T LYMPHOCYTES

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

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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 bodys 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

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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 persons own tissue antigens
• A few days are required before T cells are
  activated to launch a cell-mediated attack

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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)

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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
• ?-cell growth factor
• T-cell growth factor (interleukin 2)
• Macrophage-migration inhibition factor
• CD4CD25T cells / Suppressor T- cells(
  regulatory T cells)

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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

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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.

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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

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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

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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

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Immune System Tolerance of Self-Antigens

• Tolerance refers to preventing the immune system
  from attacking the persons own tissues
• Mechanisms involved in tolerance
• Clonal deletion
• Clonal anergy
• Receptor editing
• Inhibition by regulatory T cells
• Immunological ignorance
• Immune privilege

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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 mothers body after
  the pregnancy

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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

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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)

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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

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Type II hypersensitivity (antibody mediated
cytotoxicity)

• Immune reaction that damages antigen bearing
  cells
• Example incompatible blood transfusion

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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

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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

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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

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Mumps ??????
measles ??????
Tuberculosis ??? ????
Tetanus ??????
Diphtheria ??????
Polio ??? ???????
Hepatitis ?????? ?????
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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

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