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PSL201Y1 (124)
Yue Li (8)
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BLOOD&IMM-02,03.docx

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Department
Physiology
Course
PSL201Y1
Professor
Yue Li
Semester
Fall

Description
23 THE IMMUNE SYSTEM  Immunity refers to the immune system’s capacity to protect individuals from disease by recognizing and eliminating potentially pathogenic (disease-generating) agents, including bacteria, bacterial toxins, viruses, parasites, and fungi.  The presence in the body of such foreign and abnormal substances induces the immune system to develop an immune response, a complex series of physiological events that culminates in the destruction and elimination of these substances. Anatomy of the Immune System  Lymphoid tissues: bone marrow, thymus, spleen, lymph nodes, and tonsils, in which leukocytes develop, reside, and come into contact with foreign materials. LEUKOCYTES  The granulocytes – neutrophils, eosinophils, and basophils – have cytoplasmic granules that contain secretory products, degranulation.  The agranulocytes – monocytes and lymphocytes – lack granules.  PHAGOCYTES o Neutrophils, eosinophils, monocytes, macrophages, and dendritic cells are all phagocytes o Neutrophils release cytokines involved in inflammation. o Eosinophils’ primary role in the immune system is to defend against parasites by releasing toxic substances. o Monocytes are phagocytes in the blood, but they differentiate into macrophages in the tissue to phagocytose tissue foreign matter. There are fixed macrophages and wandering macrophages.  LYMPHOCYTES o Lymphocytes are of three major types: B lymphocytes (B cells), T lymphocytes (T cells), and null cells (lack cell membrane components that are characteristic of B cells and T cells). o Most null cells are large, granular lymphocytes known as natural killers (NK) cells. o When B cells contact foreign/abnormal molecules (antigens), they develop into plasma cells, which secrete antibodies. o Antibodies (immunoglobulins) are proteins present in the plasma and interstitial fluid that target specific antigens for destruction. o T cells do direct damage to foreign or abnormal cells. They contact infected cells, mutant cells, and transplanted cells and then take several days to develop into active cytotoxic T cells that destroy the infected or abnormal cells. o T cells secrete molecules that form pores in the target cell’s membrane. The target cell succumbs to lysis, a process in which it fills with fluid and bursts. o NK cells fight viral infections. They limit the production of new viruses in the body. o NK differ from cytotoxic T cells by exhibiting immediate readiness, which enables them to respond well before B cells and T cells as an essential part of early immune responses.  MAST CELLS AND DENDRITIC CELLS o Precursors of mast and dendritic cells are formed in the bone marrow from hematopoietic stem cells. Circulate freely and mature in the tissue. o Mast cells: found in skin and mucosal epithelial tissue; secrete histamine. o Dendritic cells: similar to macrophages in their ability to phagocytose or endocytose pathogens.  LYMPHOID TISSUE o All leukocytes develop from hematopoietic cells (blood-forming) stem cells in the bone marrow. B lymphocytes also fully mature in the bone marrow. o T lymphocytes must migrate to the thymus gland before they develop into maturity. o Central lymphoid tissues: bone marrow and the thymus (as well as the fetal liver) are sites of lymphocyte maturation. o Peripheral lymphoid tissue: spleen, lymph nodes, tonsils, adenoids, appendix, lymph nodules (GI tract), and regions in the lining of the GI (Peyer’s patches); collections of B cells, T cells, and macrophages. o Each peripheral lymphoid tissues contains a dense network of cells hat trap microorganisms and foreign particles. 23 THE IMMUNE SYSTEM o Spleen collects worn-out erythrocytes from the blood; it is also collecting bloodborne microorganisms and foreign particles. o Microorganisms and particles carried in lymph are trapped by lymph node (where lymphatic vessels converge). o Macrophage and lymphocyte networks of the spleen and lymph nodes filter blood and lymph, respectively. o Tonsils and adenoids trap inhaled particles and microorganisms. o Appendix, lymph nodules and peyer’s patches trap substances that enter the body in ingested food or water. Organization of the Body’s Defenses  Nonspecific defenses: against potentially harmful substances without regard to their precise identity. Operate before foreign material enters the body, in the form of skin and mucous membranes.  