White Blood Cells and Immunity
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Transcript of White Blood Cells and Immunity
White Blood Cells and Immunity
Prof. K. Sivapalan
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.
June 2013 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.
June 2013 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.
June 2013 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.
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.
June 2013 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.
June 2013 White Cells 8
Macropharge system.
• Kupffer cells in liver.• Osteoclasts in bone.• Alveolar cells in lungs.• Microglia in brain.• Histeocytes in tissues.
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, 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-)
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
IgG Dimer
IgA
June 2013 White Cells 20
Antibody types in blood.
Pentamer
IgM
Membrane bound
IgE
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]
June 2013 White Cells 22
Reactions of antibodies.
1. Direct action.• - Agglutination.
• [IgM]
• - Precipitation.• - Neutralization.• - Lysis.
2. Activation of complement system.
3. Activation of anaphylactic system.
4. Chemo taxis.
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.
June 2013 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}
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.
Effective against viral, fungal and some bacterial [tuberculosis] infections and cancer.
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.
[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
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- 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.
June 2013 White Cells 34
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
June 2013 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.