SC NATS 1670 Lecture & Written Notes 3 PDF

BASIC CONCEPTS IN IMMUNOLOGY part - humans have 50% human cells and 50% bacteria cells - 30 trillion human cells and 39 trillion microbial cells 20, 000 human genes make up 1% 2-20 million microbial genes (99% we neglect) we live in a symbiotic relationship with the microbes with us Role of microbes...

BASIC CONCEPTS IN IMMUNOLOGY part - humans have 50% human cells and 50% bacteria cells - 30 trillion human cells and 39 trillion microbial cells 20, 000 human genes make up 1% 2-20 million microbial genes (99% we neglect) we live in a symbiotic relationship with the microbes with us Role of microbes play defense protect from autoimmune disease and allergies train immune system differentiate bet ween disease-causing agents and innocent molecules Clostridium difficult can infect us after treatment with long-term wide range antibiotics fesces-filled capsules can treat bacterial infection ↳ About 14 000 Americans killed due to this outermost layer of the human body is home to millions of microorganisms that depend on our bodies for survival The of surface follicles , in the crevices our skin , INFECTIOUS DISEASE AND HOST DEFENSE immunology is the study of our protection from and response to foreign invading organisms and altered host cells Most important activity of the immune system is dealing with wine invading organisms - VIRUSES : activating the immune system is the only way to fight the disease ↳ vaccinations were used to manipulate the immune system making bacterial cells that can make toxins like tetanus toxins can help - BACTERIA : synergisms bet ween antibiotics and the immune system (treatment is only effective if the host defence mechanism can take care of the residual cells reduceBacterialCells ,Willneedhigher concentratiohe ↳ Breaking the balance is how we get infection and immunity issues Examples: disease called impetigo is a contagious skin infection caused by too much streptococcus or a group of streptococcus Vibrancy E. coli infects guts - can enter blood circulation and cause severe disease Influenza - mild disease, can be aggressive today there are more people immunocompromised compared to 40 years ago HIV AIDS during the 80s attacked the immune system which resulted with more infections Immune system can go down due to giving drugs - using drugs can reduce new organ rejections - people get new organs or kidneys to replace their old ones todays use old anti-cancer drugs resulted in more cases related to side effects of those drugs which affect the immune system in a negative way WHEN TOO MUCH IMMUNITY: some situations, the system is educated to fight against the pathogen and should not react against your own body Allergy Autoimmune disease Acute inflammation - sepsis, cytokine storm - sepsis bacterial cells were able to enter the blood circulation where the immune system is going to fight against this pathogen so strong but eventually cause more damage than good cytokinestome Chronic inflammation - cancer 20% of human cancer is about chronic inflammation Inflammatory response is important to deal with pathogens One of the major cause of cancer especially when it comes to cancer which is induced by viruses human papilloma virus can induce chronic inflammation on the cer vix causing cancer over there can be a problem in general if we inflammatory response cannot resolve the problem = infection is for the rest of your life Ex: hepatitis b OUR IMMUNE SYSTEM ANATOMICAL AND PHYSIOLOGICAL BARRIERS low stomach pH - not let viruses or pathogens to the gastrointestinal tract Intact skin Lysozyme in tears and saliva Ciliary clearance intrinsic defence ADAPTIVE IMMUNITY INATE IMMUNITY T cells and B cells NORMAL FLORA AND ANATOMICAL BARRIERS skin - an outer layer of intact skin which will protect us - is comprised of dead and bacterial cells - normal flora - make sure other pathogens are not going to be eastablihsed the bacterial cells on our skin (can establish biofilm) - flushing (sweat) - Phospholipids gastrointestinal tract - peristalsis - low pH: protects from different pathogens - bile salts naso-pharynx and eye - overall cavity of the nose and mouth - mucus, saliva, tears - flushing - lysozyme - destroy bacterial cells SELECTIVE CELL WALL DAMAGE lysozyme (enzyme) cuts Glucosamine-Muramic acid linkages Lysozyme is abundant in a number of secretions such as tears, saliva, human milk, and mucus OUR IMMUNE SYSTEM NON SPECIFIC (INNATE) SPECIFIC (ADAPTIVE) THE SPECIFIC IMMUNE RESPONSE SPECIFIC OR ADAPTIVE IMMUNITY A response to a specific molecule/organism The system can remember invaders and react more quickly to second exposures to infection - only an exposure to the same molecule/organism will activate this memory response the specific immune system can distinguish bet ween self and non self and only reacts against non self normally Specific response - one antibiotics can recognize only one molecule Immunological memory - made up of cellular (T