The Lymphatic System

Lymphatic System consists of fluid called lymph flowing inside the lymphatic vessels, some structure and tissues that contain lymphatic tissue and bone marrow. Bone marrow houses Stem cells that develop into lymphocytes and provide immunity.

When interstitial fluid passes in to lymphatic vessels, it is called Lymph i.e. Clear water. Interstitial fluid and lymph are basically same except for location.

Filtration forces water and dissolved substances from the capillaries into the interstitial fluid. Not all of this water is returned to the blood by osmosis, and excess fluid is picked up by lymph capillaries to become lymph.

Functions of the lymphatic system:

1) Draining Interstitial fluid: To maintain the pressure and volume of the extracellular fluid by returning excess water and dissolved substances from the interstitial fluid to the circulation.

2) Protecting against invasion: Lymph nodes and other lymphoid tissues are the site for production of immuno-competent lymphocytes and macrophages in the specific immune response. T lymphocytes rupture foreign cells or produce toxins while B lymphocytes differentiate in to plasma cells that secrete antibodies.

3) Transporting Dietary lipids: Lymphatic vessels carry lipids and lipid soluble vitamins (ADEK) absorbed by gastro- intestinal tract.

Lymph capillaries: Close ended vessels lies in the space between cells. It carries many pores which allow interstitial fluid including large lipids to get inside the lymphatic circulation but do not allow coming out.

Lacteals: (Lacteal = Milky) Each Villi in the small intestine has centrally placed lymphatic vessels called Lacteal. It transport lipids absorbed in the intestine.

From lymph capillaries fluid flows into lymph veins (lymphatic vessels) which virtually parallel the circulatory veins and are structurally very similar to them, including the presence of semilunar valves.

Lymphatic Vessels: Lymph capillaries unite to form Lymphatic vessels. Resemble vein in structure except it is thin and have more valves.

Lymph capillaries containing lymph are found through out the body except in

1. Avascular tissue2. Central Nervous System 3. Spleenic pulp4. Bone marrow

Lymphatic Ducts: The lymphatic veins flow into one of two lymph ducts. 1. The right lymph duct drains the right arm, shoulder area, and the right side of the head and neck. It is half inch in length.

2. The left lymph duct (thoracic duct), drains everything else, including the legs, GI tract and other abdominal

organs, thoracic organs, and the left side of the head and neck and left arm and shoulder. It is 15-18 inches in length and is a major vessel of the system.

These ducts then drain into the subclavian veins on each side where they join the internal jugular veins to form the brachiocephalic veins.

Formation and flow of lymph:

The excess fluids in the interstitial space i.e. about 3 lit/ day drains in to the lymphatic vessels and become lymph.

Arteries (blood plasma) Blood capillariesInterstitial space Lymph capillaries (Lymph)

Lymphatic Vessels Lymphatic Ducts Subclavian vein Heart

Lymph nodes lie along the lymph veins successively filtering lymph. Afferent lymph veins enter each node, efferent veins lead to the next node becoming afferent veins upon reaching it.

Lymphokinetic motion (flow of the lymph) due to:

1) Lymph flows down the pressure gradient.

2) Muscular and respiratory pumps push lymph forward due to function of the semilunar valves.

Other lymphoid tissue: 

        1. Lymph nodes: Lymph nodes are small encapsulated organs located along the pathway of lymphatic vessels. They vary from about 1 mm to 1 to 2 cm in diameter and are widely distributed throughout the body,

with large concentrations occurring in the areas of convergence of lymph vessels. They serve as filters through which lymph percolates on its way to the blood. Antigen-activated lymphocytes differentiate and proliferate by cloning in the lymph nodes. 

        2. Diffuse Lymphatic Tissue and Lymphatic nodules: The alimentary canal, respiratory passages, and genitourinary tract are guarded by accumulations of lymphatic tissue that are not enclosed by a capsule (i.e. they are diffuse) and are found in connective tissue beneath the epithelial mucosa. These cells intercept foreign antigens and then travel to lymph nodes to undergo differentiation and proliferation. Local concentrations of lymphocytes in these systems and other areas are called lymphatic nodules. In general these are single and random but are more concentrated in the GI tract in the ileum, appendix, cecum, and tonsils.

