Overview of the Lymphatic System: cells, tissues, and organs responsible for defending the body against both environmental hazards (pathogens) and internal threats (cancer) Pathogens: viruses, bacteria, fungi, and parasites capable of not only surviving but thriving inside our bodies Immune response: cells of the immune system that provide a specific response as a defense against pathogen Immunity: Ability to resist infection and disease through the activation of specific defenses. Organization of the Lymphatic System Lymph: plasma-like fluid Lymphatic vessels: begin in tissues and end in connections to veins Lymphoid tissues and organs Lymphocytes and other cells The body has between 501 and 700 lymph nodes (the number of nodes varies from individual to individual). About half of the nodes are in the middle of your body (stomach or abdominal cavity). The lymph nodes near your armpits and groin have about 100 nodes. Functions of the Lymphatic System Produce, maintain and distribute lymphocytes Produced inside the lymphoid tissues and organs Tonsils, spleen, thymus, red bone marrow, appendix Provide defense against infections and environmental hazards Must be able to detect problems Must be able to reach the infection or injury site Circulate in the blood Lymphatic Vessels Lymphatic vessels carry lymph from the tissues to the venous (veins) system. Vessels have valves to allow entrance into the vessels for fluids, proteins, viruses and bacteria but prevents them from flowing back into the intracellular spaces Lymphatic capillaries are the smallest of these vessels Present in almost every tissue and organ in the body Lymphatic Vessels Occur in association with blood vessels but are smaller and more numerous Major lymph collecting vessels Superficial lymphatics: located in the deep subcutaneous layer of the skin and in the lining of the digestive, respiratory, urinary, and reproductive tracts Deep lymphatics: larger, accompany deep arteries and veins in the limbs and trunk Deep and superficial come together to form larger vessels called trunks These empty into two large collecting vessels Lymphatic Vessels Thoracic duct begins below the diaphragm collects lymph from the left side of the head, neck, thorax and inferior portion of the body empties it into the left subclavian vein to reenter into venous circulation Right lymphatic duct formed from the merging of major blood vessel trunks on the right side of the body empties into the right subclavian vein. Lymphodema Blockage of lymphatic drainage from the limbs Fluid accumulates in the limb and gradually becomes swollen Can be permanent if the condition persists Dangerous if an infection develops in that area Why? Lymphocytes “Lymph cells” 3 classes Each has it’s own biochemical and functional characteristics T cells (thymus-dependant) B cells (bone marrow- derived) NK cells (natural killer) “pit bulls of the lymphatic system T cells: 80% of lymphocytes Cytotoxic T cells Attack foreign cells or body cells infected with a virus Helper T cells Suppressor T cells Inflammatory T cells Stimulate the activation and function of both T cells and B cells Inhibit the activation and function of both T cells and B cells Stimulate regional inflammation and local defenses in injured tissue Other lymphocytes B cells NK cells 10-15 % of lymphocytes Can differentiate into plasma 5-10 % of lymphocytes cells Responsible for producing antibodies These bind to specific chemical targets called antigens Antigens are typically pathogens, parts of pathogens Some lipids, polysaccharides and nucleic acids can stimulate antigen body production lymphocytes Attack foreign cells, normal cells infected with viruses, and cancer cells (often Dr.s measure #s of these to measure if cancer cells are growing or declining) Continuous “policing” is called immunological surveillance Also known as large granular Life span and circulation of lymphocytes They are not evenly distributed throughout the blood T cells move around the body quickly B cells are much slower Majority of lymphocytes have long life spans (4 years +) Some may live up to 20 years You maintain your lymphocyte populations by making new lymphocytes in bone marrow and lymphiod tissue Lymphocyte Production Lymphopoiesis (lymphocyte production) involves bone marrow, thymus, and peripheral lymphoid tissues. Lymphocytes originate from stem cells Division of stem cells in the bone marrow that produce immature B and NK cells, as they mature they begin to circulate in the blood stream. Second division of stem cells migrates to the thymus In the thymus these cells produce various kinds of T cells, when they mature they enter the blood stream. Lymphoid Tissues: Connective tissue dominated by lymphocytes • Lymphoid nodule: lymphocytes are densely packed • Large clusters of nodules exist Tonsils: most people have 5 • When the pair in the base of the pharynx become infected we get tonsillitis • Germinal center: central zone of the nodule where lymphocytes divide • Lymphoid Tissues: dominated by lymphocytes MALT: Mucosa-Associated Lymphoid Tissue Collection of lymphoid tissue linked with the digestive tract Peyer’s patches are cluster of nodules in the lining of intestines Lymphoid Organs Lymph nodes: small lymphoid organ surrounded by connective tissue Bean shaped Hilus is the indentation of the “bean” where nerve and blood flow reach the node Lymph flow: through open passageways with incomplete walls called sinus Then through the outer cortex of the node Then continues to the deep cortex and into the core or medulla of the lymph node Lymph Node Function Purifies lymph before it reaches the vessels Like a water filter Early warning system for the body Pathogens stimulate macrophage/lymphocyte production in nodes Lymph glands at the groin, axilla (armpit), and base of the neck act as guards to protect the trunk for pathogens Minor injury/infection causes “swollen glands” when lymph nodes respond to injury/infection by increasing production Thymus Pink, grainy organ located behind the sternum Produce T cells Surrounding blood vessels allow T