T CELL TYPES

Maheshwari, t cell types, immunology

1. SRI PARAMAKALYANI COLLEGE Reaccredited with A+ grade by NAAC with CGPA 3.39 in 3 rd cycle affiliated to Manonmaniam Sundaranar University ALWARKURICHI-627412 Post graduate & Research Centre – Department of Microbiology (government aided) II Sem core : IMMUNOLOGY T CELLS AND ITS TYPES SUBMITTED TO: DR. S. VISHWANATHAN, HEAD OF MICROBIOLOGY DEPARTMENT . SUBMITTED BY: MAHESWARI.A REG NO: 20221232516113 I M.Sc Microbiology

2. T-cell & Types

3. T - cells A  T cell  is a type of  lymphocyte . T cells are one of the important  white blood cells  of the immune system and plays a central role in the  adaptive immune response . It matures in the thymus and that brings about cell mediated immunity. T lymphocytes are thymus dependent cells. They mature under the influence of thymic hormones. They are highly in the blood and spleen

4. During its maturation within the thymus, the T cell comes to express a unique antigen-binding molecule, called the T-cell receptor, on its membrane. T-cell receptors can recognize only antigen that is bound to cell-membrane proteins called major histocompatibility complex (MHC) molecules.

5. When a naive T cell encounters antigen combined with a MHC molecule on a cell, the T cell proliferates and differentiates into memory T cells and various effector T cells. There are two well-defined subpopulations of T cells: T helper (TH) and T cytotoxic (TC) cells. Although a third type of T cell, called a T suppressor (TS) cell, has been identified. T helper and T cytotoxic cells can be distinguished from one another by the presence of either CD4 or CD8 membrane glycoproteins on their surfaces. T cells displaying CD4 generally function as T H cells, whereas those displaying CD8 generally function as T C cells.

6. Functions of T cell Two main important functions of T cells are : Effector : Cytolysis of cells infected with microbes and tumor cells and lymphokine production. Regulatory : Either to increase or suppress other lymphocytes and accessory cells

7. Scanning electron micrograph of a human T cell Scanning electron micrograph of a  red blood cell  (left), a  platelet  ( center ), and a T lymphocyte (right); colorized

8. T cells-Maturation The migration of progenitor T-cells from the early sites of hematopoiesis to the thymus takes place at about day 11 of gestation in mice and in 8 th  or 9 th  week of gestation in humans. In thymus, the developing T cells are termed as  thymocytes. These thymocytes proliferates and differentiates along developmental pathways that produce functionally distinct sub-population of mature T-cells. T-cells development initiates with the arrival of small numbers of lymphoid precursors migrating from the blood into the thymus where they proliferate, differentiate and undergo selection process that result in the development of mature T cells. When T-cells precursor arrive at thymus, they don’t express the signature surface markers of T cell as the T-cell receptors, the CD 3  complex or the co-receptors CD 4  and CD 8 .

9. The thymocytes early in the development lack detectable CD 4  and CD 8 . As these cells are CD 4 -, CD 8 -, they are termed as double negative (DN) cells. The cells that enter the thymus DN1 cells are capable of giving rise to all the subsets of T cells and are phenotypically C-kit + , CD 44  high and CD 25 -. The DN1 cells move from the corticomedullary junction into the deeper cortex towards the subcapsular region. Once the DN 1  cells encounter the thymic environment, they begin to proliferate and express CD 25  becoming C-kit + , CD 44  high and CD 25 +. These cells are called DN 2  cells.

10. The DN2 thymocytes then experience a rearrangement of genes and the secretion of cytokines like IL-7. The cells further differentiate into the DN3. At the DN3 stage, the cells mature into DN4, which is further upregulated into CD4 and CD8 cells achieving a double positive status in the maturation process.

11. Thymic selection of T-cell: Positive selection occurs in the cortical region of the thymus. It involves the interaction of immature thymocytes with cortical epithelial cells. This interaction allows the immature thymocytes to receive a protective signal.  This signal prevents them from undergoing cell death.  Cells whose receptors are not able to bind MHC molecules would not encounter with the thymic epithelial cells and as a result it would not receive the protective signal resulting their death by apoptosis. Negative selection The cells that survive the positive selection move into the medulla and undergo negative selection, which eliminates thymocytes with a high affinity for self-antigens. The cells that interact too strongly with the self-antigens receive an apoptotic signal resulting in cell death. During the same process, however, some cells are selected to form Treg cells. The cells that successfully complete the selection process exit the thymus as mature naïve T cells.

12. T-cell activation: T-cells activation is initiated by interaction of the TCR-CD 3  complex with a processed antigenic peptide bound to either class-I (CD 8 + cell) or class II (CD 4 + cell) MHC molecules on the surface of an antigen presenting cells. The initial signal is provided by the binding of the T cell receptor to the cognate peptide present on the class II MHC. A similar peptide is present on the class II MHC which activates the CD8+ cells. The second signal is provided as a result of co-stimulation, where the surface receptors are induced by a relatively small number of stimuli which are products of pathogens or breakdown products of cells. After the two signals, T cells also receive stimulation in the form of cytokines. The cytokine signal determines the fate of T cells, especially in the case of helper T cells.

13. T-cell Differentiation The differentiation of T cells into different types of T cells usually occurs in the form of lineage commitment which is based on the affinity of the T-cell receptor towards self-antigen.