        3. The Thymus gland:  The thymus is bilobed organ which is located in between the lungs, posterior to the sternum. The thymus is where immature lymphocytes differentiate into T-lymphocytes. The thymus is fully formed and functional at birth. Characteristic features of thymic structure persist until about puberty.

        The transformation of primitive or immature lymphocytes into T-lymphocytes and their proliferation in the lymph nodes is promoted by a thymic hormone called thymosin.  Ocassionally the thymus persists and may become cancerous after puberty and and the continued secretion of thymosin and the production of abnormal T-cells may contribute to some autoimmune disorders. 

5. The spleen: The spleen oval and largest lymphatic mass which filters the blood and reacts immunologically to blood-borne antigens. In addition to large numbers of lymphocytes the spleen contains specialized vascular spaces, a meshwork of reticular cells and fibers, and a rich supply of macrophages which monitor the blood. 

The human spleen holds relatively little blood compared to other mammals, but it has the capacity for contraction to release this blood into the circulation during anoxic stress. White pulp in the spleen contains lymphocytes and is equivalent to other lymph tissue,  while red pulp contains large numbers of red blood cells that it filters and degrades.

   The spleen functions in both immune and hematopoietic systems. Immune functions include: proliferation of lymphocytes, production of antibodies, removal of antigens from the blood. Hematopoietic functions include: formation of blood cells during fetal life, removal and destruction of aged, damaged and abnormal red cells and platelets, retrieval of iron from hemoglobin degradation, storage of red blood cells.

Immune System

I. Non-specific responses -

General mechanisms for discouraging pathogens which do not require the identity of the pathogen's antigenic nature. These are the first line of defense against invasion by pathogens.

    A. Surface Membrane Barriers

        1. Skin

            a. acidic pH

            b. Keratinization protects unbroken skin against acids and bases of bacterial enzymes and toxins.

        2. Mucous membranes

            a. HCl in the stomach kills many pathogens, denatures proteins

            b. Saliva contains lysozyme, a bactericide

            c. Lacrimal fluid contains lysozyme

            d. Mucus traps organisms

    B. Cellular And Chemical Defenses

        1. Phagocytes - engulf particulates, including microorganisms, which pass through the external barriers.

Examples: histiocytes in the lungs, Langerhans cells in the skin, Kupffer cells in the liver, microglia in the nervous system, macrophages in other tissues.

        2. Natural killer cells - these large lymphocytes lyse and kill tumor and virus-infected cells before activation of a specific immune response. 

    3. Inflammation

            a. reduces spread of damaging agents to nearby tissues

            b. increases disposal of cell debris and pathogens

            c. facilitates repair processes

            d. caused by histamine and prostaglandins released

by basophils and other cells.

4. Anti-microbial proteins

            a. Non-Specific complement activation

            b. Interferons - block tumor and viral reproduction

            c. Interleukin I - stimulates the immune response

5. Fever

            a. Due to pyrogens secreted by leucocytes

            b. Disrupts metabolism of pathogens

II. Specific Responses –

These second line of defense responses are activated by, and directed against, a specific antigen.

Antigen - a protein or other substance which elicits immune system activation in a "foreign" host.

    A. Humoral Immunity - the B-cell response

        1. Antigen challenge - "non-self" antigen binds to antigen-specific surface receptors on generic B-cell.

        2. Clonal selection - multiplication of B-cells produces cells which all contain the same antigen-specific surface receptor.

            a. Primary response - plasma cells secrete free antibodies of the same structure as the antigen-specific surface receptor. The primary response takes 7 to 10 days to reach maximum antibody levels.

            b. Secondary response - memory cells which retain the ability to quickly clone to produce more plasma

cells should the antigen be encountered again. The secondary response takes from 1 to 2 days to reach maximum antibody levels.

        3. Antibodies form antigen-antibody complexes which have the following affects:

a. Opsonization - labeling of antigens or foreign

cells

            b. Neutralization - inactivation of bacterial toxins

            c. Agglutination - clumping of cell-bound antigens

            d. Precipitation - removes soluble antigen from solution

            e. Complement fixation - which causes cell lysis. Complement protein binds to a site on the constant (Fc) portion of the antibody.

