White Blood Cells and Immunity Prof K Sivapalan
White Blood Cells and Immunity Prof. K. Sivapalan
WHITE BLOOD CELLS. • • • Colorless. Seen clearly only after staining. Blood count is 4, 000 – 11, 000 / mm 3. 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. June 2013 White Cells 2
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 / day. June 2013 White Cells 3
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. June 2013 White Cells 4
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. June 2013 White Cells 5
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. June 2013 White Cells 6
Monocyte. • Less than 10 % of the white cells. • Kidney shaped single nucleus. • Abundant clear cytoplasm. • Phagocytic and shows amoeboid movement. • Becomes Macropharge in tissues. June 2013 White Cells 7
Macropharge system. • • • Kupffer cells in liver. Osteoclasts in bone. Alveolar cells in lungs. Microglia in brain. Histeocytes in tissues. June 2013 White Cells 8
Formation. Granulopoisis • Stimulated by, • Colony stimulating factors. • Granulocyte releasing factors. June 2013 White Cells 9
Defense reactions • Immunity: – Ability to resist disease by foreign agents. • Innate immunity: – Indiscriminate, first line. • Acquired [adaptive] immunity: – Specific, powerful, delayed. June 2013 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. June 2013 White Cells 11
Physical protection. • • Skin. Cilia and mucus. Acid in stomach. Flow of tears. June 2013 White Cells 12
Phagocytosis. June 2013 White Cells 13
Properties of phagocytes. • Chemotaxis: – Chemical attraction by bacterial toxins, polysacharides, complements, antigenantibody complexes. • Amoeboid movement - psudopodia [actin + myosin] • Leave capillaries through the pores- Diapedisis. • Phagocytosis – some times need opsonization. • Enzymatic digestion. [lysosomes- digestive enzymes, peroxidase(H 2 O 2), Myeloperoxidase (Cl. O-) June 2013 White Cells 14
Opsonization. • When antigens are harmful to phagocytes, the active site is covered by, Compliments or Antibodies to facilitate phagocytosis. June 2013 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. June 2013 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. June 2013 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. June 2013 White Cells 18
Antibody. • Light and heavy chains. • Variable portion – antigen binding. • Constant -1 • Hinge. • Constant 2 complement binding. • Constant 3 membrane binding. June 2013 White Cells 19
Antibody types in blood. Monomer Dimer Ig. G June 2013 White Cells Ig. A 20
Antibody types in blood. Membrane bound Pentamer June 2013 Ig. M White Cells Ig. E 21
Humeral antibodies. • Ig. G – • Ig. M – • Ig. A – • Ig. D • Ig. E June 2013 70 % [in serum- monomer] 10 % [confined to bloodpentamer] 15 % [blood- monomer, secretions- dimer] < 1 %. [ lot in membranes of B Lymphocytes]. Trace in blood [bound to mast cells] White Cells 22
Reactions of antibodies. 1. Direct action. • - Agglutination. • • 2. 3. 4. [Ig. M] - Precipitation. - Neutralization. - Lysis. Activation of complement system. Activation of anaphylactic system. Chemo taxis. June 2013 White Cells 23
Reaction of Complement System. 1. Activation of complement 1. 1. Compliments: system. [CH 2] after antigen • - C 1 q, C 1 r, C 1 s, binding. C 4, C 2, C 3, C 5, C 6, C 7, C 8, C 9 2. Lysis. 1. 2. Activation: 3. Opsonization. Ag/Ab complexes 4. Chemotaxis. [CH 2] → clasical 5. Agglutination. pathway. 6. Neutralization. Bacteria [sugar] → 7. Inflamatory effects. alternative pathway. June 2013 White Cells 24
Reaction of Anaphylactic System. Basophils and mastcells are activated by reaction of Ig. E 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} June 2013 White Cells 25
Cellular immunity. • Antibody in the membrane of the lymphocyte. • The cell is activated when antigen binds to the antibody. June 2013 White Cells 26
Mechanism of Cellular Immunity. • Cytotoxic T cell. • Attaches to bacteria, virus infected cell, cancer cell or transplanted cells. v Effective against viral, fungal and some bacterial [tuberculosis] infections and cancer. v Responsible for tissue rejections in transplantation. June 2013 White Cells 27
Lymphatic system. Thymus Spleen June 2013 White Cells 28
Development of the immune system. Lymphocyte precursors. [Bone marrow] T lymphocytes. Processing [Thymus] Helper T cells [CD 4] Memory cells. B lymphocytes. [Bursa fabrecious, liver, bone marrow] Memory cells. Plasma cells. Cytotoxic T cells[CD 8] Suppressor T cells Humeral immunity. Cellular immunity. June 2013 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. June 2013 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] June 2013 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. June 2013 White Cells 32
Immunization. • Active: – Introduce deactivated toxin and provoke immune response. • Passive: – Introduce antobody for immediate need. June 2013 White Cells 33
Hypersensitivity. • Type I: – Allergy- Ig. E. 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. June 2013 White Cells 34
Immunodeficency syndromes. [Heriditary] Pluripotent stem cell. Lymphoid progenitor. Pre- B cell In bone marrow. B - cell Immature T cell. In thymus. CD 8 cell CD 4 Cell Ig. M Ig. A Ig. G Ige June 2013 White Cells 35
Acquired immunodeficiency syndrome. • Caused by HIV [human immunodeficiency virus] • Binds to CD 4 and reduces helper T cells. • Results in failure of proliferation of CD 8 cells and B cells. • Eventually loss of immune function. June 2013 White Cells 36
- Slides: 36