hypersensitivity

Question 1

hypersensitivity

Answer 1

exaggerated or inappropriate immune response to external or self antigen that causes harm to the host

Question 2

mechanisms of reaction to self-antigens

Answer 2

contact sensitivity = foreign molecule modifies a host cell to generate new epitopes (“neoantigens”) that are recognized as foreign

molecular mimicry = cross reactivity between self and foreign antigens

Question 3

sensitization to antigen

Answer 3

1. primary exposure to antigen (or similar antigen) => immune response and production of antibodies and/or memory T cells
2. subsequent exposure => hypersensitivity responses

Question 4

preformed mediators released by mast cells

Answer 4

immediate effect due to:

• histamine
• kinins and kininogenase
• serotonin
• TNF
• proteases

Question 5

mediators produced and released by mast cells

Answer 5

delayed effect due to:

• arachidonic acid metabolites (leukotrienes and prostaglandins)
• cytokines
• chemokines

Question 6

effects of histamine

Answer 6

• vasodilation
• increased vascular permeability => edema
• smooth muscle contraction => bronchoconstriction
• itching

Question 7

type I hypersensitivity

Answer 7

• type I = immediate/anaphylactic
• time = develops in minutes
• players = mast cells, basophils, preformed IgE (from previous Th2/B cell response)
• mechanism = primary exposure and IgE formation => subsequent exposure with IgE-antigen binding and mast cell Fc receptor cross-linking => mast cells release preformed mediators and produce additional mediators => vasodilation and edema
• examples = anaphylaxis, allergic rhinitis, hives

Question 8

type II hypersensitivity

Answer 8

• type II = cytotoxic/Ab-mediated
• time = minutes-hours
• players = CD8+ cytotoxic T cells, NK cells, neutrophils, preformed IgG/IgM (from previous Th2/B cell response or natural)
• mechanism = preformed IgG/IgM binds cell surface or ECM antigens => complement activation and phagocytosis and/or ADCC by NK or CD8+ cytotoxic T cells
• examples = drug allergies, incompatible blood transfusions, rheumatic fever

Question 9

type III hypersensitivity

Answer 9

• type III = immune complex-mediated
• time = hours - days
• players = IgG antigen/antibody complex, neutrophils
• mechanism = abundant antigen => precipitation of immune complexes and deposition in tissues => complement activation and inflammation
• examples = serum sickness, systemic lupus erythmatosus, arthus rxn

Question 10

type IV hypersensitivity

Answer 10

• type IV = delayed type hypersensitivity
• time = days-months
• players = APCs, Th1 helper cells, sometimes CD8+ cytotoxic T cells
• mechanism = on primary exposure APC’s prime T cell response to antigen and drive Th1 CD4+ helper T cell response => on subsequent exposure memory T cells proliferate and activate macrophage response and cytokine release
• examples = PPD test, Mtb infection, GVHD, contact dermatitis