Immunology - Immune Responses Flashcards
1
Q
Acute-phase reactants
- General
- Positive (upregulated)
- Serum amyloid A
- C-reactive protein
- Ferritin
- Fibrinogen
- Hepcidin
- Negative (downregulated)
- Albumin
- Transferrin
A
- General
- Factors whose serum concentrations change significantly in response to inflammation
- Produced by the liver in both acute and chronic inflammatory states.
- Induced by IL-6, IL-1, TNF-α, and IFN-γ.
- Positive (upregulated)
- Serum amyloid A
- Prolonged elevation can lead to amyloidosis.
- C-reactive protein
- Opsonin; fixes complement and facilitates phagocytosis.
- Measured clinically as a sign of ongoing inflammation.
- Ferritin
- Binds and sequesters iron to inhibit microbial iron scavenging.
- Fibrinogen
- Coagulation factor
- Promotes endothelial repair
- Correlates with ESR
- Hepcidin
- Prevents release of iron bound by ferritin –> anemia of chronic disease.
- Serum amyloid A
- Negative (downregulated)
- Albumin
- Reduction conserves amino acids for positive reactants.
- Transferrin
- Internalized by macrophages to sequester iron.
- Albumin
2
Q
Complement (204)
- Overview
- Activation
- Functions
- Opsonins
- Inhibitors
A
- Overview
- System of interacting plasma proteins that play a role in innate immunity and inflammation.
- MAC defends against gram-negative bacteria.
- Activation
-
Classic** pathway—Ig_G_** or IgM mediated.
- GM makes classic cars.
- Alternative pathway—microbe surface molecules.
- Lectin pathway—mannose or other sugars on microbe surface.
-
Classic** pathway—Ig_G_** or IgM mediated.
- Functions
- C3b—opsonization.
- C3b** _b_inds bacteria.**
- C3a**, C4**a**, C5**a**—**anaphylaxis.
- C5a—neutrophil chemotaxis.
- C5b-9—cytolysis by membrane attack complex (MAC).
- C3b—opsonization.
- Opsonins
- C3b and IgG are the two 1° opsonins in bacterial defense
- C3b also helps clear immune complexes.
- Inhibitors
- Decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (e.g., RBC).
3
Q
Complement disorders
- C1 esterase inhibitor deficiency
- C3 deficiency
- C5–C9 deficiencies
- DAF (GPI anchored enzyme) deficiency
A
- C1 esterase inhibitor deficiency
- Causes hereditary angioedema.
- ACE inhibitors are contraindicated.
- C3 deficiency
- Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections
- Increases susceptibility to type III hypersensitivity reactions.
- C5–C9 deficiencies
- Increase susceptibility to recurrent Neisseria bacteremia.
- DAF (GPI anchored enzyme) deficiency
- Causes complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria.
4
Q
Important cytokines:
L 1-6 (mnemonic)
A
- “Hot T-bone stEAK”
- IL-1: fever (hot).
- IL-2: stimulates T cells.
- IL-3: stimulates bone marrow.
- IL-4: stimulates IgE production.
- IL-5: stimulates IgA production.
- IL-6: stimulates aKute-phase protein production.
5
Q
IL-1
A
- Secreted by macrophages
- An endogenous pyrogen, also called osteoclast-activating factor.
- Causes fever, acute inflammation.
- Activates endothelium to express adhesion molecules
- Induces chemokine secretion to recruit leukocytes.
6
Q
IL-6
A
- Secreted by macrophages
- An endogenous pyrogen.
- Also secreted by Th2 cells.
- Causes fever and stimulates production of acute-phase proteins.
7
Q
IL-8
A
- Secreted by macrophages
- Major chemotactic factor for neutrophils.
- Neutrophils are recruited by IL-8 to clear infections.
- “Clean up on aisle 8.”
8
Q
IL-12
A
- Secreted by macrophages
- Induces differentiation of T cells into Th1 cells.
- Activates NK cells.
- Also secreted by B cells.
9
Q
TNF-a
A
- Secreted by macrophages
- Mediates septic shock.
- Activates endothelium.
- Causes leukocyte recruitment, vascular leak.
10
Q
IL-2
A
- Secreted by all T cells
- Stimulates growth of helper, cytotoxic, and regulatory T cells.
11
Q
IL-3
A
- Secreted by all T cells
- Supports the growth and differentiation of bone marrow stem cells.
- Functions like GM-CSF.
12
Q
Interferon-γ
A
- From Th1 cells
- Has antiviral and antitumor properties.
- Activates NK cells to kill virus-infected cells
- Increases MHC expression and antigen presentation in all cells.
13
Q
IL-4
A
- From Th2 cells
- Induces differentiation into Th2 cells.
- Promotes growth of B cells.
- Enhances class switching to IgE and IgG.
14
Q
IL-5
A
- From Th2 cells
- Promotes differentiation of B cells.
- Enhances class switching to IgA.
- Stimulates the growth and differentiation of eosinophils.
15
Q
IL-10
A
- From Th2 cells
- Modulates inflammatory response.
- Inhibits actions of activated T cells and Th1.
- Also secreted by regulatory T cells.
- TGF-β has similar actions to IL-10, because it is involved in inhibiting inflammation.
16
Q
Interferon α and β
A
- A part of innate host defense against both RNA and DNA viruses.
