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

2. OC-SBT052-U01-02 Introduction Programmes and Courses  SEP – SBT052 – Unit 01

3. School of Science and Technology, Online Counseling Resource… © 2007, 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… © 2007, 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… © 2007, YCMOU. All Rights Reserved.5 Learning Objectives  After studying this module, you should be able to: Describe phagocytic cells of immune system. Discuss the functions of phagocytic cells in immunological reactions.

6. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.6 Introduction  This presentation is about Phagocytic cell, one of important cells of immune system.  You will learn about Different types of phagocytic cells Their immunological functions The mechanism of underlying these functions

7. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.7 Phagocytic Cells-1  Classes on the basis of size and nuclear shape:  Mononuclear macrophages:  Monocytes: circulating macrophages in blood.  Macrophages:  Dendritic cells (Immature macrophages in tissue)  Polymorphonuclear macrophages (granulocytes):  Nutrophiles  Basophiles  Eosinophils

8. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.8 Phagocytic Cells-2  Phagocytic cells in actions: In this diagram Phagocyte cell, is ingesting growing bacteria actively with the help of their long extending pseudopodia.

9. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.9 Phagocytes-3 Phagocytes possess capabilities of ingesting and killing microorganisms. Phagocytes after maturation migrate to the all parts of body, however they remain present in large number in spleen, liver, lungs, lymph nodes and bloodstream. There are different types of phagocytes: 1.Polymorphonuclear leucocytes such as neutrophils and granulocytes. 2.Monocytes.

10. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.10 Polymorphonuclear Leucocytes-1  Neutrophils:- is a type of phagocyte  These are specialized cells of immune system.  Polymorphonuclear cells (PMNs) or Neutrophils are motile and possess multilobed nucleus.  They possess characteristic surface antigen called as CD66.  Polymorphonuclear leucocytes are present in blood and migrate toward the site of infection and accumulate their, forming pus sometimes.  They are relatively smaller than mononuclear macrophages.  They are short lived.  They do not posses mitochondria and get their energy by the processes of glycolysis.

11. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.11 Polymorphonuclear Leucocytes-2  At the site of infection, activated phagocytes release cytokines such as granulocyte and granulocyte macrophage stimulating factor which stimulate division of myeloid precursor in bone marrow leading to increase in neutrophils count in blood (leucocytosis). Phagocytes engulf pathogens in membrane bound vesicles called as phagosomes. Phagosomes fuse with potent granules in the cytoplasm forming phagolysosomes.

12. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.12 Types of Polymorphonuclear Leucocytes-3 In phagolysosomes, killing of pathogens is brought about by two different reactions. The first type of reaction is oxygen dependent and is also called as respiratory burst in which there is sequential reduction by NADPH oxidase producing toxic oxygen metabolites such as hydrogen peroxide, hydroxyl radicals and singlet oxygen. The second type of reaction is oxygen independent and uses highly toxic cationic proteins (defensins ), enzyme myeloperoxidase and lysozyme.

13. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.13 Types of Polymorphonuclear Leucocytes-4  The second type of granules contain lysozymes, NADPH (oxidase which is involve in production of toxic oxygen products.) and  B12 -binding proteins and lactoferin, an iron chelating proteins.  The phagocytic cells possess number of receptor molecules on their cell surface:  Fc receptor: IgG antibody reacted with its Ags can bind to this Fc receptor. Thus bacterial cells coated with IgG antibody can be easily engulfed by the phagocytic cells, this process is called as opsonization.  Complement receptor: phagocytic cells possess complement receptor for the 3rd component i.e. C3b of the complement system.

14. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.14 Polymorphonuclear Leucocytes-5  Receptor Molecules on Phagocytic Cell surface: phagocytes also possess scavenger receptors which can bind to variety of plyanions present on the cells surface of bacteria.  Scavenger receptors: phagocytes also possess scavenger receptors which can bind to variety of plyanions present on the cells surface of bacteria.  Toll like receptors:Toll like receptors which can bind to number of patterns of surface antigen present of bacterial cells.  Binding of Toll like receptors with their corresponding antigens result into the production of INF-gamma which further initiate production of nitric acid by phagocyte to kill engulfed pathogens.

15. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.15 Polymorphonuclear Leucocytes-6  Eosinophils:- They are motile like Neutrophils. They can kill eukaryotic parasites with the help of their potent chemicals in the granules. Eosinophils possess Fc receptors for IgG and IgE. When parasites such as worm get coated with these antibodies, eosinophils get attached such antibodies coated antigen, here membrane of parasite, and get activated,such activated eosinophils release inflammatory mediators such as major basic proteins, leucotriens, cationic proteins, platelet-activation factors and eosinophil-derived neurotoxins by the process called as degranulation of eosinophils. These inflammatory chemicals of eosinophils can kill number of eukaryotic parasites including helminthes.

16. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.16 Polymorphonuclear Leucocytes-7  Mast Cells and Basophiles:- Basophiles and mast cells also possess Fc receptors for IgE. These cells get activated when there is cross-linking of these receptor molecules by the polyvalent antigens. The activated basophiles and mast, like eosinophils release inflammatory chemicals in their surrounding by the process of degranulation. These mediators of inflammation are responsible for type I hypersensitive reaction (Allergy) These mediators also cause local or systemic vasodilation and smooth muscle contractions.

17. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.17 Monocytes  It is a type of phagocyte  Like neutrophils, monocytes can migrate to the site of infection where they change their size and shape and become macrophages.  Macrophages can kill fungi and obligate intracellular pathogen such as M.tuberculosis.  Macrophages in skin is called as Langerhans’ cells.  Macrophages in liver tissues are called as Kupffer cells  In bone they are called as osteoclasts  In brain they are called as microglia

18. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.18 Monocytes  Morphological features of monocyte and phagocyte:- H ere the relative Size difference has been Shown. N ote that the monocyte is relatively smaller than macrophage. Monocyte Macrophage

19. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.19 Functions of Macrophage

20. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.20 Role of Macrophage-1  Activated macrophages secrete IL-1 and Tumor Necrosis Factor in response to lipopolysaccharide and endotoxin of Gram negative bacteria.  Serum level of TNF rises remarkably during infections caused by Gram negative bacteria such as meningococcal septicemia, malaria caused by P. falciparum, H.I.V. infection and Epstein-Barr virus infection.  Severity of these infection can be correlated with the serum level of TNF.  EBV infection in malaria patient causes development of Burkitt’s lymphoma (monoclonal tumor of B lymphocyte).

21. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.21 Role of Macrophage-1  Activation of Macrophage N ote that here macrophage is Activated by lipopolysaccharide of Gram Negative bacteria and interferon Gamma. N ote that activated macrophage Developed some more receptors such as MHC calls II,B7.

22. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.22 Role of Macrophage-2  The raised level of TNF prevent development of Burkitt’s lymphoma by inhibiting proliferation of B lymphocytes.  However in H.I.V. infection, raised level of TNF increases H.I.V replication in T lymphocytes.  TNF enhances MHC class I molecules on many types of cells.  TNF stimulate recruitment of neutrophils and monocytes to the site of infection and activate these cells to eliminate pathogens.  Both IL-1 and TNF secreted by activated macrophages act as endogenous pyrogen.

23. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.23 Role of Macrophage-3  There are also some adverse effects caused by TNF in their excessive production. E.g. prolonged production of TNF causes cachexia i.e. wasting of muscles and fat cells.  High level of TNF (i.e. 10-7 M) causes inhibition of myocardial contractility and smooth muscle tone which result into fall in blood pressure or shock.  TNF causes intravascular thrombosis because of loss of normal anticoagulant property of endothelium.  TNF causes necrosis of tumor because of thrombosis in the artery providing blood supply to the tumor.  High level of TNF causes metabolic disturbances.

24. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.24 Mechanism of Pathogens Killing-1  Production of bactericidal chemical by phagocytes

25. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.25 Mechanism of Pathogens Killing-2 Role of Myeloperoxidase:-

26. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.26 What We Learn…..  Different types phagocytic cells  Process of phagocytosis  Process of opsonization  Underlying mechanisms of phagocytosis and opsonization.  Other immunological functions of phagocytic cell.

27. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.27 Critical Thinking Questions  Why Infants who is not fed with mothers’ milk are more prone to pneumonia than infants fed with mothers’ milk?

28. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.28 Tips for Critical Thinking Questions  Infants’ pneumonia is commonly caused by H. Influenzae and S. pneuminae which are capsulated bacteria.

29. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.29 Study Tips  Book Title: Immunology, 5 th ed. Title: Immunology, 5 th ed. Author:Richard A. Goldsby & Thomas J. Kindt, etc. Author: Richard A. Goldsby & Thomas J. Kindt, etc. Publication: Publication: W.H. Freeman and Company, New York.

30. End of the Presentation Thank You !