The Lymphatic System

The Lymphatic System System which launches fight against infections

Lymphatic System The major components of the lymphatic system are lymphatic vessels, lymph, lymph nodes, and some other lymphatic organs Lymphatic vessels carry lymph, a colorless liquid, throughout the body. Along lymph vessels are small bean-shaped glandular nodules called lymph nodes. Other lymphatic organs are: Tonsil: clusters of lymphatic tissues just under the mucous membranes that line the nose, mouth, and pharynx. Spleen: it is similar to a lymph node in shape and structure but it is much larger. Thymus: a soft organ with two lobes that is located anterior to the ascending aorta and posterior to the sternum. Peyer patch: lymphoid tissue on the visceral surface of the small intestine.

Lymphatic System • Primary Lymphoid Organs • Bone marrow and Thymus • Secondary Lymphoid Organs • Spleen, tonsils, Peyer’s patches • Lymphatic system, upper respiratory system and muscular system ALL contain lymphatic vessels

Lymphatic Vessels • Lymphatic vessels carry excess fluid from tissues and return it to the bloodstream. • Have flaplike valves that help prevent backflow of lymph • Vessels lead to lymph nodes • After leaving the nodes, the vessels merge to form lymphatic trunks

Lymphatic Capillaries • Thinned walled capillaries which allow fluid to enter. • Fluid inside is called “lymph” • Lacteals: lymphatic capillaries located in lining of small intestines which absorb fat and transport them to venous circulation

Lymph nodes and ducts The right lymphatic duct drains lymph from theupper R side, whereas the thoracic ductdrains lymph from the rest of the body. Lymphatic capillary Lymphatic vessel Lymph node Lymphatic vessel Lymphatic trunk Collecting duct Subclavian vein

Lymph nodes • Glands which are located along the lymphatic pathways • Contain large #s of lymphocytes and macrophages • Located in neck, thoracic cavity, armpit (axillary), abdomen, pelvic area, inguinal area and supratrochlear nodes (where is this???) • 2 functions: filtration and providing lymphocytes and macrophages for immunity • Do not trap wbcs but they do trap bacteria, and toxins

Immunology The body’s defense system

Terminology • Immunology: the study of how body components respond and interact • Immunoglobulins: class of proteins that make up antibodies • Phagocytosis: process where cells engulf and destroy foreign particles such microorganisms or damaged cells. Macrophages and segmented neutrophils are the most important phagocytic cells

Terminology • Immunogenicity: the degree to which an antigen elicits an immune response • Immunogen: antigen that stimulates an immune response • Soluble antigen: free floating antigen recognized by B cell receptors

Terminology • Epitope: the small piece of an antigen that is bound by an antibody or a T cell receptor • Chemotaxis: release of substances which attract phagocytic wbc to bacteria. Cells move from an area of low to high concentration of chemokines.

Immune System • Immune System: cells in our bone marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that function to protect us. • Function is to recognize self from nonself and to defend the body against nonself.

Lines of Defense • 1st line of Defense • Non specific • Innate or inborn • General response which protects us daily • Non Specific Responses • Inflammation • Phagocytosis • Physical barriers • Chemical barriers

Immune System • 1st line of defense: • Skin and mucosal membrane surfaces • Secretions: mucous on membranes in nose trap microorganisms and are secreted through sneezing. What other secretions can you think of? • Tears, saliva, ear wax, sweat, production and elimination of urine • Phagocytic wbc in the mucous membrane

Immune System • 1st line of defense continued: • Normal flora deter penetration of microorganisms • pH of body fluids such as gastric juices • Cilia movement helps protect the respiratory tract • The enzyme lysozyme which is found in tears and saliva attacks and destroys the cell wall of susceptible bacteria especially some gram positive bacteria

Immune System • Non specific cellular and chemical response • Fever production resulting from pyrogenic secretions from pathogens • Interleukin 1 produced resulting from stimulated macrophages. • Polypeptide secreted by macrophages, enhance T cell activation and activity • Phagocytosis: process of surrounding and engulfing foreign matter. • Antibodies coating an invading microbe for phagocytosis is called opsonization.

