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THE LYMPHATIC SYSTEM AND IMMUNITY

INTRODUCTION

1. The lymphatic system includes a network of lymphatic vessels that carry lymph , a fluid similar in composition to interstitial fluid.A series of lymph organs are associated with the vessels of the system.

2. The lymphatic system returns interstitial fluid to the general circulation, prevents local variations in the composition of tissue fluids, and provides specialized defenses against infection.

3. Lymphocytes are the cells of the lymphatic system.

ANATOMY OF THE LYMPHATIC SYSTEM

1.Lymph flows along a network oflymphatics that originate in theterminal lymphatics of lymph capillaries.

2. The lymphatic vessels from areas below the diaphragm and from the left half of the upper body are connected to the large thoracic duct that empties into the venous system at the left subclavian vein near the junction of the left internal jugular.

3. The lymphatics servicing the right half of the body above the diaphragm are connected to the smallerright lymphatic duct that empties into the venous system in the same region on the right side.

The Lymphocytes

1. There are three distinct populations of lymphocytes, T cells, B cells, and NK cells.

2. There are several different populations of T cells.Regulatory T cells include helper and suppressor T cells that regulate the immune response. Cytotoxic (killer) T cells attack invading, infected, or abnormal cells.These T cells are responsible for cellular immunity.

3. B cells are concerned with the production of antibodies, special proteins that can either cause or facilitate the destruction of specific antigens. These proteins are dissolved in body fluids, and they provide what is known as humoral immunity.

4. NK cells detect the presence of abnormal antigens on cell membranes; they are responsible for immunological surveillance and the removal of cancer cells from normal tissues.

The Life Span and Circulation of Lymphocytes

1. Lymphocytes are found in the blood, bone marrow, spleen, thymus, and peripheral lymphatic tissues. The ratio of B cells to T cells varies from one site to another.

2. Lymphocytes are continually migrating in and out of the blood and through the lymphatic tissues and organs.

3.Lymphocytes are relatively long-lived, and some survive for decades.

Lymphopoiesis

1. Lymphocytic stem cells are produced in the bone marrow. B cells and NK cells are primarily produced in the bone marrow. T cells are produced by stem cells that have migrated to the thymus.

2. The thymus produces the hormone thymosin. Thymosin stimulates the mitosis of stem cells in the thymus. Mature T cells leave the thymus and reside in other tissues, including the bone marrow.

Lymphatic tissues

1. Lymphatic tissues are connective tissues dominated by lymphocytes. A lymphatic tissue has no clearcut boundaries, for the lymphocytes are not surrounded by a fibrous capsule.

2. A lymphatic nodule consists of a dense aggregation of lymphocytes in an area of loose connective tissue, usually beneath an epithelium.

3. Lymphatic nodules often have a pale central area, the germinal center, where mitosis occurs.

4. The pharyngeal(adenoid), palatine , and lingual tonsils are large lymphatic nodules embedded in the walls of the pharynx.

5.Peyer's patches are lymphatic nodules beneath the epithelium of the small intestine.

6. Large lymphatic nodules are also found beneath the epithelium of theappendix and large intestine.

Lymphatic Organs

1. Lymphatic organs have a clear internal organization, and they are surrounded by a dense fibrous capsule. Lymphatic organs include the thymus, lymph nodes, and the spleen.

The Thymus:

1. The thymus lies within the mediastinum behind the sternum. It reaches its maximum size during puberty, and slowlyinvolutes thereafter.

2. There are two thymic lobes, partitioned by septae into lobules. Each lobule has an outer cortex and an inner medulla. Epithelial cells scattered among the lymphocytes produce the thymic hormones.

Lymph Nodes:

1. Lymph nodes are encapsulated masses of lymphatic tissue up to 25 mm in diameter. Blood vessels, nerves, and lymphatics are connected to each node. The cortical zone contains T cells, and the medullary cords are dominated by B cells.

2. Lymph arrives at a lymph node via lymphatics that penetrate the capsule opposite the hilus. The lymph flows through a network of cortical sinuses.

