IMMUNE SYSTEM OVERVIEW Lecture – 9 Dr. Zahoor

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

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)

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

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

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

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

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

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

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

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

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

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

Innate Vs. Adaptive Immunity

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

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

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

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.

SELF TOLERANCE Why Immune System is tolerant to self that it does 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

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 antigen 3- Receptor Editing B-cells receptors encounter body antigen and never target them

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

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

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)

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

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

EXTERNAL DEFENSES OF THE BODY Skin – outer protective epidermis and inner connective tissue dermis Defenses of the digestive system Defenses of the respiratory system Defenses of the urogenital system

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

Thank you