STRUCTURE & FUNCTION OF IMMUNE SYSTEM © Major ima i system of the body is Iymphoreticular system. Lymphoreticular system is a complex organization of cells of diverse morphology distributed widely indifferent organs and tissues ofthe body responsible for the immunity + Lymphoreticular system is divided into : 1) Lymphoid system It includes lymphotd organs and following cells i) Teeells and B-celtsrotm, 4i) Null cells (Large granular lymphocytes) : NK cell, LAK cells, antibody dependent cytotoxic cells (ADC), lit) Lymphoid (plasmacytoid) dendritic ells, 2). Reticular system : It includes - 1) Phagocytes"” : Macrophages”, Microphages (newtrophils*"*"*, eosinophils) 8) Reticutar system : Interstitial (follicular) dendritic cells, Langerhans dendritic cells. + The lymphoid system consists ofall of the tissue aggregates and organs composed of lymphoid tissue which function together to produce specific resistance to immunity. © The lymphoid organs are divided into 1) Primary (central) lymphoid organ > “The sites where cells of lymphoid system are produced. ii). Seconstary ( peripheral) lymphoid organ => ‘he sites where the cells of lymphotd system function. Lymphoid organs Centrat (Primary) Peripheral (ceconttary) © fa these organs, precursor After maturity, lymphocytes accumnlate lymphocytes proliferate, {in these organs develop and acquite © Examples ae: immunological capability . Bebe + Examples are: . = Tiymin © Mucoue auc npold tame Bone marrow onanne f= Lymph sve in gut, lange Ever and bone marrow © Bone marrow acts as central as well as peripheral lymphoit! orga. © Spleen isthe largest Iymphold organ, © Thymus is the frst organ to become predominantly lyephot, Scanned wth CamScanner© T cells re amongst the two important cells of adaptive immune system (others are B-cells). T cel precursors arse inbone marrow (also in yolk sac & liver before birth) and migrate to the thymus. Maturity of T-cells takes place in thethytms (So, ‘T-cells arise in bone marrow and mature in thymmus!"2""4), © T-cells constitutes 60%-70% of the circulating peripheral lymphocytes. Rased on their surface markers, target cells and functions the following T cell Category have been identified :. A) Helper T-cells (Inducer T-cells) + Thesecells constitute 60% of total T-celle. These have CD4 surface marker and biad to MHC class IT (MHC class W restricied), There are following types of CD4 cells (Helper T-cells) = 1) Effector cells (Effector CD4 helper T-cells) © There aredivided into ) TH tells wow. , These arc activated by LEN-y and themselves produce 11-26% mi severe, [ENey We! Tee erent ne aes ey immunity, macrophage activation!"*" "710 and Killing of intracellular microbes (Me tuberculosis, M. leprae). + These cells also induce destruction of target cells by actfvating T-cells to become cytotoxte Teeclls008104 5 and by activating NK cells i) TH-2eetls = These are activated by IL-4 and themselves produce IL-t, IL-5, IL-6 and IL-13. These cells faciltste synthesis ofall antiboides except IgG2 & These cells induce synthesis of fF more ‘efficiently and cause activation of mast cells and eosinophils. Therefore these cells provide defence against Helminthic parasites, ii) TH17 celle These cells are powerful recruiters of neutrophils and monocytes to play a role tn severe inflammatory diseases. These cells produce 1L-17, 1L-22 and chemokines which recruit, neutrophils and monocytes. TH-17 cells produce I-21, which amplifies the TH-17 (elf response 2) Memory cells (Memory CD4 helper T-cells) © Provide memory!" ie. retain the antigenic affinity ofthe originally activated Tcelleand are used toact as ater efector cells during 3 second immune respanee = Helper Feels do not price antibodies themselves! 841%, but they ate very inportan preducton of antibodies by Dll. tx antibody formation Texts are involve! carter Juv Bell Afet ntgea exponue,oatgsn presening eels present antigen to CD 4 helper clly, which thea seceie ‘jtokines that induce diferenttion of cel (which have sleady been exposed to same antigen) 1 plac cell Plasma cells form antibody against that specific antigen © Thus Helper Tells (CDA T-cells) are known Master regulator of fmimune sysiem, B) Cytotoxic T-cells (Cytotytie T-cells) © These cells constitute 30% of total T-cells. These cells have CDS surface marker!" S11? and are MHC class 1 restricted. © They killand jyce target cells including tumor cells, virus infected cells! and allograt; end participate in type AL Hypersensitivity - J G@ € « < a cc 2 