* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Notes on Allergy
Survey
Document related concepts
DNA vaccination wikipedia , lookup
Lymphopoiesis wikipedia , lookup
Monoclonal antibody wikipedia , lookup
Molecular mimicry wikipedia , lookup
Immune system wikipedia , lookup
Complement system wikipedia , lookup
Anaphylaxis wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Adaptive immune system wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Innate immune system wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
Transcript
Immunology: Allergy and Hypersensitivity (Sundick) DEFINITIONS: Allergy: a type of hypersensitivity reaction (type I) mediated by IgE o Poylgenic: MHC, IL4 gene cluster, other loci Hypersensitivty: an exaggerated immune response to an innocuous agent that yields tissue injury and disease Allergen: substance that induces IgE; proteins, drugs that bind protein (penicillin); helminthic worms also stimulate high IgE HYPERSENSITIVTY REACTIONS: Type I: Immune Reactant: IgE Antigen: soluble Ag Effector Mechanism: mast cell activation Examples: o Systemic Anaphylaxis: vascular permeability, laryngeal edema, shock; usually due to drugs, venom or peanuts (IV/oral route) o Rhinitis (Hay Fever): nasal edema, sneezing; usually due to pollen or dust mite feces (inhalation route) o Asthma: bronchial constriction, mucus production; usually due to dander, pollen, or dust (inhalation) o Food Allergy: vomiting, hives, anaphylaxis; common examples are peanuts, shellfish and eggs (oral) Type II: Immune Reactant: IgG Antigen: cell or matrix associated Ag Effector Mechanism: activate complement, attract FcR+ cells (phagocytes, NK cells) to bind IgG; these can damage self-cells Examples: some drug allergies (ie. penicillin- however, can also stimulate IgE release) Type III: Immune Reactant: IgG Antigen: soluble antigen Effector Mechanism: formation of immune complexes that activate complement and attract phagocytes, resulting in localized tissue damage Examples: Serum sickness (immune complexes deposit in vascular system), Arthus reaction Type IV: Two Major Pathways: o Immune Reactant TH1: Antigen: soluble, stimulates TH1 cells to be produced Effector Mechanism: TH1 cells activated macrophages (IFN-gamma), causing cytokines, chemokines, and cytotoxins to be released Examples: contact dermatitis, tuberculin reaction o Immune Reactant CD8+ T cell: Antigen: cell associated Effector Mechanism: cytotoxicity Examples: contact dermatitis (poison ivy) TYPE I HYPERSENSITIVITY: First Phase- Sensitization: exposure to allergen induces B cells to produce IgE IgE production requires TH2 cells (produce IL4 and IL13) IgE is short lived in the blood but persists for months bound to mast cells in tissues and basophils in the blood; bound via FcεRI receptors (bind Fc portion of IgE) Second Phase- Activation: IgE present on mast cell is crosslinked, causing activation and rapid release of granules Allergen must be at least bivalent (in order to cross-link) Third Phase- Effector Phase: allergic symptoms result due to substances produced and released by mast cells Preformed Substances: o Histamine: major agent involved in allergic symptoms Binds H1 receptors on smooth muscle (bronchial constriction) and on endothelial cells (vascular permeability); lead to systemic anaphylaxis Binds H2 receptors involved in mucus secretion, vascular permeability and secretion of stomach acid o Chemotactic factors: IL8 (PMNs) and eosinophil chemotactic factor (ECF) o Other Cytokines: IL3, IL4, IL5, GM-CSF (attract/activated inflammatory cells) Newly Synthesized Substances: play major roles in antihistamine-resistance astham o Leukotrienes: cause prolonged constriction of smooth muscle o Thromboxanes, Prostaglandins: constrict bronchi; also chemotactic for PMNs and eosinphils o Platelet Activating Factor (PAF): cause release of histamine and thromboxanes Late Phase Reaction to Allergens: Eosinophils and PMNs come to site and prolong symptoms (occurs 7-8 hours after exposure) o Eosinophils release: leukotrienes, PAF, toxins for helminths (eosinophilic cationic protein), enzymes and chemotactic factors o PMNs release: leukotrienes, PAF, and lysosomal enzymes Current Treatments: Epinephrine: systemic anaphylaxis (prevents blood vessel leakage and relaxes bronchial/tracheal smooth muscle) Pharmacological Agents: Type Agent Effect Clinical Use Beta Agonists Epinephrine Antagonist of antihistamine Anaphylaxis Xanthine Derivatives Aminophylline Relaxes smooth muscle Asthma Mast Cell Membrane Cromolyn sodium Prevents degranulation Ashtma Stabilizers Leukotriene Modifiers Binds leukotriene R or inhibit Ashtma formation of leukotrienes Antihistamines Many Block H1 receptors Rhinitis, Dermatitis Corticosteroids Many Anti-inflammatory Asthma, rhinitis Specific Desensitization: inject patient with small amount of allergen and increase the dose weekly for several months o Mechanism: elevates IgG Ab, which binds allergen and prevents it from reacting with IgE on mast cells; also induces a switch from TH2 to TH1 cells; may induce Treg cells o Useful for: allergic rhinitis, bee stings, asthma and peanut allergies (more recently) Clinical Tests for Allergy: Patient history Skin tests: small amount of allergen injected; positive reaction is wheal and flare, swelling and redness (occurs in 10-15 minutes) Radioallergosorbent Test (RAST): quantitates the amount of serum IgE for a specific allergen Mast Cells, Eosinophils and IgE also Protect Against Parasitic Worms: Worms stimulate IgE production Mast cells recruit eosinophils that bind IgE on the worm and release cytotoxins Prevalence of Allergy: More prevalent in poorer countries due to increased early exposure to infectious agents Results in prolonged TH1 bias on subsequent exposure to foreign substances, including potential allergens - TYPE II HYPERSENSITIVITY REACTIONS Antibody to cell-bound antigen Isotypes Involved: IgG (or IgM) Mechanism: activates complement or assists with ADCC (antibody dependent cell-mediated cytotoxicity; only IgG) Examples: ABO or Rh incompatability; various drugs binding to platelets and RBCs TYPE III HYPERSENSITIVITY REACTIONS Antibody to soluble antigen Isotypes Involved: usually IgG as part of an immune complex Mechanism: fixes complement, and complexes accumulate in joints, kidneys and elsewhere; size of immune complexes and clearance by phagocytes determines pathology Examples: SLE antibodies to DNA; Ags can also be foreign serum or purified monoclonal Abs (serum sickness) TYPE IV HYPERSENSITIVITY REACTIONS Examples: Delayed-Type Hypersensitivity: o Ag: proteins (insect venom, mycobacterial proteins like tuberculin and lepromin) o Consequence: local skin swelling (erythema, induration, cellular infiltrate, dermatitis) - Contact Hypersensitivity: o Ag: haptens (poison ivy, DNFB), small metal ions (nickel, chromate) o Consequence: local epidermal reaction (erythema, cellular infiltrate, vesicles, intraepidermal abscess) Gluten-Sensitive Enteropathy (Celiac Disease): o Ag: gliadin o Consequence: villous atrophy in small bowel, malabsorption T cell mediated hypersensitivity takes many hours: need to recruit cells to the site