Specific immune responses: highly selective (meaning they target specific substances) and come into pla y after nonspecific responses have already begun. Mediated by lymphocytes. This response strengthens with each exposure to a particular offending agent. NONSPECIFIC DEFENSES  Includes physical barriers, inflammation (a complex series of events causing accumulation of proteins, fluid, and phagocytic cells in an area of tissue that has been injured or invaded by microorganisms), interferons (a family of related proteins that can induce virus resistance to other cells), complement system ( a group of plasma proteins that act to lyse foreign cells).  PHYSICAL BARRIERS o Skin and mucous membrances. o Skin consists of an outer epidermis and inner dermis. Epidermis consists of tightly packed epithelial cells and lacks blood vessels. o Outermost layer is composed of dead cells and keratin. o Within the dermis are sebaceous glands, which secrete an acidic oily substance, sebum that inhibits bacterial growth. o Viscous mucus, which bathes the surfaces of exposed epithelia and can trap foreign matter and potential pathogens. Have ciliated epithelial cells that line the trachea  INFLAMMATION o Microbial invasion or damage to tissue triggers a complex series of events that rapidly lead to inflammation of the affected tissue. o 5 major events: 1) nearby macrophages engulf debris and foreign matter 2) nearby capillaries dilate and become more permeable to proteins and fluid 3) foreign matter is contained 4) addition leukocytes migrate into the region 5) recruited leukocytes continue to help clear the infection, mainly by phagocytosis.  PHAGOCYTOSIS OF PATHOGENS AND DEBRIS BY NEARBY MACROPHAGES o Macrophages detect bacteria using receptor proteins. The resulting attachment initiates phagocytosis. o Also stimulates the macrophages to secrete cytokines, proteins that are secreted by cells in response to a stimulus. o Cytokines secreted by macrophages contribute to subsequent steps in inflammation.  DILATION AND INCREASED PERMEABILITY OF CAPILLARIES o Nearby blood vessels dilate. The capillary walls become more permeable. o Increased blood flow brings additional leukocytes and defensive proteins into the local circulation. o Increased permeability allows these proteins to move into the tissues. o Leukocytes that gather in these dilated vessels migrate from the blood into the tissue spaces. o Vasodilation and increase capillary permeability are induced by histamine released from a variety of cells in response to injury. o Histamine 4 characteristic symptoms: redness, swelling, heat, and pain. o As the capillaries become engorged with blood, the resulting increase in hydrostatic pressure plus the increased interstitial osmotic pressure that accompanies the leakage of plasma proteins causes fluid to filter out of the capillaries and into the tissue spaces, resulting in edema. 23 THE IMMUNE SYSTEM o The edema exerts pressure against the surrounding tissue and skin, which contributes to pain (pain- inducing chemical, bradykinin) o Even though these vascular changes bring discomfort, they help gather nonspecific defenses to the site of injury.  CONTAINMENT OF FOREIGN MATTER o Mast cells and basophils release anticoagulant heparin (suspends blood clotting and allows leukocytes to get into injured tissues). o Clotting factors become active and form clots around clusters of bacteria, inhibiting spread. o Other plasma proteins and proteins released from damaged tissue aid process of clot formation. o Portion of the clot that is at the skin’s surface dries and hardens, hence a scab which will get replaced with new cells.  LEUKOCYTE MIGRATION AND PROLIFERATION o After an hour neutrophils accumulate in great numbers within the affected tissue. o Ten hours later, monocytes begin to move to the tissue, where they develop into large, active macrophages. o Signaling that tells leukocytes to move through blood vessel walls is achieved by margination, attachment, diapedesis, and chemotaxis. o Margination: weak interaction of leukocytes with endothelial cells lining the blood vessel near the site of injury. Cytokines released to signal endothelial cells to express adhesion molecules (selectins); loosely bind to leukocytes in the blood. Leukocytes also receive signals from other cytokines to get other adhesion molecules called integrins that bind cells tightly to blood vessel wall. o Attachment: soon followed by the cell’s transit across the wall, known as diapedesis (jump across). Leukocyte crawls between endothelial cells of the blood vessel wall through and through the basement membrane. o Chemotaxis: once at the point of injury, chemicals released from the bacteria and injured tissues attract leukocytes. The phagocytic leukocytes are now at the original site of injury and bacteria invasion. o A common sign of bacterial infection is leukocytosis, a 4-5fold increase in the number of circulating neutrophils. Reason: cytokines secreted by macrophages eventually reach the bone marrow (stimulate proliferation of neurotrophils to be rel
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