S es S S f= & c S = = o ~ o o o SS ol al ol cl Te ratio of CDA and COR Teel i normally 2:1. C) Suppressor T-cells These cellshave CD, surface marker and ate MHC case. restricted. These cells dow) vegulate namue response. ‘Scanned wih CamScannerPy “Grwnton Ft: Structure & Function of immune System 663 4 T-cell receptors (TCR) ‘©The Tell receqmor isa molecule found on T cells that is responsible for recognizing antigens bound ta MHC molecules TCR of CD, T cells recognises the antigens hound to MHC clase 1 TER of CD, T cele rec i. to MHC class. TCR ts3 heterodimer made up ofan a and a fehsin (TCRe fi in 95% of cases. anda yand a Schaum in 5% ofcases (TER 8). TCR y§ binds to antigens-without MHC involvernent. TCR oft recognises antigens presented on MHC molecule of antigen presenting cells # There arealso some aecesrory molecules associated with TCR > CD, and proteins These accessory molecules do gat bind w antigen, but involve in signal transduction after TCR has bound to antigen TCR diversity is generated ly somatic rearrangements of the genes that encode TCR, Rearrangement of these genes ‘occur only in T-cell during their development in thymus hence the presence of TOR gene rearrangements demanstrated by molecular analysis is marker of Tlineage cells. TCR Co-receptors 4 ‘Thesignal from the T-cell complex is enhanced by simulataneous binding of the MECmolecules by a spectic co-receptor. © On helper T cell, this co-teceptor is CD, that exchisively binds jo the class It MIIC on antigen presenting celle On cytotoxic T cell, this co-receptor is CD, that is specifi for clase MHC on antigen presenting cells. + The Co-receptor not only ensuresthe specificity of the TCR forthe correctly - prescnted antigen but also allows prolonged eengayement between antigen presenting cells and the T-cell TCReostimulator ‘@ Beside TCR, MHC, CD,/ CD, interaction there is another molecule on cell that activate the T-cell + costimulator. Is €D-28 on the surface of T cells that interact with B?-1 (CD-80) and B7:2(CD-86) expressed on antigen presenting cells So, for activation of T-cells, two signals are required :- Signal 1 > via TCR by TCR, MHC, CD, /CD, interactions, Signal 2-5. CD-28, B7-1 / B7-2 interaction ells ‘© Beellsare part of adaptive immunity. cells constitute 10% fo 20% of the circulating peripheral lymphocytes. B cells originate as well as mature in bone marrow"?! (contrast to Tells), ‘© Bees recognize antigen via the B-cell antigen receptor complen. 1g Mand Ig D, presenton the surface ofall naive B cls, constitute the antigen binding component of B-cell receptor complex. © Ajter antigenic stimulation, & cells form plasma cells that secret immunogtobul Plasma cells © Plasma cells are the antibody secreting cells", On contact with ts appropriate antigen, the mature B cell undergoes clonal proliferation. The majority of activated I cells are transformed into plasta cells and secrete antibodies. ‘# Piasmia cells make an antibody of a single specifiy, ofa single inenunoglabulin class arutellolypesand ofa single ight chain Iype ony: Am exception is seen in the priory autibody response, when a plasma cel producing IgM fnitialy, may later be sawtcied to IgG production (called isotype switching oc says switching). While lasna call the best anibody producing cll, Iymphocyes. fpmphbasts and transitional clls way alo synthesve I to some extent. 2D 9 Role of T-cells in antibody formation ‘e Antigen with class II MIG on antiger: presenting cells activates the CDM helper T cells. CD¢ helper T cells pr {ytokines that stimulate B cells whieh have already exposed to similar antigen. ‘© Thouph antibody is produced by 1 cell (afler differentiating into plasma eels), coortination of helper endive (CD 4) Toetis ts also necessary, © In antibody formation T cells are involved eartier than B cells, G2 RP wd ‘Scanned with CamScannerS64 Chweren F.1 Structure & Function of immune System * Aller antiven exposure, antigen ne en esesag cel pet ate a Lele {cl which hencatecqobestat ncace differen ot cells (which have seeady been exposed to sate setae ta plastna eal © Mist cabaraiinitmdvagintiaiqedicomme “ Cs « : Ansigen + Antigen pesring cel mth NBIC lass 4 Cc CDi T etlestnsion 4 & Kéleneat arenes e e Stimulation of B cells bounty speci erlgen c Plasma cll < | 4 ‘Antibody production e Clonal selection ¢ © Bcellsazeable to make specific antibody agaast a spetine antigen itis due to present of specie receptor on Bealls Beeell receptor (BCR), thats usally an immunoglobulin fg M or ig D. An antigen interacts with B-cell that shows best fit by vite ofits BCR. ‘the antigen binds to this receptor, and the B-cells stinulstedto divide and forma cone (clonal selection’) This clone of celle wll become plasma cells that wil secretes antibody of a patter specificity and same class. S * Aldiough, B-cells ae the maor source of anibodies (sir thet conversion into plasma cells) Teper = ces are also iniportant. Helper T-celic activate B-cells by secreting eytkines (lymphokines). These lympholknes than stimaate the specific ctonc B-cells 1o diferente into plasms cells (clonal selection’*?