Compendium 11 Notes PDF

Compendium 11 Notes Lecture 1 Pathogens and antigens - Pathogen: Foreign agent - Bacteria - Infection e.g. staphylococcus - Food poisoning e.g. salmonella - Fungi e.g. candida - Protozoa e.g. amoeba - Parasites e.g. worms - Pathogens introduc...

Compendium 11 Notes Lecture 1 Pathogens and antigens - Pathogen: Foreign agent - Bacteria - Infection e.g. staphylococcus - Food poisoning e.g. salmonella - Fungi e.g. candida - Protozoa e.g. amoeba - Parasites e.g. worms - Pathogens introduce foreign (non self) proteins to the body called antigens - Antigenic receptors on T-cells and B-cells recognise these foreign proteins as not being 'self' and aims to remove them from the body - One pathogen has many antigens Immunity - Ability to resist damages from foreign substances and internal threats - The body can distinguish between 'self' and 'non self' - External -- micro-organisms e.g. bacteria, fungi, virus and toxins - Internal -- cancer cells - Categories - Innate or non-specific immunity - The way the body responds to a pathogen irrespective of what it is - Adaptive or systemic immunity - B cell and T cell immunity which recognises pathogens more specifically - Innate and adaptive immunity are fully integrated in the body - You don't just have an innate or adaptive response Immune vs lymphatic system - Lymphatic system - Transport system for cells of the immune system and antigens to move around the body - Tissues where cells of the immune system reside - Immune system - A collection of proteins, cells, tissues and organs widely distributed throughout the body Immune system - Immunity - Innate (non specific) - Physical barriers (skin and mucous membranes) - Inflammation - Chemical mediators - White blood cells (leukocytes) e.g. macrophages - Adaptive (specific) - Cell mediated immunity (T cells) - Antibody mediated immunity (B cells) Innate immune system - Non-specific defence which is present at birth - Each time the body is exposed to a substance the response of the innate immune system will be the same (has no memory) - Provides immediate protection from pathogens and antigens - The first line of defence are external features - Physical barriers -- prevent entry or remove microbes - Skin: a literal barrier to infection, bacteria on skin is ok but if it gets into a cut, it could cause infection - Mucous membranes: breathing exposes us to a lot of pathogens in the air so the respiratory passageways protect us from a lot of these pathogens, epithelia, cilia, mucous - Saliva: antimicrobial properties - Tears: if you get something in your eye tears help to wash out the irritant - Acid in the stomach, urinary tract and vagina: acidity kills a lot of bacteria - Urine flushes the urinary passageways - Cilia in respiratory passages, coughing and sneezing: beating and brushing microbes out of the system - Second line of defence - Chemical mediators: promote phagocytosis and inflammation - Histamine: causes vasodilation, increased vascular permeability, attract white blood cells and stimulate phagocytosis - Cytokines: secreted by one cell and stimulates a nabouring cell to respond. It regulates the intensity and length of an immune response - Complement: stimulate lysis of an invading pathogen - Interferons: antiviral activity - White blood cells (phagocytes- engulf bacteria and debris) - Produced in bone marrow or lymphatic tissue - Released onto the blood and transported around the body - When a tissue is damaged it releases a chemical which attracts the white blood cells to a site of injury/invasion - White blood cells ingest foreign particles (phagocytosis) - White blood cells produce chemicals to attract other immune cells to the local area - Neutrophils -- the first cells to arrive at the site of insult, acute inflammation; phagocytosis - Macrophages -- the most effective phagocyte, important in the later stages of inflammation and repair, help activate cells of the specific immune system (antigen presenting cell) - Basophils -- immunosurveillance and produce histamine - Eosinophils -- parasitic infection, allergy - Natural killer cells -- can cause lysis of virus-infected cells or cancer cells - B and T lymphocytes -- adaptive immunity - Inflammation - Local tissue response to damage - Pathogens - Cuts and abrasions/injury - Aims to - Rid the body of debris/invaders - Prevent further pathogen entry - Features of inflammation - Redness: increased blood flow to the region - Heat: increased blood flow to the region - Swelling: capillaries become leaky (increased permeability) fluid leaves the capillaries -- surrounding tissue - Pain: increased fluid stimulates pain receptors; chemicals released by cells also stimulate pain receptors - Fever - Generalised response of the body to tissue damage and infection - Common in inflammation and infection - Can cause macrophages to release chemicals - Body temperature is abnormally high - High temperatures - Increase some microbial substances - Decrease microbial growth - Increase body reactions that help tissue repair - 38ish degrees Lecture 2 Adaptive immunity - Specificity: ability to recognise a particular antigen - Memory: ability to remember previous encounters with a particular