The lymphatic system is composed of lymph vessels, lymph nodes, and organs. The functions of this system include the absorbtion of excess fluid and its return to the blood stream, absorption of fat (in the villi of the small intestine) and the immune system function.
Lymph vessels are closely associated with the circulatory system vessels. Larger lymph vessels are similar to veins. Lymph capillaries are scatted throughout the body. Contraction of skeletal muscle causes movement of the lymph fluid through valves.
Lymph organs include the bone marrow, lymph nodes, spleen, and thymus. Bone marrow contains tissue that produces lymphocytes. B-lymphocytes (B-cells) mature in the bone marrow. T-lymphocytes (T-cells) mature in the thymus gland. Other blood cells such as monocytes and leukocytes are produced in the bone marrow. Lymph nodes are areas of concentrated lymphocytes and macrophages along the lymphatic veins. The spleen is similar to the lymph node except that it is larger and filled with blood. The spleen serves as a reservoir for blood, and filters or purifies the blood and lymph fluid that flows through it. If the spleen is damaged or removed, the individual is more susceptible to infections. The thymus secretes a hormone, thymosin, that causes pre-T-cells to mature (in the thymus) into T-cells.
THE LYMPHATIC SYSTEM consists (1) of complex capillary networks which collect the lymph in the various organs and tissues; (2) of an elaborate system of collecting vessels which conduct the lymph from the capillaries to the large veins of the neck at the junction of the internal jugular and subclavian veins, where the lymph is poured into the blood stream; and (3) lymph glands or nodes which are interspaced in the pathways of the collecting vessels filtering the lymph as it passes through them and contributing lymphocytes to it. The lymphatic capillaries and collecting vessels are lined throughout by a continuous layer of endothelial cells, forming thus a closed system. The lymphatic vessels of the small intestine receive the special designation of lacteals or chyliferous vessels; they differ in no respect from the lymphatic vessels generally excepting that during the process of digestion they contain a milk-white fluid, the chyle.
The Development of the Lymphatic Vessels.—The lymphatic system begins as a series of sacs 108 at the points of junction of certain of the embryonic veins. These lymph-sacs are developed by the confluence of numerous venous capillaries, which at first lose their connections with the venous system, but subsequently, on the formation of the sacs, regain them. The lymphatic system is therefore developmentally an offshoot of the venous system, and the lining walls of its vessels are always endothelial.
In the human embryo the lymph sacs from which the lymphatic vessels are derived are six in number; two paired, the jugular and the posterior lymph-sacs; and two unpaired, the retroperitoneal and the cisterna chyli. In lower mammals an additional pair, subclavian, is present, but in the human embryo these are merely extensions of the jugular sacs.
The position of the sacs is as follows: (1) jugular sac, the first to appear, at the junction of the subclavian vein with the primitive jugular; (2) posterior sac, at the junction of the iliac vein with the cardinal; (3) retroperitoneal, in the root of the mesentery near the suprarenal glands; (4) cisterna chyli, opposite the third and fourth lumbar vertebr? . From the lymph-sacs the lymphatic vessels bud out along fixed lines corresponding more or less closely to the course of the embryonic bloodvessels. Both in the body-wall and in the wall of the intestine, the deeper plexuses are the first to be developed; by continued growth of these the vessels in the superficial layers are gradually formed. The thoracic duct is probably formed from anastomosing outgrowths from the jugular sac and cisterna chyli. At its connection with the cisterna chyli it is at first double, but the two vessels soon join.
All the lymph-sacs except the cisterna chyli are, at a later stage, divided up by slender connective tissue bridges and transformed into groups of lymph glands. The lower portion of the cisterna chyli is similarly converted, but its upper portion remains as the adult cisterna.
Lymphatic Capillaries — The complex capillary plexuses which consist of a single layer of thin flat endothelial cells lie in the connective-tissue spaces in the various regions of the body to which they are distributed and are bathed by the intercellular tissue fluids. Two views are at present held as to the mode in which the lymph is formed: one being by the physical processes of filtration, diffusion, and osmosis, and the other, that in addition to these physical processes the endothelial cells have an active secretory function. The colorless liquid lymph has about the same composition as the blood plasma. It contains many lymphocytes and frequently red blood corpuscles. Granules and bacteria are also taken up by the lymph from the connective-tissue spaces, partly by the action of lymphocytes which pass into the lymph between the endothelial cells and partly by the direct passage of the granules through the endothelial cells.
The lymphatic capillary plexuses vary greatly in form; the anastomoses are usually numerous; blind ends or cul-de-sacs are especially common in the intestinal villi, the dermal papill? and the filiform papill? of the tongue. The plexuses are often in two layers: a superficial and a deep, the superficial being of smaller caliber than the deep. The caliber, however, varies greatly in a given plexus from a few micromillimeters to one millimeter. The capillaries are without valves.