Activation of the Complement System Complement System Activation of complement proteins Opsonization: enhancing phagocytosis of Ags Chemotaxis: attracting macrophages and neutrophils Lysis: rupturing membranes of foreign cells Clumping of Ag bearing agents Altering the molecular structure of viruses

Inflammatory Response • Involves granulocytes such as basophils and eosinophils. • Mast cells are activated during an allergic reaction and release histamine • Delayed hypersensitivity is also called Cell Mediated response

Immune Responses • 2nd line of Defense • Specific • Production of Abs in response to Ag • Specific Responses • Associated with Ag and Ab reaction • Ab response occurs after exposure to Ag • Ab may neutralize, kill, or cause clumping of foreign microorganisms • Complement system also works w/Abs to destroy the invader • Complement system is a group of proteins produced in the liver, circulating in the plasma and enhance the work of Abs

Types of Immunity

Natural Immunity • Also known as innate (inherited) immunity • Mechanism which kicks in after bacteria gets past the first lines of defense • Natural immunity is a non specific mechanism

Natural Immunity • Components of Natural Immune System • Cellular components • Mast cells • Neutrophils: most abundant and 1st to arrive • Macrophages • Humoral (fluid) • Complement • Lysozyme • Interferon

Leukocytes

Effector Cells • Plasma cells: derived from lymphocytes (white blood cells) and are the cells which secrete antibodies. They live a short time and are constantly being replaced. • Macrophages: derived from monocytes (wbc) w/primary function of phagocytosis

Adaptive Immunity • Also known as acquired immunity • Active immunity can leave the host w/specific immunologic memory which allows the host to respond more effectively if re-infection with the same microorganism occurs

Specific Immune Response • Primary Immune Response: 10 to 17 days after initial exposure to Ag. Selected lymphocytes generate a maximum effector cell response. • While effector cells are developing an infected person may become ill but eventually the symptoms of the illness disappear as Abs and effector T cells clear antigens from the body. • Secondary Immune Response: later exposure to the Ag that results in a much faster (2-7 days), much faster, and more prolonged response by Abs and effector T cells

Immunoglobulin Structure • Composed of glycoproteins • 4 protein chains held together w/ disulfide bonds • Fcregion: constant region dictates the type of immunoglobulin A, E, D, M, or G • Fab portion: antigen binding region of the Ab. This region is highly diverse so that the variety of antigens recognized by these receptors is extremely numerous • Heavy chains • Light chains

Immunoglobulin Structure Composed of 2 identical Heavy chains and 2 identical light chains Constant regions are located on both the light and heavy chains The very end of the variable Regions is called the hypervariable as that is the region where the amino acid sequencing varies the most

Antibodies • Variable region is what determines the antigen specificity • The constant region (Fc) is what determines the antibody immunological class or isotype (A,E,M,G, D) • Antibodies do not destroy antigens directly • Neutralize • Target for elimination • Agglutination, precipitation, complement fixation

Antibodies • IgM: first type of antibody secreted during a primary immune response (promotes agglutination or clotting) • IgG: major type of antibody secreted during a secondary immune response • IgE: type most associated with allergic reactions (promotes release of histamine)

Antibodies • IgA: this is the antibody found in most abundance in bodily secretions such as saliva and mother’s milk • IgD: this antibody serves as a B cell surface receptor. • Soluble antibodies are involved in the following • Cause clotting • Can bind active sites on toxins • Tag foreign microbes for destructions

Antibodies • IgM and IgD are the first antibodies expressed by a B cell • Each B cell has ~ 100,000 IgM or IgD receptors on its surface • These antibodies can bind free Ags whereas T cell receptors can only bind to Abs when they are presented by Ag presenting cells (discussed later)

Antibodies • Binding the IgM or IgD on the B cell surface provokes a primary immune response resulting in secretion of IgM, B cell division, and clonal expansion • Secretion of the IgM Abs stimulates the activation of the complement system • IgG Abs are then produced and promote phagocytosis