*5 Antigen exporure 4 eigen presentngells reset tic antigen tohelper cells ‘ ‘Veetisare activated Secretion of iymysiobine by T-cells [-celk thatearry BCR specificto that anton ate tirmulated (etonsl selec Becells proliferate and dierentiste in te plaenia cells t ymtnoglabulin of samespecifcityas that carried by the B-cell precursors Plasmas eels sya B-cell receptor (BRC) # Bhcells cecognize untiyents via the B-cell receptors. Ig M and Ig D pyesent on the surface of B-cells are the major BORE Aswith TCR, chversny of BR is generated by rearrengement of these immunoglobulin genes» Presence of rearrangeit immunoglobulin somes ina Iyinphotd eell i used at a molecular marker of Blineage cell fe BER (ike TCK ais tusaccessory molecules» tea & Ig (sinllarto CD-3oCTCR) > these dda nt tin! toantigen, but | involve in signal tra qfuctian after CGR has bound to antigen to TCR, CR ean be activated by artes, without UIC livolyement-+ Sa, antigenprecessing syn peesenvation hy antigen presenting celled ret acciae ow Hells (in contrast 1o"T cells) 2020.04.09 V4; scanned withChapyen Fo: Structure & Function of immune System 665.» ho ultimate source ofall Dlod cets including fymphocytes (T end B cells). Note ty etal and eacly nnconatal ie var andl yolk sae proshice Bowl ces + Allblood eel! originate from stem cell which diferntiste into four major cel lineage 1) Enythroid precursors —+—_‘Diflerentinte wnt RDC i) Mepakaryocyre precursors > Differentiate into platelets 14 Myeloid precusoes “+ Diflerentine into neutrophils, monocyte, cosinephil, basophil 1) Lymphoid precursors =» —_Dillecentiate unto lymphocytes ( T arad cells) © So, both T anit B cells originate from sane cell incage > Lymphoid lineage ‘© But. differntiation occurs at diferent sites- 1) Teeell maturation takes place in Thymus. 2) Bell maturation takes place in Bone marrow itelf © Afier maturity Tecells and B-cells are selectively seeded into thymus-itependent and thymus-independent areas, respectively = Tells 1) Origin + —-Bone martow (also in liver end yolk-sac of fetus) 1) Maturation > Thymes = Bealls 1) Origin + Bone marrow (also ia liver anu york sac of fetus) i) Maturation —» Bone marrow Location of B and T-cells in lymphoid tissues ‘© In peripheral lymphoid tissues, T-cells and B-cells are located in thymus dependent and thymus independent areas, respectively, ‘Thysnus dependent (Tcellscollect) 8 1. Spleen 1. Spleen f= Periartrial lymphoid collect, © Perifolicular region ‘© Malphigian corpuscle a white pulp™"" Mantel layec 2, Lymph node 2 Lymph node = Paracortical area" Cortical follicles © Germinal centres # Medullary cords CD acceptor * : 2 Surface immunoglobating 3 : : Receptor for Fe pace of fg : i E EAC rosette (C3 receptor; CR3; EBV receptory™"e4004 . sone a8) == ‘HNC wosete (C2; Measles eeeptory™=” rd - : “Thymus specific antigens . inom ‘Numerous microvilli, on surface - * » RRR RAR QO a de dda ddd ddddlddddder “AGATA GINO ‘Scanned wih CamScanner666 ClnrteR 4 ‘Structure & Function of immune System last rarsforration with : : : Anti CD3 + = bam tp CPHA (Phytohemapplutinin) 7% Concanavalin A © Endeteains Phapocytc action Adherence topless surface (Large granular 5 oF LGL| Null cells are called 30 because. they lack features of surface markers of both B and T lymphocytes. “The account for $ 10 10% of peripheral blood lymphocytes" u) ‘hey are also called “large granatar lymphocytes (LGL)” as they contain large azurophiliceytoplaenc granules. They express CD16 and CD56 markers. They proliferate in response to Ik-2. LGLs arse In Bodh bome marrow and thyme microenvironment. tn contrast t0 T-cells, they are not ANIC restricted. Vatious types of LUts are 1) Antibody dependent cytotoxic cells (ADCC) # These celsklliyse target celle which are sensitized with IgG. 2). Natural killer cells (NK cells) = These cells possess cytotonic activity against virus infected cells", tumor