19. Ab-Mediated Tissue Damage and Diseases Flashcards Preview

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disorders caused by immune responses are called what?

hypersensitivity diseases


the clinical and pathological characteristics of hypersensitivity diseases are determined by what?

1. 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?



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)?



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



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)


therapy for bronchial asthma?

corticosteroids (reduce inflamm)

leukotriene antagonists (relax bronchial smooth muscle and reduce inflammation)

phosphodiesterase inhibitors (relax bronchial smooth muscle)


therapy for various allergic reactions?

desensitization (unk - may inhibit IgE production and increase other Ig isotypes, may induce T cell tolerance)

anti-IgE antibody (neutralize and eliminate IgE)

antihistamines (block actions of histamine on vessels and smooth muscles)

cromolyn (inhibits mast cell degranulation)


type II hypersensitivity

caused by IgG and IgM that bind to cellular antigens). Following the transfusion of mismatched blood, anti-red blood cell (RBC) antibodies in the recipient bind to the donor RBCs causing the lysis of these cells (hemolysis). Antibodies can also bind to a noncollagenous protein in the basement membrane of renal glomeruli or lung alveoli (Goodpasture syndrome), to the acetylcholine receptors at the neuromuscular junction (myasthenia gravis), or to the cell adhesion molecules in mucosa and skin (pemphigus) and cause tissue damage and functional abnormalities. Another example is hemolytic disease of the newborn (HDN) (aka “Erythroblastosis fetalis”). In this disease, the pregnant mother is sensitized to fetal RBC antigens leading to the production of maternal IgG (against these antigens), which then can cross the placenta and destroy fetal RBCs.


type III hypersensitivity

caused by the formation of antibody-antigen complexes in circulation followed by their deposition in tissues. This leads to complement (C’) activation, inflammation, and cell-mediated injury (for details regarding C’-mediated effector functions and the influence of certain C’ factors on the clearance of immune complexes. Diseases in which this reaction occurs are represented by systemic lupus erythematosus (SLE; lupus). Arthus reaction is a localized form of experimental immune complex-mediated vasculitis (antigen is injected intradermally; it binds to the antibody and forms immune complexes, which then activate platelets, mast cells, macrophages, and neutrophils; and this reaction takes about 5-12 hours to develop).


glomerulonephritis in goodpasture syndrome

Type II hypersensitivity

target antigen: non collagenous protein in basement membranes of kidney glomeruli and lung alveoli

- nephritis
- lung hemorrhage


pemphigus vulgaris

Type II hypersensitivity

target antigen: proteins in intracellular junctions of epidermal cells (epidermal cadherin)

- formation of skin vesicles (bullae)


Grave's disease

type II hypersensitivity

target antigen: TSH receptor

- hyperthyroidism (agonist)


myasthenia gravis

type II hypersensitivity

target antigen: Ach receptor

- muscle weakness (no contraction)


thrombocytopenic purpura

type II hypersensitivity

target antigen: platelet membrane proteins

- bleeding


autoimmune hemolytic anemia

type II hypersensitivity

target antien: erythrocyte membrane proteins (Rh blood group antigens)

- hemolysis, anemia


pernicious anemia

type II hypersensitivity

target antigen: IF of gastric parietal cells

- abnormal erythropoiesis
- anemia


rheumatic fever

type II hypersensitivity

target antigen: streptococcal cell wall antigen; antibody cross-reacts w/myocardial antigen

- myocarditis
- arthritis


erythrocyte ____ helps to clear immune complexes from the circulation



SLE (systemic lupus erythematosus)

type III hypersensitivity

target antigen: DNA

- glomerulonephritis


arthus reaction

type III hypersensitivity

target antigen: various protein antigens

- cutaneous vasculitis