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Transcript
Immunology L1 Dr. Hayder Naji Immunity :- is defined as resistance to disease, specifically infectious disease. Immune system :-The collection of cells, tissues , and molecules that mediate resistance to infections . Immune response :- the coordinated reaction of immune cells and molecules to infectious microbes. Immunology :- is the study of the immune system and its responses to invading pathogens. The physiologic function of the immune system is to prevent infections and to eradicate established infections. Innate and adaptive immunity / innate immunity (also called natural or native immunity), which mediates the initial protection against infections, this type of host defense is always present in healthy individuals, prepared to block the entry of microbes and to rapidly eliminate microbes that do succeed in entering host tissues. The first line of defense in innate immunity is provided by epithelial barriers and by specialized cells and natural antibiotics present in epithelia, all of which function to block the entry of microbes. If microbes do breach epithelia and enter the tissues or circulation, they are attacked By phagocytes, specialized lymphocytes called natural killer (NK) cells, and several plasma proteins, including the proteins of the complement system. All these mechanisms of innate immunity specifically recognize and react against microbes but do not react against noninfectious foreign substances. innate immune responses enhance adaptive immune responses against the infectious agents. 1 Immunology L1 Dr. Hayder Naji Adaptive immunity ( also called specific or acquired immunity), which develop more slowly and mediates later, even more effective, defense against infections . it stimulated by microbes that invade tissues. The adaptive immune system consists of lymphocytes and their products, such as antibodies. Whereas the mechanisms of innate immunity recognize structures shared by classes of microbes, the cells of adaptive immunity, namely, lymphocytes, express receptors that specifically recognize different substances produced by microbes as well as noninfectious molecules. These substances are called antigens. Adaptive immune responses generate mechanisms that are specialized to combat different types of infections. For example, antibodies function to eliminate microbes in extracellular fluids, and activated T lymphocytes eliminate microbes living inside cells. Types of Adaptive Immunity :- There are two types of adaptive immunity, called Humoral and cell mediated immunity, that are mediated by different cells and molecules and are designed to provide defense against extracellular microbes and intracellular microbes, respectively. Humoral immunity is mediated by proteins called antibodies, which are produced by cells called B lymphocytes. Antibodies neutralize and eliminate microbes and microbial toxins that are present in the blood and in the lumens of mucosal organs. Antibodies do not have access to microbes that live and divide inside infected cells. Defense against such intracellular microbes is called cell-mediated immunity because it is mediated by cells called T lymphocytes Some T lymphocytes 2 Immunology L1 Dr. Hayder Naji activate phagocytes to destroy microbes that have been ingested by the phagocytes into phagocytic vesicles. Other T lymphocytes kill any type of host cells that are having infectious microbes in the cytoplasm. The antibodies produced by B lymphocytes are designed to specifically recognize extracellular microbial antigens, whereas T lymphocyte recognize antigens produced by intracellular microbes. Another important difference between B and T lymphocytes is that most T cells recognize only microbial protein antigens, whereas antibodies are able to recognize many different types of microbial molecules, including proteins, carbohydrate, and lipids. Immunity may be induced in an individual by infection or vaccination (active immunity) or conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual (passive immunity). Passive immunity is therefore useful for rapidly conferring immunity, but it does not induce long-lived resistance to the infection. An excellent example of passive immunity is acquiring antibodies from mothers through the placenta and milk. Cells of the Immune System I. Agranular Leukocytes White blood cells with a single, unlobed nucleus and cytoplasm that contains few or no granules are known as agranular leukocytes. Agranular leukocytes derive from lymphoid or myeloid lineage precursors and account for approximately 35% to 38% of the leukocytes in circulation. 