substance and respond rapidly - Acquired during a person's lifetime depending on their exposure - Fights invaders once the innate system is over-run - Mediated by lymphocytes (a special type of white blood cell) -- B and T cells - Activation of lymphocytes - Lymphocytes (clone of lymphocytes) must recognise the antigen - After recognition, lymphocytes must increase in number to destroy the antigen - Helper T cells - Effector (cytotoxic/killer) T cells - B cells Cell mediated immunity - Cell mediated immunity occurs through T cells - Important for intracellular antigens/virus - This is because the virus infects the cell and then lives within the cell body - Cells display their proteins on the cells surface for quality checking (MHC class one molecule) - These proteins will be strange if the cell is infected with a virus and this is detected by the cytotoxic T-cells through its receptors which recognise an antigen very specifically - The CD8 binds to the MHC class molecule - Once the cytotoxic t cell has recognised the virus the helper t cells help the cytotoxic t cells to perlipherate (make more copies of the specific T cell which has recognised the antigen) - The new t cells spread out and destroy any cells they find which have been infected - Cytotoxic t cells - Eliminate the antigen/pathogen - Release cytokines which produce inflammation, initiate phagocytosis and activate T cells - Make holes in the cell walls causing them to explode - Memory cells - If the same antigen reappears the response will be faster (memory) - Most effective against intracellular pathogens Antibody mediated immunity - B cells - Phagocytosis of an extracellular pathogen (usually bacteria as they are their own individual organism and do not require a host cell) that matches the specific B cell receptor on that B cell - Requires co-stimulation by a helper T cell which also recognises the same antigen, the stimulation is via interleukins produced by the T cell - B cell divides to form... - Plasma cells -- make antibodies which bind to the antigen and neutralise it - Memory B cells -- if the same pathogen is encountered again the response is much faster - Effects of antibodies - Inactivate the antigen - The antibody binds to the antigen and inactivates it - Bind antigens together - Antibodies bind several antigens together - Facilitate phagocytosis - An antibody binds to antigen and then to a macrophage, which phagocytizes the antibody and antigen Antibody production - Primary response - When a B cell is first activated by an antigen - B cell proliferates - Secondary response - Occurs during later exposure to the same antigen - Memory cells divide rapidly to form plasma cells and additional memory cells. Faster and greater response. - Vaccination triggers a primary response so that when the person comes into contact with the respective pathogen their bodies response is secondary and they are unlikely to be impacted by the pathogen Ways to acquire immunity Active Passive ------------ ---------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------- Natural Antigens are introduced to the body through natural exposure Antibodies from a mother are transferred to her child across the placenta or via her milk Artificial Antigens are deliberately introduced in a vaccine and this causes the body to produce memory cells Antibodies produced by another person or animal are injected (antiviral and antibiotics) Immune interactions - An antigen is presented to the body - It first has to get past the physical barriers, neutrophils, macrophages, basophils and eosinophils and the chemical mediators, inflammation, phagocytosis ect. Which weakens the infection however is not quite enough - The macrophage takes up the pathogen/antigen - A helper T cell will investigate and if it is identified as non self they trigger an immune response - The helper T cell can activate a B cell which has identified the pathogen and in doing so causes the b cell to proliferate into plasma cells which make antibodies and also B memory cells which wait in the immune system in case of a second exposure - The helper T cell alternatively could communicate with a cytotoxic T cell which has identified the pathogen/antigen - If the helper t cell verifies that the cytotoxic T cell has correctly identified a non-self-antigen the cytotoxic T cell will proliferate and create more cytotoxic T cells to kill any cells containing the pathogen as well as memory T cells Immune system disfunction - HIV - HIV = human immunodeficiency virus - Virus binds to CD4 protein and infects helper T cells - Cells infected with HIV are destroyed by the virus or immune response - Destruction of helper t cells impairs antibody mediated and cell mediated immunity - A normal amount of helper T cells is 1200 per cubic mm - When helper T's get below 200 per cubic mm the person has potentially contracted AIDS (acquired immunodeficiency syndrome) - Antibody levels decline and immunity is reduced - It is believed to have spread from the Congo to Haiti to US in the late 1960s/70s - First described by the CDC in the US in 1981 - The body is venerable to ordinary infections which could now be lethal - Pneumonocytes pneumonia - TB, syphilis - Candidiasis - Increased risk of cancer - Infection is due to contact with the bodily fluids of an infected person - Treatment - When first described there was no treatment available and HIV was considered a 'death sentence' - Control HIV replication - Highly active anti-retroviral therapy (HAART) - Can live for many years - Chronic disease rather than a 'death sentence' - Manage secondary infections/malignancies Lecture 3 Functions of the lymphatic system - Fluid balance - Excess interstitial fluid enters the lymphatic capillaries and becomes lymph (30L from capillaries into interstitial fluid, 27L returns leaving 3L, called lymph) - Fat absorption - Absorption of fat and other substances from digestive tract via lacteals - Defence - The lymphatic system fights infection, micro-organisms and other foreign substances are filtered by lymph through lymph nodes and from blood by the spleen Anatomy of the lymphatic system - Lymph: the fluid which is contained within the lymphatic system - Lymphatic vessels: vary in sizes, part of the tubular network, immunosurveillance - Lymphatic tissues: part of the tubular network, immunosurveillance - Lymphatic nodules: part of the tubular network, immunosurveillance - Lymph nodes: part of the tubular network, immunosurveillance - Tonsils: lymphatic organ - Spleen: lymphatic organ - Thymus: lymphatic organ Lymph - Water plus solutes from two sources - Plasma: ions, nutrients, gases, some proteins - Cells: hormones, enzymes, waste products - Returns to the circulatory system via veins; essential for fluid balance - This is very important because a build up of interstitial fluid will cause swelling and pain Lymphatic vessels - Cary lymph away from the tissues - Lymphatic capillaries are much more permeable than blood capillaries as ther is no basement membrane - The epithelium functions as a series of one way valves - Found in all parts of the body except the nervous system, bone and avascular tissues (tissues without blood vessels - cornea and epidermis) - Lymphatic capillaries: join to form lymphatic vessels - Lymphatic vessels: have valves that ensure one way flow (beaded appearance) - Lymph nodes: distributed along lymph vessels and filter lymph - Lymph trunks: jugular, subclavian, bronchomediastinal, intestinal, lumbar - Lymphatic ducts: drain tissues of the body and move lymph into major veins - Right lymphatic duct drains right side of head, right upper limb, right thorax - Thoracic duct: drains remainder of the body - Lymph is moved through the vessels by the contraction of skeletal muscles - Lymph drainage into veins - Lymphatic trunks and ducts connect back to venous circulation just above the superior vena cava draining back into the right atrium of the heart - What the lymphatic system looks like varies a lot from individual to individual Lymphatic tissue and organs - Lymphatic organs contain lymphatic tissue (lymphocytes, macrophages, dendritic cells) - Lymphocytes: B and T cells -- white blood cells derived from the bone marrow. Haematopoiesis - Bone marrow makes blood cells including red and white blood cells and platelets - This is important as blood cells have quite a short lifespan - Fine network of reticular fibres produced by reticular cells (connective tissue). These act as filters lymph to trap microorganisms and other particles - Network for lymphocytes and macrophages to anchor to - May be encapsulated (in a connective tissue capsule) - Encapsulated -- e.g., lymph nodes, spleen, thymus - Nonencapsulated -- e.g., mucosa-associated lymphoid tissue (MALT). Found beneath the epithelium as the first line of attack against invaders. Lymphatic tissue and lymphatic nodules - Diffuse lymphatic tissue: dispersed lymphocytes, macrophages; blends with other tissues, spread out/dispersed, found in the mucosa and in the periphery of lymphoid nodules - Lymphatic nodules: denser aggregations. Numerous in loose connective tissue of digestive (Peyer's patches), respiratory, urinary, reproductive systems Lymph nodes - The only structures which filter lymph - Substances like bacteria are removed by phagocytosis (macrophages) or stimulate lymphocytes to proliferate - Cancer cells often migrate to lymph nodes, are trapped there and proliferate. They can move from the lymphatic system to the circulatory system spreading cancer through the body - Afferent and efferent vessels - Afferent = into the node - Efferent = out of the node - The lymph nodes activate immune responses - Organised into cortex and medulla with dense connective tissue capsule surroundings Tonsils - Large groups of lymphoid tissue in the nasopharynx and oral cavity - Provide protection against bacteria and other harmful material - Palatine (tonsils) - The largest and most common - Pharyngeal (adenoids) - Posterior wall of the nasopharynx - Lingual - Base of the tongue - Made up of stratified squamous epithelium - Play a role in immune memory Spleen - The spleen is posterior to the stomach, superior to the kidney, just inferior to the diaphragm in the left hypochondriac region - Similar size to kidney but increases in size with disease and age - The spleen has a medium hilum where blood vessels and nerves enter - Blood enters the spleen via the