cells), humoral (B cells) HIV infection which is the T cells are the target of this virus Antibodies HUMORAL ADAPTIVE IMMUNITY ANTIGENS (AG) are substances (specific molecule/organism) that induce a specific immune response and subsequently react with the products of a specific immune response ANTIBODIES (AB, Immunoglobulins, IG) are protein molecules that are produced by plasma cells in response to an antigen and can bind specifically to that antigen Some cases you want to raise immune system: Example- surgical material you want the hypo immunogenicity material because you want to avoid the immune system to react against them (hip replacement is an example), has to be certain material that won’t raise immunity Antibodies: main role secreted by plasma cells is to tag foreign molecules or microbes for destruction binding of antibodies to antigens can trigger some effector mechanisms Neutralization occurs when antibodies bind to antigens blocking their activity and making them harmless - example: it covers surface proteins of this virus preventing it from hooking up onto the host cells other antibodies may bind to toxic molecules on a bacteria by phagocytosis Have at least t wo binding sites that allows them to form a clump of microbes by binding to t wo antigens in tel different cells agglutination traps microbes and makes it easy for macrophages to capture them and dispose of them by phagocytosis Precipitation is similar to agglutination except it clumps together free antigen molecules dissolved in the body becoming inactive One of the most important mechanisms of humoral immunity is the activation of complement proteins binding if antibodies to a foreign cell triggers implement proteins in body fluids to form a hole in the membrane of the target cell Hole allows water Neutralization: AB neutralizes toxins and binds to attachment molecules Neutralization: neutralizes bacteria, binds to molecules on their surface such as flagellum, bacteria will not move Neutralization: AB neutralizes toxins such as A-B toxins (Active Virulent and Binding) antibodies can bind to free proteins and inactivate them in t wo major ways 1. Binds to important protein site that bunds to the cell 2. Can precipitate the protein Agglutination: create complexes of cells Precipitation: creates complexes of molecules Complement activation: a process occurs in antibodies bound to a pathogen, making holes in the membrane of the pathogen Opsonization: AB binds to pathogens surface molecules and link them to phagocyte cell The uptake of bacteria by phageocytes is an active process which requires the triggering of specific receptors on the phagocyte fc receptors which bind antibody-coated bacteria are one of the receptors capable of triggering phagocytosis binding of the aggregated antibody molecules to fc receptors on the phageocyte causes the cell to engulf the bacterium the phagocyte first produces pseudopods or ruffles that surround the bacterium and then fuse trapping the bacterium within what is now an intracellular vesicle the phagosome within the phagocyte lysosomes fuse with the phagosome delivering their enzymatic contents to degrade the engulfed bacterium How does our body make antibodies? high concentration of antibodies in the circulation How does our body make antibodies? protein that play a integral role in the comple system of specific immunity Antibodies are secreted from cells and recognize antigen, these will be a (B cell receptor on naive B cells) in the surface of the cell B cell very specific to one antibody which can bind to one specific antigen Recognize the same High specificity where one cell can recognize one pathogen We have a problem: we need to recognize a 10^12 of possible antigens Each lymphocyte makes antibodies with only one specificity, one cell for one antigen Sufficient cells(~10^6) specific for the antigen in question 10^6 x10^12x 10^18 cells for woeful immunological response - our body - 5-10 cells for each Ag - when a cell encounter it’s specific Ag: - extensive replication - 5-10 cells -> 10^6 in 1960 sir frank mcfarlane burnett was awarded the nobel prize for his contribution to the field of immunology burnett's clonal selection theory revolutionized our understanding of the immune system to this day burnett's research remains the foundation of the way we think about disease and how the body responds to it clonal selection is the central mechanism by which your body fights infection Lymphatic net work detects any infections arise in the body B cells are guardians of your immune system and scans for foreign material M protein hairs arrive at the lymph node from the bacteria The activated B cell migrates and begin to migrate, the copies that are made from the selected cell supports burners CLONAL selection theory Burnetts theory us that one cell is selected out of billions of B cells and identical clones have been created from it will stay longer mom take time L -> Unlikely >casediscs a - ↓ Immune