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Date Created: 10/23/15
BIOMI 494G STRUCTURE AND FUNCTION OF LYMPH NODES AND SPLEEN FALL 2009 Overview 1 Secondary lymphoid tissue Lymph 1 2 7 Spleen 1 2 3 nodes Location Structure a Cortex b Paracortex c Medulla d Primary FolliclesGerminal Centers e Locations of Tcells B cells Macrophages and Dendritic Cells f Other structural features stroma Lymphatics a Afferent Vessels b Efferent Vessels c Cortical and Medullary Sinuses Blood Supply a Lymphatic Artery and Vein b Post Capillary Venules c High Endothelial Cells Lymphocyte Trafficking recirculation and homing a Homing Receptors b Vascular Addressins c Mechanisms i Homing ii Rolling iii Activation iv Shape change v Diapedesis extravastion Lymphatic System Lymphatic Vessels b Lymph c Lymphatic Flow d Function Function Location Entrance of antigen Structure a General anatomic features b Red Pulp c White Pulp White pulp in more detail a Periarteriolar Lymphoid Sheath PALS i Tcell Rich b Follicle Germinal Center i BCell Rich c Marginal Zone Function Fig i The distribution of lymphoid tissues in the body Lymphocytes arise from stem cells in bone marrow and differentiate in the central lymphoid organs yellow B cells in bone marrow and T cells in the thymus They migrate from these tissues and are carried in the bloodstream to the peripheral or secondary lymphoid organs blue the adenoid tonsil right subclavian vein left subclavian vein thymus lymph nodes spleen and lymphoad lymph Ode 39 he tissues associated with mucosa like the A gut associated tonsils Peyer s patches momquot Gum and appendix The peripheral lymphoid kidney Spleen Organs are the sites of lymphocyte payers patch in activation by antigen and lymphocytes small intestine recirculate between the blood and these appendix large intestine organs until they encounter their specific antigen T cells receive survival signals from dendritic cells DCs in the periphery whereas the source of the survival signals for B cells is thought to be in the lymphoid follicles Lymphatics I drain extracellular fluid from the lymphatics bone marrow peripheral tissues through the lymph nodes and into the thoracic duct which empties into the left subclavian vein This fluid known as lymph carries antigen taken up by DOS and macrophages to the lymph nodes and recirculating lymphocytes from the lymph nodes back into the blood Lymphoid tissue is also associated with other mucosa such as the bronchial linings not shown a Cervical lymph nodes Right lymphatic duct Thoracic duct left lymphatic duct Lymphatic vessels of upper limb Right subclavian vein Lymphatic vessels Tm Left subclavian vein or mammary gland Axillary lymph nodes 7quot lt Cisterna chyli 7 I Intestinal and mesenteric lymph nodes 7 w Abdominal lymph nodes 4 K 4 7 7 inguinal lymph A nodes Area drained by right lymphatic duct asquot A Area drained by thoracic 39 duct Lymphatic vessels a L of lower limb 7 Popliteal lymph nodes ELA u l Blood circulation 3139 Capillary f beds Afferent lymphatic vessels 8 cell region Paracortex T cell region I Medulla Plasma cell region Efferent lymphatic vessel Fig 2l4 The Lymph Node Lymphoid follicle Ar 7 Capsule Subcapsular sinus cortical sinus M secondary lymphoid lollicle wilh germinal center afferent lymphatic vessel paracorlical area mostly T cells germinal center A Fig 118 Organization of a lymph node As shown in the diagram on the left which shows a lymph node in longitudinal section a lymph node consists of an outermost cortex and an inner medulla The cortex is composed of an outer cortex of B cells organized into lymphoid follicles and deep or paracortical areas made up mainly of T cells and dendritic cells When an immune response is under way some of the follicles contain central areas of intense B cell proliferation called germinal centers and are known as secondary lymphoid follicles These reactions are very dramatic but eventually die out as senescent germinal centers Lymph draining from the extracellular spaces of the body carries antigens in phagocytic dendritic cells and phagocytic macrophages from the tissues to the lymph node via the afferent lymphatics primar a lymphoid lollicle mostly B cells medullary cords macrophages and plasma cells medullary sinus artery vein efferent lymphatic vessel