Immunology Flashcards
What are the functions of the complement system?
- Kills pathogens immediately when they enter the body
- Alerts the immune system to the presence of invaders
- Regulates inflammation
- Removes damaged or altered cells
- Regulates adaptive immune responses
- Clearance of antigen-antibody complexes
- Blood vessel formation
- Tissue regeneration
What is the function of IFN-γ?
- Upregulates MHC I and MHC II expression
2. Activates macrophages
How are macrophages activated?
- IFNγ
- TNFα
- IL-2
What are the adverse effects of chlorambucil
- GI upset
- Myelosuppression (delayed 1 month)
- Alopecia
- Fanconi like syndrome in cats
Which portions of the complement system are involved in cell lysis?
- Membrane attack complex
* Ruptures bacterial cell wall
Which portions of the complement system are involved in chemotaxis?
- C3a → attracts eosinophils
- C5a → attracts neutrophils and macrophages to where antigen is present
- C567 → attracts neutrophils and eosinophils
What is the effector mechanisms for type I hypersensitivity reactions?
- Mast cell activation → release of vasoactive mediators
What expresses CD8?
Cytotoxic T cell
*Receptors for MHC I
What is detected by a gel agglutination test?
- Antibody
Describe neutrophil emigration
- PAMPs and DAMPs detected → endothelial cells express P-selectin
- L-selectin on neutrophils binds to P-selectin
- Nearby chemokine and leukotrienes trigger neutrophils to express leukocyte associated antigen 1 (LFA-1)
- LFA-1 binds intercellular adhesion molecule 1 (ICAM-1) on endothelial cells → causes firm adhesion to the endothelium
- Neutrophils can then undergo diapedesis
How is cytokine signaling regulated?
- Changes in receptor expression
- Presence of specific binding proteins
- Cytokines that exert opposing effects
What are the adverse effects of azathioprine?
- GI
- Myelosuppression
- Hepatotoxicosis (idiosyncratic)
- Pancreatitis
What do PRRs recognize for acid fast bacteria?
Glycolipids
What are contraindications for leflunomide?
- Pregnancy → teratogenic
What is the effector mechanisms for type IV hypersensitivity reactions?
Sensitized Th1 cells release cytokines that activate macrophages (IFN-γ or TNF) or cytotoxic t lymphocytes that mediate direct cellular damage
Name the hypersensitivity reaction:
- Leishmania
Type III
What cytokines produce Th2 cells?
- IL-4
2. IL-1
What cytokines produce Th17 cells?
- IL-6
2. TGF-β
What expresses CD3?
T lymphocytes
Rank the immunoglobulins from largest to smallest
- IgM
- IgA
- IgE (think mast cells)
- IgG
- IgD (not in cats)
What is detected by TLR-4?
LPS
What are 3 ways that antibodies can participate in host defense?
- Opsinization
- Complement
- Neutralization
What are interleukins?
Signal between lymphocytes and other leukocytes
What are drug interactions for azathioprine?
- Allopurinol → xanthine oxidase inhibitor → need to reduce the azathioprine dose
What are type 2 interferons?
- Produced by macrophages, lymphocytes, and fibroblasts
- γ
- Promotes a cytotoxic T cell response → immunomodulatory when used for treatment
Name the hypersensitivity reaction:
- Anaphylaxis
Type I
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
What are the 3 mechanisms for central self tolerance?
- Clonal deletion (apoptosis)
- Clonal anergy (inability to respond)
- Suppression (inhibition of reactivity)
What is significant about IgA?
It cannot activate complement
What are contraindications for azathioprine?
- DO NOT GIVE TO CATS
- Cats do not have the enzyme needed for the detoxification pathway (TPMT)
What is the function of IL-8?
- Chemotaxis and activation → especially neutrophils
What is produced by Th17 cells?
- IL-17
What lab findings would be associated with X-linked SCID?
- Low lymphocyte counts
- Low IgG, IgA
- Normal IgM
How do macrophages act as sentinel cells?
- Produce many cytokines: IL-1, IL-6, IL-12, IL-18, TNF-α
2. Produce chemokines: CXCL8 (IL-8) → recruits and attracts neutrophils
What are the major cytokines released by sentinel cell promoting inflammation?
- TNF-α
- IL-1
- IL-6
MHC class II pathway involves (exogenous/endogenous) antigens
Exogenous
Th1 cells are primarily involved in (cell mediated/humoral) immunity
Cell mediated
What is produced by Tregs?
- IL-10
2. TGF-β
What regulates production of neutrophils?
Granulocyte colony stimulating factor (G-CSF)
How do macrophages act in inflammation?
- DAMPs → IL-6, TNF-α
- Recruit neutrophils
- Produce reactive oxygen species
How long do neutrophils live?
Short lived → 7-10 hours
What is the MOA of chlorambucil?
- Alkylating agent → cross links DNA
- Cell cycle non-specific
What is the MOA of IVIG?
- Blockage of Fcγ receptors
What are B cell functions?
- Antigen presentation (secondary immune response)
2. Immunoglobulin production
What is a type IV hypersensitivity reaction? What is it mediated by?
- Delayed hypersensitivity reaction
- Th1 cells
- Antigen: Soluble proteins
How do macrophages perform phagocytosis?
- Oxidation mediated (respiratory burst, nitric oxide synthesis)
- Non-oxidative mechanisms
- Synthesis pro- and anti- inflammatory cytokines, antimicrobial peptides, and enzymes
- Produce proteases to soften up local connective tissue matrix
Name the hypersensitivity reaction:
- Effusive FIP
Type III
What are drug interactions with cyclosporin?
- Ketoconazole → need a lower dose if also receiving cyclosporine
Name the hypersensitivity reaction:
- Allergic Contact Dermatitis
Type IV
Patients with a T cell deficiency are more susceptible to (bacterial/intracellular) infections
Intracellular
What is opsonization? What is it driven by?
- Coating of pathogens and foreign particles with antibodies to facilitate ingestion by phagocytes
- IgG, IgE, C3b, C5b
Which interleukins are anti-inflammatory?
- IL-10
- TGF-β
- TNF-β
Which TLRs recognize viruses?
- TLR-3
- TLR-7
- TLR-8
- TLR-9
What is a type II hypersensitivity reaction? What is it mediated by?
- Cytotoxic hypersensitivity reaction
- IgG
- Antigen: Cell or matrix, cell surface receptor
What is produced by Th1 cells?
- IL-2
2. IFN-γ
What is the MOA of cyclosporine?
- Intracellular receptors (immunophilins)
- CALCINEURIN inhibitor → NFAT cannot be phosphorylated
- NFAT normally translocates to the nucleus to promote cytokine production → IL-2!, IL-3, IL-4, TNFα
What do PRRs recognize for gram positive bacteria?
Peptidoglycans
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
What stimulates fever? How?
- Triggered by IL-1, IL-6, TNF-α
- Induces cyclooxyrgenase 2 (COX-2) in the hypothalamus
- Prostaglandin E2 production
- Alters thermostatic set point