Lymphatic System and Immunity

Transcription

1 Lymphatic System Lymphatic System and Immunity Anatomy & Physiology-Honors Turner College & Career High School One way system: to the heart. Return of collected excess tissue fluid. Return of leaked protein. Lymph is this fluid. Edema results if system blocked or surgically removed. Lymph Capillaries Have one way mini valves allowing excess fluid to enter but not leave. Picks up bacteria and viruses as well as proteins, electrolytes and fluid(lymph nodes destroy most pathogens). Lymphatic System Lymph capillaries o Absent from bone, bone marrow, teeth, CNS. o Enter lymphatic collecting vessels. Lymphatic collecting vessels o Similar to blood vessels (3 layers), but thin & delicate. o Superficial ones in skin travel with superficial veins. o Deep ones of trunk and digestive viscera travel with deep arteries. o Very low pressure. o Distinctive appearance on lymphangiography. o Drain into lymph nodes. Lymph nodes: bean shaped organs along lymphatic collecting vessels. Up to 1 inch in size. Clusters of both deep and superficial LNs. 6 1

2 Functions of Lymphatic System 1. Draining interstitial fluid. 2. Transporting dietary lipids. 3. Protection. Lymphatic Vessels Begin as closed ended lymph capillaries in tissue spaces between cells. NOT A CIRCULATING FLUID. Interstitial fluid drains into lymphatic capillaries, forming lymph. Lymph capillaries merge to form lymphatic vessels. Lymphatic vessels carry lymph into and out of lymph nodes. And finally back to the vascular system. Lymphatic Capillaries Made of a single layer of squamous epithelial cells. Slightly larger than blood capillaries. Cells overlap and act as one-way valves. Opened by pressure of interstitial fluid. Anchoring filaments attach cells to surrounding tissue. 2

3 Lymphatic Vessels Resemble veins (same 3 layers). Found throughout body except: o Avascular tissues. o Central nervous system. o Splenic pulp. o Bone marrow. Lymphatic Vessels Lymphatic vessels join to form lymphatic trunks. Lymphatic trunks join to form : o Thoracic duct (3/4 of body). o Right lymphatic duct (drains right arm, and right side of head, neck and upper torso). These empty into subclavian veins at junction with internal jugular vein. Formation of Lymph Fluid leaves capillaries by diffusion and filtration. Escaped proteins. If lymph flow blocked = tissue swelling or edema. Specialized lymphatic capillaries in vili of small intestine transport lipids - they are called lacteals, and the fluid is called chyle. 3

4 Lymphatic Organs Red bone marrow Thymus gland Lymph nodes Lymph nodules Spleen Primary organs Secondary organs Lymph Nodes Lymph is filtered through lymph nodes. Found in clusters. Waste water treatment plants. Vary in size. Principal groupings in cervical, axillary and inguinal regions. Provide biological filtration. Site of cancer growth and metastasis. Vessels enter node on convex side. Lymph passes through irregular channels called sinuses. Leaves node through one or two efferent vessels at the hilum or hilus. Capsule, cortex and medulla. Cortex contains lymph nodules. Follicular dendritic cells. Germinal centers B cells proliferate. 4

5 Lymph Nodules Lymph nodules are also found singly or in groups throughout the mucous membranes of the respiratory, urinary, reproductive and digestive tracts. MALT mucosa associated lymphoid tissue. Peyer s patches in ileum. Tonsils. Some in appendix. Development of Lymphocytes Originate in bone marrow from lymphoid stem cells B cells stay in bone marrow, hence B cells T cells mature in thymus, hence T cells These divide rapidly into families Each has surface receptors able to recognize one unique type of antigen=immunocompetence 28 Development of Lymphocytes 30 5

