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-CP3-04 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 delayed type or type IV hypersensitive reaction Describe the mechanism of type IV hypersensitive reaction Describe the diseases involving type IV hypersensitive reaction

6. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.6 Introduction  The type IV hypersensitive reaction mainly involved in intracellular pathogens such as Mycobacterium tuberculosis, Brucella, Cryptococcus, Leishmania etc.  The type IV reaction is purely cellular in its response i. e. it purely mediated by sensitized cells only.  In this module students will learn the important features of type IV hypersensitive reaction and some medically important diseases involving the type IV hypersensitive reactions.

7. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.7 Type IV Hypersensitive Reaction-1  The type IV hypersensitive reaction mainly are mediated by sensitized T H1 cells.  The delayed type hypersensitive reaction usually remained localized and is characterized by the influx of large number of non specific inflammatory cells such as macrophages.  The delayed type hypersensitive reaction was first observed by Robert Koch in 1890 in individual infected with Mycobacterium tuberculosis.

8. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.8 Type IV Hypersensitive Reaction-2  In delayed type hypersensitive (DTH) reaction macrophages are mainly recruited in inflammed tissues.  The main immune cells involved in delayed type hypersensitive reaction are various types of macrophages such as Langerhans cells, dendritic cells.  Usually in delayed type hypersensitive reaction tissue damages are limited and the reaction play an important role in defense against intracellular pathogens.

9. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.9 Type IV Hypersensitive Reaction-3  Mechanism:- The DTH begin with initial sensitization of T H1 cells by a foreign antigen presented by antigen presenting cells such as macrophages. The activated TH cells clonally expand. During the subsequent exposure of the same antigen; these activated TH cells secrete variety of cytokines that attract variety of macrophages, non specific inflammatory cells and activate them. The activation of the macrophages take 24 - 48hr time.

10. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.10 Type IV Hypersensitive Reaction-4  Mechanism:- The damages in type IV hypersensitive reaction is mainly by overactivated Macrophages by TH1 cells.

11. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.11 Type IV Hypersensitive Reaction-5  Mechanism:- The activated macrophages at the site of their recruitment carryout massive phagocytic activity secreting large amount of lytic enzymes which result in non specific destruction of infected cells and thus killing of intracellular pathogens. Usually by DTH the intracellular pathogens are cleared completely, however some time if the antigens are not cleared completely, then prolonged DTH response developed into visible granulomatous reaction producing granuloma.

12. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.12 Type IV Hypersensitive Reaction-6  Mechanism:- The immune cells involved in type IV hypersensitive reaction are  Antigen presenting cells (APC) ‏  T H1 cells  Macrophages  Cytotoxic T cells The cytokines involved in type IV hypersensitive reaction are  IL-12 –secreted by antigen activated APC and stimulate differentiation of naive T cells into activated T H1 cells and increase production of INF- γ by T cells.  INF- γ –secreted by T cells and NK cells and activate macropahges.

13. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.13 Type IV Hypersensitive Reaction-7  Mechanism:-

14. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.14 Type IV Hypersensitive Reaction-8  Diseases involving DTH:- Tuberculosis:-  Pulmonary tuberculosis caused by Mycobacterium tuberculosis is contained by cells mediated immunity.  Delayed clearance of this infection develop DTH resulting in formation of granuloma.  The infection can be diagnosed with the help of DTH reaction by injecting PPD antigen derived from cell wall of Mycobacteria intradermally.  The characteristic skin lesion developed at the site of antigen injection showing positive DTH reaction.  The positive DTH reaction on skin show that pre exposure to mycobacteria.

15. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.15 Type IV Hypersensitive Reaction-9  Diseases involving DTH:- Contact dermatitis:-  It is development of inflammation on the skin when sensitized skin come into contact with chemicals such as nickel, turpentine, formaldehyde, active agents in cosmetics and hair dyes, poison oak, poison ivy.  When these chemical come into contact of skin proteins they acquire antigenic properties and internalized by skin macrophages which sensitize the T H1 cells.  When the same chemical come into contact of skin then sensitized T H1 cells. Mount DTH response resulting in the development of contact dermatitis.

16. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.16 What We Learn…..  Delay type hypersensitive reaction  Cells involved in DTH  Cytokines involved in DTH  Mechanism of DTH  Diseases involving DTH

17. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.17 Critical Thinking Question  Why INF-γ is essential in the development of DTH ?

18. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.18 Hints For Critical Thinking Question  INF-γ activate macrophages.  Enhance TNF production by macrophages and epithelial cells.

19. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.19 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.

20. © 2008, YCMOU. All Rights Reserved.20 End of the Presentation Thank You !