Department of Pathology College of Medicine KSU Lecture 36 Foundation block Teaching objectives To describe antigen recognition by T cells To describe the pathways involved in processing endogenous and exogenous ID: 1037167
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1. Cell Mediated ImmunityImmunology UnitDepartment of PathologyCollege of MedicineKSULecture # 3/6Foundation block
2. Teaching objectivesTo describe antigen recognition by T cells To describe the pathways involved in processing endogenous and exogenous antigensTo discuss self MHC restriction in Ag presentation to T cellsTo describe the induction of cell meditated immunity (Chronic Inflammation)
3. Other cells
4. Cell Mediated Immunity(CMI)T cells (lymphocytes) via their receptors bind to the surface of other cells (Antigen Presenting Cells) that display the processed antigen and trigger a response Mononuclear cell inflammatory process usually associated with chronic inflammations
5. Monocytes : Peripheral bloodMacrophages : TissuesDendritic cells : Lymphoid tissues Langerhans cells : EpidermisB-cells : Lymphoid tissue, Blood Antigen Presenting cells
6. MacrophageLymphocyteLymphocyte
7. Cell-Mediated Immunity (CMI) Antigen+MHC(Major HistocompatibilityComplex)T-lymphocytes Immune responses
8. Major Histocompatibility Complex (MHC)Major histocompatibility complex (MHC) proteins were discovered for the first time when tissue transplantation startedThe success of tissue and organ transplantation depends upon the match of donor’s and recipient’s “human leukocyte antigens” (HLA) encoded by HLA genesGenes for HLA proteins are clustered in the MHC complex located on the short arm of chromosome 6
9. MHCThree genes code for Class I MHC moleculesHLA-A, HLA-BHLA-C HLA-D loci encode for Class II MHC molecules ie,DP DQ DREeach group of MHC consists of several glycoproteins
10. MHCEach individual has two “haplotypes” ie, two sets of these genes one paternal and one maternalMHC Class I molecules are found on the surface of virtually all nucleated cellsMHC Class II molecules are normally present of the surface of antigen presenting cells such as: Marophages, Dendritic cells Langerhans cells of skinB cells
11. Biologic Importance of MHCAntigen recognitionT cytotoxic (CD8) cells kill virus infected cells in association with class I MHC proteinsT helper (CD4) cells recognize antigen in association with class II MHC proteinsThis is called MHC restrictionTransplantationSuccess of organ transplant is determined by compatibility of the MHC genes
12. Endogenous antigen (Cytoplasm)2. Exogenous antigen (Membrane Bound)
13. Target cellVirus
14. Target cell
15. Target cell
16. TranscriptionTranslationHost cellViral proteinTarget cell
17. Exogenous antigenMicrobesProteinsCell-mediated immunity
18. Exogenous antigenCD4+ T-lymphocytes(CD4+ cells) CMI(Cell Mediated Immunity)APCAntigen presenting cellsMonocytes/MacrophagesDendritic cellsLangerhans cellsB-cellsAPCClass II MHC
19. Antigen Presenting CellsDendritic cells and macrophages digest invading microbe and then present the antigen of the microbe to lymphocytes in lymphoid organs.
20. Antigen Presenting CellAntigen processingexogenousendogenousAntigen
21. Two signals are required of activation of T cellsTwo signals are required to activate T cellsFirst signal Class II MHC + antigen – TCR IL-1, LFA-1 with ICAMSecond signal (Costimulatory signal) B7 on APC interacts with CD28 on lymphocyte
22. CD28LFA-1CD2CD4CD3HLA-DRAgTcRVbVaICAM-1LFA-3CD80/86(B7) auxillarymoleculesTrimolecular complex
23. T lymphocytes ("T cells"): CMISubsets include:CD4+ helper T cells enhance CMI and production of antibodies by B cellsCD8+ cytotoxic T lymphocytes (CTLs) that kill virus-infected and tumor cells
24. Out come of T helper cell activationProduction of IL-2 and its receptorIL-2 is also know as T cell growth factorProliferation of antigen specific T cellsEffector and regulatory cells are produced along with “memory” cellsIL-2 also stimulates CD8 cytotoxic cellsProduction of InterferonsEnhances anti-microbial activity of macrophages
25. Granuloma Formation(Chronic Inflammation, e.g., TB)
26. Out come of T helper cell activationMemory T cellsRespond rapidly for many years after initial exposure to antigenA large number of memory cells are produced so that the secondary response is greater than the primary Memory cells live for many years and have the capacity to multiplyThey are activated by smaller amount of antigenThey produce greater amounts of interleukins
27.
28. Examples of Cell Mediated ImmunityDelayed type of hypersensitivity (DTH) reaction: the tuberculin testMediated by CD4+ T cells and takes about 72 hours to develop2. Contact hpersensitivityMany people develop rashes on their skin following contact with certain chemicals such as nickel, certain dyes, and poison ivy plant The response takes some 24 hours to occur and like DTH, is triggered by CD4+ T cells
29. Necklace RashContact Dermatitis
30. Take Home MessageCell mediated adaptive immune response is specific and develops after exposure to a pathogen (antigen) Initial antigen exposure results in generation of memory cells for a stronger and a quicker response against future exposures to the same pathogenIt is usually associated with chronic infectionsAntibodies are not involved