14. T Cell (T Lymphocyte) Types T cells can be grouped into categories depending primarily on their function. 1. Helper T cells (CD4+ T cells) 2. Cytotoxic T cells (CD8+) 3. Regulatory T cells 4.T delayed hypersensitivity cells 4.Memory T cells 5.Natural killer T cells c

15. 1. Helper T cells (CD4+) T helper cells are represented by T h . The T helper cells contain glycoprotein molecules called CD4 molecules on the surface. Hence T helper cells are called CD4₊ T cells.CD4₊ is an immunoglobulin. T helper cells recognizes the antigen-class II MHC complex of antigen present cells Helper T cells play a  central role in the functioning of the adaptive immune system and are required for almost all adaptive immune responses.

16. Helper T cells: release interleukin-2 which in turn triggers the release of other cytokines. Cytokines: any soluble factor secreted that act as a signal to other lymphoid cells. There are two categories:- 1.Lymphokines: secreted by lymphocytes 2.Monokines: secreted by macrophages Certain cytokines like interferon and interleukins are secreted by both lymphocytes and macrophages

17. Activation of T H Cells Helper T cells become activated by interacting with antigen-presenting cells, such as macrophages . Antigen-presenting cells ingest a microbe, partially  degrade  it, and export fragments of the microbe—i.e., antigens—to the cell surface, where they are presented in association with class II  MHC  molecules.  A receptor on the surface of the helper T cell then binds to the MHC-antigen complex H elper T cell activation proceeds through stimulation by a  cytokine

18. There are two different kinds of helper T cells. Th1 and Th2. Th1 functions to empower macrophages so that they can destroy intravesicular pathogens (bacteria). Th2 cells function to activate B cells. Normally it is insufficient for an antigen alone to stimulate the B cell to activation. The Th2 cell when activated will bind to the B cell (CD40L and CD40LR) and release cytokines Helper T cells

19. FUNCTIONS OF T H CELL It activates macrophages to induce phagocytosis. The cytokines of t cell produce allergy reactions . It brings about humoral immune response by activating B cells. It brings about cell mediated immunity by activating T cells.

20. 2.cytotoxic T cells Cytotoxic T cells are also known as ‘killer’ T cells , their role in the destruction of infected cells, pathogens, and tumor cells. They are represented by T c or T k. Also known as CD8₊ T cells. The cytotoxic T cells can directly attack a cell by killing microorganisms.  They do this by the transfer of cytotoxic granules to infected target cells, which kill the cell and any pathogens it contains .

21. cytotoxic granules containing proteins called  perforin  and  granzymes ,  which work together to destroy target cells .   When they encounter an infected cell, cytotoxic T cells bind to the MHC I via their TCR receptors and release their cytotoxic granules. Perforin creates holes in the cell membrane of the target cell, and granzymes enter the cell via these pores.  Once inside, the granzymes initiate  apoptosis  (programmed cell death) which kills the cell and any pathogens it contains.

22. 3. Regulatory T cells R egulatory T cells  (also called  T Regs ) are T cells which have a role in regulating or suppressing other cells in the immune system.  Also called suppressor T cell, T Reg . There are two subsets of T reg cells. They are: - t T Reg cells ( thymic T Reg cells) - p T Reg cells ( pheripheral T Reg cells ) Regulatory T ( T Reg ) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases.

23. 4.Delayed hypersensitivity T cells (T D ) Brings macrophages to areas where delayed hypersensitivity reaction occur. T D similar to T H cells. T D secrete primarily macrophage chemotoxin and macrophage migration inhibition factor. By secreting these lymphokines the T D cells are directly involved in the delayed hypersensitivity reaction. Macrophage chemotoxin attracts monocytes and macrophages whereas macrophage inhibition factor inhibits the migration of macrophages and monocytes, thereby infiltration of these cells occur into tissues where a delayed type hypersensitivity reaction is occurring.

24. 4. Memory T cells Antigen-specific, long-lived  memory T lymphocytes   form following an infection.  Memory T lymphocytes  are important because they can quickly proliferate into large numbers of effector T lymphocyte upon re-exposure to the antigen . They provide the immune system with memory against previously encountered antigens. Memory T lymphocytes may either be CD4+ or CD8+.

25. memory T cell s are highly capable of responding to antigens upon reintroduction–which helps the body build  immunological tolerance . Memory cells are unique because they remember pathogens and infectious cells faster than others allowing them to fight off bacteria and viruses quickly. Memory T cells are the reason vaccines can create immunities in the body.

26. 5.NATURAL KILLER T CELLS Natural killer T cells are a type of T cell that also have certain features of natural killer (NK) cells. They can kill invading microorganisms, such as bacteria and viruses, by releasing cytokines. They can also kill certain cells, such as cancer cells, either directly or indirectly by causing other immune cells to kill them. If natural killer T cells become inactive, this may contribute to the development and progression of certain diseases, such as cancer.

27. FUNCTIONS OF T CELLS T cells bring about cell mediated immune response . They kill bacteria and viruses hidden inside cells. They kill infected cells . They kill tumor cells . Activate other cells such as B cells and macrophages .

28. References Kuby immunology, 7 th edition https://www.onlinebiologynotes.com/t-lymphocyte-types-functions/#:~:text=T%2Dcells%20originate%20in%20bone,and%20recognize%20MHC%20bound%20antigen . https://www.onlinebiologynotes.com/t-cell-maturation-activation-and-differentiation/ https://microbenotes.com/t-cell-t-lymphocyte/

29. THANK YOU