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Transcript
1 David Emerine Immune system Supplemental Instruction Nov 17 & 20 Blood Composition 2 3 Immune System First we will review the Lymphatic system which is important to the immune system. Lymphatic system The lymphatic system is important to the immune system and circulatory system. There is a small net loss of fluids from blood capillaries into the interstitial spaces (about 3 liters per day). The lymphatics act as an accessory route by which this fluid can return to venous system. Lymphatics are also important for the immune system (contain many white blood cells) Lymphatics include lymph nodes that contain large numbers of white blood cells. 4 Lymphatics are distributed throughout the body. Lymphatics contain a total of about 1 to 2 liters of fluid (i.e. “lymph”) and they returns approximately 120 ml of lymph per hour to venous system. Lymphatic capillaries pick up fluid and substances from the normal capillary bed. The cells of lymphatic capillaries are not tightly joined to one another, so fluid and other substances can enter the lympatics. So, the lymphatics act as an accessory route for getting certain substances into circulatory system. . Lymph Lymph is composed of fluid coming from interstitial spaces. 5 It is similar to blood, but does not contain red blood cells and it does not contain many of the “plasma proteins” Lymph does contain white blood cells. Some large fats and proteins that can’t get into blood capillaries can enter lymph capillaries. So lymph typically contains large amounts of fats and proteins (normally obtained from the intestines). Movement of lymph Lymph vessels have one-way valves and smooth muscle to help move lymph Additionally, contraction of skeletal muscle adjacent to lymph vessels will move lymph in similar fashion to skeletal muscle pumps of veins. Lymphatic vessels converge and connect to venous system at the junction of the subclavian veins and internal jugular veins (in the upper thoracic cavity). 6 Blockage of lymph flow can result in severe edema (can't return lymph fluid back to circulatory system). Fluid accumulates in interstitial spaces. Example: "Filariasis" or "elephantiasis" It is causes by a parasitic nematode worm. Larvae transmitted to human by mosquito bite. Adults live in, and clog lymphatics, so excess fluid accumulates in certain interstitial spaces. Believed to affect 120 million people, mostly in tropical and subtropical areas (e.g. Asia, Africa, and Western Pacific). Patients can be treated with drugs which kill the nematode and its larvae. 7 Overview of the Immune System Involves a variety of organs and tissues in the body. Bone marrow, lymphoid tissue (lymph nodes, tonsils, gut-associated lymphoid tissue, etc), spleen, thymus, liver Functions: Protects body from invading organisms that cause disease (pathogens) Remove damaged or aged cells (in particular RBCs) Destroys abnormal and/or mutant cells Non Beneficial Immune Responses a) allergies b) autoimmune disease (example: Multiple Sclerosis, GBS, etc.) 8 Immune system utilizes a variety of white blood cells White Blood Cells WBCs or "Leukocytes" 4000 to 11,000 per ul (in normal healthy individual) Can increase to 25,000 or more during infections. Most are produced in bone marrow by "stem cells", but a some are produced in lymph nodes, spleen, and thymus. WBCs divided into four basic groups 1) ranulocytes. All granulocytes are very mobile and can move out of blood and into the tissues. a) Neutrophils (polymorphonuclear leukocytes) Most abundant type of white blood cell. They are highly mobile and move out of the blood and into areas of 9 inflammation. They seek out, ingest (phagocytosis), and destroys bacteria, viruses, and foreign material. They are nonspecific in their targeting (they go after any non-self pathogen) . They give “pus” its yellowish/whitish color. b) Eosinophils They are involved in allergies, asthma, and in some parasitic infections. They release “cytokines’ which are chemical signals that have a variety of effects on parasites, pathogens, and on other immune system cells. c) Basophils They move into area of inflammation and they release histamine and cytokines. Histamine stimulates many of the symptoms of an allergy such as vasodilation and edema in the inflamed area. 10 2) Monocytes They circulate in the blood and then enter tissues and become tissue macrophage (5X increase in size). “macrophage” means large eater They are important in lymph nodes, liver, spleen, lungs, and bone marrow. They ingest bacteria, viruses, and foreign substances. The monocyte macrophages are much more powerful phagocytes in comparison to neutrophils They are nonspecific in their targeting (they attack a variety of pathogens, etc..) 3) Mast cells Similar to basophils, but they become resident in specific tissues. In response to infections, pathogens, etc, they will release a variety of chemicals including histamine.and cytokines. They are nonspecific in their targeting (they respond to variety of pathogens, etc.). 4) Lymphocytes They are initially produced in bone marrow. Then they move to lymph nodes, spleen, and thymus. They reenter circulation when needed. They are “specific” in their targeting i.e. They are important for "specific immunity" (targeting of specific antigens). 11 a) B lymphocytes (i.e. B cells) They are important for “antibody-medicated immunity” (also calls “humoral immunity” “B” refers to “bursa-derived” Their maturation was first studied in birds Precursor cells "mature" in "Bursa of Fabricius" in birds (hence "B" lymphocytes) It is an outcropping of the cloaca. In humans the B lymphocytes mature in the bone marrow. Lymphocyte maturation (both B and T) occurs during embryonic development and early childhood. Immune Response of B cells In response to exposure to specific antigens, B lymphocytes differentiate into “plasma cells” and “memory cells” Plasma cells are the antibody producing cells responsible for "antibodymediated immunity". Antibodies are produced against specific antigens 12 They are “specific” in their targeting They identify specific antigens on the pathogens. Memory cells are produced so that antibody response can occur rapidly upon second or later exposure to antigen. i.e. “adaptive or acquired immunity” This is the purpose of vaccinations: exposure to an antigen results in the production of memory cells. 