6 Lymphocytes Naive immuno-competent lymphocytes seed secondary lymphoid organs (esp. lymph nodes). Antigenic challenge full activation upon meeting and binding with specific antigen. o The B cell s antigen receptor is an antibody (see slide 20) Full activation o Gains ability to attack its antigen o Proliferates rapidly producing mature lymphocytes o Mature lymphocytes re-circulate seeking same 31 pathogens Tonsils Tonsils lymphoid tissue under the mucous membranes of the throat. o Palatine tonsils o Pharyngeal tonsil adenoid o Lingual tonsils First line of defense. Tonsillectomy. Tonsils Thymus Gland In mediastinum above the heart. Largest at age then begins to atrophy. Pre-T cells come from bone marrow and develop into T cells. T cells then go to other lymphatic tissues. Thymus produces hormone thymosin - aids maturation of T cells elsewhere in body. 6

7 Spleen Largest lymphoid organ. In upper left quadrant of abdomen. Has a hilum and a capsule. Sinuses contain blood instead of lymph. Spleen White pulp: o Little islands, mostly B cells. Red pulp: o Venous sinuses. o Splenic cords RBCs, macrophages, lymphocytes, plasma cells and granulocytes. 7

8 Functions of Spleen Blood formation o All blood cells in fetus. o Only lymphocytes and monocytes after birth. Blood filtration o Removes bacteria, particles, worn out RBCs and platelets (recycles iron). Blood storage o Can contain over one pint of blood. Nonspecific Resistance The ability to ward off disease is called resistance. Lack of resistance is susceptibility. Nonspecific resistance refers to a wide variety of body responses against a wide range of pathogens. A pathogen is any microorganism that causes disease. Nonspecific Resistance Mechanical Barriers Species (Inborn) Resistance certain species contract certain diseases, while other species do not. Skin and mucous membranes : o First line of defense. o Physical barrier. o Shedding of dead cells. o Mucus. o Hairs. o Cilia. o Coughing and sneezing, production of tears, saliva, urine, defecation and vomiting physically remove harmful substances. Chemical Protection Sebaceous glands produce sebum fatty acids inhibit growth of bacteria and fungi. Lactic acid further decreases skin ph. Accumulation of salt. Vaginal secretions are also slightly acidic. Gastric juice acid, enzymes and mucus. Lysozyme in tears, perspiration, saliva and tissue fluids. Normal Microbiota bacteria living on skin inhibit the growth of pathogens by producing antibiotics Antimicrobial Substances Transferrins are proteins that tie up the free iron in the blood and interstitial fluid. Interferon: Paul Revere Chemical a glycoprotein produced by virus infected cells that cause neighboring cells to produce anti-viral proteins. These also enhance phagocytosis and can suppress growth of tumor cells. 8

9 The Compliment System normally inactive proteins When activated, they complement or enhance certain immune, allergic and inflammatory reactions. 1. Activation of inflammation 2. Opsonization enhances phagocytosis 3. Cytolysis membrane attack complex Fever Causes liver and spleen to sequester iron. Increases phagocytosis. Inhibits growth of microbes. Speeds up body repair. Characterized by: Inflammation o Heat, swelling, redness, and pain (and sometimes loss of function) calor, tumor, rubor and dolor. Stages of Inflammation 1. Vasodilation and increased permeability of blood vessels 2. Phagocyte migration 1. Neutrophils come first 2. Followed by macrophages 3. Tissue Repair Phagocytosis Natural Killer Cells Three phases: 1. Chemotaxis 2. Adherence 3. Ingestion Next line of defense (with phagocytes) Lymphocytes but do not respond to specific antigens Can kill a variety of microbes plus tumor cells. May release perforins, or attack directly Cell may not display correct MHC antigens 9

