"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 2: The Defence – Host DiseasesInnate defences(Mims’ Chapter 9)Lecture 6Friday 21 July 2017LT12 (X2.05), 11-12 pm(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017The Innate Defencesof the BodySLE334 Medical Microbiology and Immunology, T2, 2017The body has both “innate” and“adaptive” immune defenses•? “Innate” immune system: establishedimmune defense system that preventsreplication and spread of infectious agent•? “Adaptive” immune system: comes intoaction when “innate” immunity isinsufficient to parry invasion (takes timebut eliminates infective agent)SLE334 Medical Microbiology and Immunology, T2, 2017“Innate” vs. “adaptive” systems•? Great synergy between two systems:adaptive greatly improves efficiency ofinnate response•? Specific memory imprint on adaptiveimmune system (ready for re-infection)•? Soluble factors (lysozyme & complement)and phagocytic cells contribute to innatesystem•? Lymphocyte-based mechanisms (antibodyand T lymphocyte production) are mainelements of adaptive system SLE334 Medical Microbiology and Immunology, T2, 2017Types of immune responses: Innate and Adaptive. Humoral vs. Cell-Mediatedhttp://www.youtube.com/watch?v=rp7T4IItbtM&feature=channel&list=ULSLE334 Medical Microbiology and Immunology, T2, 2017Innate and adaptive immunity•? An infectious agent first encounters elements of the innate immune system. •? These may be sufficient (1) to prevent disease but if not, disease may result (2). •? The adaptive immune system is then activated (3) to produce recovery (4) and a specificimmunologic memory (5).•? Following re-infection with the same agent, no disease results (6) and the individual hasacquired immunity to the infectious agent. SLE334 Medical Microbiology and Immunology, T2, 2017Defense against entry into the body•? Most infectiousagentsencountered by anindividual areprevented fromentering the bodyby a variety ofbiochemical andphysical barriers. •? The body toleratesa variety ofcommensalorganisms, whichcompete effectivelywith many potentialpathogens.•? Biochemical and physical barriers operate on the body surfacesSLE334 Medical Microbiology and Immunology, T2, 2017Defenses after microorganismpenetration of the body•? Phagocytosis: engulfment and killing ofmicroorganisms by “professionalphagocytes” (specialised cells)•? Soluble chemical factors: destructivebactericidal enzymes SLE334 Medical Microbiology and Immunology, T2, 2017Two types of professional phagocyte•? Consist of 2 major cellfamilies defined by theRussian zoologist ElieMetchnikoff–?Large macrophages–?Smallerpolymorphonucleargranulocytes (polymorphsor neutrophils; majordefense against pyogenic(pus-forming) bacteria)SLE334 Medical Microbiology and Immunology, T2, 2017Macrophages•? Originate as bone marrowpromonocytes•? Develop into circulating bloodmonocytes•? Become mature macrophages•? Widespread throughout tissues•? Collectively termed the “mononuclearphagocyte system”•? Long-lived cells; rely on mitochondriafor metabolic energy SLE334 Medical Microbiology and Immunology, T2, 2017Phagocytic cells(A) Blood monocyte and (B) polymorphonuclear neutrophil, both derived from bonemarrow stem cells. SLE334 Medical Microbiology and Immunology, T2, 2017The mononuclear phagocyte system•? Macrophages originate asbone marrow promonocytes,which develop intocirculating blood monocytesand finally become themature macrophages, whichare widespread throughoutthe tissues and collectivelytermed the 'mononuclearphagocyte system SLE334 Medical Microbiology and Immunology, T2, 2017Tissue location of mononuclear phagocytes SLE334 Medical Microbiology and Immunology, T2, 2017Localisation of injected carbon particlesin mice•? Carbon accumulates in organs rich in mononuclear phagocytes: lungs (L), liver (V), spleen(S) and areas of the gut wall (G). (Left) Normal organ color shown in a control mouse SLE334 Medical Microbiology and Immunology, T2, 2017Monocyte•? With 'horseshoe'– shaped nucleus(N).•? Phagocytic andpinocytic vesicles(P), lysosomalgranules (L),mitochondria (M)and isolatedprofiles of rough- surfacedendoplasmicreticulum (E) areevident. SLE334 Medical Microbiology and Immunology, T2, 2017Polymorphs•? Dominant white cell in blood stream•? Shares common hemopoietic stem cellprecursor with macrophages•? Has no mitochondria•? Uses cytoplasmic glycogen stores forenergy (glycolysis under anaerobicconditions; e.g. inflammation)•? Non-dividing, short-lived cell; segmentednucleus•? Contains variety of enzyme-containinggranules SLE334 Medical Microbiology and Immunology, T2, 2017Neutrophil•? With multi-lobed nucleus•? Lysosomal granules evidentSLE334 Medical Microbiology and Immunology, T2, 2017Phagocytosis and killing•? Phagocytes recognise pathogen- associated molecular patterns (PAMPs)on the microbe by pattern recognitionreceptors (PRRs) on the phagocytesurface.•? Phagocyte activated via PAMP recognition•? Internalised microbe is the target for avariety of killing mechanisms•? Phagocytes mobilised and targeted tomicrobes by chemotaxis (activation of thecomplement system) SLE334 Medical Microbiology and Immunology, T2, 2017PhagocytosisSLE334 Medical Microbiology and Immunology, T2, 2017Engulfing of latex particles byhuman phagocytes "