Immunology-Lecture 1 PDF

Cancer Biology & Immunology Topic 1 Introduction to Immunology Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Immunology Immunology: the study of immun...

Cancer Biology & Immunology Topic 1 Introduction to Immunology Ass. Prof. Dr. Gharieb El-Sayyad Associate Professor of Medical Microbiology & Immunology, Faculty of Pharmacy, Galala University  Immunology Immunology: the study of immunity, cellular and molecular events that occur after exposure to microbes and other foreign macromolecules. It began as a study of the response of the whole animal to infection.  Immunity  Derived from the Latin word Immunitas: which referred to free of burden or the exemption from various civic duties.  It means a reaction of the immune system to foreign substances including microbes as well as macromolecules such as proteins and polysaccharides.  Immune system The importance of the immune system is shown in the following table  Functions of Immune System Role of immune Implications system Defense against Infections Deficient immunity results in increased susceptibility to infections, exemplified by AIDS. Vaccination boosts immune defenses and protects against infections. Recognizes and responds to Immune responses are important Tissue grafts barriers to transplantation and gene therapy Defense against Tumor Potential for immunotherapy of cancer Antibodies are highly specific Immunological approaches for laboratory reagents for detecting any class testing are widely used in clinical of molecules medicine and research.  Immune system is divided into: 1. Innate (Natural or Native) 2. Adaptive (Acquired or Specific) 1. Innate (Natural or Native)  It is called so because these defense mechanisms are always present, ready to recognize & eliminate microbes.  It is the first line of defense against infectious agents.  It is present prior to exposure to infectious microbes Examples:  Physical barriers  Phagocytic cells  Eosinophils in the blood and tissues  Natural killer cells (NK, class of lymphocyte)  Blood-borne molecules. 2. Adaptive (Acquired or Specific) It is directed against microbial & non-microbial antigens. Adaptive immune system is called upon breaching of first defenses. It produces specific reaction to each infectious agent which normally eradicates that agent. It must be stimulated with microbes before it can be effective. It remembers the previous infectious agent and can prevent it (e.g. diseases such as measles and diphtheria produce a life-long immunity following infection. Its defense mechanisms increase in magnitude and defensive capability with each successive exposure to a particular macromolecule. Responses of Innate & Adaptive Immune System to Infection  Major Elements of Innate & Adaptive Immune Systems Innate immune system Adaptive immune system Action First line of defense against Second line of defense. infection. Not improved by repeated Improved by repeated infection infection Soluble factors or Lysozyme, Complement, Antibody Mediators acute phase proteins e.g. CRP, Macrophage-derived Lymphocyte-derived cytokines cytokines e.g. interferon  (e.g.  and  Interferons, tumor necrosis factor TNF) Cells Phagocytes (Neutrophil Lymphocytes Monocytes, Macrophages, and Polymorphs) Natural killer (NK) cells Physiochemical Skin, mucous membranes Antibodies in mucosal Barriers secretions Specificity Non specific Specific  Exterior defense is represented by Biochemical & Physical defenses which include:  Lysozyme in most secretions  Sebaceous gland secretions  Mucus secretion  Spermine in semen  Acid in stomach  Potent Biochemical subs. (tears, lysozyme, complements)  Skin & Mucus membrane  Cilia lining trachea  Commensal organisms in gut & vagina  Recognition of Microbes by Innate Immune System Innate immunity recognizes structures that are shared by microbes (bacteria, or viruses or fungi) & not present on host cells. For instance:  Phagocytes express receptors for bacterial LPS which is present in many bacterial species but is not produced by mammalian cells.  Phagocytes express receptors for terminal mannose residues on bacterial glycoproteins (Mammalian glycoproteins end with Sialic acid or N-acetyl Galactoseamine).  Phagocytes recognize and respond to ds RNA, which is found in many viruses but not in mammalian DNA.  Neutrophils & Macrophages express receptors for antibodies & complement proteins which are important in antibody & complement-mediated elimination of microbes.  Innate immunity recognize structures of microbes that are often essential for survival and infectivity of these microbes & may be common among microbes. Therefore a microbes can not evade innate immunity. Adaptive immunity is specific for antigens that may be microbial or nonmicrobial, not essential for survival and may differ among microbes of the same type. So, microbes can evade adaptive immunity by mutating the antigens that are recognized by lymphocytes, because these antigens are usually not required for the life of the microbes.  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. Dr. Gharieb S. El-Sayyad  Lecture 1 Questions Functions of Immune System & their implications (Table) Responses of Innate & Adaptive Immune System to Infection (Diagram) Major Elements of Innate & Adaptive Immune Systems (Table) Innate immunity is exhibited by Biochemical & Physical defenses (Explain) Recognition of Microbes by Innate Immune System Components of Innate Immunity (Enumerate) Functions of Macrophages (Enumerate)