MICR J210 1st Edition Lecture 11 Outline of Last Lecture 1. Two Artificial Methods of Immunity2. Brief History of Immunization3. Effect of immunization in reducing prevalence of disease4. Vaccine Types5. Active Immunization (Vaccine types)6. Live v Killed Vaccines7. General Vaccines Used Routinely8. Vaccine Safety9. Immunization10. Antibody Preparation11. ImmunochromatographyOutline of Current Lecture 1. Hypersensitivities and Diseases Involving Immune Function2. Type 1 Hypersensitivity3. Type 2 Hypersensitivity4. Type 3 Hypersensitivity5. Type 4 Hypersensitivity6. Autoimmune Diseases7. Immunodeficiency DiseasesCurrent LectureHypersensitivities and diseases involving immune functionThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.• Hypersensitivityo Any immune response against a foreign antigen exaggerated beyond the norm Usually against an external antigen (can cause damage to the person)o Four types (all have a different mechanism) Type I (immediate)- Classic allergy- IgE  Type II (cytotoxic)- IgG- Antibodies are formed and bind to cells (blood cells) and fixing complement with the MAC Type III (immune complex–mediated)- IgG- Systemic antigen - Large cross linked immune complexes from food or drug allergiesand they get stuck in the capillaries Type IV (delayed or cell-mediated)- No immunoglobulins- Involves T cells• Type I (Immediate) Hypersensitivityo Localized (in the tissues) or systemic reaction (in the blood stream) that results from the release of inflammatory molecules in response to an antigen Systemic response is known as anaphylaxis o Develops within seconds or minutes following exposure to an antigen Degranulation of mast cells causes responseo Commonly called allergyo The antigens that stimulate it are called allergens Once you have been sensitized to the allergen, the next encounter can cause a reaction• Mechanism Of A Type I Hypersensitivity Reactiono Consists of 2 phases Sensitization- Happens at early exposure to allergen- Sensitizes the individual for subesequent allergic response.- Mast cells (found near entrances of body) bind to IgEo Act as a receptor for the allergen because the IgE are facing outward from the mast cells- Make plasma cells that produce IgE specific for the allergeno Released into the bloodstream Degranulation- Subsequent exposure to allergen causes sensitized effector cells (primarily mast cells) to release granules.o Binds to IgE and causes mast cells to degranulation and release inflammatory mediators Histamines, kinins, proteases, leukotrienes, etc. Mast cells may have several different types of IgE that are specific for several different types of allergens- Induces an inflammatory responseo Happens within seconds- Roles of degranulating cells in an allergic reactiono Degranulation occurs after cells sensitized Mast cells (most important cells) Basophils (can be recruited) Eosinophils (can be recruited)o Degranulation of mast cells releases histamine (most important), kinins, proteases, leukotrienes, and prostaglandins 2 types of responses- Localized (majority) - Systemic Clinical signs of localized allergic reactions- Usually milder and localized- Site of reaction depends on portal of entryo Localized reaction is where the antigen enters the body and binds to the IgE on the mast cells- Small inhaled allergens may reach lungs and cause asthmao Some foods contain allergens- May cause diarrhea and other gastrointestinal signs and symptomso Local dermatitis may produce hives (rash) or urticarialType I (Immediate) Hypersensitivityo Clinical signs of systemic allergic reactions (Anaphylaxis) Occurs when the allergen gets into the blood stream Many mast cells may degranulate at once all over the body, releasing large amounts of histamine and inflammatory mediators- Acute anaphylaxis or anaphylactic shock can result Clinical signs are those of suffocation- Life threatening situation Must be treated promptly with epinephrine- Hormone that is normally released from the adrenal gland- Used in the flight or fight sympathetic response- Restores blood pressure• Diagnosis of type I hypersensitivityo Detection of high levels of IgE against specific allergen Atopic patients are highly susceptible to forming allergies- Gene cluster that contains interleukin 4 (more active transcription of this gene so they have more interleukin being produced than people that are not atopic- Best thing to do is just prevent contact with allergen o Diagnose using skin tests Specific allergens are administered sub-cutaneously and reaction is monitored Inject allergen that has been purified to see if the patient reacts to that antigen Happens within 20 minutes and it immediate hypersentivity • Prevention of type I hypersensitivity (best course of action) Identification and avoidance of allergens Food allergens identified using an elimination diet Immunotherapy (“allergy shots”) can help prevent allergic reactions to allergens you can’t really avoid- Administration of a series of injections of dilute allergeno By injecting the allergen in small quantities in routes that differ from how you normally encounter the allergen, youmay end up with a different immune response The goal it to produce IgG instead of IgE You want to neutralize the allergen with IgG before it has a chance to hit the mast cells- Must be repeated every two to three years• Treatment of Type I Hypersensitivityo Administer drugs that counteract inflammatory mediatorso For localized response Antihistamines neutralize histamine Treat asthma with a corticosteroid and a bronchodilator- Steroids reduce prostaglandin production- Bronchodilators relax smooth muscle to allow airflow to the lungso For systemic response Epinephrine neutralizes many mechanisms of anaphylaxis- Relaxes smooth muscle- Reduces vascular permeability- Used in emergency treatment of severe asthma and anaphylacticshock- Restores Blood PressureType II (Cytotoxic) Hypersensitivityo Results when cells are destroyed by an immune response Often the combined activities of complement and antibodies Formation of the MAC A component of many autoimmune diseaseso Two significant examples Destruction of blood cells following an incompatible blood transfusion- Mismatched blood types Destruction of fetal red blood