Hypersensitivity for WUHS.pdf

 Hypersensi8vity Undesirable reac'ons produced by the normal immune system, including: 1- Allergies 2 - Autoimmunity These reac'ons may be: a- Damaging b- Uncomfortable c- Occasionally fatal Excessive immune respons...

 Hypersensi8vity Undesirable reac'ons produced by the normal immune system, including: 1- Allergies 2 - Autoimmunity These reac'ons may be: a- Damaging b- Uncomfortable c- Occasionally fatal Excessive immune response in a sensitized individual leading to tissue damage. Four types of hypersensi8vity reac8ons Types I,II,III------> Immediate, Abs. Type IV ------> Delayed, T cells.  Allergy: A type I hypersensi8vity reac8on IgE an'bodies are responsible for type I hypersensi'vity = Immediate = Anaphylac'c – Allergies are ini'ated by an interac'on between an IgE an8body and a mul'valent an'gen – Free circula'ng IgE is usually very, very low in concentra'on in blood serum  Allergy: A type I hypersensi8vity reac8on Many allergens can elicit a type I response – Healthy individuals make IgE only in response to parasi'c infec'ons – Atopic individuals produce IgE against common environmental Ags Most are proteins or glycoproteins Most possess many an'genic sites (epitopes) per molecule – May contain poten'al PAMPs, s'mula'ng innate immunity Common allergens associated with type I hypersensitivity Plant pollens Drugs Rye grass Penicillin Ragweed Sulfonamides Timothy grass Local anesthetics Birch tree Salicylates Foods Insect products Nuts Bee venom Seafood Wasp venom Eggs Ant venom Peas, beans Cockroach calyx Milk Dust mites Other allergens Animal hair and dander Latex Mold spores Allergy: A type I hypersensi8vity reac8on  Allergy: A type I hypersensi8vity reac8on IgE an'bodies act by cross- linking Fcε receptors on the surfaces of innate immune cells – Abs not harmful by themselves Granule contents released include histamine, heparin, proteases, leukotrienes, prostaglandins, chemokines Mediators act on surrounding 'ssues and cells to cause symptoms  Allergy: A type I hypersensi8vity reac8on IgE an'bodies act by cross-linking Fcε receptors on the surfaces of innate immune cells – The high-affinity IgE receptor, FcεRI Responsible for most allergy symptoms Mast cells and basophils cons'tu'vely express – The low-affinity IgE receptor, FcεRII Regulates produc'on of IgE by B cells  Allergy: A type I hypersensi8vity reac8on IgE an'bodies act by cross-linking Fcε receptors on the surfaces of innate immune cells – The high-affinity IgE receptor, FcεRI Linking receptors trigger Lyn- mediated phosphoryla'on of ITAMs Triggers PKC and MAPK pathways, leading to allergic effects – The low-affinity IgE receptor, FcεRII Allergic reaction in the skin eczema  Anaphylaxis to bee venom Bee venom has Mellitin which can directly trigger mast cells Dust mite fecal pellet  Sensi8za8on against allergens and type-I hypersensi8vity B cell IL13 TH2 Plasma cell IgE Histamine, tryptase, Mast cells kininegenase, ECFA Leukotriene-B4, C4, D4, Newly prostaglandin D, PAF synthesized mediators  IgE levels in immediate hypersensi8vity Atopic diseases Helminthic Øallergic asthma Øallergic eczema (worm) Øhay fever infections IgE Immunodeficiency Miscellaneous diseases Ø hyper-IgE syndrome Ø Bronchopulmonary Ø Wiscott-Aldrich Ø aspergillosis syndrome Ø IgE myeloma 28  Allergy symptoms and cAMP cAMP β-agonist α-agonists (epinephrine, isoproterenol) phenyl epinephrine, nor- α-blocker epinephrine (phenoxybenzamine) β-blocker Phosphodiasterase (propanolol) inhibitor (theophylline) Relief from symptoms Worsening of symptoms Skin test for allergy Skin test for Allergy  Allergy: A type I hypersensi8vity reac8on Diagnos'c tests and treatments are available for type I hypersensi'vity reac'ons – Skin tes8ng is commonly used Cheap, safe Inject small quan''es of known allergens under skin Swelling and redness (resul'ng from local mast cell degranula'on) indicate allergic response – May also assess and