cells to enter the blood stream Review: Thymus also produces hormones (endocrine system) Thymosin is a hormone that promotes development of lymphocytes Spleen Largest collection lymphoid tissue Provides same services for the blood that lymph nodes do for the lymph Remove abnormal blood cells/components by phagocytosis (think of pac-man) Storage of iron recycled from red blood cells Initiation of immune response by B cells and T cells in response to antigens in the blood Spleen Blood circulates through and allows phagocytes in the spleen to engulf damaged or infected cells in the blood Infection (such as mono) can cause the spleen to become enlarged The spleen is fragile When it is enlarged any blow to the left side of the body can cause it to rupture Non-specific defenses: prevent the approach, deny entry, or limit the spread of microorganisms or other environmental hazards. Categories 1. Physical barriers 2. Phagocytes 3. Immunological surveillance 4. Interferons 5. Complement 6. Inflammatory response 7. Fever Physical Barriers Keep hazards outside the body (example: hair on your head helps keep mosquitoes off) In order for a pathogen to cause trouble it has to enter the body. Cross the epithelium (skin) through a mucus membrane (mouth, nose, eyes, etc) Accessory structures help with the barrier (eyelashes, hair, glands that secrete oil or chemicals/enzymes) Phagocytes: engulf pathogens and debris Microphages (small) Circulate in the blood, leave to travel into tissues to engulf and destroy pathogens/antigens Macrophages (big) Several types, in almost every tissue of the body Work by Engulfing particle and destroying it with and enzyme Bing or remove particle from fluid and receive help from other cells to destroy it Releasing toxic chemicals to destroy particle Fixed macrophages: permanent residents of a tissue Free macrophages: mobile and travel through the body to arrive at injury sites Phagocytes: Movement and phagocytosis Free and fixed macrophages characteristics Both can move through capillary walls Both may be attracted or repelled by chemicals ins the surrounding fluid (chemotaxis) Both use adhesion (attachment of the phagocyte to its target) and then formation of a vesicle (capsule) that is digested with help of an enzyme Immunological surveillance: destruction of abnormal cells by NK cells The immune system usually ignores your body’s own cells unless they have become abnormal in some way (such as mutated cells or cells infected with a virus) mutations-can lead to what? Immunological surveillance: NK cells monitor tissues looking for and destroying abnormal cells in any tissue of the body NK cells are highly versatile Respond very rapidly Immunological surveillance: Cancer cells’ membranes contain proteins called tumor-specific antigens NK cells recognize them as abnormal and destroy them However, some cancer cells go undetected through immunological escape: Escape destruction by: avoiding detection, covering their antigens somehow, or killing NK cells Once escaping detection, cells can multiply and spread Interferons: chemical messengers that coordinate defenses against viruses Interferons are small proteins released by lymphocytes, macrophages, and tissues infected with a virus Trigger the production of antiviral proteins which interfere with viral replication inside the cells Stimulate the activities of macrophages and NK cells Complement: chemical messengers that coordinate defenses against viruses 11 special complement proteins: complement the actions of antibodies Complement Activation: Classical Pathway (rapid and effective) One complement protein binds to an antibody molecule already attached to its antigen It then acts as an enzyme starting a series of reactions with other complement proteins Complement: Alternative Pathway (slower and less effective) Occurs when there is no antibody molecule Several complement proteins interact in the plasma to defend against bacteria, parasites, and virus infected cells Complement: chemical messengers that coordinate defenses against viruses Effects of Complement Activation Stimulation of Inflammation Enhance the release of histamine to accelerate inflammation Attraction of Phagocytes: to increase destruction of pathogens Enhancement of Phagocytosis: complement proteins make target cells easier to engulf Destruction of Target Cell Membranes: so they are easier to destroy Inflammatory response: local response to injury of infection at the tissue level (limits spread of injury, combats infection) 5 Signs of inflammation: Swelling Redness Heat Pain Loss of function Effects Injury is temporarily repaired and pathogens are kept out Spread of pathogens away for the injury is slowed Defenses are mobilized to overcome pathogens and allow for permanent repairs Inflammatory response: Tissue response to injury (in a nut shell) Mast cells release histamine in to the blood stream to start the inflammatory response Increases cell permeability and increases blood flow by vasodilation (widening of the vessels) Clot forms around the injured area Complement activation breaks down bacterial cell walls and attracts phagocytes Special defenses are activated Macrophages engulf debris (dead cells, dirt etc) and pathogens Fibroblast are stimulated to repair damaged tissue Over time the clot is broken down and the tissue is repaired to normal Tissue death (necrosis) or infection occurs if the immunological response fails Pus is accumulation fluid with dead cells and necrotic tissue Abscess is accumulation of pus in an enclosed area Inflammation (itis) Fever: elevation of body temperature that accelerates tissue metabolism and defenses Maintenance of a body temperature of greater than 99 degrees F A response to a variety of stimuli including pathogens Within limits it can be beneficial Inhibits some viruses and bacteria Increases cell metabolism (for each degree increase metabolic rate increases by 10%) Cells move faster, reactions are quicker Leads to faster defenses and repair An Antigen An antigen is any substance that causes your immune system to produce antibodies