not so antibodies response strong pathogen gives to cause a and chance disease L pathogen Effective , quick VACCINATION AND PASSIVE IMMUNIZATION Passive immunization is about the injection of antibodies and the product of the immune system BLOOD = CELLS + PLASMA PLASMA = SERUM eg. antibodies, serological test CELLS = eg. B cells BLOOD: Activating cells with antigen like cells active immunity using the plasma like passive immunity B cells Snake toxins the venom of the snake is actually needed to be inactivated by antibodies quickly as possible to reduce the effect, this is the general idea of passive immunization ACTIVE IMMUNIZATION long term activity you’re giving the active immunization when you that initially it’s not likely to work in most of the cases - initial inoculum is going to give you antibodies that are going to be part of the primary immune response PREVENTION AND THERAPY OF INFECTIONS most of the damage to cells during infections occurs very early, often before the clinical symptoms of disease appear This makes drugs treatment of infection irrelevant in most cases Prevention of infection is better and cheaper What is a vaccine? vaccines are harmless agents, perceived as enemies Cheating of immunization Trigger active immunity, stimulating the body to defend itself - provide protective immunity against a potential pathogen Active Immunization can be activated by vaccines through primary response Can be activated by pathogens through secondary response the same man was never attacked t wice acquired immunity in history of the pelopmesian war, 431 Variolation: inoculation with the wild type organism, eg. Ebola 2000 BC: sniffling of small crust in China Southern Asia and Africa is where polio is still endemic and occurs From Variolation to Vaccination Edward Jenner discovers a safe smallpox vaccine Published in 1796 Cowpox virus, a relative of smallpox in the 18th century the beauty of milkmaids was a cliche they alone seem to be spared from smallpox an english country doctor named edward jenner observed that a surprising number of milkmaids caught a mild measles-like illness called cowpox known officially as vaccinia jenner extracted the virus from blisters and infected a child his own infant son then he inoculated the boy with live smallpox virus it was shockingly risky but it worked the initial cowpox injection did cause mild sickness but it was enough like smallpox that his body eventually built an immunity to both diseases 1885 Rabies Vaccine Louis Pasteur In 1885 he developed the first attenuated vaccine against rabies virus Attenuation was achieved by creating a virus strain that were less virulent for humans Herd immunity type of immunity that occurs when the vaccination of a portion of the population provides protection to unprotected individuals vaccination is a collective activity in order for it to work, most of the population need to get the vaccine and to be immunized usually HOW TO MAKE VACCINES: VACCINATION STRATEGIES ex : Variolation starting with a virulent parental virus which is picked up from an infected person (original virus from kids) Virus can be attenuated by biological means in order to make life attenuated vaccine Virus as “live” is an organism with an ability to replicate in the host cell and the live attenuated vaccines are based on the fact that we can change the virus a bit in such a way that it cannot cause disease any longer Measles is an example of this virus and this pathogenic virus is isolated from a patient and we are letting this virus to grow in human cells in order to make enough viral cells having enough viral cells to work with, we change the cell that the virus can infect and we do that by putting the virus on a different plate that contains other type of cells so the likes to infect humans cells can find itself in animals cells virus will change in order to grow well on those animal cells and will lose ability to grow efficiently in the human cell Viral cells will be in our system for about a week, replicating slowly and exposed to the immune system which will develop the acquired immunity and be cleared soon enough so we are just kept with active adoptive immunity an adapted microbes can live better in its new host cells to become attenuated vaccine VACCINES AGAINST RABIES developed by Louis pastel in 1885 Starts with a virus from rabbit dog and took this virus and injected into the brain of rabies serial injections in one rabbit to another rabbit Attenuation was achieved by serial infection in rabbits led to a virus strain that was more virulent in the rabbit but was less so in dogs and humans This virus has no viremia stage which means that the virus cannot enter the blood circulation and which for by the blood circulation directly to the brain doesn’t work for this virus - soon can walk on neuronal cells * POST EXPOSURE VACCINE LIVE ATTENUATED VACCINE the virus in the vaccine must stay alive to replicate in the vaccine’s cells - storage: keeps their variably to keep their cells, a reason why some of the vaccination is taking place in the pharmacy and they have it at -20 degrees - maternal antibodies Live attenuated vaccines are sensitive to antibodies that are going to destroy them, wait until the baby is 12 months of age to be safe (varicella vaccine, chickenpox vaccine given to babies) - risk for back mutations can change back to virulent virus example polio attenuated virus can go back to wild type, if the wild type was originated from the attenuated virus is infecting other anonymized people, you can see cases of polio which is not coming from the natural wild type that is circulating around but from the vaccine to turn the attenuated virus into wild type Attenuated virus cannot cause a disease but can be activated be controlled by the immune system What makes attenuated vaccine to mutate backwards and to become wild types? during the time virus is developing mutations to turn from attenuated to wild type, when it comes to poliovirus the attenuated form of this virus is different from the wild type by t wo mutations - the mutations that are making these virus into an attenuated organism into wild type, the virus is not going to lose fitness, and not be controlled by the immune system - attenuated poliovirus can become wild type by acquiring one mutation then the second and that is how you have the wild type virus polio attenuated virus can mutate background to wild type because the virus doesn’t have any major cost in fitness * attenuated virus can infect non vaccinated people - better herd immunity (polio) - risk to immune-compromised people (influenza) pregnant womens Considered 150 of its the are Immunocompromised antiges are from father) LIVE ATTENUATED VACCINES MMR vaccines : measles mumps (kids can lose their fertility when older is a problem from mumps) rubella rna viruses but genetically stable No back mutations, safe vaccines for everybody human host only Influenza since 2003: for healthy and young Polio (Sabin) mimic the transmission of the wild type virus, effective Varicella Zoster chicken pox in kids Shingles in adult (>60 yr) Virus moves to neuronal tissues and stays there for rest your life Zoster is due to reactivation of varicella from the nervous system w & - - > - vaccinated even chicken pox , , likely still to have be exposed chance to to have a virus > about - had 10 of chicken persons pox with from chicken before pox , actually What happens to adults as kids will be vaccinated ? shingles in the past was restricted to the age of 60 and above Now available to people which are 50 and above Varicella zoster the vaccine is given several times during your lifetime first when you’re of 12 months of age avoid getting the chicken pox when you’re 19 years old Second booster for kids comes when they are 4-6 years old KILLED AND SUB-VIRAL/CELLULAR VACCINES visions inactivated by chemical procedures The virulent parental virus can be destroyed by chemicals such as formaldehyde detergents urea Then infected and viral ability to replicated eliminated by antigenicity is not compromised Killed proteins polio (Salk) (at present- very common use) influenza (new strain every year) Pertussis (accellular only 5 protein used) Hepatitis A (create liver disease) Modern rabies vaccine (post exposure) infection by the rabies virus has a very long way to go there because there is a long incubation period which is involved with the virus walking from your feet to your central nervous system There are examples that rabies are transmitted by organ transplantation BACTERIAL EXOTOXINS bacterial proteins (enzymes) - destroy host cellular structures and/ or functions TOXOIDS (INACTIVATED TOXINS) diphtheria - inactivated toxin ( toxoid) - the toxin is encoded by a bacteriophag tetanus HOW DO YOU GET HEPATITIS B? Blood: direct contact with infected blood - unsafe injections and transfusions - sharing or reusing needles or syringes - open wound contact Sex: unprotected sex with someone who has hepatitis B vaccination may prevent the above Birth: from an infected mother to newborn at birth (accounts for 40-50% of the cases in Asia) - up to 9 out of 10 babies born to infected mothers will end up being hepatitis B carriers for the rest of their lives - increased risk for chronic liver disease and primary cancer of the liver - cannot be prevented by vaccine only HPV vaccine PASSIVE IMMUNIZATION biological drugs like against cancer drugs like herceptine avestin are antibodies which are made in the lab monoclonal antibodies and those antibodies can inactivate certain things related to cancer in the body in the body of the patient a Weston can bind a certain factor which is promoting the growth of blood vessels towards the tumour. Herceptine can destroy cells that are expressing a certain anitgen called her2 at high concentration which are cancer cells Artificial passive required immunity is a drug in some cases vaccine is about injecting antigens