19. Ab-Mediated Tissue Damage and Diseases Flashcards
disorders caused by immune responses are called what?
hypersensitivity diseases
the clinical and pathological characteristics of hypersensitivity diseases are determined by what?
- the type of immune response involved (cellular/humoral)
2. the location of the antigen (cell surface/in circulation)
hypersensitivity diseases classification (I-IV)?
Type I: IgE mediated, mast cell activation, immediate hypersensitivity
Type II: IgM/IgG mediated, Ab vs cell surface or ECM proteins
Type III: Immune complex mediated. immune complex consisting of IgG or IgM + antigen (Ag)
Type IV: T cell mediated, delayed type hypersensitivity (DTH)
what does FcgammaRIIB (CD32) mediate?
feedback inhibition of B cells, attenuation of inflammation
what does FcERI mediate?
activation (degranulation) of mast cells and basophils
Th2 cells release what IL to stimulate IgE release?
IL-4
Th2 cells release what IL to stimulate intestinal mucus secretion and peristalsis?
IL-4, IL-13
Th2 cells release what IL to stimulate eosinophil action (w/IgE vs helminths)?
IL-5
immediate and late phase reaction of Type I hypersensitivity?
immediate: IgE cross-linkage on mast cell FcERI to cause mast cell degranulation
late phase: 12-24 hours after allergen exposure and is characterized by tissue infiltration with eosinophils, neutrophils, and CD4+ T helper 2 (Th2) cells. Mast cell derived TNF-a promotes neutrohil inflamm and IL-4 promotes eosinophil inflammation. Eosinophils activated by IL-5 produced by mast cells and Th2 cells. Th2 cells stimulate inflammation and IL-13 (produced by them) stimulates mucus secretion by the airway epith cells (as in bronchial asthma)
histamine stimulates endothelial cells to do what?
synthesize prostaglandin I-2 (PGI2) and NO, which cause vasodilation (Redness and swelling) - elicited w/antigen injection into the skin and a “wheel and flare” reaction
histamine also causes contraction of intestinal and bronchial smooth muscles (diarrhea and wheezing w/difficulty in breathing)
what are other granule contents from mast cells (besides histamine)?
neutral serine proteases (tryptase and chymase), acid hydrolase, carboxypeptidase A, cathespin G.
^^^ contib to tissue damage in chronic allergic inflammation
also contain proteoglyucans (heparin and chondroitin sulfate) = storage matrices for biogenic amines, proteases, and other mediators
anaphylaxis?
an extreme systemic form of immediate hypersensitivity in which the mediators released by mast cells or basophils cause bronchial constriction, massive tissue edema and cardiovascular collapse. Anaphylactic shock = cardiovascular collapse (a fall in blood pressure or shock) that occurs in the setting of a systemic immediate hypersensitivity reaction. Acute anaphylactic responses can occur against protein antigens (e.g., insect venom) and certain drugs (e.g., penicillin).
j. Mast cells upon activation produce lipid mediators [prostaglandin D2 (PGD2), leukotriene C4 (LTC4), LTD4, LTE4, and platelet activating factor (PAF)] as well as certain cytokines (IL-3, TNF-a, IL-4, IL-5, IL-13) and chemokines (e.g., macrophage inflammatory protein-1a (MIP-1a)). Lipid mediators and cytokines are also produced when basophils are activated. These mediators are responsible for what?
the late phase vasodilation, bronchoconstriction, mucus production, chemotaxis of neutrophils and eosinophils, and Th2 cell differentiation.
allergic asthma involves which stage of allergic response? what is the predominant cell type involved?
involves late phase allergic responses. Eosinophils are the predominant cell type in the late phase infiltrates, and their recruitment and activation is regulated by Th2 cytokines (IL-4, IL-5, and IL-13). When activated, eosinophils also produce and release lipid mediators and cytokines.
therapy for anaphylaxis?
epinephrine (causes vascular smooth muscle contraction and increases CO to counter shock; relaxes airway muscle, inhibits mast cell degranulation)
