Innate Immunity ppt..pptx

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1. I mmune System and Innate i mmunity Dr.Sherzad M Taher Medical Immunology College Of Pharmacy UoD September 12,2023

2. Immunology Immunology deals with physiological functioning of the immune system in states of both health and disease as well as malfunctions of the immune system in immunological disorders like allergies, hypersensitivities, immune deficiency, transplant rejection and autoimmune disorders . Immune system - includes all parts of the body that help in the recognition and destruction of foreign materials. White blood cells, phagocytes and lymphocytes, bone marrow, lymphnodes , tonsils, thymus, and your spleen are all part of the immune system.

3. Innate and adaptive immunity

4. Components of the Innate Immune System P hysical( Anatomical ) barriers of innate immunity Chemical barriers of innate immunity Biological barriers of innate immunity Physiological barrier of innate immunity Cellular Response Blood Proteins Inflammatory Response

5. Physical Barriers of Innate Immunity Anatomical barriers or physical barriers block the entry of pathogens into the body physically. Skin is the first mechanical barrier that makes the entry of pathogens difficult because of the epidermis . Hair , an accessory organ on the skin, also prevents the entry of pathogens . Mucous membranes (ciliated epithelial cells; ) - GI, urogenital, respiratory tracts - collectively represents a huge surface area.

6. Chemical barriers block entry of pathogens at body openings and inner body surfaces. Examples of chemical barriers include sweat , breastmilk , mucus, saliva, tears and semen . Vaginal secretion is acidic in nature and is not endured by pathogens. Semen has zinc which is intolerable by pathogens . The digestive juices (pepsin) produced in the stomach also kill foreign invaders . Chemical barriers of innate immunity : 

7. Chemical barriers of innate immunity :  Fatty acids , lactic acid Lysozyme -hydrolytic enzyme found in mucous secretions - able to cleave the peptidoglycan layer of the bacterial cell wall Anti-microbial substances which directly destroy microorganims : cryptidins and defensins a- cryptidins (produced in base of crypts of small intestine - damage cell membranes) b- defensins (produced within skin, respiratory tract - also damages cell membranes ) surfactant proteins A & D (present in lungs - function as opsonins which enhance the efficiency of phagocytosis)

8. Chemical barriers of innate immunity :  Interferons - group of proteins produced by cells following viral infection. Secreted by the cells, and then binds to nearby cells and induces mechanisms which inhibit viral replication . Acute phase proteins proteins in the plasma that increase during infection and inflammation ex: C-reactive protein (CRP) can be used diagnostically in many diseases to give an indication of acute inflammation

9. Biological barriers of innate immunity :  There are a number of harmless bacteria ( normal flora) that live inside our urinary, gastrointestinal and reproductive tracts that make the environment inhospitable for pathogens or harmful bacteria to survive in our body.

10. Physiological barrier of innate immunity Temperature - normal body temperature inhibits growth of many microorganisms. Elevated body temperature (fever) can have a direct effect on pathogenic microorganisms

11. Cellular Response The cellular response of the innate immune system involves different kinds of leukocytes that kill pathogens by phagocytosis. These leukocytes circulate in the blood and single-handedly kill the pathogens that invade our bodies.

12. Cellular Response Phagocytosis is an important cellular process where a cell engulfs larger and harmful particles by extending its plasma membrane. In this process, the phagocytic cell extends its plasma membrane to envelope the pathogen inside it and form a vesicle called a phagosome . The phagosome then fused with the lysosome, together known as the phagolysosome . Acids and digestive enzymes secreted from the lysosome kill the pathogens . The cells involved in phagocytosis include neutrophils, macrophages and dendritic cells.

13. Blood Proteins The liver cells or hepatocytes produce a range of proteins that destroy the invading pathogens . These proteins are produced as a result of the complement system .  A group of serum proteins that circulate in an inactive proenzyme state. These proteins can be activated by a variety of specific and nonspecific immunologic mechanisms that convert the inactive proenzymes into active enzymes. The activated complement components participate in a controlled enzymatic cascade that results in membrane-damaging reactions which destroy pathogenic organisms by formation of a membrane attack comples (MAC).

