L7_Lymph_Immune PDF: Lymphatic & Immune System

Lymphatic System Immune System Dr Emily Wong 1 Blood Recap from the previous lecture… - Blood is responsible for transporting oxygen to the cells and removing carbon dioxide for excretion by the lungs. - Blood carries nutrients, ions, water, hormones and enzymes to all body cells and carries away th...

Lymphatic System Immune System Dr Emily Wong 1 Blood Recap from the previous lecture… - Blood is responsible for transporting oxygen to the cells and removing carbon dioxide for excretion by the lungs. - Blood carries nutrients, ions, water, hormones and enzymes to all body cells and carries away the waste products. - Blood regulates the pH and temperature of the body. - Blood is composed of the liquid proportion plasma and solids called the formed elements. Plasma made up 55% of the total blood volume, 91% is water. 2 The Blood Cells 3 Erythrocytes (Red Blood Cells) Function in oxygen and carbon dioxide transport. Biconcave disk in shape with a flexible membrane. They have a large surface area which favors diffusion. No nucleus nor organelles – No mitochondria – No DNA, RNA (so no division of mature RBCs) Hemoglobin RBC contains hemoglobin that carries oxygen to the rest of the body and then carries away carbon dioxide. 4 Erythrocytes RBCs have a short life span and only last about 120 days. RBCs are synthesized in red bone marrow by the process called Erythropoiesis. They are filtered by the spleen and the liver. Erythropoietin (hormone from the kidneys) triggers differentiation of stem cells to erythrocytes. 5 Requirements for Erythrocyte Production Iron – Component of hemoglobin (heme portion) – Normal hemoglobin content of blood Men: 13–18 gram / dL Women: 12–16 gram / dL Folic acid – Necessary for DNA replication, thus cell proliferation Vitamin B12 – Necessary for DNA replication, thus cell proliferation 6 Leukocytes Leukocytes (white blood cells) function in the defense of the body. They can be divided into granulocytes and agranulocytes. – Granulocytes—cytoplasmic granules Neutrophils Eosinophils Basophils – Agranulocytes—no cytoplasmic granules Monocytes Lymphocytes 7 WBC Functions Neutrophils: – Phagocytic – Numbers increase during infections Eosinophils: – – – – Defend against parasitic worms Granules contain toxic molecules that attack parasites Contribute to allergic reactions by secreting histamine Phagocytic Basophils: – Non-phagocytic – Contribute to allergic reactions by secreting histamine Monocytes: – Phagocytic Migrate to tissues and become macrophages Lymphocytes: – B cells – T cells (T-helper, T-killer and T-suppressor) – Natural killer (NK) cells 8 Lymphatic System Made up of the lymph, lymphatic vessels and lymphoid organs. This system is principally a network of vessels responsible for filtering and returning the lymph to the blood circulation. Similar to blood, lymph is transported throughout the body via networks of lymph vessels and lymph capillaries. However, the lymph networks do not extend to cellular structures such as the brain and spinal cord. Unlike the blood vessels, the lymphatic vessels only carry fluids away from the tissues. 9 The Lymphatic System 10 Lymphatic System The right lymphatic duct is responsible for draining lymph from the right halves of our upper body parts and the right upper limb whereas the thoracic duct drains the left halves of our upper body, the lower limbs, the abdomen, and the left upper limb. 11 Mechanism of Lymph Flow The smooth muscle in the wall of the lymphatic vessels exerts a pumplike action, and the lymphatic vessels have valves similar to those in veins. 12 Components of Lymph Lymph is another essential fluid of the human body. It is opalescent, but slightly yellow, and is practically the interstitial fluid that resembles the plasma found in the veins. Its cellular components are mainly white blood cells. When compared to plasma, lymph is low in protein. 13 Lymphoid Organs Two very important roles: 1. House and provide a proliferation site for lymphocytes 2. Give a surveillance site to examine and clean the lymph fluid Primary lymphoid organs: – sites for supplying the secondary lymphoid organs with the mature lymphocytes that are programmed to perform their functions – E.g. bone marrow and thymus Secondary lymphoid organs – E.g. spleen, tonsils and lymph nodes 14 Lymphoid Organs The bone marrow is a hematopoietic tissue that contains many stem cells and is the origin of producing multiple populations of blood cells including lymphocytes; however, only B lymphocytes are differentiated into a mature state at the bone marrow while other types of lymphocytes are released in an immature state. 