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Dr.HamedaabdulmahdiCollegeofMedicine/Dep.ofanatomy histology2ndstage Objectives 1. Brieflydescribethecellularandhumoralcomponentsoftheinnateand adaptiveimmunesystems. 2. Describethemaindifferencesbetweentheinnateandadaptiveimmune responses. 3. BrieflydescribetheclassesofclassesofAntibodies The immune system provides defense or immunity against infectious agentsrangingfromvirusestomulticellularparasites.Histologicallythissystem consistsofalarge,diversepopulationofleukocyteslocatedwithineverytissue of the body and lymphoid organs interconnected only by the blood and lymphaticcirculation. Immunologists recognize two partially overlapping lines of defense against invadersand/orotherabnormal,potentiallyharmfulcells:innateimmunityand adaptive immunity . The first of these is nonspecific, involves awide variety of effector mechanisms, and is evolutionarily older than the second type. Among the cells mediating innate immunity are most of the granulocytes and other leukocytesdescribedinadaptiveimmunityaimsatspecificmicrobialinvaders,is mediated by lymphocytes and antigen‐presenting cells (APCs) and produces memorycellsthatpermitasimilar,veryrapidresponseifthatspecificmicrobe appearsagain. The lymphocytes and APCs for adaptive immunity are distributed throughoutthebodyintheblood,lymph,andepithelialandconnectivetissues, lymphocytes are formed initially in primary lymphoid organs (the thymus and bone marrow), but most lymphocyte activation and proliferation occur in secondarylymphoidorgans(thelymphnodes,thespleen,anddiffuselymphoid tissue found in the mucosa of the digestive system, including the tonsils, Peyer patches,andappendix). Theimmunecellslocateddiffuselyinthedigestive,respiratory,orurogenital mucosae comprise what is collectively known as mucosa‐associated lymphoid tissue(MALT),proliferatingBlymphocytesinthesecondarystructuresofMALT are arranged in small spherical lymphoid nodules . The wide distribution of immunesystemcellsandtheconstanttrafficoflymphocytesthroughtheblood, lymph,connectivetissues,andsecondarylymphoidstructuresprovidethebody withanelaborateandefficientsystemofsurveillanceanddefense. 1 Dr.HamedaabdulmahdiCollegeofMedicine/Dep.ofanatomy histology2ndstage InnateandAdaptiveimmunity The system of defenses termed innate immunity involves immediate, nonspecific actions, including physical barriers such as the skin and mucous membranes of the gastrointestinal, respiratory, and urogenital tracts that preventinfectionsorpenetrationofthehostbody,Bacteria,fungi,andparasites thatmanagetopenetratethesebarriersarequicklyremovedbyneutrophilsand otherleukocytesintheadjacentconnectivetissue. Other leukocytes orchestrate the defenses at sites of penetration natural killer ( NK ) cells destroy various unhealthy host cells, including those infected withvirusorbacteria,aswellascertainpotentiallytumorigeniccells. Leukocytesandspecificcellsofthetissuebarriersalsoproduceawidevariety of antimicrobial chemicals that Adaptive immunity, acquired gradually by exposure to microorganisms, is more specific, slower to respond, and an evolutionarily more recent development than innate immunity. The adaptive immuneresponseinvolvesBandTlymphocytes,whichbecomeactivatedagainst specificinvadersbybeingpresentedwithspecificmoleculesfromthosecellsby APCs,whichareusuallyderivedfrommonocytes. Unlike innate immunity, adaptive immune responses are aimed at specific microbial invaders and involve production of memory lymphocytes so that a similarresponsecanbemountedveryrapidlyifthatinvadereverappearsagain. AntigensandAntibodies A molecule that is recognized by cells of the adaptive immune system is calledanantigenandtypicallyelicitsaresponsefromthesecells,antigensmay consistofsolublemolecules(suchasproteinsorpolysaccharides)ormolecules that are still components of intact cells (bacteria, protozoa, or tumor cells), immune cells recognize and react to small molecular domains of the antigen knownasantigenicdeterminantsorepitopes. ClassesofAntibodies Immunoglobulinsofhumansfallintofivemajorclasses,withtheirstructural features, abundance in plasma, major locations, and functions. The classes are calledimmunoglobulinG(IgG),IgA,IgM,IgE,andIgD,andkey aspectsforeach includethefollowing: ■■ IgG is the most abundant class representing 75% to 85% of the immunoglobulin in blood. Production