Distribution — The Skin.—Lymphatic capillaries are abundant in the dermis where they form superficial and deep plexuses, the former sending blind ends into the dermal papill?. The plexuses are especially rich over the palmar surface of the hands and fingers and over the plantar surface of the feet and toes. The epidermis is without capillaries. The conjunctiva has an especially rich plexus.
The subcutaneous tissue is without capillaries.
The tendons of striated muscle and muscle sheaths are richly supplied. In muscle, however, their existence is still disputed.
The periosteum of bone is richly supplied and they have been described in the Haversian canals. They are absent in cartilage and probably in bone marrow.
The joint capsules are richly supplied with lymphatic capillaries, they do not, however, open into the joint cavities.
Beneath the mesothelium lining of the pleural, peritoneal and pericardial cavities are rich plexuses; they do not open into these cavities.
The alimentary canal is supplied with rich plexuses beneath the epithelium, often as a superficial plexus in the mucosa and a deeper submucosal plexus. Cul-de-sacs extend into the filiform papill? of the tongue and the villi of the small intestine. Those portions of the alimentary canal covered by peritoneum, have in addition a subserous lymphatic capillary plexus beneath the mesothelium.Lymph Glands
— The lymph glands are small oval or bean-shaped bodies, situated in the course of lymphatic and lacteal vessels so that the lymph and chyle pass through them on their way to the blood. Each generally presents on one side a slight depression—the hilus—through which the bloodvessels enter and leave the interior. The efferent lymphatic vessel also emerges from the gland at this spot, while the afferent vessels
enter the organ at different parts of the periphery. On section a lymph gland displays two different structures: an external, of lighter color—the cortical; and an internal, darker—the medullary. The cortical structure does not form a complete investment, but is deficient at the hilus, where the medullary portion reaches the surface of the gland; so that the efferent vessel is derived directly from the medullary structures, while the afferent vessels empty themselves into the cortical substance.Lymph — Lymph, found only in the closed lymphatic vessels, is a transparent, colorless, or slightly yellow, watery fluid of specific gravity about 1.015; it closely resembles the blood plasma, but is more dilute. When it is examined under the microscope, leucocytes of the lymphocyte class are found floating in the transparent fluid; they are always increased in number after the passage of the lymph through lymphoid tissue, as in lymph glands. Lymph should be distinguished from "tissue fluid" 109 which is found outside the lymphatic vessels in the tissue spaces.
Immunity
Immunity is the body's capability to repel foreign substances and cells. The nonspecific responses are the first line of defense. Highly specific responses are the second line of defense and are tailored to an individual threat. The immune response includes both specific and nonspecific components. Nonspecific responses block the entry and spread of disease-causing agents. Antibody-mediated and cell-mediated responses are two types of specific response. The immune system is associated with defense against disease-causing agents, problems in transplants and blood transfusions, and diseases resulting from over-reaction (autoimmune, allergies) and under-reaction (AIDS).Barriers to entry are the skin and mucous membranes. The skin is a passive barrier to infectious agents such as bacteria and viruses. The organisms living on the skin surface are unable to penetrate the layers of dead skin at the surface. Tears and saliva secrete enzymes that breakdown bacterial cell walls. Skin glands secrete chemicals that retard the growth of bacteria. Mucus membranes lining the respiratory, digestive, urinary, and reproductive tracts secrete mucus that forms another barrier. Physical barriers are the first line of defense.
When microorganisms penetrate skin or epithelium lining respiratory, digestive, or urinary tracts, inflammation results. Damaged cells release chemical signals such as histamine that increase capillary blood flow into the affected area (causing the areas to become heated and reddened). The heat makes the environment unfavorable for microbes, promotes healing, raises mobility of white blood cells, and increases the metabolic rate of nearby cells. Capillaries pass fluid into interstitial areas, causing the infected/injured area to swell. Clotting factors trigger formation of many small blood clots. Finally, monocytes (a type of white blood cell) clean up dead microbes, cells, and debris.
The inflammatory response is often strong enough to stop the spread of disease-causing agents such as viruses, bacteria, and fungi. The response begins with the release of chemical signals and ends with cleanup by monocytes. If this is not enough to stop the invaders, the complement system and immune response act.
Protective proteins that are produced in the liver include the complement system of proteins. The complement system proteins bind to a bacterium and open pores in its membrane through which fluids and salt move, swelling and bursting the cell.
The complement system directly kills microbes, supplements inflammatory response, and works with the immune response. It complements the actions of the immune system. Complement proteins are made in the liver and become active in a sequence (C1 activates C2, etc.). The final five proteins form a membrane-attack complex (MAC) that embeds itself into the plasma membrane of the attacker. Salts enter the invader, facilitating water to cross the membrane, swelling and bursting the microbe. Complement also functions in the immune response by tagging the outer surface of invaders for attack by phagocytes.
Interferon is a species-specific chemical produced by cells that are viral attack. It alerts nearby cells to prepare for a virus. The cells that have been contacted by interferon resist all viral attacks.
