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
Q

What are type 2 interferons?

A
  1. Produced by macrophages, lymphocytes, and fibroblasts
    - γ
    - Promotes a cytotoxic T cell response → immunomodulatory when used for treatment
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26
Q

Name the hypersensitivity reaction:

- Anaphylaxis

A

Type I

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27
Q

What do PRRs recognize for virus?

A

Nucleic acids

  • dsRNA = TLR-3
  • ssRNA = TLR-7, TLR-8
  • dsDNA = TLR-9

*When you see virus, think 3, 7, 8, 9

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28
Q

What are the 3 mechanisms for central self tolerance?

A
  1. Clonal deletion (apoptosis)
  2. Clonal anergy (inability to respond)
  3. Suppression (inhibition of reactivity)
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29
Q

What is significant about IgA?

A

It cannot activate complement

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30
Q

What are contraindications for azathioprine?

A
  1. DO NOT GIVE TO CATS

- Cats do not have the enzyme needed for the detoxification pathway (TPMT)

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31
Q

What is the function of IL-8?

A
  1. Chemotaxis and activation → especially neutrophils
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32
Q

What is produced by Th17 cells?

A
  1. IL-17
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33
Q

What lab findings would be associated with X-linked SCID?

A
  1. Low lymphocyte counts
  2. Low IgG, IgA
  3. Normal IgM
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34
Q

How do macrophages act as sentinel cells?

A
  1. Produce many cytokines: IL-1, IL-6, IL-12, IL-18, TNF-α

2. Produce chemokines: CXCL8 (IL-8) → recruits and attracts neutrophils

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35
Q

What are the major cytokines released by sentinel cell promoting inflammation?

A
  1. TNF-α
  2. IL-1
  3. IL-6
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36
Q

MHC class II pathway involves (exogenous/endogenous) antigens

A

Exogenous

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37
Q

Th1 cells are primarily involved in (cell mediated/humoral) immunity

A

Cell mediated

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38
Q

What is produced by Tregs?

A
  1. IL-10

2. TGF-β

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39
Q

What regulates production of neutrophils?

A

Granulocyte colony stimulating factor (G-CSF)

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40
Q

How do macrophages act in inflammation?

A
  1. DAMPs → IL-6, TNF-α
  2. Recruit neutrophils
  3. Produce reactive oxygen species
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41
Q

How long do neutrophils live?

A

Short lived → 7-10 hours

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42
Q

What is the MOA of chlorambucil?

A
  1. Alkylating agent → cross links DNA

- Cell cycle non-specific

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43
Q

What is the MOA of IVIG?

A
  1. Blockage of Fcγ receptors
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44
Q

What are B cell functions?

A
  1. Antigen presentation (secondary immune response)

2. Immunoglobulin production

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45
Q

What is a type IV hypersensitivity reaction? What is it mediated by?

A
  1. Delayed hypersensitivity reaction
  2. Th1 cells
  3. Antigen: Soluble proteins
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46
Q

How do macrophages perform phagocytosis?

A
  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
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47
Q

Name the hypersensitivity reaction:

- Effusive FIP

A

Type III

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48
Q

What are drug interactions with cyclosporin?

A
  1. Ketoconazole → need a lower dose if also receiving cyclosporine
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49
Q

Name the hypersensitivity reaction:

- Allergic Contact Dermatitis

A

Type IV

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50
Q

Patients with a T cell deficiency are more susceptible to (bacterial/intracellular) infections

A

Intracellular

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51
Q

What is opsonization? What is it driven by?

A
  1. Coating of pathogens and foreign particles with antibodies to facilitate ingestion by phagocytes
  2. IgG, IgE, C3b, C5b
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52
Q

Which interleukins are anti-inflammatory?

A
  1. IL-10
  2. TGF-β
  3. TNF-β
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53
Q

Which TLRs recognize viruses?

A
  1. TLR-3
  2. TLR-7
  3. TLR-8
  4. TLR-9
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54
Q

What is a type II hypersensitivity reaction? What is it mediated by?

A
  1. Cytotoxic hypersensitivity reaction
  2. IgG
  3. Antigen: Cell or matrix, cell surface receptor
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55
Q

What is produced by Th1 cells?

A
  1. IL-2

2. IFN-γ

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56
Q

What is the MOA of cyclosporine?

A
  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
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57
Q

What do PRRs recognize for gram positive bacteria?

A

Peptidoglycans

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58
Q

Why are problems with infection associated with X-linked SCID patients not observed until 4-8 weeks of age?

A

This is when maternal antibody protection has waned

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59
Q

What stimulates fever? How?

A
  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
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60
Q

Name the hypersensitivity reaction:

- Immune complex mediated glomerular nephritis (IMGN)

A

Type III

61
Q

Patients with a B cell deficiency are more susceptible to (bacterial/intracellular) infections

A

Bacterial

62
Q

What is X-linked SCID?