whereas passive immunization is injecting antibodies High concentration starts immediately Antibodies become degraded Active immunization starts with low concentration of antibodies (boosters help reach high concentration of antibodies) passive immunization is using the product of active immunization which took place in the body of someone else Natural Artificial placental transfer of IGS (systemic ABS) Breast feeding: transfer of IgA (mucosal ABS) antibodies from other individuals Antibodies from an immune animal towards the end of 19th century people realized that blood from someone else that had diphtheria can help someone which is coming with the disease - found that antitoxin activity is in the serum (A vial of diphtheria antitoxin, dated 1895) POST-EXPSOURE PASSIVE IMMUNIZATION-BACTERIAL TOXINS Disease Diphtheria Product Specific Ig from horse Botulism Specific Ig from horse Tetanus Ig from human Use Treatment of diphtheria infection Treatment of wound and food borne forms of botulism, infant botulism is treated with botulism immune globulin (BabyBIG) Treatment if tentanus infection Disease Rabies Product Rabies Ig Vaccina Vacccine Ig from human Varicella (chickenpox) Varicellazoster Ig Use Post-exposure, locally (administered with rabies vaccine) Treatment of progressive vaccinia infection usuallly resulting from smallpox vaccination in immunocompromised individuals Post exposure in high risk individuals We want to get chicken pox early in life because when you get chicken pox early in life, is not as strong for your immune system as when you are 18 chicken pox has 3% lethality in adults Post exposure passive immunization is a kind of drug to a problem which is already there but there some situations that the antibodies are going to be used a prevention of viral infection PREVENTION OF VIRAL INFECTIONS BY PASSIVE IMMUNIZATION Disease Product Use Cytomegalovirus (CMV) Hyper-immune human Ig Prevention, used most often in organ transplantation patients Hepatitis A Pooled human Ig Hepatitis B Hepatitis B Ig (HBIG) Prevention of Hepatitis A infection Prevention in high-risk infants (administered with hepatitis b vaccine hepatitis b is a virus that can be transmitted from mother to mother If the mother is a carrier of hepatitis b, the baby will get infected and vaccination at this stage by itself is not going to help deal with the virus HOW DO YOU GET HEPATITIS B? by blood sexual transmitted infection (sex) (Vaccination may prevent the above ) birth most infections for mothers to the new born are taking place during the process of the delivery (as the various is transmitted from the blood of the mother during the delivery to the baby, the baby is exposed to almost like “fresh infection” which can be prevented by antibodies Mother to child hepatitis B can be prevented! Passive immunization- prevention Disease Hypogammaglobulinemia Product Pooled human Ig Use Prevention of many diseases in patients with an immune disorder characterized by a reduction in all types of gamma globulins ADVANTAGES AND DISADVANTAGES OF PASSIVE (Vs. ACTIVE) IMMUNIZATION MYTHS AND MISINFORMATION ABOUT VACCINE SAFETY Part ACCEPTANCE/REJECTION OF 3 VACCINES - anti infection medicine and other factors have helped dramatically lengthen average life expectancy in the US. Males and females reached about 80 yo Success of vaccination MYTHES AND MISINFORMATION ABOUT VACCINE SAFETY vaccines are victims of their own success Most parents today have never seen a case of diphtheria, measles, or other oncecommon diseases now preventable by vaccines As a result, some parents wonder why their children must receive shots for diseases that don’t seem to exist ↳ ↳ vaccines some can be scientific known media from information is based /may on / Sir Luke Fildes ↳ The doctor > - ↳ vaccination no this > no these at time ↳ Kids - (1887) die memory diseases that are deadly be blased) creating L EGETTING fear has a price sic parents the frightened vaccine to get Vaccine: Risks vs Benefits vaccines are not absolutely always safe, there’s always some risk Vaccine safety issues allergies to egg and gelatin swine flu vaccine and GBS OPV reversion to wild type Small pox vaccine Vaccine tragedy Salk polio vaccine - the cutter incident 40 000 cases of polio virus infection, leaving 200 children with different degrees of paralysis, killing 10 Putting virus in high concentration together, the virus will be clumped wheee virus particles will combine with others which can block the excess activating agents to those viruses that are in the middle this is why activation was not working properly DTaP vaccine vaccine against diphtheria, pertussis, and tetanus once vaccine was introduced, cases declined 81% of population took vaccine around 1970 Anti vaccine movement was established initially in England, then followed by the U.S. outbreak came back in 2012 in New Brunswick parents realized vaccination was important 40 cases started in New Brunswick then over 150 