quan'fy total or allergen-specific IgE serum levels using ELISA or Western blot methods  Type II hypersensi'vity =Cytotoxic Hypersensi'vity role of complement and phagocytes  Type III Hypersensitivity Immune complexes not cleared Activation of Complement C3a & C5a Inflammation Mast cells Types of immune complex disease cause antigen site of deposition persistent bacterial, viral, infected organ, infection parasitic, etc. kidney inhaled antigens mold, plant or lung animal antigen injected material serum kidney, skin, arteries, joint autoimmunity self antigen kidney, joint, arteries, skin Serum sickness Systemic lupus erythematosus Type III hypersensi'vity mechanism Type III hypersensi'vity mechanism Immune complex- mediated (type III) hypersensi'vity Arthus reac8ons are localized type III hypersensi'vity reac'ons – An inflammatory reac'on induced by injec'on of an Ag in an individual with high levels of circula'ng Ab specific to it Swelling and localized bleeding at injec'on site Peaks 4–10 hours post injec'on – May take place a`er a rapid, localized type I reac'on to an insect bite – May develop in lungs a`er inhala'on of Ag, e.g., farmer’s lung from moldy hay  Delayed-type (type IV) hypersensi'vity (DTH) Purely cell mediated rather than Ab mediated Ini8ated by T cells Requires a delay for the reac'on to develop Characterized by recruitment of macrophages at inflamma'on site Poison ivy contact derma''s is the most common example Intracellular pathogens and contact antigens that induce delayed-type (type IV) hypersensitivity, Intracellular bacteria Intracellular viruses Mycobacterium tuberculosis Herpes simplex virus Mycobacterium leprae Variola (smallpox) Brucella abortus Measles virus Listeria monocytogenes Intracellular fungi Contact antigens Pneumocystis carinii Picryl chloride Candida albicans Hair dyes Histoplasma capsulatum Nickel salts Cryptococcus neoformans Poison ivy Poison oak Intracellular parasites Leishmania sp.  Delayed-type (type IV) hypersensi8vity (DTH) The ini'a'on of a type IV DTH response involves sensi'za'on by an an'gen – Ini'al exposure triggers produc'on of a T-cell response O`en of the CD4+ TH1 subset Takes 1–2 weeks of 'me  Delayed-type (type IV) hypersensi'vity (DTH) The effector phase of a classical DTH response is induced by second exposure to a sensi'zing Ag – Second exposure induces produc'on of TH1 inflammatory cytokines These recruit and help ac'vate macrophages – A prolonged ac'va'on of macrophages leads to granuloma forma'on  Delayed-type (type IV) hypersensi'vity (DTH) The effector phase of a classical DTH response is induced by second exposure to a sensi'zing Ag – A prolonged inability to clear Ag (as seen in TB) can result in forma'on of destruc've mul8nucleate giant cell and granulomas  Delayed-type (type IV) hypersensi'vity (DTH) The DTH reac'on can be detected by a skin test – By injec'ng a small amount of Ag under the skin If a red, slightly swollen, firm lesion develops in 48–72 hours, the test is posi've – This indicates the individual has a popula'on of sensi'zed TH1 cells against the Ag – This does NOT indicate if an ac've infec'on is occurring or if the individual already overcame an infec'on (leaving memory cells) Commonly used in the United States to test for tuberculosis exposure Delayed-type (type IV) hypersensi'vity (DTH) Delayed-type (type IV) hypersensi'vity (DTH) Contact derma88s – Sensi'za'on can occur if a reac've chemical compound binds to skin proteins Modified proteins are then presented to T cells Could be induced by cosme'cs, pharmaceu'cals, industrial chemicals, metal ions, poison ivy, poison oak – Can cause strong cell- mediated responses against skin cells, inducing blisterlike lesions and rashes Delayed-type (type IV) hypersensi8vity (DTH) Tuberculin test  Leprosy Fluid filled Severe blebs tissue with damage bacteria small skin lesion Hypo Normal Hyper response response response Granuloma in a leprosy pa'ent Thank You