The immune system also generates specific responses to specific invaders.
The immune system is more effective than the nonspecific methods, and has a memory component that improves response time when an invader of the same type (or species) is again encountered.
Immunity results from the production of antibodies specific to a given antigen (antibody-generators, located on the surface of an invader). Antibodies bind to the antigens on invaders and kill or inactivate them in several ways. Most antibodies are themselves proteins or are a mix of protein and polysaccharides. Antigens can be any molecule that causes antibody production.
Secondary immunity, the resistance to certain diseases after having had them once, results from production of Memory B and T cells during the first exposure to the antigen. A second exposure to the same antigen produces a more massive and faster response. The secondary response is the basis for vaccination.
Vaccination is a term derived from the Latin vacca (cow, after the cowpox material used by Edward Jenner in the first vaccination). A vaccine stimulates the antibody production and formation of memory cells without causing of the disease. Vaccines are made from killed pathogens or weakened strains that cause antibody production but not the disease. Recombinant DNA techniques can now be used to develop even safer vaccines.
The immune system can develop long-term immunity to some diseases. Man can use this to develop vaccines, which produce induced immunity. Active immunity develops after an illness or vaccine. Vaccines are weakened (or killed) viruses or bacteria that prompt the development of antibodies. Application of biotechnology allows development of vaccines that are the protein (antigen) which in no way can cause the disease. Passive immunity is the type of immunity when the individual is given antibodies to combat a specific disease. Passive immunity is short-lived.
Antibodies
Antibody-mediated (humoral) immunity is regulated by B cells and the antibodies they produce. Cell-mediated immunity is controlled by T cells. Antibody-mediated reactions defend against invading viruses and bacteria. Cell-mediated immunity concerns cells in the body that have been infected by viruses and bacteria, protect against parasites, fungi, and protozoans, and also kill cancerous body cells.
Antibody-mediated Immunity
Stages in this process are:
- antigen detection
- activation of helper T cells
- antibody production by B cells
Each stage is directed by a specific cell type.
Macrophages are white blood cells that continually search for foreign (nonself) antigenic molecules, viruses, or microbes. When found, the macrophages engulfs and destroys them. Small fragments of the antigen are displayed on the outer surface of the macrophage plasma membrane.
Antibodies bind to specific antigens in a lock-and-key fashion, forming an antigen-antibody complex. Antibodies are a type of protein molecule known as immunoglobulins. There are five classes of immunoglobulins: IgG, IgA, IgD, IgE, and IgM.
Antibodies are Y-shaped molecules composed of two identical long polypeptide (Heavy or H chains) and two identical short polypeptides (Light or L chains). Function of antibodies includes:
- Recognition and binding to antigens
- Inactivation of the antigen
A unique antigenic determinant recognizes and binds to a site on the antigen, leading to the destruction of the antigen in several ways. The ends of the Y are the antigen-combining site that is different for each antigen.
Helper T cells activate B cells that produce antibodies. Supressor T cells slow down and stop the immune response of B and T cells, serving as an off switch for the immune system. Cytotoxic (or killer) T cells destroy body cells infected with a virus or bacteria. Memory T cells remain in the body awaiting the reintroduction of the antigen.
A cell infected with a virus will display viral antigens on its plasma membrane. Killer T cells recognize the viral antigens and attach to that cell's plasma membrane. The T cells secrete proteins that punch holes in the infected cell's plasma membrane. The infected cell's cytoplasm leaks out, the cell dies, and is removed by phagocytes. Killer T cells may also bind to cells of transplanted organs.
The immune system is the major component of this defense. Lymphocytes, monocytes, lymph organs, and lymph vessels make up the system. The immune system is able to distinguish self from non-self. Antigens are chemicals on the surface of a cell. All cells have these. The immune system checks cells and identifies them as "self" or "non-self". Antibodies are proteins produced by certain lymphocytes in response to a specific antigen. B-lymphocytes and T-lymphocytes produce the antibodies. B-lymphocytes become plasma cells which then generate antibodies. T-lymphocytes attack cells which bear antigens they recognize. They also mediate the immune response.
Success of organ transplants and skin grafts requires a matching of histocompatibility antigens that occur on all cells in the body. Chromosome 6 contains a cluster of genes known as the human leukocyte antigen complex (HLA) that are critical to the outcome of such procedures. The array of HLA alleles on either copy of our chromosome 6 is known as a haplotype.
The large number of alleles involved mean no two individuals, even in a family, will have the same identical haplotype. Identical twins have a 100% HLA match. The best matches are going to occur within a family. The preference order for transplants is identical twin > sibling > parent > unrelated donor. Chances of an unrelated donor matching the recipient range between 1 in 100,000-200,000. Matches across racial or ethnic lines are often more difficult. When HLA types are matched survival of transplanted organs dramatically increases.
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