cells"™™" and transplanted foreign cells. Ototerisity of NK cells is neither antibody dependent nor MHC restricted #1, Activity is nonimmune as it does nos require antigente stimulation. NK.cells are positive or CD16 and CDS6™*", NK cells are wnunlly negative for CD3, but a subset is positive for CD39 called NRIT 1-2 acte as gromth factor for NK cell NK cells activity is augmented hy interferon, NK ells secrete Peroforin (resembles comlement C9") which causes transmembrane pores through which cytotoxic factors (eg, INE) enters the cells and induce apoptosis = Virus infected cell" and tumor (cancer) cells are hited by NK cells and eytotoste T-clld'*, 3) Lymphokine activated killer (LAK) cells © These are NK cells which are activated by IL-2, These eels kill tumor cells more efficiently than unstimulated NKeells Cytotoxicity of different cells © Natural killer cells Not antibody dependent NMHC restricted + Cytotonie Teel Classt MIG rested Not antibody dependent 1 Antibody dependent ttorie Antibody dependent™¥4) Tells (ADCO) (a ypeotaulleel) —NoentHCiesircied | Neutrophils * Neutrophils or polymorphonuctear leukocytes arc the primary phagocytic cells involved in host resistance to bacterial infection. Neutrophils are the major cells in early phase of acute inflammation, During maturation these cells develop following lysosome! granules 1) Primary (azurophilic) granules = These develop at promyelocytic stage and are more destructive. They contain myeloperoxidase, lysozyme, acid hydrolase, dlastares. non-specific collagenaser,defensin, cathepsin-G, bacterial permeability protein (BPI) and phospholipase & * 29209 Scanned wth CamScanner leh 4 r De ak nnn KARAAPFInANnagarnangAns(Ciupren F:1. Structure & Function of immune System. 667, 2). Secondary (specific) granules These develop at myefocytie stage and are less destructive. "They contain lactoferrin’*"*"™, bsocyme, alkaline spt sdieston malsules vitaman B., bonding pratei, ast, piospholpase A pluosphatase. type sselarinase, istarsmnave. .-mcroglobulie and cytochrome B 3). Tertiary granules (C-particles) : ‘= These develop dusing chemotaxis and contain gelatinase and acid hydrolase = Lifeof granvtocytes (neutrophite) tm circulation is 4-8 hours" ond another 2-5 days in tissues Monocytes/Macrophaces (mononuclear phagocyte system + Menonucteur phagocytes (MP) als knoven as macrophages or histioeytes are distributed throughout virtua all ssues, The macrophage is the dominant cellular player in chronic inflammation. MP arise from monablact in the marrow, and they ae released invo the ciation as monocytes. The monocytes then migrate to tissues and become part ofthe tstue (fixed) macrophages. = Mlood macrophages > Monocytes 1 Thsite macrophages > Histiocytestn™ following table « ‘© Tissue macrophages (histiocytes) in different issue are mentioned Se eee Placenta: Hester ets 2 er nefrenene ee eae 1 pow: osecaton Se 1 Shin: taneninnecte 1 Spe: et aly anta ner © Connective tissue ; Histiocytes“*** (tissue macrophages) Preteen Teese Life span of monocytes in circulation is 1-3 days whercas tissue macrophages have lifespan of 3 months to years™4, Functions of macrophages ‘©The major functions of macrophages are: 1) Phagocytosis ii) Antigen proces Seeretion of cytokines. ig and presentation ii) # The major activator of macrophages in TEN-y! 1). Classically activated macrophages (M, ) These are activated by nsicrobial products and LFN-y, These cells release lysosomal enzymes, NO, IL-l and IL- 12 They ate involved in mfcrobicidat activities and pathogenic inflammation. , Activated macrophages are divided into ~ 2). Alternatively activated macrophages (M,) fs These are activated by microbial products and IL-4/1L-5. These cells releare IL-10 and TGF-f. These cells ere ced in ant-inflammatory actions™"""” and wound repat, Eosinop! ‘© Eosinophils arethe major putticipants in allergic responses and parasitic tnfestatton, Eosinophils develop from stem cells “The major chemokine for eosinophilsis eataxin. Eosinophils have a grartule that contains major basie winophils also produce leukotrienes, PAF. peroxidase, neurotoxin, cosinophilcationic protein’. have weak phagocytic activity (The major phagocytic cells are neutrophils and In response to IL ‘protein (MBP) ‘and reactive form of Oy Eosinophils also macrophages) ‘5 MBP has following effects (i) Bactericidal, (i) Tost fo paraviter a scanned wtS68" Qummee F 1 structure ® Function of mune Sytem Mast cells and basophils © Mast cells and basophils are