Download FUNCTIONS OF THE BLOOD

White Blood Cells and
Immunity
Prof. K. Sivapalan
WHITE BLOOD CELLS.
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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
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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.
June 2013
White Cells
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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.
June 2013
White Cells
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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.
June 2013
White Cells
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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
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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.
June 2013
White Cells
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Macropharge system.
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Kupffer cells in liver.
Osteoclasts in bone.
Alveolar cells in lungs.
Microglia in brain.
Histeocytes in tissues.
June 2013
White Cells
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Formation.
Granulopoisis
• Stimulated by,
• Colony
stimulating
factors.
• Granulocyte
releasing
factors.
June 2013
White Cells
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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.
June 2013
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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.
June 2013
White Cells
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Physical protection.
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Skin.
Cilia and mucus.
Acid in stomach.
Flow of tears.
June 2013
White Cells
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Phagocytosis.
June 2013
White Cells
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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(H2O2), Myeloperoxidase
(ClO-)
June 2013
White Cells
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Opsonization.
• When antigens are harmful to phagocytes, the
active site is covered by,
Compliments or Antibodies
to facilitate phagocytosis.
June 2013
White Cells
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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
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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
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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.
June 2013
White Cells
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Antibody.
• Light and heavy
chains.
• Variable portion –
antigen binding.
• Constant -1
• Hinge.
• Constant 2complement binding.
• Constant 3membrane binding.
June 2013
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Antibody types in blood.
Monomer
Dimer
IgG
June 2013
White Cells
IgA
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Antibody types in blood.
Membrane bound
Pentamer
June 2013
IgM
White Cells
IgE
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Humeral antibodies.
• IgG –
• IgM –
• IgA –
• IgD • IgE 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
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Reactions of antibodies.
1. Direct action.
• - Agglutination.
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2.
3.
4.
[IgM]
- Precipitation.
- Neutralization.
- Lysis.
Activation of complement system.
Activation of anaphylactic system.
Chemo taxis.
June 2013
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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.
June 2013
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.
White Cells
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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}
June 2013
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Cellular immunity.
• Antibody in the membrane of the
lymphocyte.
• The cell is activated when antigen binds to
the antibody.
June 2013
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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.
June 2013
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Lymphatic system.
Thymus
Spleen
June 2013
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Development of the immune system.
Lymphocyte precursors.
[Bone marrow]
T lymphocytes.
Processing
[Thymus]
Helper T
cells [CD4]
Memory cells.
B lymphocytes.
[Bursa fabrecious,
liver, bone marrow]
Memory cells.
Plasma cells.
Cytotoxic T cells[CD8]
Suppressor T cells
Humeral immunity.
Cellular immunity.
June 2013
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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.
June 2013
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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]
June 2013
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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.
June 2013
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Immunization.
• Active:
– Introduce deactivated toxin and provoke
immune response.
• Passive:
– Introduce antobody for immediate need.
June 2013
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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.
June 2013
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Immunodeficency syndromes.
[Heriditary]
Pluripotent stem
cell.
Lymphoid
progenitor.
Pre- B cell
In bone marrow.
B - cell
Immature T cell.
In thymus.
CD8 cell
CD4 Cell
IgM
IgA
IgG
Ige
June 2013
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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.
June 2013
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