IMSE311 Week 4 PDF - T Cell Maturation

IMSE LEC: Week 04 - How T Cell Matures and what it produces T Cell Maturation ❖ Bone: Lymphocyte precursor ❖ Thymus: thymocytes ❖ 60-80% of T cells in the blood ❖ Maturation is 3 weeks ❖ Growth factors: (stromal cells) Epithelial cells Macrophages Fibro...

IMSE LEC: Week 04 - How T Cell Matures and what it produces T Cell Maturation ❖ Bone: Lymphocyte precursor ❖ Thymus: thymocytes ❖ 60-80% of T cells in the blood ❖ Maturation is 3 weeks ❖ Growth factors: (stromal cells) Epithelial cells Macrophages Fibroblasts Dendritic cells IL7 ❖ 97% dies Double-Negative Stage ❖ DN thymocytes ❖ Lack CD4 and CD8 antigens ❖ Markers: CD2, CD5, CD7, CD45R ❖ Rearrangement of the genes that code for the antigen receptor - T-cell receptor (TCR) begins at this stage Antigen diversity TCR = 2 + 6 other chains  Markers: both Cd4 and CD8 antigens on their surface as well as CD3-ab (TCR) Main function: rearrange the genes for alpha chain Positive Selection: ○ Only with functional TCR receptor ○ Must recognize foreign antigen and MHC molecule MHC Restriction ○ Apoptosis: low or high affinity Negative Selection: ○ corticomedullary region and medulla ○ Takes place among the surviving DP T cells ○ Strong reactions with self- peptides other than MHC antigens triggers apoptosis ○ clonal deletion Mature T cell Represents those population of thymocytes that had survived positive and negative selection Express only 1 of either CD4 or CD8 on their surface 12 days in medulla released from the thymus to seed peripheral lymphoid organs and recirculate through the bloodstream and peripheral organs approximately once every 12 to 24 hours. IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6 Mature T Cell ❖ 2/3 is CD4+ : ❖ Th1: produces interferon gamma (IFN-γ), interleukin2 (IL-2), and tumor necrosis factor-β (TNF-β) activates cytotoxic lymphocytes and macrophages ❖ Th2: produces IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 Help B cells produce antibodies against extracellular pathogens Regulate B-cell activity ❖ Treg Markers: CD4 and CD25;5% of CD4+ cells Suppresses immune response to self-antigens Activated T Cell ❖ When antigen recognition occurs in the secondary lymphoid tissue, T lymphocytes are activated and differentiate into functionally active small lymphocytes that produce cytokines ❖ Express receptors for IL-2 ❖ Takes 1-2 days ❖ Cytokines functions include: Assist B cells Killing of tumor and target cells Rejection of graft Stimulation of hematopoiesis Initiation of hypersensitivity 1.Interleukins 2.Tumor Necrosis Factor (TNF) 3.Chemokine 4.Transforming growth factor (TGF) 5. Interferon (IFN) 6.Colony stimulating factor (CSF) T Memory Cells ❖ Larger than T and B cells ❖ Contains a kidney shaped nucleus with condensed chromatin and prominent nucleoli. ❖ Has high cytoplasmic: nuclear ratio ❖ Cytoplasm has many azurophilic granules ❖ No specific surface markers ❖ Possess CD16, CD56, CD94 ❖ Lack CD3, CD4, and CD8 ❖ Play a complementary role to CD8+ T cells IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6 ANTIGEN ❖ A foreign substance ❖ A substance that reacts with antibody to sensitized cells but may or may not provoke an immune response ❖ substances that react with antibodies ❖ Foreign substances can be immunogenic or antigenic. ❖ Epitope IMMUNOGEN ❖ A macromolecule capable of eliciting the formation of immunoglobulins or sensitized cells in an immunocompetent host ❖ a foreign substance that induces a specific immune response. Factors Influencing Immune Response 1.Age 4.Health status of the host 2.Dose 5. Genetics 3.Route of inoculation An Immunogen 1. Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. 2. Size 10K daltons 100k daltons the larger the molecule the more immunogenic it is likely to be. 3. Chemical composition In general, the more complex the substance chemically the more immunogenic it will be. Proteins > Carbohydrates > lipids 4. the ability to be processed and presented with MHC molecules TYPES OF ANTIGEN Alloantigens → other members of the host’s species Autoantigens → antigens that belong to the host Heteroantigens → from other species Heterophile Antigen → antigens that are found in different species but are structurally similar enough to be recognized by the same antibody IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6  → antigens are typically not species-specific; heterophile antigen from one organism may cross-react with an antigen from a different organism ❖ Example: basis for the Paul-Bunnell or Monospot test: used to diagnose infectious mononucleosis. the body’s immune system produces heterophile antibodies, Epstein-Barr virus (EBV), RBC of sheep or horse HAPTENS ❖ They cannot do agglutination or precipitation Adjuvants ❖ Only vaccine adjuvants currently licensed by the FDA are Aluminum Salts ❖ Helps Antigen Presenting Cells ❖ Protects Immunogen from degradation ❖ Increases size of immunogen/antigen MHC Molecule Main function: Bring antigen to the surface of cells for recognition of t cells T-cell activation will only occur when combined with mhc molecule major histocompatibility complex (MHC) is a genetic region, whose products play a role in intracellular recognition and in discrimination between self and non self. Encoded by genes called MHC found on surfaces of cells in the body Determine whether transplanted tissue is histocompatible or recognized as foreign Glycoprotein component of cell membrane In humans, it is referred to as Human Leukocyte Antigen (HLA) Has three (3) major classes IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6  Present on all nucleated cells Highest on lymphocyte, low or undetected on liver hepatocytes, neural cells, muscle cells and sperm Binds to endogenous antigen Presents to CD8+ cells Locus: A,B,C Chain structure: -chain and β2 microglobulin Found primarily on antigen-presenting cells Lymphocytes, monocytes, macrophages and dendritic cells, neutrophils Binds to antigen found on the surface of the cell Presents to CD4+ cells Locus: DP, DQ, DR Chain structure: -chain and β chain IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6 IMSE311-Lec: Mr. Hanzel Tolentino Razon, Christ Audrey Jhoy R. BSMLS 3-Y1-6