1. Assistant professor Physiology
بسم الله الرحمن الرحيم
T LYMPHOCYTES
Dr. Shaikh Mujeeb Ahmed
Assistant professor Physiology
Al Maarefa College

2. 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

3. 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

4. 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)

5. 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)

6. 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

7. Types of T Lymphocytes: Helper T cells
Most numerous
Form lymphokines (IL-2, 3, 4, 5, 6)
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.

8. 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

9. 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

10. 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

12. 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: is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes
Clonal anergy:lack of reaction by the body's defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance.
Receptor editing: occurs during the maturation of B cells is an attempt to change the specificity of the antigen receptor of self reactive immature B-cells
Inhibition by regulatory T cells (T cells suppressor)
Immunological ignorance: Anatomical barriers can separate the lymphocytes from the antigen e.g BBB
Immune privilege:

13. 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

14. 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

15. Hypersensitivity
When an immune reaction results in considerable damage to the body its called hypersensitivity.
Four types
Type I hypersensitivity (Anaphylaxis)
Type II hypersensitivity (antibody mediated cytotoxicity)
Type III hypersensitivity (immune complex disorder)
Type IV hypersensitivity (delayed type of hypersensitivity)

16. Type I hypersensitivity (Anaphylaxis)
Mast cell degranulation
Ig E response
eg.
Allergic rhinitis
Eczema
Acute urticaria
Occurs within minutes
Mediators
Histamine
Slow reacting substance of anaphylaxis (SRS-A)
Its called Atopy

17. Type II hypersensitivity (antibody mediated cytotoxicity)
Immune reaction that damages antigen bearing cells
Example – incompatible blood transfusion

18. Type III hypersensitivity (immune complex disorder)
When antigen antibody complexes are deposited in normal tissues of the body where they fix complement.
Complement activation damages the surrounding tissue cells.
Damage of “innocent bystanders”
eg. A form of glomerulonephritis

19. Type IV hypersensitivity (delayed type of hypersensitivity)
Its mediated by macrophages that have been activated by T cells.
Hypersensitivity starts after several hours and peak at 48 to 72 hrs.
Characteristically associated with granuloma formation
eg. Hypersensitivity to tuberculin which is present in M. tuberculosis

20. VACCINE Vaccine (vaccinus – pertaining to cows)
By Edward Jenner for small pox.
Act on the principle of “mock” infection
Types of Vaccines
Live, Attenuated Vaccines
Inactivated Vaccines
Subunit Vaccines
Toxoid Vaccines
Live, attenuated vaccines - Measles, mumps, rubella, polio
Inactivated or killed vaccines- Cholera, flu, hepatitis A
Toxoid vaccine - Diphtheria, tetanus

21. الحصبة النكاف الكزاز الخناق مرض السل التهاب الكبد شلل الأطفال Polio
measles
الحصبة
Mumps
النكاف
Tetanus
الكزاز
Diphtheria
الخناق
Tuberculosis
مرض السل
Hepatitis
التهاب الكبد
Polio
شلل الأطفال

22. 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

23. Antigen (-) (-) Lymphokines Antibodies T helper cell T B cell
macrophage
Processed Antigen
cytotoxic T cell
(-)
T helper cell
(-) T
memory cell T
Suppressor
cell
Lymphokines
IL2
IL3
IL4
IL5
IL6 B
memory cell
B cell
Plasma cell
Antibodies

24. Β versus T Lymphocytes

25. 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