Immunology Lecture 2.pdf

Cancer Biology & Immunology Topic 2 Components of Innate Immunity Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Components of Innate Immunity 1. Intact skin 2. Phagocytes...

Cancer Biology & Immunology Topic 2 Components of Innate Immunity Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Components of Innate Immunity 1. Intact skin 2. Phagocytes (Neutrophils, Monocytes, Macrophages) 3. Natural killer (NK) cells 4. Soluble factors  Interferons  Lysozyme  Acute phase proteins CRP  Complement  Cytokines of innate immunity  Components of Innate Immunity 1. Intact skin It acts as good physical barrier, the importance of this barrier becomes clear when individual suffers serious burns where its epithelial barrier affected Most infections enter the body via epithelial surface of the nasopharynx, gut, lungs and genito-urinary tract. These areas are protected from most infections by physical & biochemical defenses, e.g. lysozymes which present in different body secretions.  Components of Innate Immunity 2. Phagocytes (Neutrophils, Monocytes, Macrophages) Bone marrow deliver blood monocytes which when traveled into tissues called macrophages (monocytes/macrophage series). Macrophage in tissues include alveolar macrophages, splenic and lymph nodes resident and recirculating macrophages. Bone marrow deliver directly Phagocytic cells, e.g. brain microglial cells, liver kupffer cells, kidney mesangial phagocytic cells, synovial A cells (line the synovial cavity).  Circulating Phagocytes (Neutrophils & Monocytes) when recruited to sites of infection, they recognize & ingest microbes for intracellular killing. Neutrophils (called polymorphonuclear leukocytes, PMNs) are the most abundant leukocytes in the blood (4000-10,000 /mm3). Monocytes are less abundant than neutrophils (500-1000 /mm3). Unlike neutrophils, monocytes that enter extravascular tissues survive in these sites for long periods. In the tissues, these monocytes differentiate into cells called macrophages. Blood monocytes and tissue macrophages are two stages of the same cell lineage, which is called mononuclear phagocyte system. Resident macrophages are found in the connective tissues and in every organ in the body.  Functions of Macrophages Produce cytokines that are important mediators of the host defense. Secrete growth factors & enzymes that serve to remodel injured tissue and replace it with connective tissue. Stimulate NK by secretion of IL-12 Stimulate T lymphocytes and respond to products of T cells. Phagocytosis is a process in which the phagocyte extends its plasma membrane around the microbes, the membrane closes up and pinches off, and the particle is internalized in a membrane bound vesicle, called a phagosome. The phagosomes fuse with lysosomes to form phagolysosomes. After ingestion of the microbe by phagocytes, several enzymes are activated in the phagolysosomes.  Phagocyte Oxidase, converts molecular oxygen into superoxide anion and free radicals. These substances are called reactive oxygen intermediates (ROIs) and they are toxic to the ingested microbes.  Nitric Oxide Synthase, which catalyzes the conversion of arginine to nitric oxide (NO) also a microbicidal substance.  Lysosomal Proteases, which break down microbial proteins only.  Inherited deficiency of phagocyte Oxidase enzyme is the cause of an immunodeficiency disease called Chronic Granulomatous Disease (CGD). In this disorder, phagocytes are unable to eradicate intracellular microbes. The host tries to contain the infection by calling in more macrophages & lymphocytes, resulting in collections of cells around the microbes that are called granulomas.  3. NK cells & Soluble Factors Natural killer (NK) cells NK recognizes cell surface changes or virally-infected cells, by killing infected cells and by producing the cytokine, interferon- (IFN-) which activates macrophages. Macrophages that have encountered microbes activate NK through cytokines. One of these cytokines produced by macrophages, called interleukin-12 (IL-12). IFN- NK Macrophage IL-12 4. Soluble factors Interferons are components of the innate immune system, they are produced by virally infected cells and sometimes by lymphocytes. They are produced very early in infection and act as the first line of resistance against many viruses. They activate NK cells and induce a state of viral resistance in uninfected cells. Lysozyme Breaks cell wall peptidoglycan of bacteria where it cleavages the bridge between N-acetylglucosamine (GlcNac) and N- acetylmuramic acid (MurNac).  Acute phase proteins These are serum proteins, their concentration increases rapidly during infection (up to100 fold) e.g.: CRP: C reactive protein, so called because of its ability to bind the C protein of pneumococci. Function of CRP: its binding to bacteria 1. Promotes complement activation 2. Facilitate their uptake by phagocytes. The process of protein coating to enhance phagocytosis (opsonization). Complement Mediates a cascade of enzymatic reactions that leads to 1. Target cell lysis 2. Enhanced phagocytosis (opsonization) of microbes.  Cytokines of innate immunity  stimulate inflammation (TNF, IL-1, chemokines)  activate NK cells (IL-12)  activate macrophages (IFN-)  prevent viral infections (Type I IFN)  Early defense against infections  Provide “second signals” for the activation of B and T lymphocytes.  There is a constant bi-directional cross-talk between innate immunity and adaptive immunity. Dr. Gharieb S. El-Sayyad