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
Name the hypersensitivity reaction:
- Immune complex mediated glomerular nephritis (IMGN)
Type III
Patients with a B cell deficiency are more susceptible to (bacterial/intracellular) infections
Bacterial
What is X-linked SCID?
A severe immunodeficiency that results in the diminished cell mediated and humoral immune responses
What are the actions of TNF-α?
- Adherence, migration, and attraction of leukocytes
- Causes signs of inflammation
- Later, facilitates transition from innate to adaptive immunity
Which interleukin is the most potent inducer of tumor cell destruction by NK and cytotoxic T cells?
IL-12
What are drug interactions for mycophenolate?
- Azathioprine
2. Aminoglycosides → due to renal effects
What antibody is involved in the primary immune response (produced first)?
IgM
What is the action of IL-1?
Promote inflammation
What interleukins are produced by eosinophils?
- IL-3
2. IL-5 → important
Where are B cells located?
- Cortex of lymph nodes
- Marginal zone of spleen
- Bone marrow
- Peyers Patches
What is the function of IL-11?
Hematopoietic growth factor`
What is the MOA of leflunomide?
- Reversible inhibition of dihydroorate dehydrogenase
- inhibits de nova synthesis of PYRIMIDINES
What is associated with a C3 deficiency in Brittany Spaniels?
Immune complex mediated disease
How do antigen presenting cells function?
- Break large protein molecules into small peptides within the cell
- Peptides attached to major histocompatibility complex (MHC) molecules on cell surface
- MHC-bound peptides recognized by T lymphocytes
Which portions of the complement system are involved in opsonization?
- C3b
- C4b
* Activates neutrophils and macrophages
* Results in phagocytosis
What are the adverse effects of cyclosporine?
- GI Upset
- GINGIVAL HYPERPLASIA
- Papillomatosis
- Peripheral insulin resistance
How do neutrophils kill?
- Respiratory burst (oxygen dependent)
- O2 + NADPH → superoxide anion → spontaneous degradation to H2O2
- H2O2 + Cl → hypochlorous acid - Oxygen independent
- Lysozyme: present in both primary and secondary granules
- Cationic proteins - Defensins: only in primary granules → increases permeability of bacteria
What are adverse effects of IVIG?
- Anaphylaxis
- Hypercoagulability
- Mild thrombocytopenia
What are mechanisms of peripheral self tolerance?
- Clonal deletion (apoptosis) via Fas ligand
- 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) - Suppression (inhibition of reactivity)
- T cells can become T regs
What cell type is recruited by Th17 cells?
- Neutrophils
What is the major source of IgM in the dog and cat?
Spleen
What is the MOA of mycophenolate?
- Inhibits inosine monophosphate dehydrogenase (IMPDH)
- Enzyme necessary for de novo PURINE synthesis
When is hepcidin produced? What does it do?
- Bacterial invasion → production of acute phase proteins (IL-1, IL-6) → produce hepcidin
- Hepcidin binds ferraportin in enterocytes to trigger internalization and degradation → blocks iron absorption
On what cells are TLRs found?
- Sentinel cells of innate immune system → macrophages, neutrophils, mast cells, dendritic cells
- T and B cells of adaptive immune systemp
- Epithelial cells that line respiratory and GI tracts
What produces tumor necrosis factors?
- Macrophages
2. T-cells
What is neutralization important in protecting against?
- Viruses
- Not sufficient for bacteria
What is the predominant leukocyte in the blood?
Neutrophil (60-75%)
How is complement activated?
- Antigen-antibody reaction (classical pathway)
- Mannose binding protein (lectin pathway)
- Bacterial endotoxin (alternative pathway)
What antibody is involved in the secondary immune response?
IgG
What are the adverse effects of leflunomide?
- GI upset
- Spontaneous bleeding
- Myelosuppression
Where does central tolerance occur?
Thymus
What is the effector mechanisms for type III hypersensitivity reactions?
Immune complex are deposited in various tissues → activates complement and induces tissue damage
Which portions of the complement system are involved in blood coagulation?
- C5a
* induces expression of tissue factor and plasminogen activator inhibitor 1
* thrombin acts on C5 to generate C5a
* Enhances blood coagulation and inhibits fibrinolysis
Which breed has a selective IgA deficiency?
Shar Pei
What is detected by NOD2?
Bacterial Muramyl Dipeptide
*General sensor of intracellular bacteria
What is detected by NOD1?
Bacterial peptidoglycans
What is the MOA of azathioprine?
- Thiopurine (purine analog) → affects the S PHASE of the cell cycle
What is neutralization? What is it driven by?
- Antibodies binding to pathogens or their products, blocking access to cells that they might infect or Destry
- IgA
The availability of ____ dictates the success or failure of bacterial invasion
Iron
If cells recognize MHC II they become what type of cell?
CD4
What cytokines produce Th1 cells?
- IL-12
2. IFN-γ
What cell type is recruited by Th2 cells?
- Mast cells
- Eosinophils
- IgE production
What is the MOA of glucocorticoids?