senescent 39 germinal center marginal sinus z l These migrate directly from the sinuses into the cellular parts of the node Lymph leaves by the efferent lymphatics in the medulla The medulla consists of strings of macrophages and antibodysecreting plasma cells known as the medullary cords Naive lymphocytes enter the node from the bloodstream through specialized postcapillary venules not shown and leave with the lymph through the efferent lymphatic The light micrograph shows a transverse section through a lymph node with prominent follicles containing germinal centers Magnification x7 Photograph courtesy of N Rooney FIGURE 320 Structure of lymph node a The three layers of a lymph node provide distinct microenvironments b The left side dc picts the arrangement of reticulum and lymphocytes Within the WriOl regions of a lymph node MacrOphages and dendrjtic cells which rat antigen are present in the cortex and pamconex T cells are concen trated in the paracortex B cells are loated primarily in the cortex within follicles and germinal centers The medulla is populated largely by antibodyproducing plasma cells Lymphocytes circulating in the lymph are carried into the node via afferent lymphatics purple arrows they either enter the reticular matrix of the node or pass through it and leave via the e 39erent lymphatic vessel The right side t b depicts the lymphatic artery and vein and the postcapillary ven ules Lymphocytes in the circulation can pass into the node from the postcapillary venules by a process called extravasation inset b c Postcapillary venulc 399 129 age 13 wm wmexxw lg 33 M v N e A to saga 541 nmary v Tmphoid I 9 f y g lw foUiclc 0031 quot 9 poygr 24 1 0 K W f a t a 3 30m t 00 Capsnlc npillaryvenulc Gerrninal ccnter Germinnl v ccntcr quot L39m hatican P cry E crent lymphatic vessel Lymphatic vdn ltAlferenl Lymphoiics Subcopsulor 39 Sinu 39 MEOULLA 39 CORTEX Medullory Sinuses V Superficial Cortex Medullory Cords hmrem Deep Cortex Lymphatics Figure 122 Activation of adaptive immunity in the draining lymph node Pathogens pathogen components and dendritic cells carrying pathogens and molecules derived from them arrive in the afferent lymph draining the site of infection Free pathogens and debris are removed by macrophages the dendritic cells become resident in the lymph node and move to the Tcell areas where they meet small lymphOcytes that have entered the node from the blood green The dendritic cells specifically stimulate the division and differentiation of pathogenspecific small lymphocytes into effector lymphocytes blue Some helper T cells and cytotoxic T cells leave in the efferent lymph and travel to the infected tissue via the lymph and blood Other helper T cells remain in the lymph node and stimulate the division and differentiation of pathogen specific B cells into plasma cells yellow Plasma cells move to the medulla of the lymph node where they secrete pathogen specific antibodies which are taken to the site of infection by the efferent lymph and subsequently the blood Some plasma cells leave the lymph node and travel via the efferent lymph and the blood to the bone marrow where they continue to secrete antibodies Activation of adaptive immune response in a draining lymph node pathogen i carrying bacterial dendritic eell quot cornponent afferent lymphatic V vessel tissue macrophage engul ng b39acteriunt 39 activated by dendritic cell quot 35 o 39 60 T plasmai 51C cells Q antibodies 55 efferent 39 lymphatic 39 affordu lympluu c ponapilhry vmuld lnbcculurn upwle raiculu ber rcu culu ecu medulhry Iinuu Artery Vein Venous Blood ewe Lytwhalics 3C9 Figure 52 Lymphocytes enter the node through the arteries cross 1nto the deep cortex and leave by way of the effluent lymph The cells reach the venous circulation when the major ducts connect with veins in most cases 1n the neck BLOOD lmcgrin rcccptor AUIVJlmn Hommg Adhcsmn TAdhcsion tmvzlszmon I loming IJCCPCOI SECONDARY LYMPHOID ORGAN Higllmdothc al vcnulc I FIG U RE 2 16 Lymphatic vessels Small lymphatic capil laries opening into the tissue spaces pick up interstitial tissue fluid and carry it into progressively larger lymphatic vessels which carry the uid now called lymph into regional lymph nodes As lymph leaves the nodes it is carried through larger efferent lymphatic vessels