A

A severe immunodeficiency that results in the diminished cell mediated and humoral immune responses

63
Q

What are the actions of TNF-α?

A
  1. Adherence, migration, and attraction of leukocytes
  2. Causes signs of inflammation
  3. Later, facilitates transition from innate to adaptive immunity
64
Q

Which interleukin is the most potent inducer of tumor cell destruction by NK and cytotoxic T cells?

A

IL-12

65
Q

What are drug interactions for mycophenolate?

A
  1. Azathioprine

2. Aminoglycosides → due to renal effects

66
Q

What antibody is involved in the primary immune response (produced first)?

A

IgM

67
Q

What is the action of IL-1?

A

Promote inflammation

68
Q

What interleukins are produced by eosinophils?

A
  1. IL-3

2. IL-5 → important

69
Q

Where are B cells located?

A
  1. Cortex of lymph nodes
  2. Marginal zone of spleen
  3. Bone marrow
  4. Peyers Patches
70
Q

What is the function of IL-11?

A

Hematopoietic growth factor`

71
Q

What is the MOA of leflunomide?

A
  1. Reversible inhibition of dihydroorate dehydrogenase

- inhibits de nova synthesis of PYRIMIDINES

72
Q

What is associated with a C3 deficiency in Brittany Spaniels?

A

Immune complex mediated disease

73
Q

How do antigen presenting cells function?

A
  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
Q

Which portions of the complement system are involved in opsonization?

A
  1. C3b
  2. C4b
    * Activates neutrophils and macrophages
    * Results in phagocytosis
75
Q

What are the adverse effects of cyclosporine?

A
  1. GI Upset
  2. GINGIVAL HYPERPLASIA
  3. Papillomatosis
  4. Peripheral insulin resistance
76
Q

How do neutrophils kill?

A
  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
Q

What are adverse effects of IVIG?

A
  1. Anaphylaxis
  2. Hypercoagulability
  3. Mild thrombocytopenia
78
Q

What are mechanisms of peripheral self tolerance?

A
  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
Q

What cell type is recruited by Th17 cells?

A
  1. Neutrophils
80
Q

What is the major source of IgM in the dog and cat?

A

Spleen

81
Q

What is the MOA of mycophenolate?

A
  1. Inhibits inosine monophosphate dehydrogenase (IMPDH)

- Enzyme necessary for de novo PURINE synthesis

82
Q

When is hepcidin produced? What does it do?

A
  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
Q

On what cells are TLRs found?

A
  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
Q

What produces tumor necrosis factors?

A
  1. Macrophages

2. T-cells

85
Q

What is neutralization important in protecting against?

A
  1. Viruses

- Not sufficient for bacteria

86
Q

What is the predominant leukocyte in the blood?

A

Neutrophil (60-75%)

87
Q

How is complement activated?

A
  1. Antigen-antibody reaction (classical pathway)
  2. Mannose binding protein (lectin pathway)
  3. Bacterial endotoxin (alternative pathway)
88
Q

What antibody is involved in the secondary immune response?

A

IgG

89
Q

What are the adverse effects of leflunomide?

A
  1. GI upset
  2. Spontaneous bleeding
  3. Myelosuppression
90
Q

Where does central tolerance occur?

A

Thymus

91
Q

What is the effector mechanisms for type III hypersensitivity reactions?

A

Immune complex are deposited in various tissues → activates complement and induces tissue damage

92
Q

Which portions of the complement system are involved in blood coagulation?

A
  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
Q

Which breed has a selective IgA deficiency?

A

Shar Pei

94
Q

What is detected by NOD2?

A

Bacterial Muramyl Dipeptide

*General sensor of intracellular bacteria

95
Q

What is detected by NOD1?

A

Bacterial peptidoglycans

96
Q

What is the MOA of azathioprine?

A
  1. Thiopurine (purine analog) → affects the S PHASE of the cell cycle
97
Q

What is neutralization? What is it driven by?

A
  1. Antibodies binding to pathogens or their products, blocking access to cells that they might infect or Destry
  2. IgA
98
Q

The availability of ____ dictates the success or failure of bacterial invasion

A

Iron

99
Q

If cells recognize MHC II they become what type of cell?

A

CD4

100
Q

What cytokines produce Th1 cells?

A
  1. IL-12

2. IFN-γ

101
Q

What cell type is recruited by Th2 cells?

A
  1. Mast cells
  2. Eosinophils
  3. IgE production
102
Q

What is the MOA of glucocorticoids?

A
  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
Q

What is detected by NOD-like receptors?

A

Intracellular PAMPs

104
Q

If cells recognize MHC I they become what type of cell?

A

CD8

105
Q

What happens (broadly) when TLRs are activated?

A

Promote inflammation

106
Q

What is the downstream action of activated NOD-like receptors (NLRs)

A
  1. NF-κβ pathway → pro-inflammatory cytokines

2. NOD2 → defensins (antimicrobial proteins)

107
Q

What are contraindications for mycophenolate?

