
1. IL-10 | 2. TGF-β
39
What regulates production of neutrophils?
Granulocyte colony stimulating factor (G-CSF)
40
How do macrophages act in inflammation?
1. DAMPs → IL-6, TNF-α 2. Recruit neutrophils 3. Produce reactive oxygen species
41
How long do neutrophils live?
Short lived → 7-10 hours
42
What is the MOA of chlorambucil?
1. Alkylating agent → cross links DNA | - Cell cycle non-specific
43
What is the MOA of IVIG?
1. Blockage of Fcγ receptors
44
What are B cell functions?
1. Antigen presentation (secondary immune response) | 2. Immunoglobulin production
45
What is a type IV hypersensitivity reaction? What is it mediated by?
1. Delayed hypersensitivity reaction 2. Th1 cells 3. Antigen: Soluble proteins
46
How do macrophages perform phagocytosis?
1. Oxidation mediated (respiratory burst, nitric oxide synthesis) 2. Non-oxidative mechanisms 3. Synthesis pro- and anti- inflammatory cytokines, antimicrobial peptides, and enzymes 4. Produce proteases to soften up local connective tissue matrix
47
Name the hypersensitivity reaction: | - Effusive FIP
Type III
48
What are drug interactions with cyclosporin?
1. Ketoconazole → need a lower dose if also receiving cyclosporine
49
Name the hypersensitivity reaction: | - Allergic Contact Dermatitis
Type IV
50
Patients with a T cell deficiency are more susceptible to (bacterial/intracellular) infections
Intracellular
51
What is opsonization? What is it driven by?
1. Coating of pathogens and foreign particles with antibodies to facilitate ingestion by phagocytes 2. IgG, IgE, C3b, C5b
52
Which interleukins are anti-inflammatory?
1. IL-10 2. TGF-β 3. TNF-β
53
Which TLRs recognize viruses?
1. TLR-3 2. TLR-7 3. TLR-8 4. TLR-9
54
What is a type II hypersensitivity reaction? What is it mediated by?
1. Cytotoxic hypersensitivity reaction 2. IgG 3. Antigen: Cell or matrix, cell surface receptor
55
What is produced by Th1 cells?
1. IL-2 | 2. IFN-γ
56
What is the MOA of cyclosporine?
1. Intracellular receptors (immunophilins) 2. CALCINEURIN inhibitor → NFAT cannot be phosphorylated - NFAT normally translocates to the nucleus to promote cytokine production → IL-2!, IL-3, IL-4, TNFα
57
What do PRRs recognize for gram positive bacteria?
Peptidoglycans
58
Why are problems with infection associated with X-linked SCID patients not observed until 4-8 weeks of age?
This is when maternal antibody protection has waned
59
What stimulates fever? How?
1. Triggered by IL-1, IL-6, TNF-α 2. Induces cyclooxyrgenase 2 (COX-2) in the hypothalamus - Prostaglandin E2 production - Alters thermostatic set point
60
Name the hypersensitivity reaction: | - Immune complex mediated glomerular nephritis (IMGN)
Type III
61
Patients with a B cell deficiency are more susceptible to (bacterial/intracellular) infections
Bacterial
62
What is X-linked SCID?
A severe immunodeficiency that results in the diminished cell mediated and humoral immune responses
63
What are the actions of TNF-α?
1. Adherence, migration, and attraction of leukocytes 2. Causes signs of inflammation 3. Later, facilitates transition from innate to adaptive immunity
64
Which interleukin is the most potent inducer of tumor cell destruction by NK and cytotoxic T cells?
IL-12
65
What are drug interactions for mycophenolate?
1. Azathioprine | 2. Aminoglycosides → due to renal effects
66
What antibody is involved in the primary immune response (produced first)?
IgM
67
What is the action of IL-1?
Promote inflammation
68
What interleukins are produced by eosinophils?
1. IL-3 | 2. IL-5 → important
69
Where are B cells located?
1. Cortex of lymph nodes 2. Marginal zone of spleen 3. Bone marrow 4. Peyers Patches
70
What is the function of IL-11?
Hematopoietic growth factor`
71
What is the MOA of leflunomide?
1. Reversible inhibition of dihydroorate dehydrogenase | - inhibits de nova synthesis of PYRIMIDINES
72
What is associated with a C3 deficiency in Brittany Spaniels?
Immune complex mediated disease
73
How do antigen presenting cells function?
1. Break large protein molecules into small peptides within the cell 2. Peptides attached to major histocompatibility complex (MHC) molecules on cell surface 3. MHC-bound peptides recognized by T lymphocytes
74
Which portions of the complement system are involved in opsonization?
1. C3b 2. C4b * Activates neutrophils and macrophages * Results in phagocytosis
75
What are the adverse effects of cyclosporine?
