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.


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.


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.


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.


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.


Monocyte.• Less than 10 % of the

white cells.• Kidney shaped single

nucleus.• Abundant clear

cytoplasm.• Phagocytic and

shows amoeboid movement.

• Becomes Macropharge in tissues.


Macropharge system.

• Kupffer cells in liver.• Osteoclasts in bone.• Alveolar cells in lungs.• Microglia in brain.• Histeocytes in tissues.


Defense reactions

• Immunity:– Ability to resist disease by foreign agents.

• Innate immunity: – Indiscriminate, first line.

• Acquired [adaptive] immunity:– Specific, powerful, delayed.


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.


Physical protection.

• Skin.• Cilia and mucus.• Acid in stomach.• Flow of tears.


Phagocytosis.


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-)


Opsonization.• When antigens are harmful to phagocytes, the

active site is covered by,Compliments or Antibodies to facilitate phagocytosis.


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.


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.


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.


Antibody.

• Light and heavy chains.

• Variable portion – antigen binding.

• Constant -1• Hinge.• Constant 2-

complement binding.• Constant 3-

membrane binding.


Antibody types in blood.

Monomer

IgG Dimer

IgA


Antibody types in blood.

Pentamer

IgM

Membrane bound

IgE


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]


Reactions of antibodies.

1. Direct action.• - Agglutination.

• [IgM]

• - Precipitation.• - Neutralization.• - Lysis.

2. Activation of complement system.

3. Activation of anaphylactic system.

4. Chemo taxis.


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.


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}


Cellular immunity.

• Antibody in the membrane of the lymphocyte.

• The cell is activated when antigen binds to the antibody.


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.


Lymphatic system.

Thymus

Spleen


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


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.


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]


Activation of immune system.

• First exposure of antigen:– Delay of about 2 weeks.

• Second exposure: [more memory cells]– Quick response.– Potent response.– Long lasting.


Immunization.

• Active:– Introduce deactivated toxin and provoke

immune response.• Passive:

– Introduce antobody for immediate need.


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.


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


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 blood cells and immunity

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