white blood cells and immunity prof. k. sivapalan
TRANSCRIPT
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White Blood Cells and Immunity
Prof. K. Sivapalan
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June 2013 White Cells 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.
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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.
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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.
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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.
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June 2013 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.
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Monocyte.• Less than 10 % of the
white cells.• Kidney shaped single
nucleus.• Abundant clear
cytoplasm.• Phagocytic and
shows amoeboid movement.
• Becomes Macropharge in tissues.
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Macropharge system.
• Kupffer cells in liver.• Osteoclasts in bone.• Alveolar cells in lungs.• Microglia in brain.• Histeocytes in tissues.
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Defense reactions
• Immunity:– Ability to resist disease by foreign agents.
• Innate immunity: – Indiscriminate, first line.
• Acquired [adaptive] immunity:– Specific, powerful, delayed.
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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.
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Physical protection.
• Skin.• Cilia and mucus.• Acid in stomach.• Flow of tears.
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June 2013 White Cells 12
Phagocytosis.
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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-)
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Opsonization.• When antigens are harmful to phagocytes, the
active site is covered by,Compliments or Antibodies to facilitate phagocytosis.
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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.
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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.
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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.
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Antibody.
• Light and heavy chains.
• Variable portion – antigen binding.
• Constant -1• Hinge.• Constant 2-
complement binding.• Constant 3-
membrane binding.
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June 2013 White Cells 19
Antibody types in blood.
Monomer
IgG Dimer
IgA
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Antibody types in blood.
Pentamer
IgM
Membrane bound
IgE
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June 2013 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]
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Reactions of antibodies.
1. Direct action.• - Agglutination.
• [IgM]
• - Precipitation.• - Neutralization.• - Lysis.
2. Activation of complement system.
3. Activation of anaphylactic system.
4. Chemo taxis.
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June 2013 White Cells 23
Reaction of Complement System.
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.
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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}
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Cellular immunity.
• Antibody in the membrane of the lymphocyte.
• The cell is activated when antigen binds to the antibody.
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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.
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Lymphatic system.
Thymus
Spleen
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Development of the immune system.Lymphocyte precursors.
[Bone marrow]
T lymphocytes.
[Thymus]
B lymphocytes.
[Bursa fabrecious, liver, bone marrow]
Cytotoxic T cells[CD8]
Plasma cells.
Humeral immunity.
Cellular immunity.
Helper T cells [CD4]Memory
cells.Memory cells.
Processing
Suppressor T cells
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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.
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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]
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Activation of immune system.
• First exposure of antigen:– Delay of about 2 weeks.
• Second exposure: [more memory cells]– Quick response.– Potent response.– Long lasting.
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Immunization.
• Active:– Introduce deactivated toxin and provoke
immune response.• Passive:
– Introduce antobody for immediate need.
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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.
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Immunodeficency syndromes.[Heriditary]
Pluripotent stem cell.
Lymphoid progenitor.
Pre- B cellIn bone marrow.
Immature T cell.In thymus.
B - cellIgM
IgA
IgG
Ige
CD8 cell CD4 Cell
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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.