Antibody Response Graph

B Cell Maturation • Stem cell Pro- B cell Pre B cell Immature B cell mature B cell • During this time of development the Ab/Ag specificity is being determined through a process of random genetic recombination. Also undergoes a process of negative selection to screen for self versus non self molecules. During the immature B cell stage: if the antigen receptor matches with a self antigen the cell dies by apoptosis called Clonal Deletion

B Cell Maturation and Function • When antigen binds to the B cell receptor, the B cell is activated and begins to undergo clonal expansion, which results in the proliferation of exact duplicates of the original B cell. • When B cells are mature the must undergo a process to determine self tolerance. This process is Ag dependent.

Humoral Immunity Summary • Involves the production of Abs that circulate in the blood and lymph to defend against free bacteria, toxin, and viruses • Involves B cells that eventually differentiate into plasma cells or memory cells • Also requires the use of Helper T cells and certain cytokines such as IL-2 • Plasma cells produce antibodies while memory cells wait for re-exposure • Antibodies tag foreign microbes for destruction through several processes

Cell Mediated Response Overview • Involves direct killing of infected cells via TC cells • Does not involve the production of Abs • Requires both the activation of TH cells and TC cells • Some cells will become effector cells and some cells will become memory cells to wait for re-exposure • Most important cell is the TH cell • Overlaps with Humoral Response

T Lymphocytes • Originate in the bone marrow but mature in the thymus • Stored in the secondary lymphatic tissue • Basis for Cell Mediated immunity • Lifespan: resting 1-3 weeks, activated 3-4 days, memory years/lifetime • Respond to specific Ag and cancer cells • Do not produce Abs • 2 Primary types: cytotoxic and helper T cells

T Cell Maturation • Stem Cell Pro T cell Pre T cell Double positive T cell Double positive alpha beta TCR T cell Single positive T alpha beta TCR cell • During this time of development T cell receptor (TCR) specificity is being determined • Undergoes process of both positive and negative screening for productive gene arrangement, self versus non-self molecules, and appropriate CD surface protein molecules • CD 8 = Cytotoxic T cell, CD 4 = Helper T cell

Stem Cell differentiation Stem cells originate in the bone marrow

Antigens • Elicit an immune response • 2 general types exist • Exogenous: foreign from outside the host • Endogenous: foreign from within the host • Viruses, bacteria, fungi, protozoa, and parasites are all antigens • Antigenic determinants = epitope

Antigens • Chemical composition are proteins and large polysaccharides (carbs) • Proteins make the best immunogens due to their high MW and structural complexity • Polysaccharides(carbs or sugars) are OK immunogens but their small size make them less effective than proteins

Antigens • Lipids are inferior antigens because of their relative simplicity and lack of structural stability • Nucleic acids are poor Ag due to lack of molecular flexibility and rapid degradation

Antigen Receptors • The way that B cells and T cells recognize specific molecules and trigger an immune response • Plasma membrane bound • All antigen receptors on a B cell or T cell have the same specificity • Determined by random genetic events • Occurs before any contact w/foreign antigen is made • Allows for an enormous variety of B and T lymphocytes

Autoimmunity • Immune system fails to distinguish self from non self producing autoantibodies and cytotoxic T cells that attack and damage the body’s tissues • May be caused by a virus replicating within a host cell or faulty T cells or antigen which closely resembles self Ag (example strep infection in heart valves)

Autoimmunity diseases and conditions • Cancer of the lymph nodes: when lymphocytes undergo a mutation and multiply out of control • Rheumatoid arthritis: involves the joints, RF factor is test method • Grave’s disease: hyperthyroidism, affects young women, goiter is common side effect as well as exophthalmos (protrusion of the eyes) • Pernicious anemia: mucous lining of stomach does not secrete protein called intrinsic factor which is needed for B12 absorption resulting in anemia • HIV infection: reverse transcription coverts viral RNA into DNA

The Lymphatic System