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Flashcards in Allergy and hypersensitivity Deck (22):

Inflammation 1

-Physiologic response to injury (physical, chemical, biologic)
-Characterized by cellular and biochemical changes leading to clinical manifestations
-Cellular changes: vasodilation/leakage, leukocyte infiltration, local hypoxia, secondary tissue damage
-Biochemical changes: inflammatory mediator release (histamine, cytokines, eicosanoids)
-Complement, kinin, coag systems activated


Inflammaiton 2

-Clinical manifestations: redness, hot, swelling, pain, loss of function (LOF)
-Immune system initiates, amplifies, and regulates Ag-specific or molecular pattern-specific inflammatory responses
-Good inflammation: repair, healing, recovery
-Bad inflammation: persistent cellular and biochemical changes, chronic clinical manifestations, LOF, cancer, atherosclerosis



-Heightened host responsiveness to normally innocuous substances (4 types)
-Type I: mast cell/IgE induced
-Type II/III: IgM/IgG and complement induced
-Type IV: CD4/CD8 mediated



-Immunologically mediated hypersensitivity; IgE mediated vs other mechanisms



-Genetic predisposition to IgE-mediated response


Role of the Th2 CD4 cell

-Th2 cells induce B cells to switch to IgE Abs (responsible for allergy, asthma)
-Th1 and Th17 responsible for autoimmune diseases (along w/ lack of Tregs)


IgE-mediated hypersensitivity

-Th2 cell presenting innocuous Ag on MHC binds to B cell, along w/ co-stimulator
-Th2 cell remodels cytoskeleton and begins releasing IL4
-IL4 is released btwn into the cellular synapse and activates the B cell, causing a switch to IgE producing plasma cell
-Both cells also undergo membrane changes
-IgE/Ag complexes bind to Fc(epsilon) receptor on mast cell and causes granule release (histamine, ect)


Type I hypersensitivity

-Immediate hypersensitivity; Th2, IgE, mast cells, eosinophils involved
-Mast cell-derived mediators released due to IgE-Ag complex binding to Fc receptor of the mast cell
-Also have cytokine-mediated inflammation due to eosinophils/PMNs


Type II hypersensitivity

-Ab-mediated diseases; IgM, IgG Abs against cell surface or ECM Ags
-Complement and Fc receptor mediated recruitment and activation of PMNs and macrophages (complement not required)
-Opsonization and phagocytosis of cells
-Abnormalities in cellular function function can lead to tissue damage


Type III hypersensitivity

-Immune complex-mediated disease; Immune complexes of circulating Ags-IgM/G are deposited in vascular basement membrane (inflammation of vessel wall = vasculitis)
-Complement and Fc receptor-mediated recruitment and activation of WBCs


Type IV hypersensitivity

-CD4 (Th1) T cells produce delayed type hypersensitivity rxn (activating macrophages), not Abs required
-Extended time from Ag exposure to observed response
-CD8 CTLs produce cytolysis
-Macrophage activation and cytokine mediated inflammation (no histamine released)
-Contact dermatitis is type IV, so is type I diabetes


IgE and its production

-Mast cells and basophils express high affinity receptor Fc(e)
-MHC specificity determines who gets allergic to what
-Environment plays a role; exposure to allergens/microbes drives the change from Th2->Th1 CD4 cells
-This reduces allergic rxns (hygiene hypothesis)
-Microbiome of gut also shapes allergen susceptibility


Pathways in generating allergy and asthma 1

-Impaired epithelial barrier (infection, allergen exposure) mostly in U and L RT, GI, and skin
-Generation of thymic stromal lymphopoietin (TSLP) by local epithelial cells, fibroblasts, and mast cells
-TSLP activates immature dendritic cells to drive Th2 production, leading to more IL4 and 13 (IgE switch) and IL5 (eosinophil activation)
-Damaged epithelium can also drive inflammation


Pathways in generating allergy and asthma 2

-Overall there is a net reduction in IL12 (decreases Th1), a net increase in IgE (IL4 and 13) and an increase in eosinophils (IL5)
-IgE mediates inflammatory cascade involving mast cells, basophils, eosinophils, and inflammatory mediators
-IL13 induces SMC proliferation, mucus hypersecretion, goblet cell metaplasia, eosinophil recruitment, fibrosis (asthma)


Mast cell vs Basophil

-Mast cells are mononuclear and found in tissue
-Basophils are polynuclear and found in blood
-They both have metachromatic granules, release inflammatory mediators, and have Fc(e) receptor


Activation of mast cells

-Fc(e) receptors must be dimerized (both bound to IgE/Ag complex) to activate signaling pathway
-Granule contents: histamine (acute phase rxn 10-20 min), prostaglandins, leukotrienes, cytokines (late phase rxn 4-8 hrs)
-Acute phase: edema
-Late phase: cellular infiltrate



-Protein-containing granules (major basic protein, cationic protein, neurotoxin)
-Th2 and IL5 directed production and activation
-Release cytokines IL1, TNFa, TGBa/b
-Effector functions: ADCC (Ab-dependent cell cytotoxicity) for destruction of helminths, also host tissue damage


Dx of IgE mediated allergy

-IgE serum level
-RAST (radioallergosorbent test): in vitro Ag-sepecific IgE test
-Skin test (done to confirm Dx)


Rx of IgE-mediated disorders

-Allergen avoidance
-Symptomatic Rx (antihistamines, leukotriene inhibitors, bronchodilators)
-Immunomodulation(corticosteroids, specific immunotherapy, anti-IgE monoclonal Ab)
-Specific immunotherapy (allergy shots)
-Advantages of aerosol vs oral: lower dosage, rapid onset, fewer side effects, direct delivery to airways


Wheeze vs stridor

-Wheeze is high pitch whistling sound on expiration
-Stridor is the same thing but on inspiration


Allergic rhinitis and conjunctivitis

-Itchy, watery eyes w/ stuffy nose
-Itchiness is most common factor in allergic rxns
-Most common triggers: dust mites, pollen, mold, irritants (smoke)


Things that increase one's risk to allergies

-Family Hx
-Lack of brest feeding
-Lack of exposure to Ags early on
-Destruction of gut microbiome