hypersensitivity

what are disorders caused by immune responses?

autoimmunity, reactions against microbes, and reactions against environmental ags

what are some causes of hyperS diseases?

type I (anaphylactic), type II (ab mediated cytotoxic), type III (complex mediated), and type IV (cell mediated)

what are the four types of hyperS?

type I, II, and III

which hyperS is considered immediated (min to hours)?

type IV

which hyperS is considered delayed (24 to 48 hours)?

IgE and Th2

what is the pathologic immune mechanism in type I hyperS?

IgG, IgM abs against cell surface or ECM ags

what is the pathologic immune mechanism in type II hyperS?

immune complexes of circulating ags and IgG/IgM

what is the pathologic immune mechanism in type III hyperS?

CD4 T cells and CD8 T cells

what is the pathologic immune mechanism in type IV hyperS?

mast cells, eosinophils, and their mediators (vasoactive amines, lipids, proteolytic enzymes, cytokines)

what are the mechanisms of tissue injury and disease in type I hyperS?

opsonization and phagocytosis, complement and Fc receptor recruitment and activation of leukocytes, abnormal cell fxs

what are the mechanisms of tissue injury and disease in type II hyperS?

deposition in BV walls and tissues; complement mediated recruitment and activation of WBCs

what are the mechanisms of tissue injury and disease in type III hyperS?

cytokine mediated inflammation and macrophage activation; direct target cell killing

what are the mechanisms of tissue injury and disease in type IV hyperS?

type I

commonly referred to as allergies, produce large amounts of IgE to a small concentration of allergen, mast cells, basophils, and eosinophils participate; reaction occurs in minutes; these are all factors of which hyperS?

sensitization, activation, and late

what are the 3 phases of type I hyperS?

Th2 cells release IL4,IL13-> B cells produce IgE-> IgE binds to FcεRI on mast cells and basophils-> IgE half life increases to 10 days

in the sensitization phase of type I hyperS, what happens when DCs process the allergen ags and present it to Th cells using MHCII?

cell signaling and cytokine release-> degranulation of mast cells and basophils-> histamine: smooth muscle contraction, vasodilation, and increased vascular permeability

in the activation phase of type I hyperS, what happens after repeated allergen exposure and cell bound IgE is crosslinked with allergen?

platelet activating factor, prostaglandin, leukotrienes, and cytokines released-> chronic allergic conditions-> eosinophil recruitment, bronchoconstriction, and mucus secretion

in the late phase of type I hyperS, what happens after additional release of reactant/secondary mediators?

corticosteroids, allergy immunotherapy, antihistamine, decongestants, and monoclonal abs

what are some treatment methods for type I hyperS?

allergens administered subcutaneously for 3-5 year; induce immune tolerance (Treg cells) to a specific allergen over time; shift patients IR to the allergen to a Th1 type response and induce development of Tregs

how does allergy immunotherapy help treat type I hyperS?

percutaneous or intradermal test; neg control diluent, pos control histamine; evaluate skin reaction 15-20min; pos result= appearance of wheal and flare

how does direct in vivo skin testing work for type I hyperS?

type II

abs bind to cell surface receptors, resulting in cell damage through complement, opsonization, ADCC, inhibition of cell fx, or stimulation of cell fx is all characteristics of which hyperS?

transfusion rxns, HDN, autoimmune hemolytic anemia, cold agglutinin abs, and paroxysmal cold hemoglobinuria

what are some examples of type II hyperS?

abs will target donor RBCs leading to intravascular hemolysis within mins or hours after transfusion; can lead to DIC, vascular collapse, and renal failure

what happens after a patient receives incompatible blood in a type II hyperS?

type III

formation of ag/ab complexes that precipitate in blood, can deposit in tissue causing damage; complement can be activated leading to vasodilation, increased vascular permeability, edema, and neutrophil accumulation are all characteristics of which hyperS?

glomeruli, vascular endothelium, joint lining, and alveolar membranes

what are some common sites of injury in type III hyperS?

arthus reaction, autoimmune diseases, RA, and serum sickness

what are 4 type III hyperS disorders?

humans have received passive immunization with animal serum (horse antivenoms), human makes abs to the animal serum abs; symptoms appear 7-21 days after exposure: headache, fever, vomiting, joint pain, rash, and lymphadenopathy

what is the pathogenesis and clinical presentation of serum sickness?

type IV

involves Th1 effector cells causing inflammatory reaction and tissue damage; infection or immunization sensitizes an individual and subsequent challenge with an ag from infectious agent elicits a delayed (48-72 hours) reaction manifested by induration with redness and swelling is characteristic of which hyperS?

intracellular pathogens: tuberculosis, leprosy, leishmaniasis) and contact antigens (poison ivy, metals, nickel, dyes)

what can trigger type IV hyperS?

granulomas and contact dermatitis

what are two examples of type IV hyperS disorders?

accumulation of macrophages, fibrosis, and collagen accumulation at the site of injury

what happens in granulomas in type IV hyperS?

haptens bind cells causing sensitization of Th1 cells; erythema, swelling, papules, peeling, and weeping that can last 3-4 weeks

what happens in contact dermatitis in type IV hyperS?

type IV

the mantoux PPD (purified protein derivative) test/tuberculin test is an example of which type of hyperS?

cutaneous-children, skin; systemic-adults, skin, organs, and bones (skin rxn, diarrhea, muscle/joint pain, fatigue); both have increased risk of anaphpylaxis

how does mastocytosis affect children and adults?

β-tryptase is heparin bound; a transient and rapid increase of serum tryptase within 4 hours of an anaphylactic even is considered evidence of mast cell activation; baseline >20 ng/mL is a minor diagnostic criterion; used to monitor response to cytoreductive therapy in mastocytosis

how does tryptase play a part in diagnosing mastocytosis?

anti epileptics, reverse transcriptase inhibitors, dapsone, minocycline, allopurinol; tetracyclines (hepatitis); cephalosporins with pleiomorphic clinical manifestations

what are some drugs/medications that can trigger drug and toxin related eosinophilia?

skin rash, lymphadenopathy, organ involvement, atypical lymphs, and eosinophilia

what are some symptoms of drug and toxin related eosinophilia?