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8.5: Blurry Vision, 26 year old female, Born and raised in Sweden…

- - - - Naive T cells recognising self Ags home to lymph nodes by expressing L-selectin and CCR7
        
        Naive T cells recognising self Ags re-enter the circulation by expressing S1PR and binding to high levels of S1P in the blood
        
        Naive T cells recognising self Ags are exposed to their cognate self Ag
        
        Signal 1: specific TCR binds to MHCII and Ag on APCs
        
        Activated T cells change their phenotype and proliferate
        
        Increased LFA-1, VLA-4 and CHO ligands for E- and P-selectin allow entry to peripheral sites
        
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        Decreased L-selectin and CCR7 stops T cell homing to secondary lymphoid tissues
        
        Increased S1PR1 allows exit from secondary lymphoid tissues
        
        Increased CCR6 and CXCR3 allow homing to peripheral sites
        
        Dimethyl fumarate: Activation of Nrf2
        
        Teriflunomide: inhibits dihydro-orotate dehydrogenase --> inhibit pyrimidine synthesis --> inhibit DNA replication
        
        Glatiramer acetate: suppress inflammatory response by shifting population from TH1 --> TH2
        
        Signal 2: CD28 binds to B7.1/7.2 on APCs
        
        Signal 3: cytokines from APCs direct differentiation into different subsets of effector cells
        
        Naive T cells recognising self Ags migrate through and recirculate between secondary lymphoid organs, searching for their cognate Ag
        
        S1P lypase in lymph nodes degrading S1P
        
        S1P chemical gradient between lymph nodes and circulation
      - B cells recognising self Ags become activated
        
        Present self-Ag and activate T-cells as APC
        
        Release of pro-inflammatory cytokines
        
        Release and production of proteolytic enzymes, damaging BBB
        
        Compromised BBB allows entry of immune cells and immunoglobulins into the otherwise immune-privileged CNS
        
        CSF: CSF restricted oligoclonal bands
        
        CSF: High WBCs, lymphocytes (94%)
        
        Ocrelizumab: Humanised anti-CD20 monoclonal antibody leads to B cell death
        
        Alemtuzumab: anti-CD52 monoclonal antibody leads to B & T-cell death
        
        Cladribine: Cytotoxic to dividing and non-dividing lymphocytes
        
        B cells differentiate into plasma cells
        
        Plasma cells produce immunoglobulins