A
  1. Severe renal dysfunction

2. Caution in cats

108
Q

When is IL-6 released?

A

produced by macrophages, T cells, and mast cells in response to bacterial endotoxins, IL-1, and TNF-α

109
Q

What cell type is recruited by Th1 cells?

A
  1. Macrophages
110
Q

How are B cells activated

A
  1. Antigen to BCR

2. Co stimulant (helper T cells, cytokines, complement, PAMPs)

111
Q

Name the hypersensitivity reaction:

- SLE

A

Primarily Type III but can have Type II and Type IV components

112
Q

Which leukotriene is responsible for stimulating neutrophils?

A

Leukotriene B

113
Q

What is detected by TLR-5?

A

Flagellin

114
Q

What are type 1 interferons?

A
  1. Bind to cell via INFAR
    - α, β, ω
    - Have primary roles in anti-viral and anti-cancer
115
Q

What is the effector mechanisms for type II hypersensitivity reactions?

A
  1. Complement FcR+ cells (phagocytes, NK cells)
116
Q

What cytokines produce Tregs?

A
  1. IL-10

2. TGF-β

117
Q

What is a lupus erythematous cell?

A
  1. A neutrophil that contains phagocytize nuclear material
118
Q

What expresses CD79/CD21/CD20?

A

B lymphocyte

119
Q

What are the actions of IL-6?

A
  1. Promotes inflammation
  2. Increases hepcidin → anemia of chronic disease
  3. Very important for fever!
120
Q

What are the adverse effects of mycophenolate?

A
  1. GI (diarrhea most common)

2. Hypersensitivity

121
Q

What are contraindications for IVIG use?

A
  1. Caution in patients with hypertension or AKI
122
Q

What is detected by a direct Coombs test?

A
  1. Antibodies
  2. Complement
  3. OR both
123
Q

What is a type III hypersensitivity reaction? What is it mediated by?

A
  1. Immune complex reaction
  2. IgG
  3. Antigen: Soluble antigen
124
Q

What is the function of IL-3?

A

Hematopoietic growth factor

125
Q

What are contraindications for cyclosporin?

A
  1. Hepatic or renal disease

2. History of malignant neoplasia

126
Q

MHC class I pathway involves (exogenous/endogenous) antigens

A

Endogenous (Viral proteins)

127
Q

What is produced by Th2 cells?

A
  1. IL-3
  2. IL-4
  3. IL-5
  4. IL-6
  5. IL-13
128
Q

What are interferons? What types are there?

A
  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&raquo_space; immunomodulatory
  3. Type 2: IFN-γ
    - Antiviral &laquo_space;immunomodulatory
  4. Type 3: ΙFN-λ
    - Antiviral &laquo_space;immunomodulatory
129
Q

What is a type I hypersensitivity reaction? What is it mediated by?

A
  1. Ige Dependent Reaction
  2. IgE
  3. Antigen: Soluble antigen
130
Q

What are important functions of IL-2

A

Proinflammatory

Very important in stimulating CELL MEDIATED immune response

131
Q

What is the most potent antigen presenting cell? Why?

A
  1. Dendritic cells

2. They have all of the co-stim and adhesion molecules necessary for sustained activation/priming of naive T cells

132
Q

Name the hypersensitivity reaction:

- Myasthenia gravis

A

Type II

133
Q

What are drug interactions for leflunomide?

A
  1. Rifampin
  2. Warfarin
  3. Methotrexate
  4. Chlestyramine
134
Q

What is the best marker for APCs

A

CD1

135
Q

Name the hypersensitivity reaction:

- IMHA

A

Type II

136
Q

Th2 cells are primarily involved in (cell mediated/humoral) immunity

A

Humoral

137
Q

What expresses CD45?

A

All leukocytes

138
Q

What do plasma cells produce?

A
  1. Immunoglobulin → identical specificity to BCR on parent cell
139
Q

Which portions of the complement system are involved in activation of mast cells?

A
  1. C3a
  2. C4a
  3. C5a
    * Release of inflammatory mediators (histamine, serotonin)
140
Q

How do cytotoxic T cells induce apoptosis?

A
  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
Q

Name the hypersensitivity reaction:

- Non-effusive FIP

A

Type IV

142
Q

What is recognized by DAMPs?

A

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
Q

When is IL-1 released?

A

Produced by sentinel cells in response to CD14 and TLR4 stimulation

144
Q

What breed is predisposed to a C3 deficiency?

A

Brittany Spaniels

145
Q

Name the hypersensitivity reaction:

- Tuberculosis

A

Type IV

146
Q

What expresses CD4?

A

T-helper Cell

* Receptors for MHC II

147
Q

What do PRRs recognize for yeasts?

A

Mannan- or B-glucan rich cell wall

148
Q

What do PRRs recognize for gram negative bacteria?

A

Lipopolysaccharide (LPS) → TLR-4