T LYMPHOCYTES Dr. Shaikh Mujeeb Ahmed Assistant professor Physiology Al Maarefa College.

T LYMPHOCYTES

Dr. Shaikh Mujeeb Ahmed

Assistant 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)

– 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

• 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

Self-antigens( major histocompatibility complex/MHC)

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:

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

Hypersensitivity

• When an immune reaction results in considerable damage to the body its called hypersensitivity.

• Four typesType I hypersensitivity (Anaphylaxis)Type II hypersensitivity (antibody mediated

cytotoxicity)Type III hypersensitivity (immune complex

disorder)Type IV hypersensitivity (delayed type of

hypersensitivity)

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

Type II hypersensitivity (antibody mediated cytotoxicity)

• Immune reaction that damages antigen bearing cells

• Example – incompatible blood transfusion

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

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

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

Mumps

النكاف

measles

الحصبة

Tetanus

الكزازDiphtheria

الخناق

Hepatitis

التهاب الكبد

Tuberculosis

مرض السل

Polioشلل األطفال

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

T helper

cell

TSuppressor

cell

Plasma cell

B cell

cytotoxic

T cellT

memory cell

Bmemory

cell

macrophage

Antigen

Processed Antigen

Lymphokines

IL2IL3IL4IL5IL6

Antibodies

(-)(-)

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