against it. Substance may be from the environment or formed within the body. The immune system will kill or neutralize any antigen that is recognized as a foreign and potentially harmful invader. The term originally came from antibody generator and was a molecule that binds specifically to an antibody Specific Defenses Cell mediated immunity: defends against abnormal cells and pathogens in the body Responsibility of T cells T cells cannot respond to antigens in solution Antibody mediated immunity: defends against antigens and pathogens in body fluids Responsibility of B cells Cannot cross cell membranes Forms of Immunity Innate: genetically determined Present at birth No relationship to exposure to antigen Acquired: not present at birth after being exposed to a specific antigen Active: develops after exposure to an antigen as a consequence of the immune response Naturally acquired active immunity: begins after birth, constantly changes as you are exposed to new antigens Induced active immunity: stimulation of antibodies under controlled situations: vaccination Forms of Immunity Passive immunity: produced by the transfer of antibodies from another source Naturally acquired: when a child is protected by a mother’s antibodies in utero and in breast milk Induced: antibodies are administer to fight infection or prevent disease (like when you receive antibodies after exposure to bacteria) Properties of Immunity Specificity: defense activated by a specific antigentargets that antigen and nothing else. Shape/size of the antigen determines what lymphocyte responds. Versatility: your immune system encounters tens of thousands of antigens in you lifetime, there is no way to know which it will encounter. The diversity of lymphocytes allows the body to be versatile in its defenses. When a specific lymphocyte is activated by and antigen it begins to divide and make clones. Properties of Immunity Memory: exists because when lymphocytes divide one group is allowed to destroy the antigen, and one group remains inactivated so it can be used if you come into contact with the same antigen again. Tolerance: happens when an antigen does not stimulate an immune response, such as in a constant exposure to an antigen The Creepy Virus A virus particle attaches to a host cell. The particle releases its genetic instructions into the host cell. The injected genetic material recruits the host cell's enzymes. The enzymes make parts for more new virus particles. The new particles assemble the parts into new viruses. The new particles break free from the host cell. (which usually dies) Each virus inside it goes on to find new hosts--repeat Primary Responses to Antigen Exposure Primary response: initial response to an antigen Because the presence of an antigen activates B cells that then have to differentiate into plasma, the primary response takes time to develop As plasma cells differentiate the concentration slowly rises and does not peak until about 2 weeks after exposure to the antigen Often this is slow response allows the initial exposure to the antigen to cause an infection Secondary Responses to Antigen Exposure Secondary response: extensive and prolonged immune response when an antigen is introduced more than once. Response is heightened because there is an increased number of memory cells ready to destroy the antigen B cells do not have to take time to differentiate into plasma because that has already been done with the first exposure, so response is much quicker This response often prevents exposure of the antigen a second time from causing an infection Immune Disorders: because of the complexity of the immune response, there is opportunity for things to go wrong Autoimmune disorders The immune system normally ignores (self-antigens) antigens found in the body normally Autoantibodies are B cells that activate against self antigens Rheumatoid arthritis occurs when autoantibodies attack connective tissue in the joints Diabetes can be caused by autoantibodies attaching cells in the pancreas that control insulin Immune Disorders Cont: Immunodeficiency disease Result from: Problems in the development of the lymphoid organs/tissues Viral infections such as HIV that suppresses immune function Treatment of exposure to immunosuppressive agents Severe combined immunodeficiency disease (SCID): persons born SCID fail to produce cell or antibody mediated immunity. even mild infections can be fatal Often have to be isolated (“bubble boy”) Immunosuppressive drugs: used to prevent patients from rejecting transplants Can destroy stem cells and lymphocytes and lead to complete immunological failure Allergies Inappropriate or excessive immune responses to antigens Can damage other cells in the process of destroying antigens Can trigger massive inflammation-Mast cells release histamine that starts the inflammatory process Allergens: antigens that trigger allergic reactions Antihistamine: drug that blocks the action of histamine Rapid and especially severe response to an antigen First response is typically mild or unnoticeable Second response: histamine and heparin from mast cells are released to produce massive inflammation T cells and macrophages are drawn to the area and further the response It may be isolated in a tissue, if it enters the blood stream it can be lethal Anaphylactic Shock Immediate Hypersensitivity Anaphylaxis: circulating antigens affect mast cell throughout the body Massive swelling Contraction of muscles along the respiratory tract Vasodilatation can lead to collapse or anaphylactic shock Antihistamines can prevent some of these symptoms if administered quickly Integration with other systems Gets help from: Helps out: CNS innervates the lymph system Every system by surveying and spleen all tissues and destroying any potentially harmful Circulatory system helps distribute invaders lymphocytes Helps with fluid Skeletal system produces circulation throughout the lymphocytes in red marrow body Endocrine system hormones help stimulate lymphocyte production Integumentary system is a physical barrier and home to mast cells