cases in British Columbia 1/5 will develop ammonia 1/100 will die MMR VACCINE measles, mumps, and rubella MUMPS mumps component is not as effective as measles and rubella Vaccines against mumps is effective in 70% of the cases, want to use more than once to get higher percentage When herd immunity is not working well, mumps came back around 2009 in Toronto (outbreak) People born 1957 and before are considered people who already got the disease and don’t need the vaccine - they become more susceptible MEASLES one of the diseases that are killing many people General rate around the globe is close to half a million on average 2001: 40 000 000 Infections 1 000 000 death World wide vaccination program 2004: 20 000 000 infections Measles is one of the leading causes of death among young children 2017: 110 000 death globally among kids in age of 5 despite effectiveness in vaccine measles vaccination resulted in 80% drop in measles death in bet ween 2000-2017 worldwide - measles vaccination prevented estimated 21.1 million death, making the measles one of the Best Buy in public health 500 people were killed in the U.S every year before vaccination Connected to herd immunity Vaccine available to 12 months of age - before this age, the baby relies on the genetics from the mother some cases include in Alberta in 2013 Andrew Wakefield paper, MMR vaccine and autism the paper did not prove an association bet ween measles, mumps, and rubella vaccine and the syndrome described Virologics, stupidness are under way that may help to resolve this issue feb 28, 1998 Dr. Wakefield and the public came with totally different conclusions suggesting an association bet ween MMR vaccine and autism IMPACT OF WAKEFIELD PAPPER many parents decided not to vaccinate their kids based on this paper more hospitalizations and death of kids from measles Recent outbreaks around the globe What are the motivations of the activists fighting against vaccination? 1. Getting attention (ex: Michele Bachman, claimed that the HPV VACCINE made woman’s daughter mentally retarded 2. Supporters 3. Implicatory Denial (Is about choosing to deny reality (scientific facts) as a way to avoid an uncomfortable implications Implicatory denial rejection of vaccination is not about science, rather about its IMPLICATION 1. Fact: the government is making us to do something (vaccination, restrict tobacco use etc.) implication : less freedom 2. Fact: you can prevent many infectious diseases by vaccination; Implication: you do not need to buy pseudo-treatments to “increase your child’s natural immunity) Implicatory Acceptance of Vacciantion: Public Health Facts: 1. Vaccines prevent diseases 2. Herd immunity provides protection to unprotected individuals Implication: nonimmunized community can get disease by infected outsiders Used in Africa: artemisia annua (against malaria) - active material that is protecting people from malaria ALLERGY DISEASES CAUSED BY THE EXCESSIVE RESPONSE OF THE IMMUNE SYSTEM autoimmune diseases allergies - affected about 10% of the population in western countries - can come from secretions of dust mites - allergies such as asthma are expressed together with the effect of other genes an allergy is when your body sees an ordinary substance as foreign and because it sees it as foreign it does anything it can to combat the substance It’s an inherited tendency - people inherit a general tendency of the immune system to overreact, when the immune system does overreact and cause allergy, patients makes too much of a substance called (ALLERGIC ANTIBODY IgE) - a allergy protein Anaphylaxis : life threatening full body allergic reaction Two types of allergies : SEASONAL AND CHRONIC Allergy allergies are abnormal sensitivities to antigens in the environment Allergens are antigens that cause allergies in indoor allergy = dust mite have secretions that can turn into fine powder with can come into being an allergy outdoor allergy = pollens Immunoglobulin E (IgE): type of antibodies originally evolved to defend humans and animals against parasites like certain worms immune system targeting other molecules by mistake which created allergies this hypersensitivity is mediated by IgE sensitization occurs when the antigen makes contact with some part of the body the antigen is taken up and processed by antigen antigen presenting cells and presented on a Class II MHC to T-helper cells Tissues under the mucous membrane are rich in B cells committed to IgE production and IgE producing cells are more abundant in persons susceptible to allergies T-helper cells produce cytokines which stimulate the B cells to proliferate and differentiate into IgE producing plasma cells As IgE cells is produced, molecules attach via their constant regions to receptors on nearby mast cells. Mast cells contain granules packed with chemicals that induce hypersensitivity response Once attached the IgE molecules can survive for many weeks The individual is now sensitized to the