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Transcript
Immunity Learning outcomes The Aim – You should be able to do the following; (a) [PA] recognise phagocytes and lymphocytes under the light microscope; (b) state the origin and describe the mode of action of phagocytes; (c) describe the modes of action of B-lymphocytes and T-lymphocytes; (d) explain the meaning of the term immune response, making reference to the terms antigen, self and non-self; (e) explain the role of memory cells in long-term immunity; (f) relate the molecular structure of antibodies to their functions; (g) distinguish between active and passive, natural and artificial immunity and explain how vaccination can control disease; (h) discuss the reasons why vaccination has eradicated smallpox but not measles, TB, malaria, sickle cell anaemia or cholera; First Line of Defense saliva antibacterial enzymes skin prevents entry stomach acid low pH kills harmful microbes tears antibacterial enzymes mucus linings traps dirt and microbes “good” gut bacteria out compete bad Mechanical factors • • • • Skin Epidermis Mucous membrane Body hairs Chemical factors • Lysozyme in sweat, tears, saliva, and tissue fluid • Low pH in gastric juice • Normal microorganism in the body competes with pathogen for attachment and nutrient Second Line of Defense – Nonspecific Immune Response These are defenses the body uses no matter what the invader may be. These defenses include: – Phagocytosis – done by Macrophages and Neutrophils. – Inflammation - caused by release of Histamine from leukocytes – Fever – caused by histamines. The fever (high temp) kills invaders by denaturing their proteins. Composition of Human Blood Composition of WBC Neutrophils 70% Eosinophils 1.5% Basophils 0.5% Monocytes 4 Lymphocytes 24 White blood cells are important in the body’s natural defenses against pathogens. The following table identifies the major WBCs function and the type of immune response: Phagocytic cells of the immune system • The phagocytic cells of the immune system originate from the bone marrow. • Stem cells – Cells that differentiate into other types of cells; they are self renewing and continually perform cell division. • All white blood cells (macrophages and neutrophils) arise from a type of stem cell called the haematopoietic stem cell (HSC) Phagocytes • Phagocytes are produced throughout life by the bone marrow. • They are stored in the bone marrow before being distributed around the body in the blood • They are also known as scavengers, removing dead cells and invasive microorganisms. Phagocytes Squeezing through the capillaries to patrol tissues (liver, spleen, lymph nodes) • There are two kinds (a) Neutrophils Form about 70% of the WBC in the blood. Travel throughout the body tissues. They are released in large numbers from the bone marrow during an infection They are short-lived NEUTROPHILS (Granulocytes) • The most common type of Phagocyte it makes up 50 to 70% of the White Blood Cells in the body. They then engulf and destroy any pathogens they encounter. • They move form blood vessels to injured tissues due to chemotaxis – response to chemical signals sent by damaged cells Neutrophils self-destruct as they phagocytose invaders – live only for a few days Macrophages/Monocytes • Larger than neutrophils • Tend to be found in organs (lungs, liver, spleen, kidney and lymph nodes) rather than be found in the blood. • Leave the bone marrow and travel in the blood as monocytes • Crucial role in initiating immune responses. MONOCYTES (Agranulocytes) • Only constitute 5% of the leukocytes, but very effective • Long-lived, excellent phagocytes • Some microbes can evade them • They circulate in the blood for some time, then they migrate into body tissues and become macrophages Monocytes or Macrophages also release IL1 which induces fever and also stimulates an immune response MACROPHAGES (Agranulocytes) • Phagocytes - they consume and destroy any pathogens they encounter. They also rid the body of worn out cells and cellular debris • They do not destroy the pathogens completely, but cut them up to display antigens that can be recognized by the lymphocytes. (i) • Phagocytes & phagocytosis (Non specific immune response) Phagocytes - produced & stored in bone marrow before distributed in blood circulation - ‘feed’ like Amoeba on bacteria, viruses and dead body cells. Neutrophils 70% of WBC in blood travel throughout the body (blood) Macrophages Larger than neutrophils found mostly in lung, brain, liver, kidney, spleen, & lymph nodes leave the bone marrow & travel in squeeze through the capillary wall and into the infected tissue, engulf and blood as MONOCYTES ⇒ then develop into MACROPHAGES once digest offending bacteria settle in organs short-lived cells released in large numbers during infection long-lived cells which initiate immune response by displaying antigens to be recognised by lymphocytes Stages of Inflammation 1. Vasodilation: Increase in diameter and permeability of blood vessels. Triggered by chemicals released by damaged cells: histamine, kinins, prostaglandins, and leukotrienes. 2. Phagocyte Migration and Margination: Margination is the process in which phagocytes stick to lining of blood vessels. Extravasation (Emigration): Phagocytes squeeze between endothelial cells of blood vessels and enter surrounding tissue. Stages of Inflammation (Continued) Phagocytes are attracted to site of infection through chemotaxis. Phagocytes destroy microbes, as well as dead and damaged host cells. 