Activation of T and B Cells
- 1. RANI DURGAVATI VISHWAVIDHYALAYA JABALPUR PRSENTATION ON ‘ACTIVATIONOF T ANDB CELLS’ PRSENTEDBY: AMBIKAPRAJAPATI M. SC. BIOTECHNOLOGY II SEMESTER
- 2. T CELLS T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells found in the bone marrow. Then, developing T cells migrate to the thymus gland to mature. One of its functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or CD4.) 1. CD8+ T cells, : also known as "killer T cells", are cytotoxic – this means that they are able to directly kill virus-infected cells, as well as cancer cells. 2. CD4+ T cells, : function as "helper cells". helper T cells function by indirectly killing cells identified as foreign: they determine if and how other parts of the immune system respond to a specific, perceived threat. 3. Treg cells, : also known as regulatory T cells (also called Tregs) are T cells which have a role in regulating or suppressing other cells in the immune system. Tregs control the immune response to self and foreign particles (antigens) and help prevent autoimmune disease. (peripheral t-cell)
- 3. T CELL DEVELOPMENT AND MATURATION • Progenitor T cells migrate to thymus (at about 8th or 9th week of gestation in humans). In thymus, thymocytes proliferate and differentiate. When they do arrive in thymus, T-cell precursors don’t express signature surface markers (CD3, CD4, and CD8) . • Selection process in thymus - • Positive selection - Survival of only T cells whose TCRs recognize self-MHC molecules . • Negative selection - Eliminates T cells that react too strongly with self MHC or MHC with self- peptides.
- 4. T CELLACTIVATION AND DIFFERENTIATION 1. TCR of T cell interact with antigen by MHC II expressed by APC, which initiates the activation cascade. Antigen is attached to the MHC II and TCR recognizes that antigen. 2. Costimulatory reactions occur : B7 molecules of APC interact with CD 28 of T cell. CD40 of APC interact with CD40L of T cell. CD4 of T cell place them in perfect engagement site. 3. Chemical signaling : APC Starts releasing IL-12, and there are some IL-12 receptors present on surface of T cell which recognizes IL-12 and send some activation signals inside the T cell, which allows T cell to produce IL-2 and then T cell start building the IL-2 receptors on the surface. IL-2 secreted by T cell is acting on itself and leads to activation of T cell. T cell will also secrete IL-1 and IFN- Y and IFN –Y will act on APC in turn to confirm its activation. 4. After the interaction of MHC II and TCR, assembly of signaling complex occurs.
- 5. 5. Lck Mediated Phosphorylation of ITAMs on the zeta chains of TCR complex, creates docking sites to which protein kinase ZAP70 attaches and become activated by phosphorylation. 6. ZAP-70 phosphorylates and enables the generation of many signals like SLP-76, GADS, LAT, ItK. phosphorylation of these leads to activation of G- protein mediated pathways, which further leads to changes in gene expression (functional changes, differentiation, activation). 7. Naïve cell recognized MHC-antigen complex initiate primary response. After 48 hours, enlarges into blast cell and undergoes repeated rounds of cell division and differentiate into: 1. Effector cells – cytokine secretion, B-cell help. 2. Memory cells – long lived, respond with heightened activity (secondary response).
- 6. B CELLS B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius. B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines. B cells express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response. B-cell carry many surface marker like CD19, CD21, CD22, Membranous immunoglobulin Igα and Igβ heterodimer.
- 7. STAGES OF B CELL DEVELOPMENT Stem cell → Progenitor B cell (Pro B cell) → Precursor B cell (Pre B cell) → Immature B cell → Mature B cell and each stage is characterized by distinct cell surface markers and a specific pattern of Ig gene expression. And the production of mature B-cell in bone marrow is an antigen independent phase while activation and effector cell production is an antigen dependent phase. In Negative selection of B-cells, only 10 percent of total newly cells produced cells are recruited into circulation everyday. Rest of 90 percent of newly produced B-cells die. Such cells are eliminated by programmed apoptosis. This process is called negative selection.
- 8. B-CELLACTIVATION AND DIFFERENTIATION It Occurs in the peripheral lymphoid organ. 1. Ag cross-links with membrane Ig on B cell, generating signal-1. Due to this there is increased expression of Class II MHC and co-stimulatory molecule B7. 2. T cell recognizes Ag and Class II MHC on B cell membrane and this co-stimulatory signal activates T cell. 3. T cell begins to express CD40L. Interaction of CD40 and CD40L provides signal-2. 4. B7 and Cd28 interactions provide co-stimulation to T cell, which produces cytokines. 5. B cell begins to express receptors for various cytokines produced by T cell. 6. This leads B cell to the division phase and many effector cells are produced.