White Blood Cells and Immunity

1. White Blood Cells and Immunity Prof. K. Sivapalan

2. WHITE BLOOD CELLS. • Colorless. Seen clearly only after staining. • Blood count is 4,000 – 11,000 / mm3. • Important for the defense of the body. • Life span of different cells vary. • Classification: • Granulocytes and Agranulocytes on the basis of property of the cytoplasm. • polymophonuclear leucocytes and mononuclear leucocytes on the basis of the structure of the nucleus. White Cells

3. Neutrophil • 50 – 70 % of the white cells in blood. • 3 - 5 lobed nucleus. • Fine granules in the cytoplasm [acidic and basic] – lysosomes. • First line of defense against bacteria. • Amoeboid movement and Phagocytosis (maximum 15 bacteria). • “Pus cells” • Half life is 6 hours and Production is about 100,000,000,000 / day. White Cells

4. Eosinophil • Less than 5 % of white cells in blood. • Bilobed nucleus, larger granules. • Granules take acidic dye, and are anti histaminic. • Mildly amoeboid. • Attack parasites. • Also found in GIT, respiratory, and urinary mucosa. • Blood count is increased in allergic conditions. White Cells

5. Basophil. • Less than 1 % of the white cells in blood. • Nucleus is poorly differentiated three lobes, seen as Kidney shaped. • Largest granules, take basic dye and contain histamine and heparine • Responsible for anaphylactic type of Hypersensitivity. White Cells

6. Lymphocyte. • About 20 - 40 % of the white cells in blood. 60 -70 % in babies. • Most are found in the lymphatic tissues. • Large and small cells seen • Large single nucleus. • Rim of clear cytoplasm. • Responsible for adaptive immunity. White Cells

7. Monocyte. • Less than 10 % of the white cells. • Kidney shaped single nucleus. • Abundant clear cytoplasm. • Phagocytic and shows amoeboid movement. • Becomes Macropharge in tissues. White Cells

8. Macropharge system. • Kupffer cells in liver. • Osteoclasts in bone. • Alveolar cells in lungs. • Microglia in brain. • Histeocytes in tissues. White Cells

9. Defense reactions • Immunity: • Ability to resist disease by foreign agents. • Innate immunity: • Indiscriminate, first line. • Acquired [adaptive] immunity: • Specific, powerful, delayed. White Cells

10. Innate immunity. • Physical: • Skin, cilia + mucus, acid and tears. • Biochemical: • Lyzozyme, sebaceous secretion, commensals in gut and vagina. • Phagocytes: • Neutrophil, Monocyte, Macrophage. • Natural Killer cells [lymphocytes]. • Pathological: • Inflammation. • Acute phase proteins. White Cells

11. Physical protection. • Skin. • Cilia and mucus. • Acid in stomach. • Flow of tears. White Cells

12. Phagocytosis. White Cells

13. Properties of phagocytes. • Chemotaxis: • Chemical attraction by bacterial toxins, polysacharides, complements, antigen-antibody complexes. • Amoeboid movement - psudopodia [actin + myosin] • Leave capillaries through the pores- Diapedisis. • Phagocytosis – some times need opsonization. • Enzymatic digestion. [lysosomes- digestive enzymes, peroxidase(H2O2), Myeloperoxidase (ClO-) White Cells

14. Opsonization. • When antigens are harmful to phagocytes, the active site is covered by, Compliments or Antibodies to facilitate phagocytosis. White Cells

15. Recognition by phagocytes. • Binding to receptors- polysaccharides or similar bacterial cell wall substances [nonspecific]. • Electrical charge of the surface- positive charge in living tissue. No charge in dead tissues and negative out side of bacteria. • Opsonized material is said to be “tasty” to phagocytes. White Cells

16. Inflammation. Products of tissue damage, some bacterial toxins and antigen – antibody complexes initiate inflammatory response. Vasodilatation and increased capillary permeability are important events. They facilitate entry of phagocytes and fibrin network to arrest spread of invading organisms. Cardinal signs: • Redness • Swelling • Warmness • Pain • Loss of function. White Cells

17. Acquired [adaptive] immunity. • Antigen: • A substance that can stimulate the immune mechanism. [antigenic – MW > 7000. • Antibody: • Substance that is produced in response to antigen and reacts with it. White Cells

18. Antibody. • Light and heavy chains. • Variable portion – antigen binding. • Constant -1 • Hinge. • Constant 2- complement binding. • Constant 3- membrane binding. White Cells