        4. Classes of antibodies:

        IgD - (monomer) antigen receptor on B-cell

        IgM - (pentamer) first antibody released by plasma cells during primary response

        IgG - (monomer) comprises most circulating antibodies, both 1o and 2o responses

        IgA - (dimer) antibody found in secretions

        IgE - (monomer) secreted in mucosae, mediates inflammation in allergic reaction.                               

    B. Cell Mediated Immunity - the T-cell response - requires an intermediary cell to be stimulated. These intermediary cells can be infected body cells or macrophages as below. Identification of these cells and their antigens is by means of MHC proteins. MHC (Major Histocompatibility Complex) antigens are recognition proteins which identify a cell as being "self". They are displayed together with part of the antigen from invading viruses to be recognized by T-cell lymphocytes. There are two classes of MHC antigens: Class I is present on all body cells; Class II is present only on cells of the immune system.

There are several types of T cells.

        1. generic cytotoxic T-cells

            a. respond to antigens complexed by MHC I proteins from infected body cells.

            b. attack and kill virus or bacteria-infected cells and tumor cells

            c. maintain immunologic surveillance 

            d. clone to produce mature cytotoxic cells and cytotoxic memory cells

        2. Helper T-cells

            a. respond to antigens complexed with MHC II proteins on antigen presenting cells

            b. act as costimulator cells for B-cells and other T-cells and . Activated Helper cells release interleukin II and act as a costimulator for an effective B-cell response.

            c. release interleukin I which acts as a costimulator for T-cell production.

        3. Suppressor T-cells - regulatory cells which tend to shut down B and T-cell responses.

        4. Cytokines - chemical mediators involved in cellular immunity.

            a. interleukin I - costimulator for activated T-cells

            b. interleukin II - stimulates both B and T-cell proliferation

            c. MAF - macrophage activating factor

            d. MIF - macrophage migration inhibiting factor

            e. perforin - causes cell lysis

            f. lymphotoxin - kills cells by fragmenting their

DNA

            g. tumor necrosis factor - specialized destruction

of tumors.

        C. Immunocompetence: (often called immune tolerance because it is the tolerance of your own cells) is the ability of your immune system to recognize self vs. non-self (anti-self, foreign) antigens.  This ability is conferred during childhood. For T cells the site for this is the thymus gland which ceases this activity after puberty. The site for the B cells is unknown. The name B cell comes from the Bursa of Fabricus, a gut-associated site which is the site of immunocompetence in chickens. Humans don't

have a Bursa, so a "Bursa Equivalent" confers immunocompetence, possibly the marrow, but recent evidence suggests an area analogous to the bursa in the distal GI tract. During childhood, immature or pre-lymphocytes originate in the marrow, travel to the thymus (or other area) for immuno-competence, then travel to the lymph nodes where they proliferate in response to antigenic stimulation. 

     D. Hypersensitivity 

            1. Type I Hypersensitivity - this is the basis for allergic reactions. Usually this occurs when you have been exposed to non-pathogenic foreign antigen and built up memory cells. Subsequent exposure causes these cells to become plasma cells which release large amounts of IgE antibodies. IgE antibodies bind to basophils and mast cells causing them to release  granules containing histamine and other inflammatory chemicals. This is the basis for the vascular changes seen in allergy and anaphylaxis. 

            2. Type II Hypersensitivity - this is a type of autoimmunity. Autoimmune disorders can result when host antigens are similar to invading antigens and cross reactions occur, or from mutations of antigens, or by antigens which are masked or not present during the period of immunocompetence, or which are altered by environmental or disease factors and cease to be recognized as "self", or by lack of immune tolerance (another term for immunocompetence). Among diseases which have been classified as autoimmune are: multiple sclerosis, myasthenia gravis, Graves disease,  andsome forms of Type 1 diabetes mellitus.

            3. Type III Hypersensitivity occurs when the antigen-antibody complexes produced by normal immune system reactions are not removed and lodge in the basement membrane of endothelial cells and in other connective tissues. Their presence induces massive inflammation by triggering the complement pathway with resulting cell lysis, hemorrhage, and tissue destruction. Examples include: systemic lupus erythematosus (SLE), rheumatoid arthritis and acute glomerulonephritis.