which eventually drain into the circulatory system at the thoracic duct Or right lymph duct see Figure 213 Lymphatic vessel 7 to draining lymph node Lymph collection 5 Fluid leakage Fluid return to venules Fig 2l2 The Collection of Lymph in Peripheral Tissues O Arterial blood supply gt V A a o Venou vl lood supply 4 Fig 217 Schematic Representation of Lymphocyte Reciiculation 11 Cortex 1 and 2 Follicles Bcells Paracortex Tcells Medulla rich in plasma cells 20 Follicles germinal centers Stroma makes up superstructure l Capsule 2 Trabacula 3 Reticular cells and bers Lymphatics Lymph mainly contains Tcells Afferent Efferent afferent l subcapular sinuses Tcells can enter into body of LN cortical sinuses medullary sinuses i efferent lymphatic Blood Supply Artery and vein contact at PCV Tcells can enter LN by crossing through PCV Exit via efferent lymphatic T Cells cross between high endothelial in PCV Gastric surface Renal surface 3 Hilu m Splcnic artery Spienic vein Cb Capsule Trabecula Primary follicle Vascular sinusoid zone White pulp Periartcrial lymphatic sheath PALS Red pulp Germinal center Artery I FIGURE 219 Structure of the spleen a The spleen which is about 5 inches long in adults is the largest secondary lymphoid organ It is specialized for trapping blood borne antigens b Diagrammatic cross section of the spleen The pulp surr0unds the sinusoids The white pulp forms a sleeve the periarteriolar lymphoid sheath PALS around the arterioles this sheath contains numerous T cells Closely associated with the PALS is the marginal zone an area rich in B cells that contains lymphoid follicles that can develop into secondary splenic artery pierces the capsule and divides into follicles containing germinal centers progressively smaller arterioles ending in vascular sinusoids that drain back into the splenic vein The erythrocytefilled red rquot quotmm mm quotcu rm Anergole Lymphoid follicles B cells Marginal zone PALS T cells Capsule Trabeculae Venous sinuses B Model of Blood Circulation E erent lymphatic vessel Openended capillaries Splenlc 7 r anng Splenic r j veirr Ljpee n H r WV Cin 11 1 11m J The spleen capsule trabecular vein red pulp white pulp venous sinus trabecular artery 39 L B39cell corona 39 1 39 germinal center marginal Zone quot plenlollicular 39 vz periarteriolar lyrnph0Id sheath i l licentral arteriole 3 39 red pulp Fig 119 Organization of the lymphoid tissues of the spleen The schematic at top right shows that the spleen consists of red pulp pink areas in the top panel which is a site of red blood cell destruction interspersed with the lymphoid white pulp An enlargement of a small section of a human spleen center shows the arrangement of discrete areas of white pulp yellow and blue around central arterioles Most of the white pulp is shown in transverse section with two portions in longitudinal section The bottom two schematics show enlargements of a transverse section lower center and longitudinal section lower right of white pulp Surrounding the central arteriole is the periarteriolar lymphoid sheath PALS made up of T cells Lymphocytes and antigen loaded dendritic cells come together here The follicles consist mainly of B cells in secondary follicles a germinal center is surrounded by a Bcell corona The follicles are surrounded by a so called marginal zone of lymphocytes In each area of white pulp blood carrying both lymphocytes and antigen flows from a trabecular artery into a central arteriole From this arteriole smaller blood vessels fan out eventually terminating in a specialized zone in the human spleen called the perifollicular zone PFZ which surrounds each marginal zone Cells and antigen then pass into the white pulp through open blood filled spaces in the perifollicular zone The light micrograph at bottom left shows a transverse section of white pulp of human spleen immunostained for mature B cells Both follicle and PALS are surrounded by the perifollicular zone The follicular arteriole emerges in the PALS arrowhead at bottom traverses the follicle goes through the marginal zone and opens into the perifollicular zone upper arrowheads Co follicular B cell corona GC germinal center MZ marginal zone RP red pulp arrowheads central arteriole Photograph courtesy of NM Milicevic PROPERTIES OF ANTIGENS IMMUNOGENS BIOMI 