19. Antibody types in blood. Monomer IgG Dimer IgA White Cells

20. Antibody types in blood. Membrane bound IgE Pentamer IgM White Cells

21. Humeral antibodies. • IgG – 70 % [in serum- monomer] • IgM – 10 % [confined to blood- pentamer] • IgA – 15 % [blood- monomer, secretions- dimer] • IgD - < 1 %.[ lot in membranes of B Lymphocytes]. • IgE - Trace in blood [bound to mast cells] White Cells

22. Reactions of antibodies. 1. Direct action. • - Agglutination. • [IgM] • - Precipitation. • - Neutralization. • - Lysis. • Activation of complement system. • Activation of anaphylactic system. 4. Chemo taxis. White Cells

23. 1. Activation of complement system.[CH2] after antigen binding. 2. Lysis. 3. Opsonization. 4. Chemotaxis. 5. Agglutination. 6. Neutralization. 7. Inflamatory effects. 1.1.Compliments: - C1q, C1r, C1s, C4, C2, C3, C5, C6, C7, C8, C9 1.2. Activation: Ag/Ab complexes [CH2] → clasical pathway. Bacteria [sugar] → alternative pathway. Reaction of Complement System. White Cells

24. Reaction of Anaphylactic System. Basophils and mastcells are activated by reaction of IgE attached to the membrane and release contents of the granules. • Histamine: Local vasodialatation, ↑ capillary permiability. • Slow reacting substance of anaphylaxis: prolong action- contraction of smooth muscles in broncheols. • {protective → dangerous} White Cells

25. Cellular immunity. • Antibody in the membrane of the lymphocyte. • The cell is activated when antigen binds to the antibody. White Cells

26. Mechanism of Cellular Immunity. • Cytotoxic T cell. • Attaches to bacteria, virus infected cell, cancer cell or transplanted cells. • Effective against viral, fungal and some bacterial [tuberculosis] infections and cancer. • Responsible for tissue rejections in transplantation. White Cells

27. Lymphatic system. Thymus Spleen White Cells

28. Development of the immune system. Lymphocyte precursors. [Bone marrow] B lymphocytes. [Bursa fabrecious, liver, bone marrow] T lymphocytes. [Thymus] Processing Helper T cells [CD4] Memory cells. Memory cells. Plasma cells. Cytotoxic T cells[CD8] Suppressor T cells Humeral immunity. Cellular immunity. White Cells

29. Diversity of immune system. • Types of light chain- 2, heavy chain- 8. • Variable portion:- • Random recombination of DNA in the gene. • 108 – 1010 different molecules possible [B]. • 1015 T cell receptors possible. • Recognition of self: • Clonal deletion. • Clonal anergy [prolonged hyporesponsive state]. • Suppressor T cells. White Cells

30. Activation of the immune system. • Cytotoxic T cells and B cells lie in the lymphatic tissue after processing. • When antigen enters the body ‘antigen presenting cells’ take the antigen. [dentritic cells and macropharges] • They process the antigen, expose on the surface [incorporated in the cell membrane] and find the T of B cell for the antigen. • The lymphocyte then proliferates and becomes a “clone” • Some go dormant [memory cells] for activation next time. • Others start secreting appropriate antibody [humeral immunity] or go out and attack [cellular immunity] White Cells

31. Activation of immune system. • First exposure of antigen: • Delay of about 2 weeks. • Second exposure: [more memory cells] • Quick response. • Potent response. • Long lasting. White Cells

32. Immunization. • Active: • Introduce deactivated toxin and provoke immune response. • Passive: • Introduce antobody for immediate need. White Cells

33. Hypersensitivity. • Type I: • Allergy- IgE. Asthma, eczema, hay fever, urticaria, anaphylaxis. • Type II: • Against antigens on the surface of cells or tissues:- transfusion reactions, acute glomerular nephritis, rheumatic fever. • Type III: • Reaction of serum antibodies and excessive complexes formation. • Type IV: • Cell mediated: contact dermatitis. White Cells

34. Pluripotent stem cell. Lymphoid progenitor. Pre- B cell In bone marrow. Immature T cell. In thymus. B - cell CD4 Cell CD8 cell IgM IgA IgG Ige Immunodeficency syndromes.[Heriditary] White Cells

35. Acquired immunodeficiency syndrome. • Caused by HIV [human immunodeficiency virus] • Binds to CD4 and reduces helper T cells. • Results in failure of proliferation of CD8 cells and B cells. • Eventually loss of immune function. White Cells