10 Immunity Immunity involves activation of specific lymphocytes to combat a specific foreign agent. Specific resistance to disease involving the production of a specific lymphocyte or antibody against a specific antigen. An antigen is any substance that elicits an immune response. Best antigens are: o Large o Complex o Recognized as foreign Haptens are molecules that are small, foreign and complex. To elicit an immune response, they must piggy-back on a larger molecule, often blood proteins. Epitopes: a foreign protein may result in several different antibodies. Each antibody recognizes a different portion of the protein. These regions are called epitopes. Forms of Immunity Humoral or antibody mediated immunity. B cells (mature in bone) make antibodies: specific proteins that bind to specific antigens. OR Cell-mediated immunity. Tcytoxic lymphocytes attack virus infected or tumor cells directly. The Story Macrophage destroys a bacterium Takes bacterial antigen and fuses it with MHC II complex MHC II complex and antigen are placed on cell membrane. Displays antigen (like a proud cat) so it is called an antigen presenting cell. It shows antigen to helper T cells, until it finds one that has a receptor that matches the antigen complex. The helper T cell binds to the antigen complex, and the macrophage is stimulated to produce the cytokine Interleukin -1 A cytokine is a protein hormone which regulates normal cell functions, like growth and differentiation. 10

11 Humoral or Antibody Mediated Immunity Every step needs 2 signals to proceed. IL-1 binds to receptors on the helper T cell, causing helper T-cell to clone itself and produce IL-2. IL-2 causes lymphocytes to multiply. These steps are common to both humoral and cell-mediated immunity. In order for B cells to become activated and make antibodies against an antigen, two things must happen: 1. B cell must encounter the antigen. 2. IL-2 produced by helper T cell must be present. Humoral or Antibody Mediated Immunity When both signals are present (the antigen and IL-2). The B cell becomes activated and forms two types of cells: plasma cells and memory cells. Plasma cells produce large quantities of their specific antibody into the blood. Memory cells lie in wait for the next infection. Antibody Mediated Immunity B cells and Antibody-Mediated Immunity. Characteristics of B Cells o Antibody-mediated immunity against pathogens. o Produced and mature in bone marrow. o Reside in lymph nodes and spleen, circulate in blood and lymph. o Directly recognize antigen and then undergo clonal selection. o Clonal expansion produces antibodysecreting plasma cells as well as memory B- cells. Clonal Selection Model: B-Cells 11

12 Antibodies Structure of an Antibody Y shaped proteins gamma globulins. Have a variable region that matches a specific antigen (Fab region). Have a constant region activates complement (Fc region). Antibodies are also called immunoglobulins (Ig s). Y-shaped o Constant regions o Variable regions Antibodies The first antibodies produced are IgM. Pentamers with ten combining sites very effective in opsonization and activating complement. Several days later, IgG is produced single unit antibodies, abundant in serum, cross the placenta, and have the longest half-life. Antibodies Cell Mediated Immunity A virus is a core of nucleic acid wrapped in a protein. To reproduce, it must make use of a host cell to replicate the viral nucleic acids and proteins and assemble new viruses. 12

13 Cell Mediated Immunity Infected cells put viral proteins on their membranes. This antigen is processed by macrophages. Antibodies can t get at viruses inside a cell, so we need something different : a Tcytotoxic or Tc Cell. The Tc encounters the viral antigen with the MHC -1 complex on the infected cell. Cell Mediated Immunity T cells A macrophage presents a portion of an antigen to T cells. Types of T-cells: o Helper T-cells o Cytotoxic T-cells Characteristics of T-Cells Cell-mediated immunity against virus infected cells and cancer cells. Produced in bone marrow, mature in thymus. Antigen must be presented in groove of an MHC molecule. Cytotoxic T cells destroy non-self proteinbearing cells. Helper T cells secrete cytokines that control the immune response. Clonal Selection Model: T-Cells Cell Mediated Immunity Now needs the second stimulus IL-2 from the helper T cell. Tc cell clones itself, and makes activated Tc cells and memory cells. Tc Cells bind to antigens on infected cells and release: Perforins punch holes in cell membrane. Lymphotoxins activate the cell s own selfdestruct mechanism. Cell Mediated Immunity Tc Cells are effective against bacteria which are intracellular parasites, viruses, fungi, cancer cells associated with viral infections, and transplanted cells. 13

