1. IMMUNE SYSTEM OVERVIEW
Lecture – 9
Dr. Zahoor

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

3. 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)

4. 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

5. 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

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

7. 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

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Innate Vs. Adaptive Immunity

15. 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

16. 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

17. 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

18. 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.

19. 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

20. 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

21. 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

22. 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

23. 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)

24. 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

25. 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

26. 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

28. 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

29. Thank you