494G Fall 2009 De nition ofterms 1 Antigenlmmunogen 2 Humoral antibody 3 Bcell receptor BCR and Tcell receptor TCR Types ofantigens 1 Particulate a Microorganisms eg bacteria viruses b Cells eg tumor cells RBC leukocytes 2 Soluble a Proteins b Polysaccharides c Nucleic acids d Lipids General properties required for immunogenicity 1 Foreignness 2 Size 3 Other considerations eg antigen concentration and physical form etc Antigenic determinant sites epitopes 1 De nition 2 Chemical groups involved 3 Types ofantigenic determinants a Linear sequential b Con rmation nonsequential 4 Bcell epitopes a Size b Characteristics 5 Tcell epitopes a Size b Characteristics Comparison ofantigen recognition by Bcells and Tcells Surface immunoglobulin Antibody Tcell receptor antigenbinding site antigenbinding sne variable regions r constant regions heavy chain 397 g transmembrane transmembrane 39 region region L 0i chain 3 chain Figure 116 Comparison of the basic structures of surface heavy chains of surface immunoglobulin and antibody are immunoglobulin antibody and the Tcell receptor The shown in blue the light chains in red N termini N termini C termini Antigenbinding sites Figure 22 The immunoglobulin G IgG molecule As shOWn in the top panel each lgG molecule is made up of two identical heavy chains green and two identical light chains yellow Carbohydrate Ivanable quot turquoise is attached to the heavy chains The lower panel shows region the location of the variable and constant regions in the lgG molecule The amino terminal regions red of the heavy and light chains are I hing variable in sequence from one lgG molecule to another the a Corgi reg39 remaining regions are constant in sequence blue The carbohydrate is omitted from this panel and from most subsequent figures for simplicity In lgG there is a flexible hinge region between the two arms and the stern of the Y m n 1 I 39 kl q V w I 1 2 Egan Llnearepltope 39 Dlscumil39luqus epltppe 39 annbody Figure 412 Linear and discontinuous epitopes A linear epitope of a protein antigen is formed from contiguous amino acids A discontinuous epitope is formed from amino acids from different parts of the polypeptide that are brought together when the chain folds protein antigen protein antigen Muttivalent antigen with different epitopes Muttivalent antigen with a repeated epitope Figure 410 Two kinds of multivalent antigen Many soluble protein antigens have several different epitopes but each is represented only once on the surface of the protein This situation is depicted in the left panel where four lgG molecules with different specificities all bind to the protein antigen using a single Fab arm On pathogen surfaces there are numerous copies of the same epitope as illustrated for poliovirus in Figure 48 This situation depicted in the right panel allows many IgG molecules with identical antigenic specificity to bind to the multivalent antigen with both Fab armsr COMPARISON OF ANTIGEN Ag RECOGNITION BY B CELLS AND T CELLS B cells antibody T cells TCR Binds soluble Ag Yes No Requires MHC No Yes Nature of Ag Protein polysaccharide Protein lipid nucleic acid Digested into peptides by l Usually intact cellular proteases macromolecules Epitope Accessible on surface often lnternal linear peptide conformational h ydrophilic hydrophobic mobile bound by MHC PRDF ERTlES OF ANTIGENS Some Take Home Messages There are two types of antigens Particulate and Soluble a Particulate antigens include microbes and certain other types of cells eg Tumor cells leukocytesetc I Soluble antigens include proteins polysaccharides nucleic acids and some lipids General properties required for immunogenicity include foreignness molecular size and complexity as well as other considerations such as antigen concentration physical form of the antigenetc There are two different types antigenic determinant sites epitopeslz Linear sequential and Conformational non sequential o B cells can recognize both types of epitopes while T cells only recognize linear epitopes Tcells recognize only protein antigens while B cells can recognize other types of macromolecules o Tiells recognize antigen peptides in the context of self MHC molecules BIOMl 494G Fall 2008 Introduction to Cellular Immunology Introduction and review 1 Differences between adaptive