- Decrease egress of inflammatory cells (down regulation of adhesion molecules)
- Suppress humoral immunity (reduce IgG, IgM, IgA)
- Downregulation of Fc receptors on macrophages
- Induce lymphocyte apoptosis
- Inhibition of phospholipase A2
- Suppress cytokines (IL-1, TNFα, IL-3, IL-4, IL-5) production
- Inhibit phagocytosis
What is detected by NOD-like receptors?
Intracellular PAMPs
If cells recognize MHC I they become what type of cell?
CD8
What happens (broadly) when TLRs are activated?
Promote inflammation
What is the downstream action of activated NOD-like receptors (NLRs)
- NF-κβ pathway → pro-inflammatory cytokines
2. NOD2 → defensins (antimicrobial proteins)
What are contraindications for mycophenolate?
- Severe renal dysfunction
2. Caution in cats
When is IL-6 released?
produced by macrophages, T cells, and mast cells in response to bacterial endotoxins, IL-1, and TNF-α
What cell type is recruited by Th1 cells?
- Macrophages
How are B cells activated
- Antigen to BCR
2. Co stimulant (helper T cells, cytokines, complement, PAMPs)
Name the hypersensitivity reaction:
- SLE
Primarily Type III but can have Type II and Type IV components
Which leukotriene is responsible for stimulating neutrophils?
Leukotriene B
What is detected by TLR-5?
Flagellin
What are type 1 interferons?
- Bind to cell via INFAR
- α, β, ω
- Have primary roles in anti-viral and anti-cancer
What is the effector mechanisms for type II hypersensitivity reactions?
- Complement FcR+ cells (phagocytes, NK cells)
What cytokines produce Tregs?
- IL-10
2. TGF-β
What is a lupus erythematous cell?
- A neutrophil that contains phagocytize nuclear material
What expresses CD79/CD21/CD20?
B lymphocyte
What are the actions of IL-6?
- Promotes inflammation
- Increases hepcidin → anemia of chronic disease
- Very important for fever!
What are the adverse effects of mycophenolate?
- GI (diarrhea most common)
2. Hypersensitivity
What are contraindications for IVIG use?
- Caution in patients with hypertension or AKI
What is detected by a direct Coombs test?
- Antibodies
- Complement
- OR both
What is a type III hypersensitivity reaction? What is it mediated by?
- Immune complex reaction
- IgG
- Antigen: Soluble antigen
What is the function of IL-3?
Hematopoietic growth factor
What are contraindications for cyclosporin?
- Hepatic or renal disease
2. History of malignant neoplasia
MHC class I pathway involves (exogenous/endogenous) antigens
Endogenous (Viral proteins)
What is produced by Th2 cells?
- IL-3
- IL-4
- IL-5
- IL-6
- IL-13
What are interferons? What types are there?
- Produced in response to virus infection or immune stimulation
- Interfere with viral RNA and protein synthesis - Type 1: INF-α, INF-β
- Antiviral»_space; immunomodulatory - Type 2: IFN-γ
- Antiviral «_space;immunomodulatory - Type 3: ΙFN-λ
- Antiviral «_space;immunomodulatory
What is a type I hypersensitivity reaction? What is it mediated by?
- Ige Dependent Reaction
- IgE
- Antigen: Soluble antigen
What are important functions of IL-2
Proinflammatory
Very important in stimulating CELL MEDIATED immune response
What is the most potent antigen presenting cell? Why?
- Dendritic cells
2. They have all of the co-stim and adhesion molecules necessary for sustained activation/priming of naive T cells
Name the hypersensitivity reaction:
- Myasthenia gravis
Type II
What are drug interactions for leflunomide?
- Rifampin
- Warfarin
- Methotrexate
- Chlestyramine
What is the best marker for APCs
CD1
Name the hypersensitivity reaction:
- IMHA
Type II
Th2 cells are primarily involved in (cell mediated/humoral) immunity
Humoral
What expresses CD45?
All leukocytes
What do plasma cells produce?
- Immunoglobulin → identical specificity to BCR on parent cell
Which portions of the complement system are involved in activation of mast cells?
- C3a
- C4a
- C5a
* Release of inflammatory mediators (histamine, serotonin)
How do cytotoxic T cells induce apoptosis?
- Perforin pathway
- Perforins and granzymes from secretory lysosomes
- Viral infected cells - CD95 death receptor
- Mainly used for an unwanted surplus of T cells
Name the hypersensitivity reaction:
- Non-effusive FIP
Type IV
What is recognized by DAMPs?
Molecules escaping from dead, dying, and damaged tissues
- Mitochondrial DNA → TLR-9
- High mobility group box protein 1 (HMGB1) → normally binds DNA to ensure correct folding → TLR2 and TLR4
When is IL-1 released?
Produced by sentinel cells in response to CD14 and TLR4 stimulation
What breed is predisposed to a C3 deficiency?
Brittany Spaniels
Name the hypersensitivity reaction:
- Tuberculosis
Type IV
What expresses CD4?
T-helper Cell
* Receptors for MHC II
What do PRRs recognize for yeasts?
Mannan- or B-glucan rich cell wall
What do PRRs recognize for gram negative bacteria?
Lipopolysaccharide (LPS) → TLR-4