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The Lymphatic System. Consists of lymphatic vessels and the lymphoid organs Four main homeostatic functions : Lymphatic capillaries take up and return excess fluid to the bloodstream Lacteals, in intestines, absorb fats in form of lipoproteins and transport them to the bloodstream
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The Lymphatic System • Consists of lymphatic vessels and the lymphoid organs • Four main homeostatic functions: • Lymphatic capillaries take up and return excess fluid to the bloodstream • Lacteals, in intestines, absorb fats in form of lipoproteins and transport them to the bloodstream • Responsible for production of lymphocytes • Helps defend body against pathogens
Lymphatic Vessels • Form a one-way system that begins with lymphatic capillaries • Take up fluid that has been diffused from, and not reabsorbed by, blood capillaries. Fluid inside lymph vessels is called lymph. • Vessels have valves like veins. Dependent on skeletal muscle for movement. • Edema - Localized swelling due to accumulation of tissue fluid that has not been collected by lymph system.
Primary Lymphatic Organs • Lymphatic organs contain large numbers of lymphocytes (B cells and T cells) • Red Bone Marrow • Site of stem cells which divide to produce all types of blood cells • Found in adults in bones of skull, sternum, ribs, pelvis, vertebral column & heads of femur & humerus • Place where B cells mature
Primary Lymphatic Organs • Thymus Gland • Located along trachea behind the sternum in upper thoracic cavity • Largest in children; shrinks throughout life • T cells migrate here to mature • T cells are capable of telling “self” from “nonself” • T cells that could possibly hurt your own cells are destroyed by apoptosis.
Secondary Lymphatic Organs • Lymph Nodes - Ovoid structures occurring along lymphatic vessels • Cleanse lymph - Macrophages engulf debris & pathogens - T cells fight infections & attack cancer cells • Lymph nodes named for their location • Spleen - Located in abdominal cavity behind stomach • Macrophages remove old blood cells • Lymphocytes cleanse blood of foreign particles
Lymphoid Organs • Tonsils • Patches of lymphatic tissue located in the pharynx • First to encounter pathogens that enter via the nose and mouth • Peyer’s patches & appendix • Located in the intestines • Encounter pathogens that enter the body by way of the intestinal tract
Immune System • Immunity is the body’s capability to remove foreign substances & to kill pathogens & cancer cell. • Nonspecific Defenses - occur automatically & no memory is involved. 1. Barriers to entry serve as mechanical barriers • Skin • Mucous membranes lining respiratory, digestive, and urinary tracts • Antimicrobial molecules (oily secretions on skin, lysozyme enzymes, acidic pH of stomach)
Nonspecific Defenses • Inflammatory Response - occurs whenever tissue is damaged by physical or chemical agents or by pathogens • Damaged cells and mast cells release histamine which causes capillaries to dilate and become more permeable • Enlarged capillaries lead to more blood flow which causes skin to redden & become warm • Increased permeability allows fluids to escape • Swollen area stimulates free nerve endings causing pain
Inflammatory Reaction • Fever frequently occurs also • Fever serves to: -inhibit growth of microorganisms -promotes tissue repair - aids phagocytosis -stimulates immune cells to divide more rapidly -increases production of interferon
Inflammatory Reaction • Neutrophils and monocytes migrate to the site of injury • Neutrophils and mast cells phagocytize pathogens • Monocytes differentiate into macrophages • Macrophages release cytokines, chemical signals that stimulate other white cells. • Some phagocytes die. These, with dead tissues, bacteria & living white cells, form pus. • Natural Killer Cells large lymphocytes that kill virus-infected cells & cancer cells.
Complement System • This is a collection of plasma proteins • Activated when pathogens enter the body • Amplify the inflammatory response - Proteins bind to mast cells & trigger histamine - Others attract phagocytes to scene - Some bind to pathogens coated with antibodies which ensures they will be phagocytized • Other complement proteins join to form a membrane attack complex - Produce holes in surface of bacteria & viruses - Fluids & salt enter the cell & they then burst
Proactive Proteins • Interferons - proteins produced by virus-infected cells as a warning to non-infected cells • Interferon binds to receptors of non-infected cells • Causes them to prepare for possible attack • Non-infected cells produce substances that interfere with viral replication
Specific Defenses • When nonspecific defenses have not been adequate, specific defenses come into play: • Specific defense requires that the immune system be able to recognize a specific molecule called an antigen, any foreign substance that stimulates the immune system to react • Immune system can respond to the antigen - Usually takes 5-7 days to mount a specific defense 3. Immune system can remember the antigen
Specific Defenses • Specific defenses primarily depend on action of B cells & T cells • These are lymphocytes capable of recognizing specific antigens • Have antigen receptors that combine with particular antigens • Receptor’s shape allows it to combine with a specific antigen • Each lymphocyte has only one type of receptor • Receptor & antigen fit together like a lock & key
Specific Defenses • B lymphocytes • B cells give rise to plasma cells • Plasma cells produce antibodies which are capable of combining with & neutralizing particular antigens • T lymphocytes • T cells directly attack cells that bear non-self proteins • Don’t produce antibodies • Differentiate into helper T or cytotoxic T cells
B Cells & Antibody-Mediated Immunity • B cells have receptors on their cell membrane called B-cell receptors (BCR) • Virgin B cells are activated when they bind to a specific antigen that matches their own receptor. • The specific B cell will divide by mitosis many times creating clones of itself. • Most of these clones become plasma cells which will circulate in the plasma & lymph. • Plasma cells can secrete millions of antibodies per hour. Antibodies are proteins coded for by genes. • Some of the clones become memory cells which confer long-term memory & a more rapid response the next time the antigen is encountered.