-
Interferons are glycoproteins synthesized by viral-infected cells that act locally on uninfected cells, “priming them” for viral defense.
- Interferes with viruses.
- When a virus infects “primed” cells, viral dsRNA activates:
- RNAase L –> degradation of viral/host mRNA.
- Protein kinase –> inhibition of viral/host protein synthesis.
- Essentially results in apoptosis, thereby interrupting viral amplification.
17
Q
Cell surface proteins
- All except mature RBCs have…
- T cells
- Helper T cells
- Cytotoxic T cells
- B cells
- Macrophages
- NK cells
A
- All cells except mature RBCs have MHC I.
- T cells
- TCR (binds antigen-MHC complex)
- CD3 (associated with TCR for signal transduction)
- CD28 (binds B7 on APC)
- Helper T cells
- CD4, CD40 ligand
- Cytotoxic T cells
- CD8
- B cells
- Ig (binds antigen)
- CD19, CD20, CD21 (receptor for EBV), CD40
- MHC II, B7
-
You can drink Beer at the Bar when you’re 21
- __B cells, Epstein-Barr virus; CD-_21_.
- Macrophages
- CD14, CD40
- MHC II, B7
- Fc and C3b receptors (enhanced phagocytosis)
- NK cells
- CD16 (binds Fc of IgG)
- CD56 (unique marker for NK)
18
Q
Anergy
A
- Self-reactive T cells become nonreactive without costimulatory molecule.
- B cells also become anergic, but tolerance is less complete than in T cells.
19
Q
Effects of bacterial toxins
- Superantigens
- Endotoxins/lipopolysaccharide
A
- Superantigens (S. pyogenes and S. aureus)
- Cross-link the β region of the T-cell receptor to the MHC class II on APCs.
- Can activate any T cell, leading to massive release of cytokines.
- Endotoxins/lipopolysaccharide (gram-negative bacteria)
- Directly stimulate macrophages by binding to endotoxin receptor CD14
- Th cells are not involved.
20
Q
Antigenic variation
- Classic examples
- Bacteria
- Virus
- Parasites
- Some mechanisms for variation
A
- Classic examples:
- Bacteria
- Salmonella (2 flagellar variants)
- Borrelia (relapsing fever)
- Neisseria gonorrhoeae (pilus protein).
- Virus
- Influenza (major = shift, minor = drift).
- Parasites
- Trypanosomes (programmed rearrangement).
- Bacteria
- Some mechanisms for variation
- DNA rearrangement
- RNA segment reassortment (e.g., influenza major shift).
23
Q
Type I hypersensitivity
- Reaction
- Types I, II, and III
- Test
A
- Reaction
- Anaphylactic and atopic—free antigen crosslinks IgE on presensitized mast cells and basophils, triggering immediate release of vasoactive amines that act at postcapillary venules (i.e., histamine).
- Reaction develops rapidly after antigen exposure because of preformed antibody.
- Delayed response follows due to production of arachidonic acid metabolites (e.g., leukotrienes).
- First (type) and Fast (anaphylaxis).
- Types I, II, and III
- All antibody mediated.
- Test
- Skin test for specific IgE.
24
Q
Type II hypersensitivity
- Reaction
- Mechanisms
- Test
A
- Reaction
- Cytotoxic (antibody mediated)
- IgM, IgG bind to fixed antigen on “enemy” cell, leading to cellular destruction.
- Antibody and complement lead to membrane attack complex (MAC).
- Type II is cy-_2_-toxic.
- 3 mechanisms:
- Opsonization leading to phagocytosis or complement activation
- Complement-mediated lysis
- Antibody-dependent cell-mediated cytotoxicity, usually due to NK cells or macrophages
- Test
- Direct Coombs’: detects antibodies that have adhered to patient’s RBCs (e.g., test an Rh (+) infant of an Rh (-) mother).
- Indirect Coombs’: detects antibodies that can adhere to other RBCs (e.g., test an Rh (-) woman for Rh (+) antibodies).
25
Q
Type III hypersensitivity
- Reaction
- Serum sickness
- Arthus reaction
- Test
A
- Immune complex
- Antigen-antibody (IgG) complexes activate complement, which attracts neutrophils
- Neutrophils release lysosomal enzymes.
- In type III reaction, imagine an immune complex as 3 things stuck together: antigen-antibody-complement.
-
Serum sickness
- An immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes 5 days).
- Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage).
- More common than Arthus reaction.
- Most serum sickness is now caused by drugs (not serum) acting as haptens.
- Fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5–10 days after antigen exposure.
-
Arthus reaction
- A local subacute antibody-mediated hypersensitivity (type III) reaction.
- Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.
- Characterized by edema, necrosis, and activation of complement.
- Antigen-antibody complexes cause the Arthus reaction.
- Test
- Immunofluorescent staining.
26
Q
Type IV hypersensitivity
- Reaction
- Test
- Mnemonic
A
- Delayed (T-cell-mediated) type
- Sensitized T lymphocytes encounter antigen and then release lymphokines
- Leads to macrophage activation
- No antibody involved
- Cell mediated
- Therefore, it is not transferable by serum.
- 4th and last—delayed.
- Sensitized T lymphocytes encounter antigen and then release lymphokines
- Test
- Patch test, PPD.
-
4 T’s
- T lymphocytes
- Transplant rejections
- TB skin tests
- Touching (contact dermatitis).