3. Tissue Repair: Dead and damaged cells are replaced. Second Line of Defense in Action/ Inflammatory Response The Inflammatory Response IS A NONSPECIFIC DEFENSE REACTION OF THE BODY TO TISSUE DAMAGE. 1. Despite the initial defenses of the skin and mucous membranes, pathogens sometimes enter the body. 2. When pathogens enter the body, the immune system has a second line of defense. The body's second line of defense acts when tissues are injured. 3. The mast cells found in connective tissues and basophils release a chemical called HISTAMINE, when injured - which starts a series of changes called the inflammatory response. 4. Histamine increases blood flow to the injured area and increases the permeability of the surrounding capillaries, as a result, fluid and neutrophils leak from blood vessels into nearby tissue to destroy pathogens by phagocytosis. The Second Line of Defense in Action – cont’d. 5. Pathogens are attacked by phagocytic white blood cells (leukocytes) such as Neutrophils and Monocytes in response to chemokines – chemical signals 6. Certain toxins released by pathogens may raise body temperature, but leukocytes can do the same by releasing molecules called pyrogens – fevers inhibit microbial growth, speed up chemical reactions and tissue repair 7. Antimicrobial agents collectively called the complement system lyses invading cells 8. Interferons are proteins secreted by virusinfected cells that limit cell-to-cell spread of the virus (c) describe the modes of action of Blymphocytes and T-lymphocytes; (d) explain the meaning of the term immune response, making reference to the terms antigen, self and non-self; The Immune Response Immunity: “Free from burden”. Ability of an organism to recognize and defend itself against specific pathogens or antigens. Immune Response: Third line of defense. Involves production of antibodies and generation of specialized lymphocytes against specific antigens. Antigen: Molecules from a pathogen or foreign organism that provoke a specific immune response. ANTIGENS ☺ • All cells possess antigens in their cell surface membranes which acts as markers, enabling cells to recognize each other. • The body can distinguish between its own antigens (“self”) and a foreign antigen (“non-self”) and usually make antibodies against non-self antigens. • Microorganisms carry antigens on their surface. Antigens • An antigen is a molecule which can cause antibody formation • Each antigen is recognized by a specific antibody • All cells possess antigens in their cell surface membranes • Usually proteins or glycoproteins B cells and T cells Similarities • Both B & T cells are produced before birth in bone marrow. • Only mature lymphocytes can execute immune response. • When mature, all B & T cells circulate between blood & lymph Differences B cells T cells remain in bone marrow until they are mature T cells mature once migrated from the bone marrow to the thymus gland. then spread throughout the body concentrating in lymph nodes & spleen Membrane bound antibody Concentrating in the blood T cell receptors • When the pathogen first enter the body, macrophages engulf and digest microbes (including their antigens) through a process of called phagocytosis. • Some of the digested antigens are then displayed on the surfaces of the macrophages. This is called antigen presentation • Any B cells whose cell surface receptors fit the antigens respond by dividing repeatedly by mitosis & after several generations will differentiate into PLASMA CELLS MHC class 2 (antigen presenting cell) ; MHC class 1 (all nucleated cells) Clonal selection (f) relate the molecular structure of antibodies to their functions; • 1 type of antibody molecule which responds to 1 antigen • Each cell then divides to a small group of identical cells able to produce the same type of antibody. This is known as a clone • WHAT ARE ANTIBODIES? Immunoglobulin Y-shaped globular glycoproteins that identify and neutralize foreign particles - consist of 4 polypeptide chains: 2 heavy & 2 light chains hold by disulphide bridges - the variable region which is different in each type of antibody is dictated by the amino acid sequences - The hinge region gives the flexibility for antibody to bind to antigen • Combine with viruses/toxins to prevent them from invading cells • Antibodies with multiple antigen binding sites cause agglutination of bacteria reducing the chances of spread throughout the body • Bursting bacteria cell walls – together with other molecules some Ab ‘punch’ holes in the cell walls of the bacteria causing them to burst • Attach to bacteria making it easier for phagocytes to ingest them. • Combine with toxins, neutralizing them and making the, harmless, these antibodies are called antitoxins The cells involved are lymphocytes, called T cells • Unlike B cells, which can recognize antigen alone on its membrane bound antibody, T cell receptors can only recognize antigen that is bound to cell membrane protein MHC. • T cells develop surface receptors called T-cell receptors where they become ‘programmed’ for the antigen of their specific enemy • If an antigen is presented to a T cell with a complementary shaped receptor, the T cell is stimulated, increases in size and starts to divide • T cells reproduce rapidly, however they do not produce antibodies like B cells Activated T helper