Antibodies (Immunoglobulins or Igs) • Antibodies are Y-shaped molecules with 2 arms. • Consist of 4 polypeptide chains: • 2 “heavy” (long) chains • 2 “light” (short) chains • These chains consist of: • Constant regions where amino acid sequence is set. Divided into five antibody classes by tail area. • Variable regions where a.a. sequence varies between different antibodies. These are located at the tips of the arms of the antibodies. Thus, no two antibodies are alike. All will bind to unique antigens
Antibody-Mediated (Humoral) Response • Once antibody production by plasma cells begins the antibodies begin to bind to antigens that are in the plasma or lymph. • Each antibody can bind to two antigens, so they begin to clump together creating antibody-antigen complexes. This process is called agglutination.
Antibody-Mediated Response • Agglutination triggers three reactions: • Macrophages or neutrophils may come and engulf the complexes by phagocytosis • Natural killer cell lymphocytes will destroy invader • Complement system is triggered which can lead to destruction of pathogen
T Cells • T cells have T-cell receptors (TCR). Each virgin T cell that leaves the thymus has a unique T-cell receptor just like B cells do. However, T cells cannot bind directly to an antigen without help • Requirements for virgin T cell antigen binding: • Antigen must be presented by an antigen-presenting cell (APC) such as a macrophage, a B cell, or an infected body cell. - Macrophage, or B cell, APC phagocytizes a pathogen. - APC breaks down the pathogen in a lysosome - A piece of the pathogen (antigen) is displayed on an MHC (major histocompatibility complex) protein on the cell’s surface.
MHC Proteins • There are two types of MHC proteins: • MHC-II - Found on B cells & phagocytes like macrophages - These function in stimulating the immune response - Cells with these proteins are not killed by cytotoxic T cells •MHC-I - Found on all nucleated human body cells - Cells with these proteins can be killed by cytotoxic T cells
MHC Proteins • Each MHC protein has two chains, the tips of which are variable like antibodies. • MHC proteins bind antigens and “present” them on the surface of the cell • The MHC proteins will then bind to the T-cell receptors on a T cell. •The MHC proteins are called “self-markers”. -T cells must bind to both an antigen & an MHC protein simultaneously. This ensures that T-cells will NOT destroy normal “uninfected” cells.
T Cell or Cell-Mediated Response • Steps of the Cell-Mediated (T) Response: •Virgin T cell encounters an APC presenting a specific antigen that can bind to its T cell receptor - Virgin T cell is activated and will start to clone itself •Two types of T cells will be produced depending on the type of cell and MHC protein doing the presentation: - If the APC is an immune cell with an MHC-II protein, helper T cells will be produced - If the APC is an infected body cell with an MHC-I protein, cytotoxic T cells will be produced
T Cell or Cell-Mediated Response • Cytotoxic T cells •Have storage vacuoles containing perforins. - After cytotoxic T cells bind to an infected cell they release the perforin molecules which form pores in the infected cell. - The cytotoxic T cells then deliver granzymes into the pore which cause the cell to undergo apoptosis & die.
T Cell or Cell-Mediated Response • Helper T cells •Can bind to cells with MHC-II proteins such as macrophages or B cells that have engulfed and processed the antigens of the invading pathogen -The helper T cell then divides into clones of helper T cells and memory T cells. -The activated helper cells secrete cytokines. One cytokine, interleukin-2, stimulates other cells: Stimulates division of B cells into plasma cells Helps cytotoxic T cells to become active killers Stimulates phagocytosis of pathogens Causes helper T cells to grow & divide
HIV Infections • The primary host for an HIV (human immunodeficiency virus) is a helper T cell. Macrophages can also be attacked. • After HIV enters a host cell, it reproduces inside and then many offspring bud from the cell. • Thus, the host cell produces the viruses that go on to destroy more helper T cells. • Eventually the helper T cell count drops to way below normal. • Then the person comes down with opportunistic infections. Now the person has AIDS (acquired immunodeficiency syndrome)
Induced Immunity • Immunity happens naturally through infection or by medical means. There are two types: active & passive. • Active Immunity • Active immunity develops after a person is infected with a pathogen such as measles. • Immunization • Done so future infection will not take place. • Involves the use of vaccines, substances that contain an antigen to which the immune system responds
Primary & Secondary Immune Response • Primary Immune Response • Occurs when body is first exposed to an antigen, either naturally or artificially • It takes several days for the body to recognize the antigen, make a clone of the B cells and then begin to make antibodies against the antigen • It takes about 2 weeks to reach the peak response • The antibody concentration (titer) then gradually declines almost back to nothing.
Primary & Secondary Immune Response • Secondary Immune Response • Second exposure to same antigen causes a faster & stronger response • Antibody titer rises rapidly & to a much higher level than during primary response • The antibodies also seem to work more effectively • The high response lasts for a much longer period of time & the antibody titer doesn’t return to zero • Due to the presence of memory cells that may last for decades if not for entire life. • Why vaccines are usually given a “booster” shot
Passive Immunity • Passive immunity occurs when an individual is given prepared antibodies (immunoglobins) to combat a disease • •Short-lived since antibodies were not produced by the individual’s own body • Newborns are often passively immune due to some of mother’s antibodies passing through placenta • Breast-feeding also passes antibodies to baby • If exposed to an illness, doctors may give a patient injections of gamma globulin from people or animals that have survived the disease.
Monoclonal Antibodies • Every plasma cell derived from the same B cell secretes antibodies against a specific antigen • These monoclonal antibodies can be produced in the lab, in vitro. • B cells removed from animal & exposed to antigen • The resulting plasma cells are fused with malignant myeloma cells. Fused cells are called hybridomas • These divide & produce same kind of antibody • Used today in urine test for pregnant women & in delivering radioisotopes or drugs to cancer areas.