antigen When exposed to the antigen for the second time, the antigen binds to the IgE antibodies on the mast cells to trigger a response, t wo cell bound IgE molecules must react with a specific response antigen Within seconds of the reaction, the mast cell releases histamine and other mediators of the inflammatory response from the granules, triggering a variety of symptoms Development of Allergic Reaction first exposure the inhaled allergen enters the mucous membrane living the nasal passages where it is taken up by the antigen presenting cell which presents it to the T cells These T cells activate B cells to release substances called IgE antibodies against the allergen They sit on the mast cell which have granules containing chemical mediators like histamine and prostaglandins On exposure, the allergen binds to the IgE antibodies present on the mast cells cross linking them which exults in the release of histamine prostaglandin and other mediators into the surrounding tissue These mediators cause3 dilation of the surrounding blood vessels and increases their permeability This results in the nasal stuffiness, sneezing, and mucous discharge of allergic rhinitis MAST CELLS : I Resting Must cells > - Activated Mast Cells , of 2 cells Mast Cells and Basophils contain granules filled with inflammatory chemicals such as histamine IgE-sensitized cells bind the allergen and release the potent inflammatory mediators CLINICAL SIGNS OF LOCALIZED ALLERGIC REACTIONS most allergic reactions are mild and localized Site of the reaction depends on the portal of entry - inhaled allergens may cause an upper respiratory tract response - watery nasal discharge, sneezing, itchy throat and eyes, and excessive tear production - commonly caused by mild spores, pollens, flowering plants, some trees, and dust mites pinkeye, nasal polyps, tonsillitis inhaled allergens Asthma - causes inflammation strong genetic competent to asthma - induces bronchial smooth Takes more just genetics to have an attack muscle to over-secrete mucus and to contract asthma is disorder of obstruction of breathing due to inflammation and narrowing of the bronchial tubes initially the bronchial tubes become inflamed and produce thick mucus The muscle surrounding these air ways tightens and air cannot move freely - called BRONCHOSPASM - result is shortness of breath and air moving through the tightened air ways causes a whistling sound known as wheezing pollen, pot dander, weather changes, tobacco smoke etc can trigger and worsen asthma symptoms in susceptible patients Skin allergies due to release of histamine and other mediators into nearby skin tissue, eczema Food allergies most important type of allergic reaction most common Can make people anaphylactic shock or lead to death Most common food allergy is peanuts which can lead to death > emergency - medicationen benadry FOOD ALLERGIES some foods may contain allergens Cause diarrhea, vomitting and other gastrointestinal signs and symptoms Can lead to anaphylactic shock Mainly affects kids , ANAPHYLACTIC SHOCK degranulation of many mast cells at once causes the release of large amounts of histamine and inflammatory mediators Can result in active anaphylactic or anaphylactic shock Clinical signs - bronchial smooth muscle contracts violently - swelling of the larynx - suffocation - leakage of fluid from blood vessels - drop in the blood pressure SYMPTOMS OF ANAPHYLACTIC INCLUDE: flushing Warm Hives Angioedema, swelling of the eyes and lips > - first used epipen of allergic sig M reacKon ↳ (the hold facing ↳ orange , orange tip blue and pull tip to it out bending firmly into the thigh until click push outer sound hold with down sky Without mid pen for several seconds immunotherapy - desensitization (induce IgG instead of IgE Immunotherapy a form of treatment to reduce the allergic reaction Consists of a series of injections with a solution containing the allergens that cause the allergic symptoms Decreases the sensitivity to the allergens Immunotherapy replaced the IgE with the IgG Allergy The hygiene hypothesis living in a clean environment has a better chance of an individual to get an allergic reaction strong relationships bet ween living in cleaning environment with allergies There is a lower incidence if allergy in those living on farms or in rural arsed - more exposure to bacteria and other antigens pet ownerships reduces the prevalence of allergy in kids especially for outdoor dogs by activating the immune system in the right way Lower evidence of allergy in younger children of large families with 3 or more older siblings Repeated exposure to infection from siblings Lower evidence if asthma in children that go to day carer centres - more exposed to infections How to reduce allergies in your kids 1. Have many kids or at least send the only/few children to a day care 2. Let them play in dirt 3. Live on a farm or at least have a pet (pig is better) 4. Breast-feed for at least 6 months 5. Do not smoke