14 Immune Response The first time you encounter an antigen, you have few B cells or Tc cells against that antigen = primary response. The next time, you have many memory cells, so response is much quicker, so you don t come down with the disease = secondary response. Hypersensitivity The immune system gone bad. Delayed Hypersensitivity A type of cell mediated immunity. Td cell requires usual two signals. Second time antigen is encountered, Td cell produces several cytokines that attract and activate macrophages, resulting in an inflammatory reaction. Examples: poison ivy (urushiol), TB skin test. Immediate Type Hypersensitivity Exposure to certain antigens (allergens) results in the formation of IgE antibodies. IgE antibodies bind to mast cells by the Fc end. When the antigen is encountered again, binding with the antibody causes mast cell to release histamine granules. 14

15 May be able to desensitize individual by giving allergen to stimulate IgG antibodies. These tie up antigen before they can bind with IgE. Acquired Immunity Active = person makes own antibodies Passive = person receives antibodies from someone else Natural = just happens Artificial = caused by man (often using a needle) Acquired Immunity Natural active acquired immunity: person comes down with measles. Artificial active acquired immunity: person is immunized with a vaccine. Artificial passive acquired immunity: person receives serum with antibodies. Natural passive acquired immunity: baby receives antibodies with mother s milk colostrum. Active Immunity Develops naturally after a person is infected with an antigen. A person produces an immune response against an antigen. Can be induced by use of vaccines. Is dependent upon the presence of Memory B Cells and Memory T Cells in the body. Acquired Immunity Vaccines are pathogens or their products that have been treated so they are no longer able to cause disease. 15

16 Passive Immunity An individual is given prepared antibodies to combat disease. Is temporary because there are no memory cells. Immunity Therapy Cytokines and Immunity o Signaling molecules produced by T lymphocytes and macrophages. o Interleukins Cytokines that enhance ability of T cells to fight cancer. Have many potential uses in medicine. Monoclonal Antibodies Group of plasma cells from the same B cell all produce same antibody. Use of monoclonal antibodies o Diagnostic tests Ex: pregnancy tests o Vehicles for drug delivery o Identification of infections Allergies Hypersensitivities to Substances Immediate Allergic Response o Can occur within seconds of exposure to an antigen. o IgE antibodies attach to mast cells. o Allergen attaches to IgE, causing mast cells to release histamine. o Histamine is responsible for allergy symptoms. Anaphylactic Shock o Immediate allergic response where allergen enters the blood stream. o Histamine causes a sudden, life-threatening drop in blood pressure. o Epinephrine can counteract this reaction. Blood-Type Reactions Blood-Type Reactions In the ABO system, the presence or absence of type A and type B antigens on red blood cells determines a persons blood type. If antibodies are present against a type of blood, agglutination occurs. Transfusions o Must consider recipient s antibodies and donor s antigens to prevent agglutination and transfusion reaction. o Type O is universal donor. Neither anti-a nor anti-b antibodies. o Type AB is universal recipient. Neither A nor B antigens. 16

17 Blood Transfusions Rh System Rh+ Rh antigen is present on red blood cells. Rh- Rh antigen is absent on red blood cells. Significant in Pregnancy o If a Rh- mother is pregnant with Rh+ baby. o If baby s cells leak into mother s bloodstream, she forms anti-rh antibodies. Attack baby s RBC s- hemolytic disease of newborn (HDN). This can be prevented by giving the Rh- mother anti-rh immunoglobulins in an injection. The injection must be given before the mother becomes sensitized to produce her own antibodies. Hemolytic Disease of the Newborn Disorders of the Immune System Autoimmune Disease o Cytotoxic T-cells or antibodies attack a person s own cells. Myasthenia gravis - muscle weakness. Multiple sclerosis - neuromuscular disorder. Immune Deficiencies o Immune system is unable to protect the body from disease. Acquired immune deficiency syndrome. Severe combined immunodeficiency syndrome (inherited). HIV/AIDS Human immunodeficiency virus. Attacks helper T cells. Without production of IL-2, there is no second signal, and humoral and cell mediated immunity are shut off increase in rare diseases: o TB, Kaposi sarcoma, etc. 17