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Transcript
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.
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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
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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
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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.
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