immunity and natural immunity 2 Discovery of Tcells and Bcells a Human Immunode ciency diseases eg Di George Syndrome lg immunode ciencies b Animal studies i Role ofthymus ii Role of bone marrow iii Role of bursa of Fabricius c Lymphocyte classes i Function Antigen presentation and Tcell antigen recognition Features of Tcell antigen recognition 2 The main functions of Tcell 3 MHCrestricted antigen recognition by Tcells a Tcytotoxic Tc cells recognized antigen in context of self class I b Thelper Th recognized antigen in context of self class II 4 Antigen processing and presentation by APC a Requirements for APC to initiate immune response b Distinct intracellular compartments in APC for antigen i cytosol ii vesticular 0 Processing and presentation of different types of antigens i extracellular ii cytosolic Professional APC 1 Types a Macrophage b Dendritic cell c Bcell 2 Capture and presentation of protein antigens in vivo a Routes of antigen entry 3 Other types of antigenpresenting cells a Vascular endothelial cells b Ephithelial cells eg thymus 0 Certain mesenchymal cells a scavenger receptor T cells C e TOHJWe Cdype legipn receptor lectln receptor iLRl receptor CLR CLR l l l l l l figure 41 lunate and adaptive immune recognition The innate immune recognition strategy is schematically represented here by the macrophage a which has a variety of receptors at at least three types that are expressed on all macrophages and recognize conserved distinctive features ol micro organisms The lymphocytes ofadaptive immunity schematically represented here as T cells D have only one type 0 receptor but with a vast array of variants each variant expressed on a different cell and that are not preadapted to recognize any specific feature of a microorganism Antigen recognition Effector functions 39 B lymphocyte Helper T lymphocyte ICYtOkIIYthT DC e new Natural killer NK cell Microbe Microbial antigen resented y antigen presenting cell Infected cell expressing microbial antigen Cytokines Antibody O 0 Target cell OOO Neutralization of microbe phagocytosis complement activation Activation of macrophages Inflammation Activation proliferation and differentiation of T and B lymphocytes 39 Killin infecte of cell Killin infecte of cell Figure 1 5 Classes of lymphocytes B lymphocytes recognize soluble antigens and develop into antibody secreting cells HelperT lym phocytes recognize antigens on the surfaces of antigen presenting cells and secrete cytokines which stimulate different mechanisms of immunity and in ammation Cytolytic T lymphocytes recognize antigens on infected cells and kill these cells Natural killer cells use receptors that are not fully iden tified to recognize and kill their targets such as infected cells Table 2 2 Lymphocyte Classes Class Functions Antigen Selected Percent receptor phenotype of total markers lymphocytes Lymph Blood 8 leen T lymphocytes node p CD4 Helper Stimuli for B cell grovlth and all heterodimers CD3 CD4 50 60 50 60 5060 T lymphocytes differentiation humoral immunity CD8 39 39 Macrophage activation by 39 39 secreted cytokines 39 cellmediated immunity cog ol quot0 Killing ofvirus lnfected cells all heterodimers 003 004 20 25 15 20 10 15 39 tumor cells rejection of allografts CDBJr I 39 cell mediated immunity B l hoc es Antibody production Surface antibody Fc receptors 1015 20 25 40 45 ymp y humoral immunity mmunoglobulin class If MHC 0019 0021 Natural killer cells Killing of virusinfected cells Killer cell lg like Fc receptor 10 Flare 10 tumor cells antibodydependent receptor for IgG cellular toxicity CD16 In most tissues the ratio of CD4 008 to 008 004 cells is about 21 l hocytes called r ulat cells not included function to inhibit immune responsa 39 and cytolyu39c Tegells05 ymlierpopuiations Oil lymphocy tm such as NKT cells and 15 T cells are also not listed Themajor classes of lymphocytes their functions and selected surface moleculs and numbers in different tissues are shown Some T and differ in phenotype and function from Figure 124 B cells recognize native proteins whereas T cells recognize degraded proteins bound by major histocompati bility complex MHC molecules The surface immunoglobulins of B cells and secreted antibodies bind to the native protein left panel To be recognized by a T cell receptor the protein