3 Immunology L1 Dr. Hayder Naji A. Lymphoid lineage cells B lymphocytes or B cells / reside in the bone marrow and are able to synthesize immunoglobulin molecules. In fact, B cells and plasma cells, are the only cells that are capable of immunoglobulin synthesis. T lymphocytes / lymphoid lineage cells of bone marrow origin migrate to, differentiate in, and are vetted within the thymus. natural killer (NK) cell / These large, nonphagocytic, granular lymphocytes are named for their ability to kill abnormal (e.g., infected or malignant) host cells . They account for 5% to 10% of all lymphocytes in the circulation. B. Monocytic lineage cells Mononuclear cells that differentiate from myeloid precursors are known as monocytes in the circulation or macrophages once they leave the circulation and enter the tissues. Monocytes are large mononuclear cells and account for approximately 5% to 7% of the leukocytes in the peripheral blood .Monocytes spend 1 to 2 days in the circulation (their half-life is approximately 8.4 hours), then cross the endothelium to enter tissues throughout the body, where they reside for up to several months as macrophages. They phagocytize, or pick up cellular debris, foreign cells, and particles and degrade them enzymatically. Another group of phagocytic cells with both myeloid and lymphoid origins is collectively known as dendritic cells, so named for their branchlike cytoplasmic projections II. Granular Leukocytes These cells have multilobed nuclei and cytoplasmic granules that contain amines (stained by basic dyes), basic proteins 4 Immunology L1 Dr. Hayder Naji (stained with acidophilic or eosinophilic dyes), or both (neutral staining). A. Neutrophils Comprising approximately 60% of the peripheral blood leukocytes, neutrophils are the most numerous leukocyte population. They are also called polymorphonuclear (PMN) cells because of their variable number of nuclear segments (two to five). With a half-life of approximately 7 hours, over 100 billion neutrophils enter the circulation daily in normal adults. Neutrophils are very effective at killing bacteria. An increase in the number of peripheral blood neutrophils is often an indication of acute infection. B. Basophils and mast cells The acidic cytoplasmic granules of basophils contain vasoactive amines (e.g., histamine) that cause smooth muscle contraction . These bilobed cells are found in low numbers in the peripheral blood (0% to 1%) or in their tissue resident form, known as mast cells. Both basophils and mast cells are important in allergic reactions of the adaptive immune response. C. Eosinophils So named because of their “eosin-loving” granules (eosin is a dye used in histology), eosinophils are bilobed granulocytes with cytoplasmic granules that contain basic proteins. Although they comprise 0% to 5% of the peripheral blood leukocytes, eosinophils are active participants in innate and adaptive immune responses to parasitic helminth (worm) infections . 5 Immunology L1 Dr. Hayder Naji Recognition of Microbes by the Innate lmmune System The components of innate munity recognize structures that are shad by various classes of microbes and are not present on host cells Phagocytes express receptors for bacterial lipopolysaccharide (LPS, also called endotaxin), which is present in many bacterial species but is not produced by mammalian cells. phagocytes reccgnize terminal mannose residues on glycoproteins; many bacterial glycoproteins have terminal mannose, unlike mammalian glycoproteins, which end with sialic acid or N-acetylgalactosamine. Phagocytes recognize and respond to double-stranded RNA, which is found in many viruses but not in mammalian cells. unmethylated CpG nucleotides, which are common in bacterial DNA but are not found in mammalian DNA. The microbial molecules that are the targets of innate immunity are sometimes called molecular patterns, to indicate that they are shared by microbes of the same type. The receptors of innate immunity that recognize these shared structures are called pattern recognition receptors In contrast to innate immunity, the adaptive immune system is specific for structures, called antigens, that may be microbial or nonmicrobial. The receptors of the innate immune system are encoded in the germline and are not produced by somatic recombination of genes. Therefore, the specificity of adaptive immunity is much more diverse than that of innate immunity, and the adaptive immune system is capable of recognizing many more chemically distinct structures. It is estimated that the total 6 Immunology L1 Dr. Hayder Naji population of lymphocytes can recognize over a billion different antigens; in contrast all the receptors of innate immunity probably recognize less than a thousand microbial patterns. The innate immune system responds in the same way to repeat encounter with a microbe, whereas the adaptive immune system responds more efficiently to each successive encounter with a microbe. Cellular receptors of innate immune system:- Toll-like receptors (TLRs). TLR-2 bacterial lipoglycans TLR-3, -7,-8 for viral nucleic acid TLR-4 for bacterial LPS (endotoxin) TLR-5 for a component of bacterial flagella called flagellin TLR-9 for unmethylated CG rich (CpG) oligonucleotides which are more abundant in bacteria than in mammalian cells 7