important inflammatory cells. They precipitate in hoth acute & chromic inflammation Basophils circulate in the bload, whencas sast cells reside and mature in tissues, They are the nuost important cells in cdiaste hypersensitivity and are alse the most important source of histamine, Other sectetions are Proteases, Carboxypepiudases, Glycosidoses, Proteoglycans, Sultatases. Antigen presenting cells (APCs) * Feel canvot he scivated by soluble antigens, Therefore, presentation af procested antigen by antigen presenting cells & required for actwaten of Teel + The inital step in immune response (whether humoral ar cull) ts phagocytosis ofthe antigen by antigen preserting els. These antigen presenting cells process and present the antigen to T cell. These activated cls thea interact with 8 cells (in burma immunity oe eral imonunity) oF with other Tels (in cell mediated immune tespor Important zetigen presenting cells are macrophages", B-cells!" dendriticeelis***6™ and Langherhan cee HEHE 18 Dendritic eels are thems potent an efective antigen presenting es". CD, helpar T celisare activate only when antigen i presented by MIC class I of APC > MIIC -II restricted CP, cytotocic T-cells recognize antigen that is presented by MIIC - class {> MHC - I restricted + Becellsreceptor (Le, surfacetmmmunoglobulin) can he bind in antigen and activate B-celle without ivolvernent ‘of MEIC and antigen presenting cells» Antigen processing and preseutation by APCeis not require for Beelis Gn cons to Tres) Mature Ieells before antigenic exposure are called naive 'I-cels.‘Lhese naive antigen by APCs lke mature langerhans dendritic cells™*== 4500 Dendritic calls ls are activated by presentation of Dendritic cells (sometimes called interdigitating dendritic eells) are the most important antigen-presenting cells for initiating T-cell responses against protein antigens". These cells ar locate atthe tight place to capture antigens tunder epithelia and in she Interstiia of al tisues. Dendritic cells express many receptors for capturing and responding to mictobes (and other antigens), including TLRs and lectins. In response to microbes, dendritic cells are recruited tu the ‘Teall zones of lymphoid organs, where they are {desly located ta present antigeat to cells. Dendritic cells express high levels of MHC and ether molecules needed fur presenting antigens to and activating T cells. * Asecond typeof cell with dendritis morphclogy ts present in the gertminal centers of lymphoid follictes in the spleen and lymph nodes andis calle the follicular dendritic cell. These cells beze Fe receptors for IgG and receptors for C3and «can trap antigen bound to antibodies or complement proteins. Such cells playa role in humoral immune responses by Presenting antigens te I cells" so selecting the B cells that have the highest afiity forthe antigen, thus improving the quality ofthe antibody produced, + Dendritic Cell > Presents antgent to Teel + Foliulardeedritc cells —> Presents ancigens to B cells Phagocytes + Micto:organisms enering the 1ssue fi or Bod steam are very rapidly engulfed by the ells called phagocytes © Phagocytic celsare of tivo types 1) Mononuclear macrophages” ™ : Monocytes (blood), histiocytes (tisstes) ale cells tive), nicrogti (brain), ostenclasts (bone), and mesangial cells (kidney), 2) Polymorphonuclear microphages : Neutrophils?™™) olar macrophages (lung), kupfer Hosophits aso belong ta ply morphonuclear microphages but they are not phagocytes © Eosinophils have only a limited degree of phagacytic activity, ‘Scanned wih CamScanner = Pr ts n nent —— r n « nt b f FYOFPPIN DDD DODD yi . 2920,.04,09 Sledcece mOHHEREE ROKR E Cede ddd cee: ‘The histocompatiblity antiga respanse leadhing i sev molecu v (human feikacyte antigens 111.9% a call wire antigens that yin snsmane 1 funciton of the ell surface Wistocompatibitity ‘sto bin peptide frogsnents of foreign proteins for preseutation tw antigen specific T eel 0""™, * The histocompatiility antigens are encoded by a closely linked] multiallelic cluster of genes > Major hetocompatbaty comptes (MITC) or Hanan teakocyte antigens complex (HILA ea farm of cliromesome 65" $05 0 lon of allogeas. The principal physi splee). HLA complex of genes is oeated an the short © HLA complex consists of three separate clasters of genes Y) Class 1 (MILC-1) + Bcomprising of A.B and € foci" (he, HLA-A, BILA-B, HLA-C). Is found on the surface of all nucleated cele” "an plateleis s Important calls with MECH (LILA) en surtice ate