3. The lymphocytes and macrophages of lymph nodes monitor the contents of the lymph as it proceeds towards the lymphatic ducts and the venous system.

4. Lymph nodes are largest and most abundant where the peripheral lymphatics connect with the trunk. At these sites the nodes are often called lymph glands, and their swelling usually indicates peripheral inflammation or infection.

The spleen:

1. The adult spleen contains the largest mass of lymphatic tissue in the body. Its shape is primarily determined by its relationship with adjacent structures.

NOTE: Many sources list "blood reservoir" as a splenic function, and include splenic contraction as an event that occurs under sympathetic stimulation. Such statements are valid for members of the Order Carnivora (dogs, cats, bears, and so forth), whose large spleens have layers of smooth muscle in the capsule. The human spleen does not contain smooth muscle and cannot contract; in addition, the volume of blood enclosed (150 ml) represents a relatively insignificant fraction of the venous reserve.

2.The splenic artery, splenic vein, and lymphatics are connected at the hilus of the spleen.

3.The cellular components constitute the pulp of the spleen. Red pulp contains large numbers of red blood cells, and areas of white pulp resemble lymphatic nodules.

Integration with the Immune System

1. The lymphatic system is one component of the immune system

defends the body and maintains tissue homeostasis.

2. The immune system includes nonspecific defenses and it provides specific immunity.

3. Nonspecific defenses do not discriminate between one threat and another. Such defenses include physical barriers, phagocytic cells, immunological surveillance, complement, and inflammation.

4. Nonspecific defenses are fully operational at birth, and they contribute to the natural immunity of the individual.

5. Specific immunity develops after birth as the result ofexposure to specific antigens.

NONSPECIFIC DEFENSES

1. Nonspecific defenses either prevent approach, deny access, or

imit the spread of threats to homeostasis.

Physical Barriers

1. Physical barriers include hair, epithelia, and various secretions of the integumentary and digestive systems.

Phagocytic cells

1. There are two classes of phagocytic cells, microphages (neutrophils and eosinophils) and macrophages (cells of the monocyte-phagocyte system).

2. Fixed macrophages are found in many peripheral tissues. Free and fixed macrophages are derivatives of circulating monocytes.

Orientation and Phagocytosis:

1. Phagocytes move between cells through diapedesis, and they show chemotaxis, sensitivity and orientation to chemical stimuli.

2. Phagocytized materials are destroyed by lysosomal enzymes and the residue ejected via exocytosis.

3. Phagocytic cells often have short life-expectancies, and populations must be continually replenished.

Immunological Surveillance

1. NK cells are sensitive to the presence of abnormal antigens on the surfaces of otherwise normal cells.

2. Cancer cells with tumor-specific antigens on their surfaces are killed; after immunological escape cancer cells may be treated like normal cells, and ignored by the immune system.

Complement

1. There are at least 11 different types of complement proteins. Complement binding may disintegrate the cell wall of a bacterium, inactivate a virus, stimulate inflammation, or attract lymphocytes and phagocytes.

2. The primary method of complement activation is binding to antibodies. Activation may also occur following exposure to certain bacteria; this response is sustained and enhanced by properdin.

Inflammation

1. Inflammation represents a coordinated nonspecific response to tissue injury.

2. The inflammatory response begins with the release of histamine and other chemicals by stimulated mast cells. Important events then include an increase in capillary blood flow and permeability, increased local phagocytic activities, elevated local temperature, complement entry and activation, clotting, scar tissue formation, and the activation of specific defenses.

SPECIFIC IMMUNITY

1. Specific immunity results from the activities of lymphocytes.

2. Humoral immunity results from the presence of antibodies within body fluids. Antibodies are produced by plasma cells that differentiate from activated B cells.

3. Cellular, or cell-mediated, immunity requires intimate contact between an activated T cell and its specific target. Humoral Immunity:

B cells and Antibody Production

1. Antigens are molecules that trigger the production of antibodies. Acomplete antigen has two antigenic determinant sites, and it can react with its specific antibody to form an antigen-antibody complex .

2. Molecules with a single antigenic determinant site are called partial antigens, or haptens.Haptens may bind to another compound to form a complex that acts like a complete antigen.

