Cell mediatedadaptive immunity.docx

12 Pages
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Department
Microbiology and Immunology
Course Code
Microbiology and Immunology 2500A/B
Professor
John Mc Cormick

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Cell-Mediated Adaptive Immunity Microbiology and Immunology Lecture Notes Cell Mediated Immunity - Mediated by αβ T cells - 2 types of αβ T cells: o 1) Cytotoxic T cells (CTL) = CD8+ T cells o 2) Helper T cells (Th) = CD4+ T cells  CD4 is expressed on the surface Different Cell Development - B Cells: o Develop in bone marrow o B cell is a lymphocyte cells just like T cells o B cells express immunoglobulin molecules o B cells express IgM - T Cells: o Develop in the bone marrow and thymus o Start with the same stem cells in the bone marrow this is primary lymphoid tissue o In newborns and young children the thymus is very large because lots of T cells are being produced o Both helper T cells and cytotoxic T cells express T cell receptors o Many identical copies of lg molecules on a B cell and TCRs on a T cell Structure of Ig/AB and TCR - Different chains - Lg molecules/antibodies have heavy and light chains - T cell receptor has α and β chains - Both have a variable region and a constant region - Variable region binds to antigen (epitope) - Variable region = the end segment - T cell receptor remains bound—it is not secreted as a soluble molecule - Variable region has the same function—bind to epitope - B cells: o Ig/Ab have 5 different constant regions =isotypes o B cells have 5 different constant regions - Αβ T cells o Have the same constant region Similar Generation of Ig and TCR - Diversity arises from random gene rearrangement - Ig molecule: o Different heavy and light chain genes associate o Variable region is unique to each B cell - T cell receptor o Different α- and β- chain genes associate o Variable region is unique to each T cell - Both have ~ 10^11-10^16 possible gene combinations - Each T cell is going to have own unique T cell receptor- this is essential for adaptive immunity Similar Clonal Expansion - When the variable region makes epitope and binds antigen you get clonal expansion - Naïve B cells and naïve T cells whose variable region binds an antigen will multiply by clonal expansion - Similar Generation of Memory Cells - B cells: o - T cells: o o T cells also have memory - How B and T cells bind antigens is different o B cells:  Variable region of Ig/antibody binds antigen directly o T cells:  Variable region of T cell receptor cannot bind antigen directly  Antigen must be “presented” to T cell by “other cells” How Do “other cells” Present Antigen? - On Major Histocompatibility Complex (MHC) Molecules - Form MHC: antigen complex - Variable region of T cell receptor binds MHC: antigen complex - Structurally both the variable region of T cell receptor and the MHC molecule must be able to bind together and fit o Based on structural fit - Variable region of TCR binds to epitope on an antigen Variable region of TCR - There are 2 classes of MHC molecules o Class I anti o Class II - MHC molecules bind to antigens inside the cells - MHC Class I molecules o Generally bind antigens from intracellular pathogens (= endogenous antigens) o MHC class I molecule binds antigens from intra cellular pathogens- from intracellular viruses and bacteria o Winside the cellens will be exposed is when this intracellular pathogens replicated o All nucleated cell express MHC class I molecules endogenous MHC I:antigen pathogen infects cell antigen binds complex is MHC class I transported to molecule cell surface - MHC Class II Molecules o Generally bind antigens from extracellular pathogens (=exogenous antigens) o Cells that present antigen on MHC class II molecules are called antigen presenting cells (APC) o APC express both MHC class I and MHC class II molecules o Phagocytosis leads to production of exogenous antigen Types of Antigen-Presenting Cells (**Make sure to know the type of APC**) - Mature dendritic cells - Macrophage - B cell - Mature dendritic cells and macrophages link innate and adaptive immune systems - Neutrophils are not an antigen presenting cell- they have a very short life span o This is important because there is SO many of them o They don’t live long enough to be an APC - B Cell o B cells internalize pathogen by endocytosis o Endosome fuse with lysosome o Exogenous antigens presented on MHC class II molecule o Bind an extracellular pathogen o B cells then internalize the extracellular pathogen  endocytosis o Once internalized it is the same process that happens in exocytosis o These are exogenous antigens - Adaptive immunity is initiated in secondary lymphoid tissue o Provides a meeting placewhere circulating naïve B cells and naïve T cells meet and respond to pathogens o Mature dendritic cells are only APC that can activate naïve T cells o DC initiate cell-mediated immunity o This is where the naïve T cell will meet and respond to pathogens o Mature dendritic cells are the only APC that can activate Naïve T cells o Mature dendritic cells is the only APC that can activate naïve T cells** Immature DC resident in Secondary Lymphoid tissue - Uptake pathogens arriving via: o Blood (spleen) o Lymph (LN) o Mucosa (MALT) o Present antigens to circulating naïve T cells - Reside in the blood and in tissues Immature DC Resident in Peripheral Tissue - Some immature DC that internalize an extra/intracellular pathogen migrate via Lymphatic’s to Lymph node - During migration DC matures and becomes APC - Arrives in T cell area of lymph node to present antigen via MHC to naïve T cells - Immature DC that is present in peripheral tissue- as soon as a bacteria or virus gets into the tissue the immature DC cell is right there to take up that path - Some dendritic cells actually leave the tissue and enter lymphatic’s and enter into the lymphnode o Dendritic cells take it up as a phagocyte and when it arrives in the lymphnode it shows up as an antigen presenting cell - DC leave peripheral tissue via lymphatic’s and present pathogenic antigens to naïve T cells in lymph node Primary Response- first exposure to antigen - Occurs in secondary lymphoid tissue - DC (resident DC or migrant peripheral DC) present antigen via MHC molecules to circulating naïve T cells that enter secondary lymphoid tissue - MHC: Antigen: TCR binding initiates cell mediated immunity - DC ARE CRITICAL IN PRIMARY RESPONSE - Primary response = first exposure to antigen o This is when the naïve T cell meets and responds to the antigens - DC is either resident DC or migrant peripheral tissue DC - If you get binding interaction happening you will get an activat
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