"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 2: The Defence – Host DiseasesCellular Basis of Adaptive Responses(Mims’ Chapter 11)Lecture 8Friday 28 July 2017LT12 (X2.05), 10-11 am(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017The Cellular Basisof Adaptive ImmuneResponses SLE334 Medical Microbiology and Immunology, T2, 2017This lecture will cover……•? Lymphoid tissue•? Clonal expansion and memory cells•? Stimulation of lymphocytes•? Regulatory mechanisms•? Tolerance mechanismsSLE334 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=UL SLE334 Medical Microbiology and Immunology, T2, 2017Introduction•? Adaptive immune responses generated by lymphocytesderived from stem cells of primary lymphoid organs(bone marrow and thymus)•? They then colonise secondary lymphoid tissue mediatingimmune responses to Ags •? Lymph nodes concerned with responses to Ags carriedfrom other tissues•? Spleen concerned with Ags from the bloodstream•? Thoracic duct is the major lymphatic channel forrecirculating lymphocytes•? Lymphocytes of “mucosa-associated lymphoidtissue” (MALT) recirculate between mucosal tissuesusing specialised homing receptors SLE334 Medical Microbiology and Immunology, T2, 2017Organised lymphoid tissue•? Stem cells (S) arising inthe bone marrowdifferentiate intoimmunocompetent B andT cells in the primarylymphoid organs. •? These cells then colonizethe secondary lymphoidtissues where immuneresponses are organized.MALT, mucosa-associatedlymphoid tissue. SLE334 Medical Microbiology and Immunology, T2, 2017Lymphocytes and plasma cellsSmall B and T Large granularlymphocytes lymphocyte (1)Sma ? ll B and T lymphocytes have a round nucleus and a high nuclear:cytoplasmic ratio. (2) A large granular lymphocyte with a lower nuclear:cytoplasmic ratio, an indented nucleus and cytoplasmicgranules. (3)Antibody formed when B cells differentiate into plasma cells here stained with fluoresceinated anti-humanIgM (green) and rhodaminated anti-human IgG (red)SLE334 Medical Microbiology and Immunology, T2, 2017Structure of: - lymph node - cortex is essentially a B-cell regionwhere differentiation within thegerminal centers of secondary folliclesto antibody-forming plasma cells andmemory cells occurs.- spleen SLE334 Medical Microbiology and Immunology, T2, 2017Lymphocyte traffic•? The lymphocytes move throughthe circulation and enter thelymph nodes via the specializedendothelial cells of thepostcapillary venules (HEVs). •? They leave through the efferentlymphatic vessels and passthrough other nodes, finallyentering the thoracic duct whichempties into the circulation at theleft subclavian vein (in humans). •? Lymphocytes enter the white pulpareas of the spleen in themarginal zones; they pass into thesinusoids of the red pulp andleave via the splenic vein.SLE334 Medical Microbiology and Immunology, T2, 2017Mucosa-associated lymphoid tissue (MALT)•? Lymphoid cells whichare stimulated byantigen in Peyer'spatches (or the bronchior another mucosalsite) migrate via theregional lymph nodesand thoracic duct intothe bloodstream, andthen to the laminapropria (LP) of the gutor other mucosalsurfaces which mightbe close to or distantfrom the site ofpriming. •? respond to antigensfrom the environment•? produce IgA antibodiesfor mucosal secretions SLE334 Medical Microbiology and Immunology, T2, 2017B and T cell receptors•? B and T cells distinguished by their surfacemarkers•? Each lymphocyte expresses an Ag receptor ofunique specificity on its surfaceSLE334 Medical Microbiology and Immunology, T2, 2017B-cell receptor•? Each B lymphocyte rearrangesits germline genes coding for thereceptors so that there is onlyone specificity for each receptorpolypeptide chain. •? It then expresses that receptormolecule on its surface SLE334 Medical Microbiology and Immunology, T2, 2017B-cell receptorV =Variable region (50 genes) H D=diversity (25 genes)J=Joining (6 genes)C=Constant regionVariable region ofheavy or light chainsencoded in severalpieces or genesegments•? Random fusion of V, D and J segments•? Variable region light chain domains are thenformed by random V to J recombinationL SLE334 Medical Microbiology and Immunology, T2, 2017B-cell receptor•? Variable and constant region genes respectivelyrecombine to encode a single antibody moleculewhich is expressed on the mature B cell surfaceas an sIgM antigen receptor.SLE334 Medical Microbiology and Immunology, T2, 2017B-cell receptorSLE334 Medical Microbiology and Immunology, T2, 2017T-cell receptor (TCR) SLE334 Medical Microbiology and Immunology, T2, 2017Clonal expansionof lymphocytes•? Antigen selects and clonally expandslymphocytes bearing complementaryreceptors.•? When a microbe invades the body, thetotal number of lymphocytes initiallycommitted to recognizing the antigensthat go to make up a particularmicrobe is relatively small, and mustbe expanded to provide a sufficientnumber to protect the host. •? The B cells that bind the antigenbecome activated and proliferateclonally under the influence of solublegrowth factors termed cytokines toform a large population of cells derivedfrom the original.SLE334 Medical Microbiology and Immunology, T2, 2017The role of memory cells•? Vaccination depends upon secondary immuneresponses (bigger & brisker than primary responses) SLE334 Medical Microbiology and Immunology, T2, 2017Stimulation of lymphocytesSLE334 Medical Microbiology and Immunology, T2, 2017T lymphocytes activated by Agspresented on Ag presenting cells (APCs)•? Immature IDCs in thetissues take up antigenwhich is then processedand presented on thesurface as a peptidecomplexed with MHCclass II. •? The IDC migrates to theT-cell region of thedraining lymph node,where it stimulatesseveral T lymphocyteswith which it makescontact throughrecognition of the MHC- peptide complex by thespecific T-cell receptorand by accessoryinteraction of the B7 co- stimulator with surfaceCD28 •? Interdigitating dendritic cells (IDC) are form of APCs "