Chapter 14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lymphatic System and Immunity Peanuts are a common food allergy and the amount of individuals with this type of allergy is on the rise. THE LYMPHATIC SYSTEM Similar to the cardiovascular system Transports fluid made of cells and biochemicals called lymph 1st major function: transport of excess fluid from interstitial space to return it to the blood stream 2nd major function: attack foreign invaders, toxins and cancer cells MICROVIEW OF LYMPH CAPILLARIES Many capillaries in the skin as a first defense against invaders Form complex closed ended tubes that parallel vessels and extend into the interstitial space The walls have a single layer of squamous epithelium to allow of tissue fluid entry Have valves like veins Large lymph vessels lead to lymph nodes LYMPH TRUNKS AND COLLECTING DUCTS Lymph trunks - drain lymph from lymphatic vessels Right lymphatic duct - collects from area highlighted in red Thoracic duct collects everything else After leaving the ducts the lymph becomes part of the plasma before blood returns to the right atrium LYMPH PATHWAY Lymph returns small proteins and foreign particles to lymph nodes Hydrostatic pressure drives entry of lymph into lymph capillaries Lymph vessels pump lymph with help from smooth muscles, skeletal muscle contractions and breathing LYMPH NODES Contain large numbers of lymphocytes and macrophages Afferent vessels “in” Efferent vessels “out” from hilum Enclosed in connective tissue capsule Sinuses - lots of macrophages Lymph nodules - masses of B cells and macrophages in the cortex Nodules occur in groups or singly ex: tonsils or Peyer’s Patches LYMPH NODE IN A HUMAN LYMPH NODE LOCATIONS They follow large vessel patterns Filter harmful particles from lymph before return fluid to blood Swollen lymph nodes = lymphadenitis - painful, occurs while body is fighting infection or downstream of an injury Streaking - inflamed lymph vessels secondary to bacterial infection - treated with antibacterial medications THYMUS AND SPLEEN THYMUS - immune organ - shrinks after puberty & by 70 it’s only 25% as powerful as when young -filled with Tlymphocytes (T Cells) -Thymosins released to mature T cells SPLEEN - largest lymphatic organ -filters blood -Sinuses filled with blood versus lymph WHITE PULP - has lymph nodes filled with lymphocytes RED PULP - has RBCs, lymphocytes and macrophages In the spleen RBCs are recycled by macrophages Macrophages - engulf and destroy foreign particles BODY DEFENSE AGAINST INFECTION Pathogens invade & replicate in the body to cause infection Innate response: species resistance, mechanical barriers, chemical barriers, NK cells, inflammation, phagocytosis and fever (fast responders) Adaptive response: aka immunity - targeting specific pathogens antibody production (slow responders) Both responses work at the same time T Cell Activation Response INNATE DEFENSES 1) Species resistance - we can’t develop a dog disease and we have diseases specific to us (measles, gonorrhea and syphilis) 2) Mechanical barriers - skin and mucous membranes that line the respiratory, digestive, urinary and reproductive system - hair traps pathogens - Sweat and mucus - rinses away microorganisms 3) Chemical barriers - enzymes (gastric enzymes HCl and pepsin) lethal to stomach pathogens - Lysozyme in tears kills bacteria - Salt from sweat kills skin bacteria - Interferons hormone-like peptides produced by lymphocytes and fibroblasts - Released from virus infected cells to stimulate surrounding uninfected cells to produce proteins that block viral replication - Stimulate phagocytosis to enhance cell activity to resist infection INNATE DEFENSES CONTINUED… 4) NK CELLS - lymphocytes that secrete performs that lyse cell membranes of viruses and cancer cells yet, secrete chemicals that enhance inflammation at the same time 5) INFLAMMATION - tissue response to injury or infection leads to redness, swelling, heat and pain -infected cells send chemical messages to WBCs to eat pathogens 6) PHAGOCYTOSIS - neutrophils - small invaders; monocytes - large invaders both called to injured areas via chemotaxis and leave vessels via diapedesis 7) FEVER - high body temperature maintained to fight infection -liver and spleen hold iron which prevents extra iron in the blood because bacteria and fungi require iron to survive -Phagocytic cells attack better with increased temperature LYMPHOCYTE FUNCTION T Cells - attach directly to foreign antigen bearing cells -can secrete cytokines ex: IL 1& 2 that cause T Cell proliferation and cytotoxic T Cell activation B Cells - divide into plasma cells which produce antibodies (aka immunoglobulins) -antibodies are carried in body fluid to destroy specific particles with antigens -T and B Cells with lots of varieties and each variety all come from a clone LYMPHOCYTE ORIGIN Thymus - T Cells aka T lymphos 70-80% lymphocytes in circulation -lymphocytes