B-cells, Tees, macrophoges*monacytes sweutrophils™°, Langerhans cil, denditic cel platelets (thrombocyted% ©), epiha! celle of thymus sind hegarceytes. MIC class I peesent antigen to eylotenie CD-8 T celle (MIC resected"), + MHC class tis responsible for graft rejection'®"*** and cell mediated cytolysts of viral infected or tumor cello, 2) Class 1 (MIC) =U comprises 12" region (HEA-DR, HLA-DQ HLADP) It is found only ar the cells of immune system, Le Tocelle i", Beets, hangerians lls d ndrittcells"""*, and macrophages, 5 MHC-II recognizes exegenous antigen (extraceliulor microbes, sluble protcins) and presen it to CD! helper Teele"! (SMIC-H cestricted), MUC-U1 is responsible for graft versus host response anu mixed leukocyte reaction! 3) Class 1 (MHC-1IT) = Mencodes for complement components C2 & C4!!®, properdin factor B, Heat shock protein and Tumor nnecrass factor a.nd (TNF-a ancl §Y**) SEC-IIVis involved in susceptibaly ro autoimmune dseases*™ like Ste. REC do ra have MIC moleculesiia6 Structure of MHC molecule A) MHC.I [MIC Class I molecule) © MHC class molecule consists of: i) Long & heasy'a - chan, consists of tree globeid domains aya, and a, 11) Short chain (f, microglobutiny © These twi chains ave linked to each other som eoventently, Distal domain (alpha 1 ancl alphs 2) have highly il sequences and are folded t0 form a groove between them (between alpha I and elpha 2), nto CD8-T Protein antigen pracesser by macrophages or dendritic cells are bound to this groove for presental Calls B) MIIC-I (MMC Class Il metecule) © MIC IT Heterodier, consisting of an alpha and a beta chain of almost same size (on contrast to MHC:1 in Which alr hin tongs, Each chain has two dans, the proximal ome beg conta sad he daa belng variable. The Hea distal domains (a, ane, constitute the antigen binuling site for recogwition by CD Calls, 229,04 ‘Scanned wih CamScanner670 Cinptex F:1 Structure & Function of immune System HLA Class | molecule HLA Class il molecule = Both MUCH and MUCH hat antigen bining ste on distal domains, Ie SE Laatizen binding site ls betwen and 8°, = Fe MICH antigen binding iets between a, and, MHC restriction + Teall (an contrast to B cells) cannot be activated by soluble antigens. ‘© Therclote, presentation of processed antigen by antigen presenting cells is required for induction of cell mediated trains, + Teell receptors recognizes peptide antigens that are displayed by major histo compatibility complex (MITC) molecules on the surface af antigen presenting cells #Teells develop MHC testiction that © Helper (CD) Teclls respural unty Ww foreign antigens presented wlong with HLA dass IE (MTC clas 1H", = CDS celts respon to antigens presented along with HLA class 1(MIC class 1)", (© MHC restriction refersto the fic thata geven T cell wll recagnize a peptide antigen only wher MHC molecule bound toa particulse MHC- Class | restrictlon 1. Graf rection 2 Cyluterac cell mediated eytolyal of veal infected or wan cs AMUIEC Claes I restriction 1 Graft versis host response 2 Muted leukocyte resetion Lymphocytes and other leukcytes have a number of lace antizens or marke -» leukocyte differentiation a! A particular leucocyte differentiation antigen has been given 2 CD (chester of differentuation) mamber on the base ‘of ts reaction with a duster of munoclonal antibodies, Uiicse nuarkers reflect the stage dtevenn M1 and functional properties of vel Iesportant cells with thelr CD market are 2020.04 09 VST ‘Scanned wih CamScanner Ti to Oath nnh * « ‘ ©Lddelee MRR RAR Aad ded ddd LSS Primary Tell Asociated Primary Beal assocutet Ciwrren Fo Structures Function of immune System 671. cpi,co,c0. bu ep Primaremoreccteor mavrophugeassocinied CTE. CT, Primary NK ell associatad cpg, bse Primary stem cell wad progenitor cell ausecioted — €DS¢SI™NS Activation markers Preset om all ube tes pio eps ms CDIyemme:sim¢ wen 8 ep2w 01) CD11. €D15, CD49, Cost + CD45 is called as Leukocyte commian antigen (LCA) as tis present in all leukocytes. important types af CD45 are: Y CDASRA + MedullsryT cells 1) CDASRB 5 Allleukozytes .“paive’ Teel ii] CD 45RC + Subset Z medullary thymocytes “naive T iv) CD45.RO Subset T: Cortical thymocytes “memory” sta ch © CD.3Ge brome a Ban Teall market 1 The ost clearcut dfrentition between T and cells sy thet surice markers, for example by Dessorsiraticn of GD3 of Feels and Ion Bs + Cb-95isadeathreceptoe™*™, member of TNF recep amily. If favoled in apoptosis, * Cytokines are soluble proteins (potypeptides}!"4*™!