Natural Defense mechanisms 2020 (1).pdf

Natural Defense Mechanisms Immunology Unit Dept. of Pathology College of Medicine KSU  Reference Kuby Immunology 7th Edition 2013 Chapter 4 Pages 105-110 Chapter 5 Pages 141-176 Chapter 6 Pages 187-200 & page 213 2 ...

Natural Defense Mechanisms Immunology Unit Dept. of Pathology College of Medicine KSU  Reference Kuby Immunology 7th Edition 2013 Chapter 4 Pages 105-110 Chapter 5 Pages 141-176 Chapter 6 Pages 187-200 & page 213 2  Objectives o + To know First (non-specific immunity) and second (adaptive immunity) lines of defense o + To understand the Complement system, its activation and how it involves in pathogen killing. o + To recognize the importance of accumulation of inflammatory cells for clearance of infection o + To know the role of cytokines as mediators which regulate inflammation 3  The main function of the immune system is to protect from infections: Viruses e.g. Influenza Parasites e.g. Polio Tapeworms Malaria Fungi e.g. Bacteria e.g. Candida Tubercule bacillus albicans Staphylococci First and the second lines of defense: First Line of Defense Second Line of Defense First line of defense : ◼ Natural (Innate) Immunity ◼ Physical (skin/ mucous membranes ) ◼ Mechanical (Coughing, sneezing, vomiting, action of cilia in trachea) ◼ Biochemical barriers (antimicrobial peptides, lung secretions, mucus, saliva, tears) Physical and mechanical barriers ◼ Skin, impermeable to microbes. ◼ Mucous membranes lining the gastrointestinal, genitourinary and respiratory tracts. ◼ Other protective mechanisms:  Shedding of outer skin layers.  Coughing and sneezing.  Flushing of urine.  Vomiting.  Mucus and cilia in respiratory tract. Biochemical barriers ◼ Body secretions contain anti-bacterial substances e.g. saliva, tears and sweat. ◼ Antimicrobial peptides (e.g., defensins, hepcidins) ◼ Normal bacterial flora. (Compete with pathogenic bacteria for nutrients) ◼ Inflammation: ◼ Inflammation is the first response of the immune system to infection or irritation. ◼ It consist of a series of vascular & cellular changes that occur in response to various stimuli e.g. infections, injury, radiation etc. 9 Microbial infections initiate inflammation As bacteria possess an array of pro-inflammatory molecules:  e.g. Lipopolysaccharides (LPS) 10 Inflammation  Goals ◼ Prevent and limit infection and further damage ◼ Interact with adaptive immune system ◼ - For example Monocytes / Macrophages serve as a link between the adaptive and innate immunity by antigen presentation ◼ Prepare the area of injury for healing  The Complement system ◼ Consists of a group of serum proteins initially present in inactive form ◼ Activation occurs in cascade (one component or more activating another) after enzymatic cleavage. Once components become activated they produce important biological effects that initiate inflammation. ◼ This system plays an important role in linking Innate & Adaptive immunity 14 Membrane Attack Complex formation C5-activation b C3b C4b Components of the Membrane Attack Complex C7 C6 C 9 Membrane Attack Complex components Assembly C6 C7 b  Membrane Attack Complex formation : insertion of lytic complex into cell membrane C6 C7 b CC C C 9 9 9 9 C C 9 C C C 9 9 9 9 Biological effects of complement activation 1. Anaphylatoxin functions (e.g. C3a, C5a): - Trigger degranulation (release of substances) of endothelial cells, mast cells or phagocytes. - Induce smooth muscle contraction and increased vascular permeability. - Attract additional inflammatory cells to the site of activation. 2. Opsonization: C3b is the main opsonin and to a lesser extent C4b. - Coating of bacteria enhances phagocytosis 3. Direct cell lysis: - Destruction of bacteria. 19 Process of chemotaxis: Rolling on vessel wall. Adhesion (attach) Pass through. : 20 Types of Cells attracted to the site of infection that mediate inflammation : Monocytes : ◼ Become Macrophages when they leave the blood and enter the tissues. Neutrophils: (Phagocytic cells) Eosinophils: (Allergy and Parasitic infections) Natural Killer (NK) cells: (Kill tumor cells and virus infected cells) 21 Phagocytic cells (neutrophils & macrophages) at site of infection start the process of phagocytosis which is the process by which a cell engulf a solid particle such bacteria to form internal vesicle known as phagosome 22 Macrophage attacking E. coli Phagocytosis 24 Cytokines Soluble molecules, produced by different cells, that control cell functions e.g. differentiation, proliferation activation or inhibition. e.g. Interleukins ◼ Produced primarily by macrophages and lymphocytes in response to a pathogen. ◼ Many types ◼ Examples IL-1, IL-2, IL-3….... Cytokines  Interferons: ◼ Protects against viral infections ◼ Produced and released by virally infected cells in response to viral infections. Cytokines  Tumor necrosis factor (TNF) ◼ Secreted by macrophages. - Induces fever by acting as an endogenous pyrogen (a substance released from inside the body that produces fever) - - Increases synthesis of inflammatory serum proteins - - Increase expression of adhesion molecules on endothelial cells and vascular permeability  Take home message  1. Non-specific (innate immunity) acts as a first line of defense against invading pathogens  2. Innate immunity is an important initial step for generation of adaptive immune response  3. Inflammation is vital for controlling infection and limiting tissue damage 28 Thank you 29