Immune Lecture 23 Study Notes.docx

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Microbiology and Immunology
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Microbiology and Immunology 3300B
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Prof

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Immune Lecture 23 Study Notes 1. What is an allergy? -an immune response to something foreign that is not associated with a pathogen -the response itself is pathogenic -had to have developed an immune response to it already, so an allergic reaction is a memory response -the allergen is the antigen that induces the reaction 2. What is hypersensitivity? -hypersensitivity kind of means allergy -term used clinically for allergy -also a description of the immune mechanism -not exclusive to the term allergy as defined above -immune system is causing problems when it shouldn’t be 3. What is type 1 hypersensitivity? -immediate hypersensitivity (very fast) -IgE mediated  not a lot in circulation, mainly bound to mast cells (FceR1) -TH2 (IL4/5 cytokines)  directed towards parasites that get in through the mucosal or epithelial barriers, class switch to IgE -some basophils (although rare) are found in tissues where parasites invade you and are covered in IgE -ex/ asthma 4. What are some mast cell products? -histamine: good at increasing permeability in vasculature (leaky blood vessels, vasodialation, airway constriction) -enzymes in these granules are able to degrade the extracellular matrix 5. What is the immediate response of type 1? -response is due to mast cell and basophil degranulation -mast cells are activated and granules are released (happens within seconds) GI tract: increased fluid secretion/peristalsis = diarrhea/vomiting Eyes, nasal passages and airways: decreased diameter, increased mucus secretion = congestion/blockage of airways (wheezing, coughing etc), swelling and mucus secretion in nasal passages Blood vessels: increased blood flow/permeability = increased fluid in tissues = increased flow of lymph to lymph nodes, hypotension = anaphylactic shock 6. What is welting? -allergy test; response within 5 minutes to an allergen if you were previously exposed 7. What is allergic rhinitis? -runny nose 8. What is allergic conjunctivitis? -watery eyes 9. What is allergic urticaria? -welting 10.Discuss the route of allergen entry and the mast cell activation. (i) intravenous high dose allergen  general release of histamine which acts on blood vessels to increase permeability leading to anaphylaxic sock (ii) Subcutaneous: low dose  local release of histamine causes flaring -air born allergies can also cause eczcema (iii) Inhalation: low dose  allergic rhinitis (upper airway) caused by increased mucus production and nasal irritation; asthma due to contraction of bronchial smooth muscle and increased mucus secretion (lower airway) (iv) Ingestion  contraction of intestinal smooth muscle induces vomiting; outflow of fluid into the gut causes diarrhea; antigen diffusing into the blood vessels is disseminated causing urticaria, anaphylaxis or eczema Slide 15 11.What are treatments for acute responses? -for anaphylaxis: epinephrine -for asthma: bronchodilators -these are direct blockers to mast cell products 12.How do we block mast cell products? -IgE binding to a mast cell: bind to an IgE Fc region and prevent IgE binding to Fc receptors on mast cells -anti-IgE antibodies such as omalizumab 13.How do we inhibit mediators? -want to inhibit effects of mediators on specific receptors or inhibit synthesis of specific mediators -use antihistamines, beta blockers, lipoxygenase inhiitors 14.Antiinflammatory? -corticosteroirs 15.Th2 response? -induction of Tregs -desensitization therapy by injections of specific antigens 16.What are some other ways to treat acute responses? -desensitization protocols: short term – clinical requirements so that certain drugs can be used, repeated administration with increasing dose -permanent: restore tolerance, will induce a Treg response (shutting off immune system) 17.Discuss the intermediate and late phase responses. -intermediate is caused from IgE responses and starts within seconds/minutes of exposure -histamines/prostaglandins and other mediators released by mast cells = huge increase in permeability = visible edema/reddening of the skin (welts) -late phase response is dependent on allergen dose -these reactions over hours afterwards; much increased area of edema; this is caused by continuous synthesis and release of inflammatory mediators by mast cells -delayed responses include TH2 responses which are heavily dominated by eosinophils -they express Fcgamma, Fcalpha and CR3 -they contain very toxic chemicals in their granules 18.What are the eosinophil products? -they contain enzymes that will degrade the extracellular matrix, start producing cytokines (proinflammatory responses) and cytokines to amplify the support of TH2 19.Discuss asthma and the TH2 response. -asthma occurs in the lower airways -can have an allergic asthma (acute attack)  mast cells let granules go and will recruit TH2 cells -inflammatory mediators cause increase mucus secretion and smooth muscle contraction leading to airway obstruction -can have airway constriction 20.What are the mast cell products? -pro-inflammatory cytokines/enhance TH2 response -make IL4/13 = TH2 -IL3/5/GM-CSF = eosinophil production and activation -TNFalpha = promote inflammation, sitmulate cytokine production by many cell types and activate the endothelium 21.What is the TH2 response? -a delayed response -chronic IgE response -inflammatory response initiated by activated mast cells -recruite more Th2 and eosionophils 22.What is a part of the delayed response? -get tissue remodeling -allergic asthma (airway remodeling and fibrosis: muscle walls thicken, mucus inside) -changing it so that it can function properly -in eczema: get dermis remodeling (breaking down; no longer have a cornified barrier – it loses its function) 23.What are some treatments for TH2 hypersensitivity? -treatments for chronic inflammation include anti inflammatory therapies (corticosteroids?) -future is to turn off or to change the response 24.What is atopy? -tendency towards a TH2 disease -its can allergic disease that can be Type 1 or TH2 associated -babies can get eczema, allergies, hay fever or asthma -have a genetic susceptibility to it -rates are increasing 25.What are
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