splenic artery where its filtered and then brought back to the heart via the splenic vein - Red pulp associated with veins (75% of spleen volume) -- fibrous network of macrophages and red blood cells - White pulp associated with arteries (25% of spleen volume) -- lymphatic tissue - Functions - Filters and monitors blood, detects and responds to foreign antigens/bacteria - Macrophages that are there can act to phagocytose and lymphocytes can mount an immune response - Destroys defective red blood cells (old and fragile red blood cells rupture as they are squeezed through the fine capillaries of the spleen, they die and are phagocytosed by macrophages) - Regulates blood volume by transferring excess blood plasma into the lymphatic system - Limited reserve of red blood cells -- red blood cells can be stored in the spleen and are released when they are needed - Can be ruptured in traumatic abdominal injuries and is hard to repair - Splenectomy: the removal of the spleen , a person can live without a spleen but they will be extremely prone to infections Thymus - Located in the superior mediastinum - The thymus is fully developed at 12 months of age - The thymus is surrounded by a connective tissue capsule - Cortex (numerous lymphocytes) and medulla (fewer lymphocytes) - Site of maturation of T cells: many T cells are produced in the thymus but most regenerate - Once matured they can enter the circulatory system - Those that remain can remain can react to foreign substances - Endocrine functions Overview 1. Lymph is picked up from interstitial space and goes into lymphatic capillaries 2. There are valves which ensure a one way flow 3. Nodes filter lymph 4. Capillaries/vessels merge to become ducts 5. Lymph can enter back into venous circulation 6. Lacteals in the small intestine absorbs fatty acids and the 7. Chyle (lymphatic fluid coming from the digestive system which has a lot of fatty acids in it) eventually moves into venous circulation 8. The spleen filters blood, the splenic artery takes blood into the spleen and the splenic vein takes blood out of the spleen 9. Lymphocytes originate from the bone marrow 10. T cells mature in the thymus and B cells mature in the bone marrow 11. Lymphatic fluid and lymphocytes and blood circulates around the body Disorders (not assessed) - Tonsilitis: inflammation of the tonsils, a bacterial infection - Lymphoma: cancer (benign or malignant) of lymphoid tissues or cells, often begins in the lymph nodes, immune system is supressed - Hodgkin's disease: malignancy in lymphoid tissue (malignant B cells) chemotherapy/radiation - Non-Hodgkin's lymphoma: any cancer of the lymphoid tissue except Hodgkin's disease. Can effect cells, nodes and organs. Young vs old alters the pathology and treatment - Bubonic plague: the black death, a severe bacterial infection spread by fleas and rats, enlarges the lymph nodes and causes septicaemia (blood poisoning) Tutorial 1. Fluid balance, immunity, lymphatic capillaries, interstitial space, capillaries, permeable, lymphatic vessel, lymph nodes, macrophages, lymphocytes, recognised, cancer cells, increase Redness Caused by increased blood flow to the area, vasodilation ------------------------ ------------------------------------------------------------------------------------------------------------------------------- Heat/burning sensation Caused by increased blood flow to the area, vasodilation Swelling Caused by increased interstitial fluid leaked by lymph and blood vessels. Increased permiability Pain Caused by the pressure of the swelling and some of the chemicals being produced, the excretion of bacteria can be quite toxic Billie had a fever because their body was using an innate response to try and fight off the infection, increasing the body temperature can kill off certain pathogens so the body tried using this non-specific response to fight the strep throat. The swollen lymph nodes occur as there is an increased amount of B and T cells in the lymphatic system causing swelling of the lymph nodes. Macrophage takes the antigen and presents it to the helper T cell, the helper t cells perlipherate to become more in number and then activate the cytotoxic t cells which proliferates again and lysis of the cells Fingernails Keyboard Door handle Ear Benchtop Soil ------------- ---------- ------------- ----- ---------- ------ 3 1 4 5 6 2 1 4 2 5 6 3 Ear and fingernails due to neglection of cleanliness, open to the external environment, provide a nice warm and moist environment which is good for growing bacteria Because there is nutrients in the soil, warm, moist No nutrients on the bench and door handle, its cold, dry and regularly cleaned Probably not harmful Natural flora also resides in the vagina, the mouth, your nose and digestive tract and urinary tract Clean Contaminated Transmission 1 Transmission 2 Transmission 3 ------- -------------- ---------------- ---------------- ---------------- 0 ++++ +++ \+ 0 The transmission decreased over time The body was protected by the skin from infection This is a part of innate immunity This could be breached if you have a cut Factors which may influence microbial growth (TAMPON) Temperature Atmosphere Moisture PH Osmolarity Nutrients