13 Actions of antibodies 1) Neutralize toxins directly 2) Agglutination of antigens Clumping of antigenic cells. Formation of clumps which hinders pathogen’s ability to affect cells (Agglutination refers to antibody/antigen reaction. Do not confuse this with coagulation which refers to blood clotting). 3) Mark invading cells 14 Allows for binding of monocyte/macrophage, neutrophils, etc b) T lymphocytes They are important for “cell-mediated immunity” They are specific in their targeting and will bind directly to their targets. Precursor cells "mature" in thymus during embryonic development and early childhood. They differentiate into four types of cells: 1) Cytotoxic T Cells (killer T cells) 2) Helper T cells 3) Regulatory T cells (i.e. Suppressor T Cells). 4) Memory T cells 1) Cytotoxic T cells (i.e. killer T cells) or aka natural killer/NK cells They are specialized for killing virus-infected cells Cells infected by virus display viral antigen on cell surface cytotoxic T cells destroy cells with specific antigen i.e. they are specific in their targeting Cytotoxic T cell binds to cell and then releases substances that kills the cell.. They releases "perforin" which is a protein that inserts itself into the cell membrane of infected cells creates holes in membrane that kills cell 15 2) Helper T cells enhance both "antibody and cellular-mediated immunity" They are the most numerous of the T cells (60 to 80% of circulating T cells). They activate other immune cells, including both B and T cells As such, they are considered a “master switch” for turning on the specific immunity portion of immune system. They produce "lymphokines" which stimulate both B and T cells Lymphokines are chemicals released by lymphocytes They can have a variety of effects. Helper T cells are the target of the HIV virus. Results in a decreasing levels of Helper T cells This eventually compromised the immune systems ability to respond to infection. 3) Regulatory T Cells (Suppressor T cells) They suppress immune responses and prevent over activity of the immune system. Helps maintain tolerance to self antigens. Researcher are trying to use these to treat autoimmune diseases. 4) Memory T Cells Produced during initial exposure to pathogen. Allow for rapid production of other T cells and strong immune response during second and subsequent exposure to pathogen. 16 "Clonal selection theory" During embryonic development millions of different T and B lymphocytes are formed, each capable of identifying a specific antigen. This is done by the reshuffling of gene fragment to produce millions of different types of T and B cells. Each of the lymphocytes can produce "clones" of itself Antigen on invading organism selects for a clone and "activates" it Clone will then begin to divide and produce large numbers of lymphocytes specific for a particular antigen Nonspecific Immune Responses i.e. “Inflammation” Nonspecific response to tissue damage and/or foreign invasion Inflammation functions to isolate and destroy invading organisms as well as remove debris to prepare for healing Following the invasion of tissue by pathogens: 1) Tissue macrophage migrate into the area and ingest and destroy invading organisms 2) Mast cells in the tissue release histamine in response to tissue damage and invading organisms 17 Histamine results in: a) local vasodilation b) increased capillary permeability So plasma proteins leak into interstitial spaces and cause edema by attracting water osmotically allows for movement of white blood cells out of capillary and into affected area.. 3) Increase number of phagocytic WBCs (neutrophils and monocytes/macrophage move into inflamed area due to a) edema b) and they are attracted to area by chemoattractants release by mast cells and macrophage. They ingest and destroy foreign organisms and materials "Pus" is an accumulation of the phagocytic WBCs and the material they have digested 4) Inflamed area is "walled off" Edema also results in more of the plasma protein fibrinogen entering inflamed area. Fibrinogen is the precursor to fibrin which is used to form blood clots and to wall off inflamed areas Fibrinogen is converted to fibrin by thrombin which is activated by factors in the damaged tissue 18 A mesh of fibrin walls off inflamed area. This delays or prevents spread of pathogens. After inflammation Cells in surrounding tissue may repair damaged area (e.g. skin) or in the case of nonregenerating tissue (e.g. muscle) tissue is replaced by scar tissue. Primary Organs/Tissues involved with Immune System 1) Bone marrow Important for blood cell production Important for B lymphocyte maturation 2) Lymphoid Tissue: Lymph nodes, lymph vessels, gut-associated lymphoid tissue (Peyer's patches in small intestines), tonsils, and adenoids. It helps produce lymphocytes for lymph and blood. It has resident lymphocytes that produce antibodies and sensitize T cells when needed.. It has resident macrophage that ingest microbes 3) Spleen Same functions listed above for lymph nodes, but they do these functions for blood system Additionally: macrophage in spleen remove old RBCs 19 4) Liver Blood sinuses lined with specialized macrophage (called Kupffer cells). They destroys large numbers of bacteria and other invading organisms in blood coming from intestines 5) Thymus Site of T lymphocyte maturation ****Please ignore the pictures presented below. For some reason I am not able to delete them**** 20