TOPIC 6 REVISION SHEET.docx

Autoreactive t cells are removed again this process

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Autoreactive T cells are removed – again, this process is not perfect o How do T cells recognise their antigen? Intracellular antigen (peptides) recognised bound to MHC molecules - Proteins present in the cytosol, or in vesicles are catabolised to small peptides - These become complexed with carrier molecules (MHC molecules) and are transported to the cell surface - Any pathogen the cell is infected with or engulfs also provides peptides to be carried to the surface by MHC molecules. - T cell receptors (TCR) recognise pathogen peptides displayed on the cell surface in MHC molecules o Differences in antigen recognition for T cells and B cells - Whereas free antigens drain via the lymphatics to the lymph nodes and activate B cells
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- Antigen presenting cells which have internalised antigen in the tissues migrate via the lymphatics to the lymph nodes, display antigen peptides on the cell surface in MHC molecules and activate T cells o MHC Major Histocompatibility Complex - MHC genes are highly polymorphic, co-dominantly expressed - A particular allele can bind a restricted range of diverse peptides. - Individuals with different alleles bind a different but still diverse range of peptides - Protein antigens may be processed (degraded into peptides) either in endosomes or in the cytosol - MHC class I displays cytosolic peptides, Expressed on all nucleated cells - MHC class II displays endocytic peptides, Expressed on antigen presenting cells (dendritic cells, macrophages, B cells) o CD4 and CD8 T cells and their roles – interaction with peptide antigen o Antigen Presenting Cells: Characteristics - APCs are specialised to take up antigens, and display the peptides on their MHC molecules - APC’s become activated by binding PAMP’s - When activated, APC’s migrate to local lymph nodes to present the antigen to T cells Interaction with T cells (3 signals) - Signal 1: peptide MHC - TCR - Signal 2: CD80, CD86 - CD28 - Signal 3: various cytokines - cytokine receptors resulting in at least 5 differentiation pathways o Th1, Th2, Th17 – what are their roles/functions o T cell help for B cells (CD40L - CD40) - Antigen peptides are displayed on the B cell Class II MHC - the B cell can present the peptide antigen to T cells allowing T cells which have been previously activated to provide help for B cells o T cell help for macrophages (CD40L - CD40 and cytokines, eg IFN-g)
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Activated T cells induce MAC activation including increased killing of phagocytosed organisms, and release of a range of cytokines o CD8 T cell activation Activated, virus specific CD8 cells migrate to the infected site and can now kill virus infected target cells Cytotoxic T cells trigger death by creating holes in the target cell membrane (perforin), and inducing apoptosis (granzyme, Fas) HOST-MICROBE RELATIONSHIPS: HOW WE LIVE WITH MICRO-ORGANISMS \ - Pathogen1: induce CD8+T cells as the response - Pathogen 2: induce CD4+T cells as the response.
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