must first be processed into peptide antigens by denaturation and proteolytic degradation two center panels Second the peptide antigens must be bound to MHC molecules Only then can the antigen be presented to the T cell right panel MHC dassll Figure 125 There are two types of MHC molecule MHC class I and MHC class II T cell contact residue of peptide Polymorphic residue of MHC molecule Anchor residue of peptide 39Pocket39 of MHC molecule Figure 3 1 A model at how a T cell receptor TCR recog nizes a complex of a peptide antigen displayed by a maior histocompatibittty MHC molecule MHC molecules are ex pressed on antigenpreseoting cells and lunction to display pep tides derived from protein antigens Peptides bind to the MHC molecules by anchor residues which attach the peptides to pock ets tn the MHC molewles The TCR 0t every T cell rangnizes some residues of the peptide and some polymorphic restduesot the MHC molecule Table 5 1 Features of T Cell Antigen Elliognilion Features of antigens recognized by T cells Explanation Most T cells recognize Only peptides bind to MHC molecules peptides and no other molecules T cells recognize linear and not Peptides bind to clelts of MHC molecules conformationa determinants in linear extended conformation and of peptide antigens extended peptides cannot torm conformational determinants T cells recognize cell associated MHC molecules are membrane proteins and not soluble antigens that display stably bound peptides on cell surlaces CD4 and CD8 T cells preferentially Pathways of assembly of MHC molecules recognize antigens sampled from the extra ensure that class II molecules prelerentiaily ceuar and Cytosonc eols respectively display peptides that are derived from extra cellular proteins and taken up into vesicles in APCs and class I molecules present peptides from cytosolic proteins CD4 and CD8 bind to nonpolymorphic regions of Lciass II and class 1 respectively LAbbrevialions APC antigenpresenting cell MHC major histgompatibility complex a Cytotoxicin CD8 cytotoxic T cell cell death MHC class I vimsinlected body cell it Help 04 helper T cell Figure 42 The main functions at T lymphocytes 3 Cytotoxic T cells recognize peptide antigens generated in the cytosoi not shown trom viruses as illustrated here or cytosolic bacteria and presented by MHC class I molecules on the surtace ol inlected cells this activates the cytotoxic T cell to kill the inlected cell limiting the replication ol the inlected agent it Helper T cells recognize peptide lragments generated from internalized microorganisms in phagocytes or internalized antigen in B cells and are thereby activated to secrete cytokines and activate these cells in turn to kill the microorganisms or to secrete antibodies respectively Infect strain A mouse with lymphocytic chonorneningitis virus LCMV Strain A Infect target cells with LCMV Cytotoxicity assay Coculture CTL and target cells and measure lysis of target cells I Strain B Self peptide CTL recognizes foreign peptide self MHC Failure to recognize self peptide selfMHC Failure to recognize foreign peptide allogeneic MHC Figure 51 MHC restriction of cytolytic T lymphocytes 011 Virusspeci c CTL mm a strain A mouse lyse only syngeneic strain A target cells infected wtm that vi ms The CTL do not lyse unin fected strain A targets which ex press self peptides but not viral peptides or infected strain 8 far gets which express different MHC alleles than does strain Al By using congenic mouse strains that differ only at class I MHC loci it has been proved that recognition of an tigen by 908 CTls is sen class I MHC restricted MHC maior histo compatfoil39rty complex gure 5 2 Antigenpresenting cell are required for T cell cuvatlon Puri ed CD4 T cells do not respond to a protein antigen by itself but do respond to the antigen in the pmsence of an antigen presenting cell APO The function of the AFC is to present a peptide derived from the antigen to the T cell APCs also express costimulators that are important for T cell activation these are not shown Antigen recognition quot60 I w r 4WJMHC39N ukch T Li and T cell response CD4 r Antigen gum mm preseniin Peptide epitope of cell APC antigen presented by APC secretory vesicle Figure 316 There are two major compartments within cells separated by membranes One