Immunology Revision 2 PDF

Immunology  Key terminology Immunology - Study of the body’s immune system and how it protects against disease. Microbe - Organisms of microscopic size, some pathogenic and others beneficial in health. (Bacteria, viruses, fungi, Protozoa, algae)...

Immunology  Key terminology Immunology - Study of the body’s immune system and how it protects against disease. Microbe - Organisms of microscopic size, some pathogenic and others beneficial in health. (Bacteria, viruses, fungi, Protozoa, algae) Antigen - Substance/maker on infection-causing organisms that triggers immune response in the body. (Bacteria, viruses, chemicals, toxins, pollen) Cytokine - Small proteins important for controlling/signalling immune cell growth and activity. (Interleukins, interferons, lymphokines) Antibody - Special proteins produced by activated B cells to attack/weaken antigens. (Immunoglobulin) Phagocyte - Immune/white blood cells that engulf and digest pathogens and present pathogens. (Macrophages, neutrophils, monocytes, dendritic cells, granulocytes) Antigen presenting cells (APCs) - Cells that process antigens and expose them in recognisable T cell form on the surface. (Crucial for initiating adaptive immunity) (Macrophages, dendritic cells, B cells) Proteins (within immune system) - Large molecules of one or more chains of amino acids in specific order. (Antibodies, cytokines-signalling proteins, complement proteins) Opsonins - Molecules that coat pathogens, making them more recognisable to phagocytes. (IgG, C3b) Phagocytosis - The process by which phagocytes engulf and digest pathogens. (Neutrophils phagocytosing a bacterium) Apoptosis - Programmed cell death that eliminates unwanted cells during development and maintains tissue homeostasis. Complement system - Aid with eliminating/removing pathogens and damaged cells, helps body heal after injury or infection. Polymorphonuclear leukocytes (PMNs) - Type of white blood cell, first line of defence in response tissue injury, infection or inflammation within the body. (Neutrophils, eosinophils, basophils & mast cells) Key organs & tissues of the immune system - Primary organs; make specialised immune system cells; lymphocytes. - Secondary organs; within these organs, immune system cells ‘fight off’ foreign substances. - Mucous membranes in nose and throat - Tonsils - - Lymph nodes - Thymus - Bone marrow Skin - - - Spleen · Bowel - Mucous membranes in bladder and genitals PRIMARY Bone marrow - produce immune system cells, B lymphocytes mature here. Thymus - site of T lymphocyte maturation, coordinates immune responses. SECONDARY Spleen - filters blood, stores platelets and white blood cells, breaks down old red blood cells. Tonsils - prevents foreign substances from entering through nasal and oral cavity. Lymph nodes - filters lymph fluid and traps pathogens to trigger antibody production. Mucous membranes - immune system cells lie under mucous membrane, acts as protection barrier. Innate VS. Adaptive Immunity Innate immunity - Adaptive immunity - First line of defence, immediate or hours. Develops over time, days or weeks. Non-specific, non-antigen dependent. Specific, antigen dependent. No immunological memory. Immunological memory. Includes barriers; such as skin & mucous membranes, and Involves B and T lymphocytes and immune cells like phagocytes. production of antibodies. Barriers ass. with oral cavity - Oral mucosa - physical barrier & contains immune cells. Saliva - IgA & antimicrobial peptides. Tonsils - trap pathogens & activate immune response. Key barriers of innate immune system TYPE MECHANISM EXAMPLE Skin, mucous membranes; respiratory Anatomic Initial physical barrier - stops pathogens. tract and oral & nasal cavities. Low pH/acid in stomach, body Physiological Regulates immune response through body temperature and chemical systems. mediators; saliva, tears. Phagocytic/ Engulf and digest pathogens - break down Macrophages & neutrophils - pathogen Endocytic of foreign. targeted sites within body. PRRs detect & trigger immune response to Cytokine and histamine release at Inflammatory injury - protect from pathogens and tissue site of trauma/infection; internal or damage. external.  Phagocytosis Cells of the immune system - ALL white blood cells! Depend on T cell help for activation Antigen presentation to T cells Targets: old, damaged and & Releases cytokines - recruit other Release perforin - dead cells. Target: tumour Activated by foreign antigens - phagocytic cells induce apoptosis cells & viruses Recognise and bind to undergo proliferation and specific antigens to differentiate into… Natural Macrophage Destruct contain rapid productions Derived from killer cells Mononuclear leukocyte infected cells monocytes Phagocytosis Phagocyte Plasma cells that Memory cells Degranulation Mature B cells secrete antibodies B Cells Most common leukocyte Targets: Remember foreign Neutrophil Humoral/antibody Degranulation bacteria & Activate T helper and antibodies - quicker Granulocyte mediated immunity Mature in Release of enzymes, growth fungi memory cells antibody response Phagocyte bone marrow factors, cytokines First line defence - PMN Main antigen- all infections Eosinophil presenting cells Activated by pathogens Derived from Adaptive Granulocyte and differentiate into Lymphoblast Immunity PMN Immune Dendritic cells mature forms Targets: parasites, Innate Mononuclear leukocyte allergic tissues system cells Regulatory T cells - Immunity limit immune Derived from Link innate & adaptive - Capture and process response to prevent Memory T cells - Myeloblast - NOT Once activated messengers & regulate pathogens damage to tissue. remember prev. macrophages release inflammatory immune response mediators (cytokines) When cross antigen presenting cell Granules produce displaying antigen fragments on major T helper cells (Th) - Secrete cytokines Mast cells histamine & heparin histocompatability complex (MHC), immune response - help B cells Basophil Granulocyte differentiate into… mediators multiply Degranulation Granulocyte PMN Located in loose Release of histamines, PMN Cytotoxic T cells - (killer) - connective tissue enzymes, cytokines Targets: parasites, Only recognise antigens T Cells release cytokines - destroy Targets: various allergic reactions and ass. with MHC on antigen infected & diseased cells allergic reactions infections presenting cell surfaces when activated Cellular Mature in thymus immunity Antibodies - Immunoglobulin (Ig) Special proteins produced by activated B cells. Specifically recognise and bind to antigens to attack/weaken and mark them for destruction. Body can create new antibodies in response to pathogens or vaccines. Each antibody has a different role in fighting infection; 5 main types; Contains virus proliferation during acute phase — NOT capable of eliminating virus once infection occurred. Immunoglobulin A (IgA) 2 forms; secretory & serum IgA. Secretory - found in linings of respiratory & digestive system, saliva, tears and breast milk. Antiseptic part of mucous membranes. Activate complement system in presence of lysosomes to kill certain organisms. Serum - cannot activate complement system. Immunoglobulin D (IgD) Low levels in blood, cannot activate complement system. Found on surface of B cells. Half of antigen specific receptors on B lymphocyte membranes are composed of IgD. Supports B cell maturation and activation. Immunoglobulin E (IgE) Found mainly in skin, lungs, mucous membranes; small amounts. Most attach to mast cells and basophils to cause release of anti-histamine in bloodstream. High levels found in those with allergies; hay-fever, asthma. IgE antibodies can cause allergic reactions. Immunoglobulin G (IgG) Most common antibody in blood tissue & fluid; 75%. Protect body from viral and bacterial infections; diffuse toxins and spread microbes. Mainly occurs in acquired/secondary immune response. Immunoglobulin M (IgM) Found in blood and lymph system; large role in immune regulation. Largest immune molecule and short lived. Usually first antibody to respond in defence against infections; innate/primary immune response. Immune response Humoral/antibody-mediated immunity Adaptive immunity. Mediated by B cell antibody production. Starts when the B cells antigen-binding receptors recognise and bind to antigens. T helper cells secrete cytokines — aid with multiplying and direction of antibodies from B cells. Some cytokines help B cells to mature into plasma cells (secrete antibodies). Secreted antibodies bind to antigens on pathogen surface — flagging them for destruction! Destructed through; complement activation, opsonin promotion and phagocytosis. Complement system clears antigen-antibody complexes. Cell mediated immunity Adaptive immunity. Does NOT involve antibodies. Primarily directed at microbes that; survive phagocytosis and infect non phagocytic cells. Most effective at eliminating virus-infected and cancer cells. Major role in transplant rejection. Defends against; fungi, Protozoa, cancers and intracellular bacteria. Involves; — Activation of antigen- specific cytotoxic T cells — induce apoptosis (cell death) of virus-infected cells, cells with intracellular bacteria and cancer cells displaying tumour antigens. — Activation of macrophages and natural killer cells — to destroy intracellular pathogens. — Stimulation of cytokine production — mediates effective immune response.  Acquired/adaptive immunity Passive immunity Active immunity Natural Artificial Natural Artificial Mother’s Therapeutically Antibodies Antibodies antibodies (Snake toxin, developed in developed in through placenta/ antibody response to response to breast milk transplant) infection vaccination Injecting exogenous antibodies Production of antibodies against (immunoglobulin) to target specific specific antigen or pathogen antigen or toxin. after exposure to antigen. Short duration — person at risk when Response is specific to particular immunity runs out. antigen. Used; Immunological memory to — When high risk of infection antigens. — When immune system has insufficient time to develop — To reduce symptoms of chronic or immunosuppressive disease. Immune disorders Hypersensitivity = Overactive immune response. Production of excessive immune response. Causes gross tissue damage when body meets antigen for second or succeeding times. Type I — Anaphylaxis Most common Rapid — 1hour Caused by re-exposure to specific type of antigen/allergen. Plasma cells secrete high levels of immunoglobulin E. IgE binds to receptors, mast cells and basophils, causing them to be sensitised. In succeeding exposure to same allergen, antigen binds to IgE molecules, this initiates degranulation of mast cell and release of active mediators (histamine). Localised (heyfever, asthma) OR generalised/stystemic (penicillin, bee stings). Results in allergy, anaphylaxis and atopic disease (skin). Treatment = avoid triggers, pharmacological or