1. Online Counseling Resource YCMOU ELearning Drive… School of Architecture, Science and Technology Yashwantrao Chavan Maharashtra Open University, Nashik – 422222, India

2. © 2008, YCMOU. All Rights Reserved.2 OC-SBT052-CP3-05 Introduction Programmes and Courses  SEP–SBT052–Unit-03

3. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.3 Credits  Academic Inputs by Arun Punaji More. M.Sc. (Microbiology) ‏ Experience: 11 Years arunmesh@hotmail.com

4. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.4 How to Use This Resource  Counselor at each study center should use this presentation to deliver lecture of 40-60 minutes during Face-To-Face counseling.  Discussion about students difficulties or tutorial with assignments should follow the lecture for about 40-60 minutes.  Handouts (with 6 slides on each A4 size page) of this presentation should be provided to each student.  Each student should discuss on the discussion forum all the terms which could not be understood. This will improve his writing skills and enhance knowledge level about topics, which shall be immensely useful for end exam.  Appear several times, for all the Self-Tests, available for this course.  Student can use handouts for last minutes preparation just before end exam.

5. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.5 Learning Objectives  After studying this module, you should be able to: Describe the immunological tolerance Describe the autoimmunity Describe the mechanism of development of autoimmune diseases

6. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.6 Introduction  The immune system has intrinsic characteristics of recognizing the foreign antigen and mount the immunological response against it.  The immune system has also one very important ability to differentiate the self antigens from that of foreign antigens.  However sometimes the ability to differentiate the self antigen from that of foreign antigen break down and immune system mount the immune response against self antigen as against foreign antigen resulting in disease condition.  This immune response against the self antigens is called as autoimmunity; students will learn about the autoimmunity and autoimmune diseases in this modules.

7. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.7 Immunological Tolerance-1  The indiscriminate immunological response against the self antigens by the immune system is called as autoimmunity.  The autoimmunity result due to break down of self tolerance mechanism of immune system.  Self tolerance of immune system is an ability of immune system to discriminate the self antigen from that of the foreign antigen by the immune system.  The capability of self tolerance by the immune cells is acquired in the thymus gland.

8. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.8 Immunological Tolerance-2  Immunological tolerance:-  The immunological tolerance is defined as the capability of immune system ( T cells and B cells ) to recognize the self antigen from the non self and not mounting the immunological response against them.

9. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.9 Immunological Tolerance-3  Mechanism:- T cells and B cells are trained to differentiate the self antigen from that of foreign antigen. T cells are produced in the bone marrow and are transported to the thymus where the self antigen reacting cells are eliminated. However if the self reacting T cells enter the blood circulation, they are eliminated in spleen and lymph nodes.

10. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.10 Immunological Tolerance-4  Mechanism:-

11. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.11 Autoimmunity-1  The initiation of immune responses against self antigens is called as autoimmunity.  The main causes of development of autoimmunity are as follow: Failure of immune system to eliminate the self reactive immune cells. Activation of self reactive tissue immune cells due to inhibition of normal activity of suppressive immune cells. Foreign antigen stimulating production of anti-idiotype antibodies against self antigen. Failure of clonal inhibition and clonal deletion mechanisms.

12. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.12 Autoimmunity-2  Mechanisms:- Broadly the mechanisms of development of autoimmunity are grouped into the two categories  Mechanisms involving self reactive T cells  Mechanisms without the involvement of T cells.

13. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.13 Autoimmunity -3  Mechanisms:- Mechanisms involving the self reactive T cells:  Molecular mimicry by the foreign antigens  Abnormal expression of class II MHC molecules  Inhibition of immunoregulation  Impaired immunoregulation  Released of sequestered self antigens Mechanisms without the involvement of T cells:  Clonal activation of B cells by T-independent self antigens  Binding of foreign antigens with the self antigens  Anti-idiotype reactivity

14. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.14 Autoimmunity-4  Mechanisms:- Mechanisms involving the self reactive T cells:  Molecular mimicry by the foreign antigens:- Sometimes the foreign antigens share structural similarity with the self antigens; in this situation antibodies produced against the foreign antigens also cross react with the self antigens resulting in the destruction the tissues with these antigens. The rheumatic fever is autoimmune disease involving the autoimmunity developed due to molecular mimicry. In rheumatic fever, the antibodies produced against the proteins M of Streptococci cross react with the cardiac muscles causing inflammation of cardiac muscles. Both the protein M and antigens of cardiac muscles share sequence similarity.

15. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.15 Autoimmunity-5  Mechanisms:- Mechanisms involving the self reactive T cells:  Molecular mimicry by the foreign antigens:- Post Chagas disease myocardial heart injury is another example of autoimmune disease involving the molecular mimicry mechanism. The ribosomal proteins of Typanosoma cruzi and β -1 adrenergic receptors of heart muscles share sequence similarity. In this mechanism the tissue damages result from both cross reactive antibodies as well as from the self reactive T cells. Whether cross reactive antibodies or self reactive T cells are produced predominantly in this autoimmune response depend upon the nature of the foreign antigens.

16. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.16 Autoimmunity-6  Mechanisms:- Mechanisms involving the self reactive T cells:  Abnormal expression of class II MHC molecules: The class II MHC molecules are expressed normally on the antigens presenting macrophages, dendritic cells and B lymphocytes. When other cells get infected with viruses, they abnormally expressed class II MHC molecules on their cells surface; such cells which abnormally expressed the class II molecules are killed by auto-reactive B lymphocytes and cytotoxic T lymphocytes. In persistent infections, the INF- γ is produced in more quantity; the INF- γ induces expression of class II MHC molecules on healthy non-immune cells leading activation of T cells against such cells. The examples of autoimmune diseases involving this mechanism are post Cox-sakie virus infection type 1 diabetes.

17. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.17 Autoimmunity-7  Mechanisms:- Mechanisms involving the self reactive T cells:-  Inhibition of immunoregulation:- CD4 + CD25 + cells play important roles in regulation of immune response. Patient having CD4 + CD25 + cells having impaired suppression or regulation activity are more susceptible to spontaneous autoimmune diseases. The finding that patients having immunodeficiency are more prone to autoimmune diseases support the role of immuno-regulation of CD4 + CD25 + cells.

18. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.18 Autoimmunity-8  Mechanisms:- Mechanisms involving the self reactive T cells:-  Released of sequestered self antigens:- The sperm antigen, lens proteins, DNA, ribosomal proteins, nucleosomes proteins are isolated from the immune system and normally never come into contact of immune system. When such sequestered proteins come into the contact of immune system immune responses are produced against them. Uveitis is example of autoimmune disease of eye lens when the lens proteins are exposed to the immune system. Mump orchitis is example of autoimmune disease of sperm cells when the sperm antigens are exposed to the immune system.

19. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.19 Autoimmunity-9  Mechanisms:- Mechanisms involving the self reactive T cells:-  Released of sequestered self antigens:- DNA, nucleosomes and ribonucleoproteins are sequestered proteins or antigens. When such antigens come into the contact of immune system due to faulty apoptosis, auto-antibodies are produced against them. Systemic lupus,a autoimmune disease of connective tissues, involves the above mentioned mechanism. In system lupus auto-antibodies against DNA, nucleosome proteins and ribonucleoproteins are produced.

20. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.20 Autoimmunity-10  Mechanisms:-  Mechanisms without the involvement of T cells:-  Clonal activation of B cells by T-independent self antigens:- Many T-independent antigens of gram negative bacteria and viruses such as cytomegalovirus and Epstein-Barr-virus can induce activate B cells to produce polyclones. The auto-antibodies are produced due to sequence similarity or binding of these antigens to the self antigen. The auto-antibodies are predominantly of IgM class. Auto-antibodies produced in this mechanism is transient phenomenon and production of auto- antibodies stop after the infection subsides.

21. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.21 Autoimmunity-11  Mechanisms:-  Mechanisms without the involvement of T cells:-  Binding of foreign antigens with the self antigens The antigens of pathogens such as Typanosoma cruzi, Trepanoma pallidum and Cox-sakie virus can spontaneously bind to the host cells. Therefore the antibodies produced against such antigens also partially or completely react with the self antigens. If such infections persist for longer time the auto- antibodies produced have severe pathological effects leading development of chronic auto-immune diseases.

22. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.22 Autoimmunity-12  Mechanisms:-  Mechanisms without the involvement of T cells:-  Anti-idiotype reactivity:- During immune response along with normal antigen some anti-idiotype antibodies are also produces. These anti-idiotype antibodies react with idiotype determining portion of antibody which react with epitope of antigen. The viral antigens react with number of receptor molecules of the host cells; and therefore the anti- idiotype antibodies also react with these receptors or host antigens as shown in the figure.

23. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.23 Autoimmune Diseases-1  The persistent autoimmunity result into the pathological conditions in the body leading to the development of autoimmune diseases.  The autoimmune diseases are grouped into two categories as follow: Organ specific autoimmune diseases Systemic autoimmune diseases

24. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.24 Autoimmune Diseases-2  Organ specific autoimmune diseases:- Pernicious anemia  Involved gastric parietal cells; intrinsic factors Graves disease (thyrotoxicosis) ‏  Involved thyroid stimulating hormone receptors. Type I diabetes  Involved islet cells of pancreas Myasthenia gravis  Involved acetylcholin receptors Hashimoto thyroiditis  Involved thyroid peroxide, thyroglobulin Pemphigus  Involved desmoglein 3 of epidermal cells.

25. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.25 What We Learn…..  The phenomenon of immune tolerance  The mechanism of development of immune tolerance  Auto-immunity  Mechanisms of development of autoimmunity  Auto-immune diseases and their classification.

26. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.26 Critical Thinking Question  Why the incidence rate of autoimmune diseases after viral infections is more than the incidence rate of autoimmune diseases after bacterial diseases?  Why women are more prone to autoimmune diseases?

27. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.27 Hints For Critical Thinking Question  Involvement of TH1 cells  Molecular mimicry  Sharing of cell membrane by enveloped viruses  The more active TH1 responses in women

28. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.28 Study Tips  Book Title: Immunology Title: Immunology Author: Author: Richard A. Goldsby, Thomas Kindt, Barbara A. Osborne. Publication: Publication: W.H. Freeman and Company, New York.  Book Title: Textbook of Microbiology Author: Author: R. Anathanarayan & C.K.J. Paniker Publication: Publication: Orient Longman publication, Chennai.

29. © 2008, YCMOU. All Rights Reserved.29 End of the Presentation Thank You !