compartment is the cytosol which is contiguous with the nucleus via the pores in the nuclear membrane The other compartment is the vesicular system which consists of the endoplasmic reticulum the Golgi apparatus endocytic vesicles lysosomes and other intracellular vesicles The vesicular system is effectively contiguous with the extracellular fluid Secretory vesicles bud off from the endoplasmic reticulum and by successive fusion and budding with the Golgi membranes move vesicular contents out of the cell in contrast endocytic vesicles take up extracellular material into the vesicular system Fig 42 Pathogens and their products can be lound In either the cytosolic or the vesicular comth of cells Left panel all viruses and some bacteria replicate in the cytosoiic camartment Their antigens are presented by MHC class i molecules to 008 T cells Center panel other bacteria and some parasites are engulfed into endosomes usually by phagocytic cells such as macrophages and are able to pmlilerate within the endocytic vesicles Their antigens are presented by MHC class II molecules to CD4 T cells Right panel proteins derived from extracellular pathogens Degmdedh may enter the vesicular system of cells by binding to surface molecules followed by endocylosis This is illustrated for pro Peptides bind to teins bound by surface immunoglobulin of B cells which thereby present antz Presented to gens to CD4 helper T cells stimulating the B cells to produce soluble antibody The endoplasmic reticulum and Golgi Effector apparatus have been omitted for simplidty Other types of cell may also internalize antigens in this way and be able to activate T cells xtracellular foreign protein antigen A Endocytosis ol39 Oval bumin Class II MHC Processed peptide bound to class It MHC 39 Class ltj 39 restricted CD4 helper T cellsf w Yes No Bf Translection Ovalbumin gene Endogenous synthesis at ioreign protein antigen Processed peptide bound to class l MHC No Yes of foreign protein antigen into cytoplasm 6 Arti cial introduction ovagbumin and release into Osmotic shock Antigen uptake cytosol Processed peptide bound to class I MHC Figure 5 6 Presentation of extracellular and cytosolic antigens No Yes When ovalbumin is added as an extracellular antigen to an antigen presenting cell APE that expresses both class I and class II MHC molecules ovalbuminderived peptides are presented only in association with class II molecules A When ovalbumin is synthesized intracellularly as a result of transiection of its gene Bl or when it is introduced into the cytoplasm through vesicles made leaky by osmotic shock C ovalbumimderived peptides are presented in association with class I MHC molecules The measured response of class Il restricted helper T cells is cytokine secretion and the measured response of class l restn cted cytolytic T lymphocytes CTle is killing of the APCs MHC maior histocompatibility complex lymphoidlissues H Macropinocytosis Ami Antigen and phagocytosis Phagocylosis I a 09 uptake by tissue dendritic cells we Viral infection H MHC Low on tissue dendritic cells Inducible by Cons lulive 33300 High on dendritic cells in bacteria and cylokines increases on activation ewe to to H J Constitutive by mature Costimulator Wgocy c Whom lnducrble delivery dendmic cells 39 to to Hi Am Peptides Partiwlate antigens Soluble antigens 9826 Viral antigens kitracellular and Toxins presen Allergens extracellular pathogens Viruses Location Figure 638 The properties of the professional antigen presenting cells Dendritic cells macrophages and B cells are the main cell types involved in the presentation of foreign antigens to naive T cells These cells vary in their means of antigen uptake MHC class II expression costimulator expression the type of antigen they39present effectively their locations in the body and their surface adhesion molecules not shown Gastrointestinal tract I n v quotQi393439l 7 gtl 3 at Q Epithelium z quot quotgt tquot quot39 139quot saoofsl p Dendr39rtic celi enters blood stream Ventite To ckcutation and spteen Spleen Blood home antigens are captured by antigen presenting celts In the Spleen Lymph node captures antigen from epithelium and connective tissue i 39 I Figure 5 5 Routes of antigen entry Miaobial 39 5 common en
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