Cellular Immune Response I PDF 2024-2025 Lectures

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor exp...

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Ali Aljaziri Faisal Aloraifi 221-222-223 notes References Student explaintion Deleted Lecture Outline 1. Main phases of T lymphocytes responses. 2. Antigen recognition by T lymphocytes & Role of CD4, CD8 & Adhesion molecules. 3. Activation signals & Co-stimulation molecules for CD4+ T lymphocytes. 4. How are CD8+ T lymphocytes activated? 5. Functional responses & relevance of activated T lymphocytes. 6. Memory T lymphocytes features. End point of cellular immune response. 7. Migration of effector T lymphocytes to infection site. The doctor said, every objective is a question, and you should know the answer for them It’s very important to know this  Both naïve and effector T lymphocytes have CD3 along with CD4 or CD8. They differ in their functions. Naïve CD4+ becomes Th1, Th2 or Th17. Naïve CD8+ becomes cytotoxic T lymphocytes (CTLs). You should know the steps of CMI: 1. Antigen Recognition: Naïve T lymphocytes recognize antigens presented by APCs in peripheral lymphoid organs. 2. Activation: Cytokine secretion and signalling for clonal expansion and differentiation. 3. Clonal Expansion: Activated T cells proliferate (clonal expansion), producing antigen-specific effector and memory T cells. 4. Differentiation: Proliferated T cells specialize into effector T cells and memory T cells. 5. Effector Function: Effector T cells perform: CD4+ for activate macrophage, B cell via cytokines. CD8+ for killing infected cells, via releasing cytotoxic molecules. Final result would be the inflammation, that’s mean the immune system is working.  T cells recognize the antigen by so many things the most important of them: 1. On T cell surface: TCR CD3 & zeta protein CD4 or CD8 2. On APC surface: MHC I or II CD28 and ICOS are co-stimulatory receptors on T cell, CTLA-4 and PD-1 are inhibitory receptors on T cell. CD3 and zeta are signal transduction protein in T-cell (signal 1 ). We have 5 things to activate T cell: 1. Signal 1 (Receptor): from TCR with MHC. 2. (Co-Receptor): CD4 or CD8 stabilizes interaction with MHC. 3. Signal 2 (Co-Stimulators): CD28 bind to B7. 4. Integrins: LFA-1 with ICAM-1 to stabilize the interaction. 5. Signal 3 (Cytokines): APCs release cytokines IL-12 derive Th1 differentiation. IL-4 derive Th2 differentiation. IL-6 derive Th17 differentiation. Activated T cells secrete IL-2, which acts as an Don’t confuse with IL-7 and IL-2 autocrine signal to: IL-7: for pro-T lymphocyte in central lymphoid Promote proliferation (clonal expansion). organ (Thymus). Drive differentiation into effector cells. IL-2: for mature T cell in peripheral lymphoid organs(Lymph node). Doctor said it’s very important to know the role of CD4+ & CD8+ Normal (Activation): Activated APCs express: a. Signal 1: TCR recognizes antigen presented by MHC on APC. b. Signal 2: Co-stimulation through B7 binding to CD28. c. Signal 3: Cytokines secreted by APCs guide T cell differentiation depend on the infection & environment. Outcome: T cells become fully activated. Abnormal (Tolerance): Reciprocal, means exchange of signals between two interacting cells. If APCs are resting : a. Signal 1 is present (TCR-MHC interaction). b. Signal 2 is absent because resting APCs do not express co-stimulatory molecules like B7. Outcome: T cells become anergic (non-functional) or Importance of second signal is to prevent false alarm. undergo apoptosis. it ensures the T-cell responds only when there’s a genuine infection Naïve T cells express a low-affinity IL-2 receptor with beta and gamma chains. After activation by Signal 3 (IL-12), they upregulate the alpha chain, forming a high-affinity IL-2 receptor. Binding of IL-2 to this receptor drives T cell proliferation. Naïve CD4+ T cells differentiate into: Tfh (T Follicular Helper) : Remain in the lymph node (light zone of germinal center). Th1, Th2, Th17: Migrate to infection sites. CD4+ helper T cells activate phagocytes and B cells via CD40L and cytokines. Interaction of CD40L with CD40 enhances co-stimulation, helping B cells produce high-affinity antibodies. Effector T cells and antibodies circulate to infection sites for microbe elimination. Memory cells are a hallmark of successful immune response. After an infection is cleared, the immune system returns to homeostasis by eliminating excess T cells through apoptosis, maintaining only memory cells for rapid response to future infections.  The doctor said every slide is important and you should know it.  team Wishes you the best