1. GI Upset 2. GINGIVAL HYPERPLASIA 3. Papillomatosis 4. Peripheral insulin resistance
76
How do neutrophils kill?
1. Respiratory burst (oxygen dependent) - O2 + NADPH → superoxide anion → spontaneous degradation to H2O2 - H2O2 + Cl → hypochlorous acid 2. Oxygen independent - Lysozyme: present in both primary and secondary granules - Cationic proteins 3. Defensins: only in primary granules → increases permeability of bacteria
77
What are adverse effects of IVIG?
1. Anaphylaxis 2. Hypercoagulability 3. Mild thrombocytopenia
78
What are mechanisms of peripheral self tolerance?
1. Clonal deletion (apoptosis) via Fas ligand 2. Clonal anergy (inability to respond) - Lack of cross-linking IgM - Lack of costimulatory molecules to bind with Th cell costimulatory molecules → follicular exclusion (cant migrate into T cell paracortex to get stimulated) 3. Suppression (inhibition of reactivity) - T cells can become T regs
79
What cell type is recruited by Th17 cells?
1. Neutrophils
80
What is the major source of IgM in the dog and cat?
Spleen
81
What is the MOA of mycophenolate?
1. Inhibits inosine monophosphate dehydrogenase (IMPDH) | - Enzyme necessary for de novo PURINE synthesis
82
When is hepcidin produced? What does it do?
1. Bacterial invasion → production of acute phase proteins (IL-1, IL-6) → produce hepcidin 2. Hepcidin binds ferraportin in enterocytes to trigger internalization and degradation → blocks iron absorption
83
On what cells are TLRs found?
1. Sentinel cells of innate immune system → macrophages, neutrophils, mast cells, dendritic cells 2. T and B cells of adaptive immune systemp 3. Epithelial cells that line respiratory and GI tracts
84
What produces tumor necrosis factors?
1. Macrophages | 2. T-cells
85
What is neutralization important in protecting against?
1. Viruses | - Not sufficient for bacteria
86
What is the predominant leukocyte in the blood?
Neutrophil (60-75%)
87
How is complement activated?
1. Antigen-antibody reaction (classical pathway) 2. Mannose binding protein (lectin pathway) 3. Bacterial endotoxin (alternative pathway)
88
What antibody is involved in the secondary immune response?
IgG
89
What are the adverse effects of leflunomide?
1. GI upset 2. Spontaneous bleeding 3. Myelosuppression
90
Where does central tolerance occur?
Thymus
91
What is the effector mechanisms for type III hypersensitivity reactions?
Immune complex are deposited in various tissues → activates complement and induces tissue damage
92
Which portions of the complement system are involved in blood coagulation?
1. C5a * induces expression of tissue factor and plasminogen activator inhibitor 1 * thrombin acts on C5 to generate C5a * Enhances blood coagulation and inhibits fibrinolysis
93
Which breed has a selective IgA deficiency?
Shar Pei
94
What is detected by NOD2?
Bacterial Muramyl Dipeptide | *General sensor of intracellular bacteria
95
What is detected by NOD1?
Bacterial peptidoglycans
96
What is the MOA of azathioprine?
1. Thiopurine (purine analog) → affects the S PHASE of the cell cycle
97
What is neutralization? What is it driven by?
1. Antibodies binding to pathogens or their products, blocking access to cells that they might infect or Destry 2. IgA
98
The availability of ____ dictates the success or failure of bacterial invasion
Iron
99
If cells recognize MHC II they become what type of cell?
CD4
100
What cytokines produce Th1 cells?
1. IL-12 | 2. IFN-γ
101
What cell type is recruited by Th2 cells?
1. Mast cells 2. Eosinophils 3. IgE production
102
What is the MOA of glucocorticoids?
1. Decrease egress of inflammatory cells (down regulation of adhesion molecules) 2. Suppress humoral immunity (reduce IgG, IgM, IgA) 3. Downregulation of Fc receptors on macrophages 4. Induce lymphocyte apoptosis 5. Inhibition of phospholipase A2 6. Suppress cytokines (IL-1, TNFα, IL-3, IL-4, IL-5) production 7. Inhibit phagocytosis
103
What is detected by NOD-like receptors?
Intracellular PAMPs
104
If cells recognize MHC I they become what type of cell?
CD8
105
What happens (broadly) when TLRs are activated?
Promote inflammation
106
What is the downstream action of activated NOD-like receptors (NLRs)
1. NF-κβ pathway → pro-inflammatory cytokines | 2. NOD2 → defensins (antimicrobial proteins)
107
What are contraindications for mycophenolate?