15 Lymphocyte Origins 16 Lymphoid Organs At the thymus, the maturation of T lymphocytes is promoted. Once mature, the T lymphocytes leave the thymus and circulate in the lymphatic system. They are mainly responsible for the immunological responses in fighting against pathogens. Similar to the thymus, the spleen also aids in the maturation of lymphocytes. 17 Lymphoid Organs Lymph nodes are the clusters along the lymph vessels and are usually embedded in connective tissue. Large clusters occur in the regions where vessels join to become trunks. By passing through the lymph nodes, the lymph is filtered of pathogens, abnormal cells and cellular waste. There are approximately 600 to 700 lymph nodes present in the body of an average adult. The tonsils are a group of small, rounded organs lie one on each side of the throat. 18 Lymphoid Organs 19 Clinical Issues If lymph nodes become overwhelmed they can become swollen and painful. These are called “swollen glands.” Some infected lymph nodes become visible and are called buboes. These are a prominent symptom of the bubonic plague (also known as the Black Death (spread by fleas) — killed ¼ of the population of Europe in the Middle Ages and still makes appearance in the western United States in the parts). These are also a site where metastasizing cancers live and spread. This is why they are biopsied during cancer treatment. Those nodes are swollen but not usually painful. 20 21 Immune System Defense mechanism against invaders Involves a series of specialized cells and many complex chemical reactions Two main types of immunity: – Innate / Non-specific immunity – Acquired / Specific immunity When exposed to antigens, your body's immune system recognizes them and produces antibodies to fight against the disease 22 Non-specific Immune Defenses It is present before any exposure to pathogens and is effective from the time of birth; It is our first line of defense. It defends against foreign cells or matter without having to recognize specific identities. The responses of the innate immunity are rapid, often occur within hours, and react essentially the same way to repeated infections. The non-specific defenses include: – – – – – Physical barriers Inflammation Natural killer cells Complement system Interferons, etc. 23 Defenses at Body Surfaces The body’s first lines of defense against microbes are the barriers offered by surfaces exposed to the external environment and their various antimicrobial secretions. Examples: skin and mucous membranes 24 Discussion What happen if our skin was punctured with a needle? 25 Macrophage: – Means “large phagocyte” – Derived from monocytes – Acts as a guard, constantly patrolling the body looking for foreign invaders – Its cell membrane will surround and “swallow” bacteria – Swallow and destroy even 100 bacteria at a time – Attack bacteria and pathogenic organisms through a process called phagocytosis 26 27 28 29 30 Phagocytosis 31 32 Inflammation Four signs – Redness, swelling, warmth and pain 33 NK Cells Natural Killer (NK) cells are a class of lymphocytes similar to cytotoxic T cells, whose major targets are virus-infected cells and cancer cells; however, they are not antigen-specific. 34 Complement System The complement system is composed of plasma proteins that lyse foreign cells, especially bacteria. Approximately 30 proteins participate in the cascades e.g. C3 Forming a Membrane Attack Complex (MAC) on the surface of the invading bacteria. The MAC ruptures the bacterial membrane causing lysis of the bacteria and death of the organism. 35 Complement C3b One portion of C3 binds nonspecifically to carbohydrates on the surface of the bacterium, whereas another portion binds to specific receptor sites for C3b on the plasma membrane of the phagocyte. (The structures are not drawn to scales) 36 Interferons a) b) c) d) Virus-infected cell secretes type I interferons Type I interferons bind to type I interferon receptors on the secreting cells Synthesis of antiviral protein If the cell is then infected, the viral replication will be inhibited 37 WBC Functions Neutrophils: – Phagocytic – Numbers increase during infections Eosinophils: – – – – Defend against parasitic worms Granules contain toxic molecules that attack parasites Contribute to allergic reactions by secreting histamine