are in lymph nodes, thoracic duct, white pulp of the spleen -B-lymphocytes aka B-Cells - in red bone marrow till mature - go to lymph organs (2030% lymphocytes in circulation) B Cells respond quickly to invaders they have seen before TYPES OF ANTIBODIES IMMUNOGLOBULIN G (IgG) - in plasma and tissue fluids - effective against bacteria, viruses and toxins; activates complement IMMUNOGLOBULIN A (IgA) - in exocrine gland secretions, breast milk, tears, nasal fluid, gastric juice , intestinal juice, bile and urine IMMUNOGLOBULIN M (IgM) - antibody present in plasma in response to contact with certain antigens in foods or bacteria; activates complement -ex: antiA and antiB antibodies in blood are IgM IMMUNOGLOBULIN D (IgD) - surfaces of B cells, activates B cells IMMUNOGLOBULIN E (IgE) - in exocrine secretions and associated with allergic reactions ANTIBODY ACTIONS Antibodies attack antigens Activate complement or stimulate inflammation Prevent spread of pathogens Direct attack: antibodies combine with antigens causing them to clump so that phagocytic cells recognize and eliminate cells displaying antigens -antibodies can also cover toxic portions of antigen displaying molecules and neutralize their effects -Complement is activated when IgG or IgM antibodies bind to antigens -What does complement activation do? Lets see the next slide… COMPLEMENT ACTIVATION Figure 14.16 All memory B and T Cells here Activation of B and T cells after 1st encounter an antigen THE MAKING OF AN ANTIBODY CLASSIFYING IMMUNE SYSTEM RESPONSES ALLERGIC REACTIONS ALLERGENS - antigens that trigger allergic responses Delayed reaction allergy - occurs due to repeated exposure of skin to certain chemicals usually after 48 hrs; ex: detergents, lotions -after repeated exposure - the foreign substance activates T cells and macrophages which cause eruptions and inflammation (dermatitis) - can affect anyone - do not need genetic tendency -Immediate reaction allergy - occurs within minutes of contact with an allergen -Affects those with inherited tendency to over produces IgE antibodies in response to certain antigens -Activates B Cells -IgE attaches to mast cells and basophils and histamine, prostaglandin and leukotrienes are released -Vessels dilate, become permeable and edema occurs -Contraction of bronchial and intestinal smooth muscles as well as increased mucus production occur -ANAPHYLACTIC SHOCK - severe immediate reaction allergy where mast cells release histamine throughout the body causing itching, hives, vomiting, diarrhea, swelling of the face, tongue and larynx Treatment: epinephrine needed within 5 minutes Common causes: penicillin, insect stings and peanuts TRANSPLANTATION AND TISSUE REJECTION Tissue rejection reaction - recipient’s immune system recognizes the donor’s cell surfaces as foreign and tries to destroy the transplanted tissue -similar to cellular immune response against non-self antigens -The greater the difference between cell surface molecules the quicker and severe the reaction -Matching up donor and recipient tissues better prevents severe reactions -Immunosuppressive drugs are given to decrease rejection -T cells and the formation of antibodies are suppressed to prevent humoral and cellular immune responses AUTOIMMUNITY Occurs when the immune system fails to differentiate between self and non-self thus making antibodies to it’s own cells Ex: type I diabetes mellitus, rheumatoid arthritis, systematic lupus erythematosus Why would the body do such a thing? - A virus while replicating “borrowed” proteins from the host cell and put it into it’s surface so when the immune while attacking viral invaded cells also attacks self-cells that have the same protein - T cells may never learn to distinguish self from non-self or a non-self antigen resembles a self antigen as in the case of the bacterium streptococcus triggering inflammation of the heart valves HIV AND AIDS -the immune system gradually shuts down as infected T cells die -When T cells die bacterial infections set in -Later in the infection the virus kills cytotoxic T cells -1st HIV enters macrophages -2nd the virus adheres to gp120 on CD4 and CCR5 cells - reverse transcriptase makes a strand of DNA just like the viral RNA and it is incorporated in to that cell’s DNA HIV TREATMENT HIV replicates, mutates and hides often making it tricky to treat For a few years after infection one can produce enough new B and T Cells to counter the ones that are infected - thus one may show no symptoms TREATMENTS AVAILABLE: Generally it is a combination of the following: those that block viral replication Protease inhibitors to prevent HIV from making it’s proteins Entry inhibitors - block binding and/or fusing of HIV to T Cells VACCINES ARE BEING TESTED - to target molecules on it’s viral envelope or proteins that the virus uses to package itself for replication CURRENT GOALS: keep viral levels low so health and life span improved