T LYMPHOCYTES
Dr.Mohammed Sharique Ahmed QuadriAssistant professor Physiology
Al Maarefa College
T (thymic) Lymphocytes
• Lymphocytes migrate from bone marrow to the thymus for preprocessing to form “T” lymphocytes
• Preprocessing in the thymus :– Cells divide rapidly - each thymic lymphocyte developing
specific reactivity for one antigen
– End result: thousands of T lymphocytes each with different specific reactivities for different antigens
– Insuring that each T lymphocyte will not react with the body’s own antigens (self antigen)
• Then the preprocessed cells leave thymus to lymphoid tissues
• Most preprocessing of T lymphocytes occurs prior to and completely after birth
T Lymphocytes
• Carry out cell-mediated immunity
• Clonal and antigen specific – acquire receptors in the thymus
• T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens
• Learn to recognize foreign antigens only in combination with a person’s own tissue antigens
• A few days are required before T cells are activated to launch a cell-mediated attack
The T cell System
• Exposure to specific antigen causes marked reproduction in specific T lymphocytes
• Memory T cells are created (T-lymphocyte memory cells)
• Mature T-cells have T cell receptors which have a very similar structure to antibodies and are specific to one antigen.
• T cells respond to antigens only when they are bound to MHC proteins on the surface of antigen-presenting cells (macrophages, B lymphocytes, dendritic cells)
T Lymphocytes
• 2 main types of T cells – CD8 cells (cytotoxic, or killer T cells)
• Destroy host cells harboring anything foreign
– CD4 cells (mostly helper T cells)• Modulate activities of other immune cells• Secrete chemicals that amplify the activity of other immune
cells– Β-cell growth factor– T-cell growth factor (interleukin 2)– Macrophage-migration inhibition factor
– CD4+CD25+T cells / Suppressor T- cells( regulatory T cells)
Cytotoxic T Cells
• Direct attack (killer cells)
• Secrete perforins (punch holes in cells)
• Releases toxic substances directly into cells
• Kills multiple cells
• Important in destroying virus infected cells
Types of T Lymphocytes: Helper T cells
– Most numerous– Form lymphokines (IL-2, 3, 4, 5, 6 and BCSF, BSDF)
– Regulatory functions of lymphokines:
• Stimulation of B cell growth and differentiation
• Activation of the macrophage system
• Positive feedback effect on the helper cells
• They help in the functioning of Cytotoxic T – cells.
HIV virus destroys these cells & hence both the types of immunity are lost.
Suppressor T Cells
• Capable of suppressing actions of cytotoxic and helper T cells
• Prevent excessive damage to the body tissue – Immune tolerance
• Known as regulatory T cells
Antigen Presentation• T-Lymphocytes respond only to antigens presented to them by
antigen-presenting cells– Macrophages can be antigen-presenting cells
• As macrophage engulfs and ingests microbe, it digests the microbe into antigenic peptides
• Antigenic peptides bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to passing lymphocytes
• Antigen-presenting macrophages secrete interleukin– Enhances differentiation and proliferation of now-
activated T-cell clone
Self-antigens( major histocompatibility complex/MHC)
• Plasma membrane-bound glycoproteins called MHC molecules
• Synthesis is directed by group of genes called major histocompatibility complex (MHC)
• Exact pattern of MHC molecules varies from one individual to another ( BIOCHEMIAL FINGER PRINTS/ “MOLECULAR IDENTIFICATION CARDS).
FUNCTIONS:
- Directing response of T-lymphocytes
- Rejection of transplanted tissue
Immune System Tolerance of Self-Antigens
• Tolerance refers to preventing the immune system from attacking the person’s own tissues
• Mechanisms involved in tolerance
– Clonal deletion
– Clonal anergy
– Receptor editing
– Inhibition by regulatory T cells
– Immunological ignorance
– Immune privilege
Autoimmune Diseases
• Arise from loss of tolerance to self-antigens
• e.g. multiple sclerosis, rheumatoid arthritis , myasthenia gravis
• Causes :
– Exposure of normally inaccessible self-antigens sometimes induces an immune attack against these antigens
– Normal self-antigens may be modified by factors such as drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system.
– Exposure of the immune system to a foreign antigen structurally identical to a self-antigen
– May be related to pregnancy, arising from lingering fetal cells in the mother’s body after the pregnancy
Immune Diseases
• Due to abnormal functioning of the immune system• 2 general ways
– Immunodeficiency diseases• Too little immune response• Examples
– severe combined immunodeficiency– AIDS
– Inappropriate immune attacks• Too much or mistargeted immune response• Categories of inappropriate attacks
– Autoimmune responses– Immune complex diseases– Allergies
Mechanisms of Immunity: A Summary
• Recognition of an antigen as foreign – accomplished by macrophages and helper T-cells
• Foreign antigen is phagocytized by a macrophage
• Macrophage presents antigen material on its cell membrane
• Helper T-cell is exposed to this part of the macrophage membrane and becomes sensitized
• Once an antigen has been recognized, the activated helper T cells initiate one or both immune mechanisms.
– Cell Mediated Immunity– Humoral Immunity
Β versus T Lymphocytes
References
• Human physiology by Lauralee Sherwood, seventh edition
• Text book physiology by Guyton &Hall,11th edition• Text book of physiology by Linda .s contanzo,third edition