Phagocytic Basophils: – Non-phagocytic – Contribute to allergic reactions by secreting histamine Monocytes: – Phagocytic Migrate to tissues and become macrophages Lymphocytes: – B cells – T cells (T-helper, T-killer and T-suppressor) – Natural killer (NK) cells 38 Specific Immune Defenses Lymphocytes recognize specific foreign molecules called antigens. Involves B cells and T cells 39 Lymphocyte – Produced by the bone marrow, thymus gland and spleen – B cells: secrete antibodies – T-helper cells: secrete cytokines as messengers to activate the immune system – T-killer cells: bind to antigens to destroy the target cells – T-suppressor cells: stops the T-killer cells from fighting and signals them that the battle is over 40 41 Functions of B Cells and T Cells 42 43 Antibody Function The antibody functions to bind the specific antigen. This leads to inactivation and destruction of the foreign antigen. 44 45 Immunoglobulin (Ig) B cell receptors Initiates immune response by blinding specific antigens to immunoglobulin Secretes antibodies Subtypes, e.g. Ig A, D, E, G, M Vander’s Human Physiology, 13th Ed Development of Immune Tolerance Immune tolerance develops during fetal and early postnatal life due to clonal deletion or clonal inactivation of cells that match body antigens. Autoimmune diseases are caused by failure of self-tolerance. 46 Memory Primary immune response: (1st exposure) – Generally takes 10–17 days to occur after exposure – Symptoms of illness occurs during these days – Antigen-selected B and T cells proliferate and differentiate into effector cells Secondary immune response: (all other exposures) – Takes 2–7 days to occur – Greater response – Occurs due to memory cells 47 Memory 48 Factors that Alter the Body’s Resistance to Infection Factors include nutrition, pre-existing disease, stress, physical exercise, sleep deprivation, and genetic deficiency. 49 Immunity Active immunity is an immune response to vaccine or pathogen in an individual and gives immunity because of the production of memory cells. Vaccine is the introduction of a microorganism or its antigens in a form not expected to cause disease, which induces an immune response including production of memory cells 50 Immunity Passive immunity comes from the administration of synthetically produced antibodies. This results in no memory cell production, so there is no long-term memory and immunity. Passive immunity can also come from mother to fetus or baby because antibodies pass in the placenta (IgG) and breast milk (IgA). 51 Harmful Immune Responses Graft Rejection Transfusion Reactions Allergy (Hypersensitivity) Autoimmune Disease Excessive Inflammatory Responses 52 Tissue Grafts and Organ Transplantation HLA molecules (Histocompatibility Complex; MHC) stimulate rejection by inducing immune response, so there must be as close a match in the MHC between the donor and recipient as possible. The recipient will have to suppress the immune system pharmacologically to prevent rejection. – Cyclosporin 53 Transfusion Reactions Transfusion reactions are the illness caused when erythrocytes are destroyed during blood transfusion. It is caused by antibodies rather than cytotoxic T cells. Erythrocytes do not have MHC proteins, but they do have plasma membrane proteins and carbohydrates that can function as antigens. The ABO system of carbohydrates is the most important for transfusion reactions. Another group of erythrocyte membrane antigens of medical importance is the Rh system of proteins. 54 Blood Typing 55 * Antigen reacts with antibody 56 Immediate Hypersensitivity Allergic Response 57 Anaphylactic Shock Anaphylactic shock is a severe allergic reaction that results from a massive release of histamine from mast cells throughout the body. This causes a massive drop in systemic blood pressure and can also cause circulatory collapse. 58 Autoimmune Diseases The immune system treats a part of itself like an invading pathogen. – – – – Examples: Insulin-dependent diabetes mellitus (type I) Lupus Rheumatoid arthritis Multiple sclerosis 59 Immunodeficiency Diseases Immunodeficiency diseases result from weak or under-active immune systems. Examples: – SCID = severe combined immunodeficiency disease – Hodgkin’s Disease = cancer of lymphatic system – AIDS = affects helper T cells 60 Acquired Immune Deficiency Syndrome (AIDS) Human immunodeficiency virus (HIV) infects and kills helper T cells resulting in impairment of the immune response to other infectious organisms. 61