IMM250 Midterm Study Notes

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Michael Ratcliffe

IMM250 MIDTERM REVIEW Immunity the ability to resist infection Immune system the tissues, cells and molecules involved in protecting the host and responding to foreign antigens primary defence against pathogens Variolation the inoculation of scab material into the skin of individuals Thucydides - Reported the concept of immunity after exposure to disease during a plague outbreak Ar-Razi - Diagnosed smallpox versus measles - Recognized the epidemic force of smallpox - Described allergic asthma - Understand that fever is a mechanism for fighting infection Avicenna - Father of modern medicine - How to run a clinical trial - Experimental medicine - Evidence-based medicine - Contagious nature of infectious disease - Acquired immunity Francastoro - Suggested contagious particles transmitted disease by direct or indirect contact or even without contact over long distances Pasteur - The first production of attenuated chicken cholera vaccine Tyndall - Discovery of penicillin Mechnikov - Discovered role of phagocytes in invertebrates (star fish) - White blood cells could engulf and destroy harmful bodies such as bacteria Behring - Developed a serum-based therapy for diphtheria and tetanus Ehrlich - Proposed the side-chain theory was that antibodies are naturally occurring macromolecules within the body whose specificity for antigen and complement depends on the presence of certain sterio-chemical configurations - Discovered mast cells Koch - Described the delayed-type hypersensitivity (DHT) response - An animal previously infected with tuberculosis organisms is re-infected intra-cutaneously, a local inflammatory reaction marked by necrotic lesions will develop rapidly and heal quickly Landsteiner - Discovery of human blood groups Medawar - Described the discrimination of self versus non-self - Cells acquire the ability to distinguish between their own tissue substances on the one hand and unwanted cells and foreign material on the other Burnet - Proposed the clonal selection hypothesis - Each lymphocyte bears on its surface specific immunoglobulins reflecting the specificity of the antibody that will later be synthesized once the cell is activated by an antigen - The antigen serves as a selective stimulus, causing preferential proliferation and differentiation of the clones that have receptors for that antigen - Proposed the theory tolerance to self-antigens Edelman - Discovered the structure between antigen and antibody Tonegawa - Discovery of V(D)J recombination to form the vast array of available antibodies Milstein - Antibodies undergo hypermutation/selection to neutralize pathogens Bretscher and - Two signals are delivered to T cells before they may be activated Cohn Davis and - Cloned the TCR Mak Zinkernagel - Responses to virus occur by MHC restriction and Doherty Steinman - Dendritic cells present antigen in the context of MHC Janeway - Recognition of exogenous microbial products Matzinger - Recognition of endogenous danger signals (dead or dying cells) Marshall - Infects himself to prove Kochs postulates for Helicobacter pylori Volhard - Drosophila Toll receptor involved in embryonic neural tube development Gay - Cytoplasmic domain of Toll receptor related to human IL-1 receptor called TIR domain Lemaitre and - Drosophila Toll receptor involved in adult immunity to fungus Hoffmann Medzhitov - Discovery of human Toll receptor (TLR4) and Janeway Rock and - Identified five human TLR Bazan Beutler - TLR4 activated by LPS - Mutation in C3H/HeJ mice affecting cytoplasmic domain of TLR4 making them resistant to LPS - C57/Bl6 mice undergoes cytokine storm and inflammatory response Tschopp and - Link between NLRP3 and associated diseases McDermott Innate barriers Anatomical barriers (physical barriers) o Mechanical factors System or organ Cell type Mechanism Skin Squamous epithelium Physical barrier Desquamation Mucous Non-ciliated epithelium Peristalsis membranes (GI tract) Rapid cell turnover Ciliated epithelium Mucociliary escalator (respiratory tract) Epithelium (nasopharynx) Flushing action of tears, saliva, mucus, urine The epithelium Most commensal bacteria are maintained at the top of villi Crypts of villi produce antimicrobial products Antimicrobial products kill commensal bacteria or pathogens Microvilli increases surface area of intestine to increase absorption of nutrients Tight junctions enhance tightness Play an active in host defence o Function within seconds of detecting pathogen o Produce mucins o Produce cytokines o Produce chemokines o Produce antimicrobial peptides (defensins and cathelicidins) Antimicrobial peptides are positive Bacterial cell membrane is negative Interaction causes conformational change within bacterial membrane forms pore Huge osmotic gradient of water bursts bacteria o Transport antibodies from inside (blood) to outside (epithelial cells) o Chemical factors System or organ Cell type Mechanism Skin Sweat Antimicrobial fatty acids Mucous HCl (parietal cells in Low pH membranes stomach) Lysozyme Tears Phospholipase A Saliva Defensins (respiratory Cationic anti-microbial peptides tract and GI tract) Surfactants (lung) Opsonin (enhances uptake by phagocytes)o Biological factors System or organ Cell type Mechanism Skin and mucous Normal flora Antimicrobial substances membranes Competition for nutrients and colonization The normal microbiota More bacterial cells (10 ) in the human body than human cells (10 ) Found on skin and mucosal surfaces exposed to external environment Composition of normal flora varies Harmful effects o Antibiotic use perturbs normal flora Overgrowth of less common and more resistant bacteria Clostridium difficile diarrhea (pseudomembraneous colitis), ulcer Candida albicans vaginitis, thrush (oral cavity) o Re-establishing normal proportions of flora Use of probiotics and prebiotics o Possible implication in other diseases Obesity Inflammatory bowel disease Allergy The core gut microbiota Highly variable between individuals Family members have more similar microbiota Early environmental exposure is the key determinant Metabolic outputs seem to remain constant Factors that impact
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