B AND T LYMPHOCYTES MEDIATERS OF ADAPTIVE IMMUNE RESPONSE Dr.Mohammed Sharique Ahmed Quadri

1. بسم الله الرحمن الرحيم B AND T LYMPHOCYTES MEDIATERS OF ADAPTIVE IMMUNE RESPONSE Dr.Mohammed Sharique Ahmed Quadri Assistant professor Physiology Al Maarefa College

2. Objectives • Describe the different types of lymphocytes • Discuss the formation and preprocessing of the different types of lymphocytes • Define clonal selection theory • Explain the concept of humoral(antibody mediated ) immunity . • Describe mechanism of action of antibodies • Emphasis the importance of memory cell ( primary and secondary response)

3. Immunity • Body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells • Immune system activities • Defends against invading pathogens • Removes “worn-out” cells and tissue damaged by trauma • Identify and destroy abnormal or mutant cells • Immune surveillance • Identifies and destroys abnormal or mutant cells that have originated in the body • Mounts inappropriate immune responses that lead either to allergies or to autoimmune diseases

4. Leukocytes • Effectors of the immune system • 5 Types • Neutrophils • Highly mobile phagocytes that engulf and destroy unwanted materials • Eosinophils • Secrete chemicals that fight parasites • Involved in allergic reactions • Basophils • Release histamine and heparin • Involved in allergic reactions • Monocytes • Transformed into macrophages (tissue-bound phagocytic specialists) • Lymphocytes • Β lymphocytes (β cells) • Transformed into plasma cells that secrete antibodies • T lymphocytes (T cells) • Responsible for cell-mediated immunity

5. Lymphocytes • Mainly produced from lymphoid colonies in lymphoid tissues • Lymphoid tissues • Tissues that produce, store, or process lymphocytes • Include • Bone marrow • Lymph nodes • Spleen • Thymus • Tonsils • Adenoids • Appendix • Peyer’s patches (GAIT)

6. IMMUNITY • Mechanism by which the body is able to resist or overcome disease causing micro-organisms. Broadly there are 2 types - • I. Innate/Non-specific/Natural Immunity • II. Acquired /Specific/Adaptive Immunity

7. I. Innate/Non-specific/Natural Immunity. Provides first line of defense against infections. • Intact skin & mucous membranes. • Secretions such as tears, saliva, HCl acid. • Phagocytes & Natural Killer Cells. • Complement system,(a group of 20 proteins activated by immune complexes)

8. Immune Responses • Innate immune system • Nonspecific • Responses work immediately when body is exposed to threatening agent • Nonselectively defend against foreign invaders • First line of defense • Rapid but limited responses • Neutrophils, macrophages, several plasma proteins are important in innate defense

9. Immune Responses • Adaptive or acquired immune system • Specifically targets foreign material to which body has already been exposed • Body has taken time to prepare to attack • Ultimate weapon against most pathogens • Responses are mediated by β and T lymphocytes • Formation of memory cells allows system to react more swiftly against specific invaders in the future

10. Adaptive Immunity • 2 classes of adaptive immunity • Antibody-mediated or humoral immunity • Involves production of antibodies by B lymphocyte derivatives known as plasma cells • Cell-mediated immunity • Involves production of activated T lymphocytes • Directly attack unwanted cells

11. Adaptive ImmunityOrigins of β and T Cells After early childhood most new lymphocytes are derived from peripheral lymphocyte colonies rather than from bone marrow

12. Lymphocytes

13. Adaptive Immunity • Antigen • Large, foreign, unique molecule • Induces an immune response against itself • In general, the more complex a molecule is, the greater its antigenicity

14. β Lymphocytes: Antibody-Mediated Immunity • Each lymphocyte has surface receptors for binding with one particular type of possible antigens- named as BCRs- B-cell receptors • These are eyes of adaptive immune system

15. T-Dependent and T-independent Antigen • Binding with Antigens stimulate B cells to convert into plasma cells that produce antibodies • T-independent: after binding with polysaccharide antigen B cells are activated without assistance from T- helper cells • T-dependent: polypeptide antigen cannot stimulate B cells without the help of T- helper cells The majority of antigens to which B cell respond are T-dependent

16. β Lymphocytes: Antibody-Mediated Immunity • On binding with processed and presented antigen • Most B cells differentiate into active plasma cells • Other B cells become dormant memory cells • A mature plasma cell then produces antibodies rapidly (2000 antibodies/sec) • All antibodies eventually enter blood where they are known as gamma globulins or immunoglobulin's

17. B -Lymphocytes

18. Plasma Cells • Antibody (Immunoglobulin) subclasses • IgM • Serves as the β cell surface receptor for antigen attachment • Secreted in early stages of plasma cell response • IgG • Most abundant immunoglobulin in blood • Produced in large amounts when body is exposed to same antigen • IgE • Helps protect against parasitic worms • Antibody mediator for common allergic responses • IgA • Found in secretions of digestive, respiratory, and genitourinary systems; also in milk and tears • IgD • Present on surface of many β cells • Function is uncertain

19. Y-shaped molecules Composed of 4 interlinked polypeptide chains Two long, heavy chains Two short, light chains Properties of tail portion determine functional properties of the antibody( what it will do after binding with antigen) Identical antigen-binding fragments (Fab) at tip of each arm (unique for each different antibody) Tail (constant region) regions within each subclass are identical Antibodies

20. Mechanism of Action of Antibodies • Can physically hinder antigens • By neutralization, they prevent harmful chemicals from interacting with susceptible cells • Can bind to foreign cells by agglutination • Enhance activity of other defense systems by • Activating complement system • Enhancing phagocytosis • Stimulating naturalkiller (K) cells

21. Mechanism of Action of Antibodies

22. Mechanism of Action of Antibodies

23. Immune Complex Disease • Occurs when overzealous antigen-antibody response causes damage to normal and invading foreign cell • Antigen-antibody complex normally form in response to foreign invasion and are removed by phagocytic cells • If large numbers of these complexes are continuously produced, phagocytes can’t clear away all immune complexes formed • Antigen-antibody complexes not removed continue to activate complement system • Excessive activated complement damage normal cells • Can occur in bacterial, viral, or parasitic infections

24. Clonal Selection Theory(how matching B cell responds to its antigen) • During fetal life B cells are genetically preprogrammed to produce antibody against particular antigen , before ever being exposed to it. • All offspring of particular b lymphocyte form family of identical cells, on exposure to specific antigen . i.e. ( clonal expansion ).

25. Clonal Selection Theory(how matching B cell responds to its antigen)

26. Primary and Secondary Response • Memory cells • Small percentage of β lymphocytes become memory cells • Remain dormant • Upon re exposure to same antigen, they are more ready for immediate action than the original lymphocytes of the clone • Secondary response is quicker, more potent, and longer-lasting • Can be induced by disease or vaccination Formation of memory cell can occurs through the person either actually having disease or being vaccinated

27. Primary and Secondary Immune Responses

28. Active and Passive Immunity • Active immunity • “self-generated” • Results from exposure to an antigen • Passive immunity • “borrowed immunity” • Results from transfer of preformed antibodies • Can provide immediate protection • Example of passive immunity is transfer of IgG antibodies from mother to fetus • Tetanus toxins, anti snake venom, rabies virus

29. 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