14. Blood Proteins The complement system is a biochemical cascade that complements the ability of  antibodies  to kill pathogens. The proteins of the complement system work in the following ways : They help in the recruitment of inflammatory cells. They coat the surface of the pathogen, making it an easy target for destruction. It forms a hole Called membrane attack complex (MAC) in the pathogen cell wall, causing its cytolysis and destruction. It filters the neutralised antibody-antigen complexes out of the body.

15. Inflammatory Response The inflammatory response is observed when a pathogen is able to break anatomical barriers and enter our body. Inflammation is recognized as redness , swelling , pain and loss of function in the infected area. It is triggered by chemicals such as histamine and cytokines that are secreted by injured cells or immune system cells such as macrophages . These chemicals recruit leukocytes to the site of injury for pathogen killing and tissue repair. Some cytokines are anti-viral in nature such that they block the protein synthesis in host cells which is a prerequisite for the virus to survive and divide .

16. Cells involve in the innate immunity

17. Neutrophils These cells are most abundant and effective during the inflammation and phagocytosis processes. Neutrophils (PMN) are characterized as being the first cell line that is recruited at the inflammation site after chemotactic stimuli.

18. Eosinophils These granulocytes are present in the respiratory, gastrointestinal, and urinary tract, and they are less abundant than neutrophils. Their effector function is mediated by degranulation and release of histamine, cationic proteins, major basic protein, and chemotactic factors such as leukotrienes and prostaglandins

19. Basophils and mast cells These cells are not phagocytic in nature and have several receptors including IgE receptors. The proportion of basophils in circulation is lower than the proportion of other granulocytes. Mast cells are located in tissues, mainly in mucosa, and their granules contain heparin, serotonin, and histamine.

20. Monocyte and macrophages are considered important actors in both innate and adaptive immunity . Monocytes circulate in peripheral blood and have the ability to not only migrate to the inflammatory site but also exhibit the plasticity to transform themselves into tissue macrophages . Thus, macrophages take different names according to their tissue location, such as osteoclasts (bone), alveolar macrophages (lung), microglial cells (brain), histiocytes (connective tissue), Kupffer cells (liver), Langerhans cells (LC) (skin), etc

21. Monocyte and macrophages macrophages functions : i ) they are phagocytic and exhibit a microbicidal mechanism through oxygen -dependent and-independent mechanism; ii) they are able to present antigens and activate lymphocytes; iii) once activated, they release and stimulate cytokine secretion; iv) they modulate the immune response; v) they participate in tissue reorganization after the inflammation process has ceased through production of extracellular matrix proteins (i.e., collagen and elastase ) and matrix metalloproteinases ; vi ) they produce cytotoxic factors involved in the immunity against tumors

22. Dendritic cells (DCs) DCs are considered to be professional antigen-presenting cells (APC). They reside in and patrol the skin and mucosal surfaces, thus playing an important role in the innate immune system with subsequent activation of T cell responses to provide a cell-mediated immunity against microbial pathogens.

23. Natural killer (NK) cells NK cells exhibit an immunomodulatory role in the cell-mediated immune responses due their cytotoxic activity. They are also involved in antimicrobial defense and in the immunological surveillance by controlling tumoral growth and maintaining the immunological homeostasis.

24. Epithelial and endothelial cells In addition to acting as a physical barrier, epithelial and endothelial cells express PRRs on their surface that recognize pathogen-associated molecular patterns (PAMPs) from microorganisms; secrete proinflammatory cytokines including IL-1, IL-6, and IL-8; and release antimicrobial peptides

25. Platelets Platelets are recognized by their participation in the coagulation process, control of bleeding, and defense against infectious agents . These cells express PRRs on their surface and produce cytokines and chemotactic molecules to recruit leukocytes at the inflammatory site. Platelets interact with leukocytes and endothelial cells through the expression of the adhesion molecule, P- selectin , which mediates proinflammatory events