3. An activated B cell undergoes repeated mitoses. Some of the daughter cells develop into plasma cells and begin producing antibodies. Others remain as memory B cells that will respond following subsequent exposure to the same antigen.

4. The production of antibodies in response to the initial exposure constitutes the primary response . The maximum antibody titer appears during the secondary , or anamnestic response that follows subsequent exposures.

Antibody Structure and Function:

1. An antibody changes shape when it binds to its antigen. Effects that appear subsequent to binding include complement activation, opsonization, phagocyte attraction, stimulation of inflammation, and prevention of bacterial adhesion.

Antibody Diversity:

1. Five different classes of immunoglobulins have been identified.

2. IgG is the largest group, providing specific immunity against many viruses, bacteria, and bacterial toxins.

3. IgA antibodies are primarily found in glandular secretions that attack potential pathogens before they enter the body.

4. IgM appears shortly after exposure to an antigen, but its production declines as IgG titers rise. Plasma agglutinins are IgM antibodies.

5. IgE antibodies bind to the exposed surfaces of basophils and mast cells. If the specific antigens appear these cells break down and cause an immediate and pronounced inflammation.

6.IgD resides on the surfaces of B cells, where it may help to bind specific antigen molecules to the cell membranes.

Cellular Immunity

1. T cells responsible for cellular immunity undergo mitoses to produce memory T cells and cytotoxic (killer) T cells . Cytotoxic T cells migrate to the site of invasion or infection and attack bacteria, fungi, foreign tissues, infected cells, and some cancer cells. Their targets are destroyed by direct contact or by the production of lymphotoxins.

The Regulation of the Immune Response

1. T cells and B cells are particularly sensitive to foreign or abnormal antigens bound to otherwise normal cell membranes.

2 Molecules are found on the surfaces of almost every cell in the body. Class II molecules are restricted to the membranes of macrophages and lymphocytes. Each of the proteins in this complex has a distinctive shape, and binds specific antigens.

3. Lymphocytes are sensitive to antigens bound to normal HLA proteins, abnormal HLA molecules, and the HLA proteins of foreign cells.

4. Active macrophages accumulate antigenic materials on their surfaces, bound to Class I and Class II molecules. T cells sensitive to antigens bound to HLA Class I receptors differentiate into cytotoxic T cells, memory T cells, and suppressor T cells. Those sensitive to antigens carried by HLA Class II molecules differentiate into helper T cells.

5. Regulatory cells modify the sensitivities and immune responses of T cells and B cells.

6. In many cases B cells only become activated after antigen presentation by helper T cells. Suppressor T cells inhibit B cell maturation and antibody production; ordinarily helpers outnumber suppressors by a factor of 3 to 1.

Chemical Communication and Coordination:

1. Chemicals released by macrophages and lymphocytes adjust the timing and intensity of the immune response. Monokines are produced by macrophages and lymphokines are secreted by lymphocytes.

2. Important monokines and lymphokines include the interleukins, interferons, BCGF, BCDF, and factors attracting and keeping phagocytes in the affected area.

PATTERNS OF IMMUNE RESPONSE

Immunological competence

1. Immunological competence is the ability to respond to the presence of an antigen by the production of antibodies and cytotoxic T cells.

2. Cellular immunity can be demonstrated after the third month of embryonic development.

3. The developing fetus receives passive immunity from the maternal blood stream.After delivery the infant begins developing acquired immunity as the result of exposure to environmental antigens.

Tolerance:

1. Tolerance, the acceptance of an antigen as "normal" by the immune system, usually continues only as long as the individual is exposed to the antigen on a regular basis.

Stress and the Immune Response

1. Interleukin-1 released by active macrophages triggers the release of ACTH by the anterior pituitary. Glucocorticoids produced by the adrenal cortex moderate the immune response.

2. Chronic stress reduces resistance to disease by depressing both specific and nonspecific defenses. Effects attributable to glucocorticoid activities include inhibition of the immune response, depression of phagocytic activity, and reduction in interleukin secretion.

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