increases during immune responses following infections, etc. Unlike the other classes of antibodies, IgG is highly soluble, stable (half‐life >3 weeks), and crosses the placental barrier into the 2 Dr.HamedaabdulmahdiCollegeofMedicine/Dep.ofanatomy histology2ndstage fetal circulation. This confers passive immunity against certain infections until thenewborn’sownadaptiveimmunesystemisacquired. ■■ IgA is present in almost all exocrine secretions, IgA is produced by plasma cells in mucosae of the digestive, respiratory, and reproductive tracts, another proteinboundtothisimmunoglobulin,thesecretorycomponent,isreleasedby the epithelial cells as IgA undergoes transcytosis, the resulting structure is relativelyresistanttoproteolysisandreactswithmicroorganismsinmilk,saliva, tears,andmucuscoatingthemucosaeinwhichitismade. ■■ IgM constitutes 5% to 10% of blood immunoglobulin and IgM is mainly producedinaninitialresponsetoanantigen.IgMboundtoantigenisthemost effectiveantibodyclassinactivatingthecomplementsystem. ■■ IgE,usually a monomer, is much less abundant inthe circulation andexists bound receptors on the surface of mast cells and basophils. When this IgE encounterstheantigenthateliciteditsproduction,theantigen‐antibodycomplex triggers the liberation of several biologically active substances, such as histamine,heparin,andleukotrienes. Antigen‐PresentingCells Most specialized antigen‐presenting cells (APCs) are part of mononuclear phagocytesystem, including all typesofmacrophagesand specializeddendritic cellsinlymphoidorgans.FeaturescommontoallAPCsareanactiveendocytotic system and expression of MHC class II molecules for presenting peptides of exogenous antigens. Besides dendritic cells (not to be confused with cells of nervous tissue) andall monocyte‐derived cells, “professional” APCs include the epithelialreticularcellsofthethymusandBlymphocytes.Duringinflammation transient expression of MHC class II is induced by interferon‐γ in certain local cells that can be considered “nonprofessional” APCs, including fibroblasts and vascularendothelialcells. Lymphocytes Lymphocytesbothregulateandcarryoutadaptiveimmunity.Inadultsstemcells for all lymphocytes are located in the red bone marrow, but cells of the major lymphoidlineagesmature andbecomefunctionalintwodifferentcentralorprimarylymphoidorgans.Cells destinedtobecomeBlymphocytesremainanddifferentiatefurtherinthebone marrow. Progenitors of T lymphocytes move via the circulation into the developingthymus.Aftermaturationintheseprimarystructures, B and T cells circulate to the peripheral secondary lymphoid organs, which include the MALT, the lymph nodes, and the spleen (see Figure 14–1). Lymphocytes do not stay long in the lymphoid organs; they continuously 3 Dr.HamedaabdulmahdiCollegeofMedicine/Dep.ofanatomy histology2ndstage recirculatethroughthebodyinconnectivetissues,blood,andlymph.Becauseof the constant mobility of lymphocytes and APCs, the cellular locations and microscopicdetailsoflymphoidorgansdifferfromonedaytothenext.However, therelativepercentages ofTandBlymphocytesinthesecompartmentsarerelativelysteady(Table14– 3). Lymphoid tissue is usually reticular connective tissue filled with large numbersoflymphocytes.Itcanbeeitherdiffusewithinareasoflooseconnective tissue or surrounded by capsules, forming discrete (secondary) lymphoid organs. Because lymphocytes have prominent basophilic nuclei and very little cytoplasm,lymphoidtissuepackedwithsuchcellsusuallystainsdarkblue.Inall secondary lymphoid tissue the lymphocytes are supported by a rich reticulin fiber network of type III collagen . The fibers are produced by fibroblastic reticular cells, which extend numerous processes along and around the fibers. Besides lymphocytes and reticular cells, lymphoid tissue typically contains variousAPCsandplasmacells.Althoughmostlymphocytesaremorphologically indistinguishable in either the light or electron microscope, various surface proteins (“cluster of differentiation” or CD markers) allow them to be distinguished as B cells and subcategories of T cells by immunocytochemical methods. Key features of B and T lymphocytes also include the surface receptors involvedinactivatingtheirdifferentresponsestoantigens.ReceptorsofBcells areimmunoglobulinsthatbindantigensdirectly;thoseonTcellsreactonlywith antigenonMHCmoleculesandthisrequirestheadditionalcellsurfaceproteins CD4orCD8. 4