1. Severe renal dysfunction | 2. Caution in cats
108
When is IL-6 released?
produced by macrophages, T cells, and mast cells in response to bacterial endotoxins, IL-1, and TNF-α
109
What cell type is recruited by Th1 cells?
1. Macrophages
110
How are B cells activated
1. Antigen to BCR | 2. Co stimulant (helper T cells, cytokines, complement, PAMPs)
111
Name the hypersensitivity reaction: | - SLE
Primarily Type III but can have Type II and Type IV components
112
Which leukotriene is responsible for stimulating neutrophils?
Leukotriene B
113
What is detected by TLR-5?
Flagellin
114
What are type 1 interferons?
1. Bind to cell via INFAR - α, β, ω - Have primary roles in anti-viral and anti-cancer
115
What is the effector mechanisms for type II hypersensitivity reactions?
1. Complement FcR+ cells (phagocytes, NK cells)
116
What cytokines produce Tregs?
1. IL-10 | 2. TGF-β
117
What is a lupus erythematous cell?
1. A neutrophil that contains phagocytize nuclear material
118
What expresses CD79/CD21/CD20?
B lymphocyte
119
What are the actions of IL-6?
1. Promotes inflammation 2. Increases hepcidin → anemia of chronic disease 3. Very important for fever!
120
What are the adverse effects of mycophenolate?
1. GI (diarrhea most common) | 2. Hypersensitivity
121
What are contraindications for IVIG use?
1. Caution in patients with hypertension or AKI
122
What is detected by a direct Coombs test?
1. Antibodies 2. Complement 3. OR both
123
What is a type III hypersensitivity reaction? What is it mediated by?
1. Immune complex reaction 2. IgG 3. Antigen: Soluble antigen
124
What is the function of IL-3?
Hematopoietic growth factor
125
What are contraindications for cyclosporin?
1. Hepatic or renal disease | 2. History of malignant neoplasia
126
MHC class I pathway involves (exogenous/endogenous) antigens
Endogenous (Viral proteins)
127
What is produced by Th2 cells?
1. IL-3 2. IL-4 3. IL-5 4. IL-6 5. IL-13
128
What are interferons? What types are there?
1. Produced in response to virus infection or immune stimulation - Interfere with viral RNA and protein synthesis 2. Type 1: INF-α, INF-β - Antiviral >> immunomodulatory 3. Type 2: IFN-γ - Antiviral << immunomodulatory 4. Type 3: ΙFN-λ - Antiviral << immunomodulatory
129
What is a type I hypersensitivity reaction? What is it mediated by?
1. Ige Dependent Reaction 2. IgE 3. Antigen: Soluble antigen
130
What are important functions of IL-2
Proinflammatory | Very important in stimulating CELL MEDIATED immune response
131
What is the most potent antigen presenting cell? Why?
1. Dendritic cells | 2. They have all of the co-stim and adhesion molecules necessary for sustained activation/priming of naive T cells
132
Name the hypersensitivity reaction: | - Myasthenia gravis
Type II
133
What are drug interactions for leflunomide?
1. Rifampin 2. Warfarin 3. Methotrexate 4. Chlestyramine
134
What is the best marker for APCs
CD1
135
Name the hypersensitivity reaction: | - IMHA
Type II
136
Th2 cells are primarily involved in (cell mediated/humoral) immunity
Humoral
137
What expresses CD45?
All leukocytes
138
What do plasma cells produce?
1. Immunoglobulin → identical specificity to BCR on parent cell
139
Which portions of the complement system are involved in activation of mast cells?
1. C3a 2. C4a 3. C5a * Release of inflammatory mediators (histamine, serotonin)
140
How do cytotoxic T cells induce apoptosis?
1. Perforin pathway - Perforins and granzymes from secretory lysosomes - Viral infected cells 2. CD95 death receptor - Mainly used for an unwanted surplus of T cells
141
Name the hypersensitivity reaction: | - Non-effusive FIP
Type IV
142
What is recognized by DAMPs?
Molecules escaping from dead, dying, and damaged tissues 1. Mitochondrial DNA → TLR-9 2. High mobility group box protein 1 (HMGB1) → normally binds DNA to ensure correct folding → TLR2 and TLR4
143
When is IL-1 released?
Produced by sentinel cells in response to CD14 and TLR4 stimulation
144
What breed is predisposed to a C3 deficiency?
Brittany Spaniels
145
Name the hypersensitivity reaction: | - Tuberculosis
Type IV
146
What expresses CD4?
T-helper Cell | * Receptors for MHC II
147
What do PRRs recognize for yeasts?
Mannan- or B-glucan rich cell wall
148
What do PRRs recognize for gram negative bacteria?
Lipopolysaccharide (LPS) → TLR-4

ACVIM General Exam (15 decks)

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