™) They are produced by a wide variety of hematopoietic and ‘tonhematopaterc cell types. They regulate immunological, inflammatory!" 45" and reparstive host responses © Cytokines mediate their effects by binding to specific hi ‘mediate specific reactions?" 0") Selected important cytokines TFN (interferon) "TNF-a (tumnae necrosis tact alpha) "TNE -B (tumor necrosistactor beta, ET lymphotoxin) Tat (verleukia = 1) 12 Cincerteukan 113 Ciera 3) ThA Geereukin a) 1-5 Gimerleukin 5) 11-7 Gmerleukin -7) Cytokines in inflammation ls take part ia inflaimatwon These ate: h alfinity recept Teall, NK cells Macrophages! 6". NK cells Tells Bells Macrophages!" epithelial eels ‘Tealls(CD4 Helper Tees") ‘Teals, thymiceputhelil celle eels, mast cells*r™, NK colts reals Bone marrow stromal etm jokines are soluble proteins (palypeptdes) They are mainly valved in Immune responce, but 9 Leukocytes (IFN) fibroblasts (TEN) Antiviral pyrogenic ars on their target cells, Specific cytokines Activates monuruclear phagocytes Call activation, fever, cachexia, antitumor Activates leukocytes antitino Tell al macrophage activation! ") fever cachesa "Teall growth anu eteation Hematopoiesis cell prediecaton anal wtchny ob Differentation of cosnap hil Lymphald progee tne slitfereiation Je cytohines may ‘Scanned wih CamScanner72 Ciueren F Strtue& Function of mmune Sith 1 I | 1 I 1+ Metal ani inmentery ropey wih sponsor scion 1 i | ne =| | renin satiate | tural defence mechanism possessed by vertebrate cells against viral infection. - NpPHoONNNNAANANNHAN ‘Scanned wih CamScanner= 5 oer ‘e BER GueTER F.1 Structure & Function oftmmuine System 673 oe # Uhirtobines sees furally small pois that aot primary sy civ Atos Reespwsiic tyes ot feos tes They are te thearrangement of the conserveleysteine(C) resilues in mature pene, 1) GX.Cehemokines inchewokines) > They primanly act on nesleuptils, eg HS 1A aad NE 2) G-Cchemokines!¥¥'™!(fchermokines):-Attractall leukocytes except neutrophils. Exanyplesare Eotaxin's"™ 1 nophils|, MCP-# (maocyte chemoatiraclant protein), RANTES [regulated ond ermal Tell hissed ine faur ajar groups aceon “F&F OCNAR eS PE {specific for eo expressed und secteted), apa MIP Ja (mactephage snlurmmatiry’pyetet 13) 8). C= themuines (y-temakines) = Brey ste speci lie Impact tes. e Eynaplatactia' a mionocytes and T-cells, eg fructalkine!s®™m!, a. ddd dhemokines They promotes sit adhosion et Bg, dd 1 1.ischenostesctan! fr reutroplals, wherese otoxla iapociforesinophil, ae uf Acute phse reactants ate a chs oF pratelne whoge plasms concentration insreases er decreases in response to Uoflammaiion. Ths response is called the acute phase reaction {acute phine response). 1) Positive + Those preteins re increased during iflammation. important examples re C-reactive protein! PE (0)- slettin, a1 annieypsin, fibrinogen’ #4" feria, serum amyloid AY", hepatogtebul cetuloplasmin, and? misroglabulin ig d ute phase proteins y d 2). Negativeacute phase proteins + These proteins are deereased during inflammation. linportant examples are albumin, prealbumin, leansferrin™"™, cranscartin, ransthysetin and retinal binding paocein, Ana 1 Gencnity pextveucte phase proteins are consitered at ect phase protein teactive Protein (CRP) CRP iss nonspecic Inflammatory acute phase pratein'"4 itis 2 bets-globuin®™! which is produced in lis production is increased by iniecton (including prreuimococeal infection Aestruction ae eh lemmution, malignancies and tise Inchcappeats when inflammatory ceactions subside CRP is used 95,9 Ince of response to treatment i theumatictever and cettain other conditens, Festung is done by passive Forex agetutanation®™ ™ 4 presipres wth soveatc“C"amtigen of prenmacece, bu is not an payne, # Greacive protein binds w phesphorylcholine residues in cell wall of eertain meroonganisms. This copes is very sHiectve of activating the esssial complement pathway ee In G-teactive pote stn fr capsular pelyaccharide of paeumacocens™™9, is(cy + Central prary) ymphoid organs: Tyrrus, Bose marzo, + Pepa cunt) npn org; Ly nedes tes 1A LT bane mao mpl tue a gutter lange + Meola hymeciomy will cans atrophy afT cel dependent aes (parcomtsal acuof mph nee fewiae pupal pee + cit mation ene lace ws: oe stow. Teal mannan tes place w1< Thyra + Teal depertentrectns: Paracotcal2res of yrph me, oalphgin crate i ite palo aye ‘Scanned wih CamScannerS74 Chwerce F:1 Stnicture ® Function ot mmune System + Helper 7 celts ure postive fors CDA 9 Gottesie Teri ait wares Tcl are poitive for CT + Nota function of CD4 