IMMUNE SYSTEMOVERVIEW

Lecture – 9Dr. Zahoor

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OBJECTIVE

You should know • About innate and adaptive immunity• Self tolerance• Immune surveillance • Auto immune diseases• Transplant rejection

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IMMUNE SYSTEM

What is the function of Immune System?• To defend the body against foreign invaders (bacteria, virus) and

cancer cells• Immune System recognizes the normal body cells and destroys the

material that are not “normal self” • Immune response can lead to allergic reaction or auto-immune

diseases (anti-bodies against body’s own cell)

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IMMUNE SYSTEM

• Leukocytes are effecter cells of immune system• We have discussed Neutrophils, Eosinophils, Basophiles, Monocyte• Most important part played in the Immune System is by

Lymphocytes 1. B-Lymphocyte – Antibody mediated immunity 2. T-Lymphocyte – Cell mediated immunity

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IMMUNE SYSTEM

Lymphocyte • Originally derived from bone marrow, but later they arise from

lymphoid tissue

What is Lymphoid Tissue? • Lymphoid Tissue include bone marrow, lymph node, spleen, thymus,

tonsils, appendix and lymphoid tissue in the lining of digestive tract called Peyer’s Patches

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IMMUNE SYSTEM

• Bone marrow process B-Lymphocyte • Thymus process T-Lymphocyte• Lymphoid tissue produces, stores, and process lymphocytes in adults

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IMMUNE RESPONSE

They are of two types of Immune Response: 1. Innate or Inborn – non specific 2. Adaptive or Acquired – specific

1. Innate or Inborn Immunity It is natural, inherent defense mechanism It is non-selective It comes into play on exposure to foreign or abnormal material

e.g. infectious agent, chemical irritants

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Innate or Inborn Immunity

• Innate immunity is done by - Neutrophil - Macrophages - Plasma protein_ Complement system _ Dendritic cells _ Natural killer cells

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Innate or Inborn Immunity

- Body defends itself against invading organism by 1- Inflammation – it is response by the body to tissue injury in which

Neutrophil and macrophages play role 2- Interferon – a family of protein that defend the body against viral

infection

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Innate or Inborn Immunity

3- Natural Killer cells – Lymphocyte like cells that cause destruction of viral infected cells and cancer cells

4- Complement System – it is group of inactive plasma proteins, when activated bring destruction of foreign cells by attacking their plasma membrane

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IMMUNE RESPONSE

2. Adaptive or Acquired• It is specific • It is response by the body against a particular foreign material • It is mediated by T-Lymphocyte and B-Lymphocyte• Each B and T Lymphocyte can recognize and defend against one type

of foreign material e.g. bacteria

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Adaptive or Acquired Immunity

• There are millions of B and T Lymphocytes • One type of cells (clone) are called against one agent • It is selective attack to limit the pathogen • It is done by antibody mediated immunity and cell mediated

immunity

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Adaptive or Acquired Immunity

• B-cells recognize bacteria and few viruses and they respond by producing antibodies which are specific for the invader• T-cell recognize virus infected cells and cancer cells• Each of us has about 2 trillion lymphocytes, they remain on constant

surveillance

Both Innate and Adaptive Immunity work together

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Innate Vs. Adaptive Immunity

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TISSUE TRANSPLANT

Why tissue transplant is rejected?• Tissue transplant is rejected because T-cell bind with MHC (Major

Histocompatibility Complex) antigens present on the surface of transplanted cells and trigger the rejection of transplanted or grafted tissues • To minimize the rejection phenomenon, tissue of donor and

recipient are matched according to MHC antigens as closely as possible

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TISSUE TRANSPLANT

How to prevent tissue transplant rejection?• Drugs are given to suppress the immune response • Before immunosuppressive therapy included - Radiotherapy and drugs given to destroy lymphocytes - That treatment affected both T and B cells, therefore, immune

protection was lost against bacteria and virus

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TISSUE TRANSPLANT

• In recent years, new treatment is aimed at selectively suppressing T-cells mediated immune activity, while leaving B-cell antibody immunity intact e.g. Cyclosporin

How Cyclosporin acts?• It blocks IL-2 which is secreted by T-helper Lymphocytes to help

cytotoxic T-cells

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TISSUE TRANSPLANT

Future therapy • New methods are under investigation which may prevent rejection of

unmatched donor. How ?By giving antibodies that block specific process involved in rejection.

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SELF TOLERANCE

Why Immune System is tolerant to self that itdoes not attack persons own tissues? Because during development of lymphocyte, immune system does

not produce antibodies or activated T-lymphocytes against body’s own self antigen

At least 8 different mechanism are involved in tolerance

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DIFFERENT MECHANISM INVOLVED IN TOLERANCE

1- Clonal Deletion• B and T Lymphocyte clones which are capable of attacking self

antigens are destroyed in the thymus 2- Clonal anergy (loss of energy)• T-Lymphocyte which work against self are inactivated by body

antigen3- Receptor Editing • B-cells receptors encounter body antigen and never target them

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DIFFERENT MECHANISM INVOLVED IN TOLERANCE

4- Active suppression by regulator or suppressor T-cell• Suppressor T-cell help in tolerance

5- Some antigen are hidden from immune system e.g. thyroglobulin in thyroid gland and they never come in direct contact with immune cells

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DIFFERENT MECHANISM INVOLVED IN TOLERANCE

6- Immune Privilege • Eye cornea transplant escape immune attack even when

transplanted from unrelated person Why? It is discovered that plasma membrane in these tissues have

molecule that triggers the Apoptosis of Lymphocyte that attack these tissues

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DIFFERENT MECHANISM INVOLVED IN TOLERANCE

7- Activation induced cell death of B-cells

8- Release of IL-10 by T-helper, cytotoxic T-cell, B-cell • IL-10 is cytokine that inhibits macrophage and dendritic cells which

are Antigen Presenting Cells (APCs)

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AUTO IMMUNE DISEASES

What is Auto Immune Disease?• Loss of tolerance to self antigen, therefore, there is auto immune

disease (auto means against self) Why it occurs?It is due to combination of genetic and environmental factors e.g.

modification by virus, drugs, bacteria

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AUTO IMMUNE DISEASES

There are more than 80 auto immune diseases Few examples - Type 1 Diabetes Mellitus - Rheumatoid Arthritis - SLE - Thyroid Disease Auto immune disease is three times more common in female

than male Auto immune disease affects 1 in 20 people world wide

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EXTERNAL DEFENSES OF THE BODY

1. Skin – outer protective epidermis and inner connective tissue dermis

2. Defenses of the digestive system 3. Defenses of the respiratory system4. Defenses of the urogenital system

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APPLIED Cigarette smoking suppresses the normal respiratory defenses. It

affects movements of cilia in respiratory system, it affects function of alveolar macrophage

It has toxic effect on lung tissue and there is increased incidence of chronic respiratory diseases and lung cancer

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Thank you

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