cells T Helper Killer T recognise the non-self antigen (from the foreign cells) that the macrophages display on their outer surface. Cytotoxic (kill cell) attack & kills body cells that have been infected by virus, bacteria or fungus. release a powerful group of chemicals called cytokines to stimulate B cells to proliferate Kill the infected cells by secreting proteins (perforin) that punch holes in the membrane of the cell, and the stimulate macrophages to carry out contents ooze out. phagocytosis more vigorously. In addition to helper & killer cells, memory T cells are produced which remain in the body & become active quickly during secondary response (e) explain the role of memory cells in long-term immunity; Memory cells • Remain circulating in the body for a long time for rapid response • If the same antigen is reintroduced a few weeks or months after the first infection, memory cells will divide rapidly and develop into plasma cells and more memory cells. • This allows rapid response to future infection. Primary response is slow because at this stage there are very few B cells that are specific to the antigen Secondary response is faster because there are many memory cells which quickly divide and differentiate into plasma cells • Many more antibodies are produced in the secondary response • Memory cells are the basis of immunological memory • The ability of the immune system to • Each time a pathogen respond quickly to with different antigens antigens that it infects us, the primary recognizes as having response must occur entered the body before we become before immune and during that time we often feel ill. (g) distinguish between active and passive, natural and artificial immunity and explain how vaccination can control disease; • Natural active immunity (immunity gained following infection) ⇒ body manufactures antibodies when exposed to an infectious agent. • Artificial Active Immunity (immunity gained by antibodies made other than in the host) ⇒ vaccination or immunisation • small dose of antigen is usually safe because the pathogen is either killed or attenuated • individual does not contract the disease itself, but is stimulated to manufacture antibodies against the antigen. • second, booster, injection is given and this stimulates a much quicker production of antibody • Natural passive immunity (immunity gained by antibodies made other than in the host) ⇒Antibodies made in one individual are passed into another individual of the same species. • Artificial passive immunity ⇒Antibodies which have been made in one individual are extracted and then injected into the blood of another individual which may, or may not, be of the same species. (h) discuss the reasons why vaccination has eradicated smallpox but not measles, TB, malaria or cholera; Eradication of smallpox • Smallpox was caused by variola virus & transmitted by directed contact It is distinguished by red spots containing transparent fluid appearing over the body & swollen eyelids • 12-30 % of sufferers died while many who recovered were often blinded. • Reasons for the success of the vaccine included: - The variola virus did not mutate and change its antigens. - It was made from a live harmless strain of a similar virus - Infected people were easy to identify. - Smallpox does not infect animals. - It could be freeze-dried & kept for 6 months aiding distribution Measles • Measles is caused by a virus by airborne droplets. It causes rash & fever & fatal complications e.g. blindness & brain damage • However, measles is still a major disease in overcrowded cities, insanitary conditions & places with high birth rate • This disease easily transmitted among malnourished infants suffering Vit. A deficiency, thus have low resistance • This disease offers the promise of eradication if worldwide surveillance was followed-up by vaccination. • However, so far it has failed because: - poor response to the vaccine been shown by some children, who need nutrition. - High birth rates and shifting populations make following-up cases difficult. - Migrants and refugees may spread the disease. - Measles is highly infectious & 95% immunity of a population is required to prevent transmission. - The vaccine only has a 95% success rate. Poor response - Some people do not respond at all, or not very well, to vaccination - This could be due to defective immune system & thus, do not develop B & T cells OR suffer from malnutrition & do not have protein to make antibodies Antigenic variation - Although each time you get a cold you have a similar set of symptoms, each new cold is in fact caused by a slightly different virus with slightly different antigens. The virus that causes colds has > 113 different strains due to high mutation rate - No effective vaccines against malaria & sleeping sickness - This is because the pathogens (e.g. Plasmodium & Trypanosoma) can have numerous antigens on their surfaces at different stages in its life cycle. - This makes it impossible for immune system to respond effectively Antigenic concealment - Some pathogens escape from attack by immune system by living inside cells e.g. Plasmodium enters liver cells or RBC & protected from antibodies - Some pathogens remain invisible to immune system by covering their bodies in host proteins - It is difficult to develop effective vaccines because there is a short period of time for an immune response to occur before the pathogen “hide”