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This video is about T-Lymphocyte development and function Content: 0:00 Introduction 0:06 T-Cell Development 3:43 How CD4+ (T Helper Cells) is Activated 6:48 How CD8+ (T Cytotoxic Cells) is Activated 10:01 Th17 (Activation/Function) 14:46 T-Cell Tolerance (T-Regulatory Cells) 17:11 Time Needed for Immunological Memory ------------------------------- 🫀 Join: / @taimtalksmed 📷 Follow my IG: / taimtalksmed 💝 Donation link: https://www.buymeacoffee.com/taimtalk... ------------------------------- —————————————————————- All information in my immunology videos are from: Book: Immunology, Eighth Edition by David Male, Jonathan Brostoff, David Roth and Ivan Roitt Additional research in PubMed University lecture materials —————————————————————— Development of T-lymphocytes: 1. In red bone marrow as Multipotent lymphoid stem cell 2. Goes to the Thymus to develop further there Thymus: Grow to max around puberty, and then gradually become replaced by fat tissue Stages of t-cell development in thymus: 1. Double negative stage: Check if the cell lack CD4/CD8 2. Double positive stage: check if they express cd4/cd8 3. Positive Selection: Check if recognize self MHC 4. Negative Selection: Check if recognize self antigen 5. Single positive selection: Become either CD4+ or CD8+ T-lymphocyte 6. Then goes to the secondary lymphoid organs They undergo apoptosis if fail in one of the stages CD4+ activation - T helper Cells 3 activation signal needed to activate naive T cells 1st activation signal: MHC - TCR (Receptor + CD4 + CD3) 2nd activation signal: B7 - CD28 3rd activation signal: Interleukin 4 (IL4) give Th2, Interleukin 12 (IL12) give Th1 - Then it secretes IL2 (Autocrine) to help itself grow Th2 cell release: IL10 - supresses Th1 response IL4 IL5 IL6 - Stimulate B-cell for IgG/IgE/IgA synthesis Th1 cell (inflammatory t helper cell) release: Interferon gamma (IFN-g) - Activate amcrophages, IgG synthesis and decreases Th2 response IL2 - Help growth of B- and T-cells CD8+ activation - Cytotoxic T-cell: When Virus infects a normal cell: become Non-professional APC and usually gets phagocytosed by APC - MHCII/I When virus infects an APC - present on MHC II/I 1. T-Cytototoxic cell binds to MHC I through TCR (3 activation signals needed) 2. Th0 binds to MHCII and becomes Th1 which help Tcyt further differentiate by releasing IFNg and IL-2 Activated T-cyt undergoes clonal expansion and expresses Fas-L to kill infected cells who express Fas by releasing Perforin (make hole on surface) and Granzyme B (fragments DNA) Activated Th1: Activated macrophage by CD40L/CD40 and IFN-g which will phagocyte the remaining parts of the virus/cell Th17: Good against infections by Fungi Severe fungal infection is on immunesurpressed people. How to get Th17: Macrophage phagocytes fungi presents 3 activation signals on naive T helper cell (Th0) Macrophage release IL1, IL6, IL23 and Transforming growth factor beta (TGF-a) which makes Th0 into Th17 Activated Th17 release: IL17 - recruite neutrophiles. Neutrophils will promote inflammation by releasing granuoles, lysozymes and reactive oxygen species IL22 and IL17 will stimulate epitheliual cells to produce antimicrobial proteins into releasing defensins Activates Th1 (by IL12): Activate macrophages by CD40L/CD40 and IFNg and release pro inflammatory cytokines (IL1, IL6 and TNF-a) T cell tolerance: Eliminating cells that react to self antigens Central Tolerance in Thymus: Kill self reactive T cells Peripheral Tolerance (Extrathymus): Escaped T cells go to secondary lymphoid organs. Inhibited by direct inactivation (clonal deletion) and T-regulatory cell T-reg release: IL35: supresses immune funtion IL10: decreases function of Th1 TGF-b inhibits macrophages They decrease function of dendritic cells They can sense amount if IL2 and regulate function based on that. How many days does it take to gain immunological memory? Start as naive Clonal expansion until around 7 days Give Effector Response Decreases until it becomes memory cells. Memory cells decrease slowly at 14 days.