immunotherapy (extreme cases). Type II - Cytoxic/antibody Rare 2 — 24 hours IgG and IgM bind to antigens on host cell surfaces. Mediated by complement system or killer cells. Results in opsonization, clumping of red blood cells and cell lysis. Examples; hemolytic reactions/anaemia, some drug reactions, autoimmune anaemias. Treatment = No cure. Systemic glucocorticoids (immunosuppressants) and IV immunoglobulin infusions. Type III — Immune complex Develops over hours, days, weeks. Antigen—antibody immune complex mediated reaction. Soluble antigen in the circulation is bound by IgG and IgM, forming immune complexes. Triggers classical complement pathway, leading to inflammatory and tissue damaging reactions. Examples; serum sickness, rheumatoid arthritis, systemic lupus erythematosus (painful long term conditions). Treatment = No cure. Systemic glucocorticoids (immunosuppressants) to suppress inflammatory response and to avoid triggers. Type IV - T cell mediated Second common. Delayed hypersensitivity, 2+ days. Overstimulation of T cells and macrophages. Leads to release of cytokines (inflammation, cell death and tissue damage). Prolonged inflammation damages normal tissues. Examples; contact dermatitis, rash. Treatment = trigger avoidance and/or use of corticosteroids. Dental implications Vital to ask patients at every appointment about any allergies/hypersensitivities, make notes, along with detailed history taking. Examples: Contact dermatitis Allergies to.. Latex Chlorhexidine Benzocaine topical anaesthetic Sodium metabisulphite (LA) Dentine bonding agents  Diseases that make a patient Immunodeficiency = immunocompromised: Ineffective immune response. Poorly controlled diabetes Compromised or absent immune system. HIV infection May need routine use of antibiotics/antivirals. Anaemia Life long complex treatment and care. Some malignancies (Hodgkin More prone to recurrent infections and disease, lymphomas, myeloma) autoimmune conditions. Malnutrition Vit D deficiency Kidney failure Primary immunodeficiency Spleen removal Rare but life threatening. Genetically determined. Increased incidence of malignancy and/or autoimmune disease. Live vaccines must be avoided for some types. Important for heard immunity in community for protection. 5 types:. B cell T cell Severe combined immunodeficiencies immunodeficiencies immune deficiencies (adaptive) (adaptive) SCID (adaptive) Phagocyte disorders Complement disorders (innate) (innate) Secondary immunodeficiency More common, result of primary infection. Secondary or environmental factors that weaken immune system. Treatment of primary condition enables resolution of immunodeficiency. Malnutrition Chronic infections Drug regimens Dental implications with immunosuppressant drugs Oral candidiasis (common) Increased risk of malignancy and bacterial & viral infections Periodontal disease Gingival swelling (ciclosporin) Oral ulceration Poor healing  Dental care professional role 1. Risk assessment and full detailed histories to be taken. 2. Liaise with physician (Specalist GP, consultant), with patients permission. 3. Antibiotic cover might be required before dental treatment or probing. 4. Prevention is key! 5. Aggressive treatment may be needed for oral infections. 6. Excellent infection control and management of waterlines. 7. Check post-op bleeding risk. 8. Close monitoring and follow up. Autoimmunity = Inappropriate reaction to self-antigens = breakdown of body’s own cells. Increases with age. Natural T cell suppression (prevents autoimmunity) reduces with age. (may cause self- antigens to be viewed as foreign) Factors leading to autoimmunity include; — viral infections — emergence of hidden antigens (released when tissue or organ becomes damaged and immune system fails to recognise them as self-antigens) — drugs (penicillin) — genetics — endocrinological changes (hormones) Autoimmune disease Chronic and progressive disorder. Healthy tissue is targeted and destroyed by body’s own immune system. Immune system recognises body cells as foreign cells and releases antibodies to attack them. May target one organ (organ specific) or the whole body (generalised systemic disease). Treatment options No cure for autoimmune diseases. Immunosuppressants reduce immune response and therefore reduce inflammation. Non-steroidal anti-inflammatory drugs to reduce inflammation and pain. Supplements, physical therapy, regular exercise and well balance diet. Oral manifestations in autoimmune disease Oral signs are usually the initial manifestation of autoimmunity. Early diagnosis can aid with treatment and quality of life. Examples include; Systemic lupus erythematosus — Severe, chronic and progressive autoimmune disease — Redness on skin on cheeks or nose — Oral ulcerative lesions — Layers of gingiva separating — No invasive dental treatment unless prior blood tests. Sjögren syndrome — Xerostomia and dryness of eyes — Cracking of tongue and soft tissues — Minimal or no saliva present — Increased risk of poor oral hygiene and caries. Pemphigus vulgaris — Very sore and tender, inhibits oral hygiene — Breakage of blisters — Leaves painful erosion — Triggered by stress, hormones, drugs, viruses — Dental treatment painful. Mucous membrane pemphigoid — Very sore and painful, inhibits oral hygiene — Blistering lesions on mucous membranes — Found on gingivae — Remain intact in oral cavity for 48 hours. Important to take detailed medical history from every patient at each visit