Helper T els: Antibodies production. © Important functions of CDA heper T ec: Activate macrophegen, microbes, desrction of target ceils by activation of eytotonie eels production by plana cel, + Tet helper Tees produce“ WL2,1FN-yALA2, CMM, delayed ypersenstivty, bling of straceuat ind NK lb, antigenic memory, fxcinatlon ef antibody + TH Phelper T ecto prosuce IL-4, 15.106, ets 4 Plasma cells arc etived from: Weel: Antibodies producing ets are: Plasma eels (derive For B-cells, © Production of specif antibodies against a particular antigen is due to Clonal selection. © N&cells are: Not MEG restricted, not require antibodies + Apart from T and Shee, ether clasroflymiphoxytes: Null ells (ADCE,NK eel, LAKelle 1+ NK cele activtyicenbaced by IL, 1S. * Common ta NK ces and eytotoste Terls: Cytotoxic activity gainat virus infected cells and tumor cel. 1 Markers of WK cells: CD36 and CDI © brunnanity against cancer cells: Kel 1+ Antigen presenting els: Macrophages B-cells, Dendritic cll, Langeshane cele + Most potent and efectve antigen presenting els: Dendritic eee. Most potent stimulutar of Naive Tels: Mature Langerhans dendritic eels 1 Langerburs cells in skin are: Antigen presenting cel’ Helper cells belong ta: T-cells + Normal 96 af CD-A Tels in adults 65% of total T-cells 1+ Normal 85 af CD et Teel ina neonate: 75-80% of total Tel gD tight © Large granular typhocytesare: NK cells, ADCE or illerclls(K-cell), LAK cell, ‘© Antigen binding componont om B-cell recep trate immunity atnst virus infected cells: NK celle, mserophages NK cells und eytoinrc cel activity are diferentiatr by: Natibaay spect. 1 Mucsuphayes are derived rom: Blood mionveytes, + Important monoractear-macropheges: Monocytes, hstocytes, alveolar macrophages. microglia kafer cell osteoclasts, I cell resus 1 Mlonunactene phigeeytes ore produced in; Rone marrow (all blood cells arc produced in bone marrow) = Common function nentropis and moneys escrephages:Phagocytosin te Gis secrete by; Pasa cells (ll antibodies ate secreted by plasma cell), FAC sete with heap erythrocytes cel = sen ee UE aasette th sep erythrocytes Tells, Blast forever Conshipheation) of Peels is Hota by: Phytohemaggltnin (HAD concanavalin A, a CD + Gelatronoanny inde by Teli especialy 7 esti + Teallenepion. CO,C03,60 + Pan Teel murber C3. Memory Tuell waster: CDS RO LA complec(84Ceompls goin iocate eo : 2020,0:409 iL ‘Scanned wih CamScannersik Mie Chnmea FA Structure & Funetion of mmune System 675 + Ato mein of MH (HLA): Present arcigen wo T-cell for rceyiion By Tell receptor HAE (MHC ic preset On all cleat cli al plated (+ F1LA-tEu present: Only on cells memune system. + Hid (NMED wo present on RCS + WIA (MAC compres: A,B, cnt Clock By Bs Wy + MLAS (ABIEC-10 compres: 0 Wc ay ay SHOEIE AE ID encoes for “€.8 . ropertn foes USP. TMF 4a fh 911A GC: 1 volved in Gra rejecton, cell mediated eyo of al fected or tumor eae + HEAL (StHtC-t1) w nveted in Groh versus host sespanse, Med leukocyte reaction + HEAATI (MCT is wavedved in Susceptible utvinnvune dscns, + Gyotonie Peels MMC restricted 2 + (comune: MP sas MIP a RANTES garama ly 1+ Ovher chemokines: C2X-Cialpha (1-1, 1-8, TNE), Nore chemokine: Histamine Three most onportant proinflamautory eytakines: Ney TNT-0, 15,21,23, IFNy, GBL SE. 1 Other promperamatoryestakines1L2.4,5.8, 11, + Teo most emportantani: inflammatory prakines:1L:10, TGF, + Nota prorafammatory cytokine: PAR. + Typeaf Tynphoeytes involved i hiacerrpiilty rection elper-T ces (MHC-(0, cytotoxi Tell (MHC), + Jit produces: T-eel acivation, B-cells probation, neutrophilic chemotass (ncrsael temperature, bane marraw cell prokiferation. + Ie-1 produced by: Macrophages and epithelia cells are major sources; Bcll. endothelial coll fbrobless ‘+ Cachectn (ENF) produced by : Monocytes and macrophages. #17 is produced by: Somal cells # Ayregenicetokines: 1! (most important), TNF-a, IL-6 1 Perforcs are produced by NK.cells, cyto Teel 1 Interfronsure: Fist coded proteins Istegferon produce by fibroblasts TEN Aiton of TEN: tahibition of viral replication, = CmCRD stands for: Capsule polysccharide of rcummococcus, ve about C-reetive protein: Beta globulin. non-specific inflammatory pretsin, produced in liver, raised Gnclading preumoceccal iniction) Se inflammatery conditions (ike RA), detected by pasive alee agglutination. 1 Imporian weute phase proiems CRP, Sbrinegen, hepstoglobulsa,ceruloasmin, transferrin, MBP, al antrypsin, frst, infections Scrtim ammo A. BSWHERLE LLL EE deed LY ‘Scanned wih CamScanner