Immune System Disorders PDF

Immune system disorder Primary immunodeficiency Immunodeficiency lack of a proper functioning immune system. Primary deficiency Signs & symptoms Primary deficiency is an in born error that Patients wi...

Immune system disorder Primary immunodeficiency Immunodeficiency lack of a proper functioning immune system. Primary deficiency Signs & symptoms Primary deficiency is an in born error that Patients with primary limits the function of the barrier defenses and immondeficiency experience SPUR can lead to deficit immunity Severe, Persistant, Uncommon, Recurring Factors: - Can be treatable but also fatal These are caused by uncommon - Not inherited, but rather a spontaneous agents— often opportunistic pathogens mutation or innate. - Occurs due to 50% of B cells and 30% of T cells Treatment options Types of primary immunodeficinecies Since it’s due to genetics that aren’t inherited Humoral defeciencies this can involve: B cell or antibody defeciency Bone marrow transplant Cellular deficiencies Cytokine therapy Absent thymus or low count of T cells Stem cell transplants Gene therapy Combined (SCID Severe combined immunodefeciencies of both Innate Phagocytes deficiencies Complement proteins Deficiencies of c2, c4, c9  Immune system disorder Secondary immunodeficiency Secondary immunodeficiency Other infectious agents Occurs in individuals who have a healthy Epstein Barr virus immune system and then experiences a Human T cell lymphocyte virus decline in their immune system rigor. These infectious agents can lead to blood Factors: cancer such as leukemia and lymphoma Much more common Occurs due to medical interventions(drugs), Measles systemic disorder(hepatitis, alcoholism, malnutrition), Reduces B and T cell function Suppressed immunity can increase old age, infectious agents other infectious diseases Known as acquired immunodeficiency (tuberculosis) Depends on the underlying issue (kidney problems, liver problems) Measles are less common Elderly patient (Age) Except in developing countries due to vaccine limitations When caring for elderly, it is common to assume that the person has reduced immune function. Forms of medications that cause secondary immunodeficiency (Medications) Cancer treatment(radiation or chemotherapy) Anticonvulsants (antiseizure drugs) Immunosuppressants (chronic inflammation, limit patient transplant rejection/risk, autoimmune disorder Corticosteroids(inflammation and autoimmune disorder) HIV (Infectious agent) Known as human immunodeficiency, HIV infects T helper cells and kills them. Lowers the population needed to kill cytotoxic cells and other abnormal cells AIDS (Acquired immunodeficiency) If one is HIV+, does not mean they have AIDS Enough low number of T cells help develop AIDS Immune system disorder Immunodeficiency can lead to cancer Immune system deficiency can lead to cancer Cancer would be considered a failure of the immune system eliminating abnormal cells Defect can lead to a mass destruction of T cytotoxic tens that eliminate abnormal call causing deficiencies. AIDS patient AIDS patient are more likely to be at risk to have rare blood cancer such as kaposki sarcoma. And other blood cancer Transplant patients Since transplant patients take immunosuppressant antirejection drugs they are 3 times more likely to develop cancer than nontransplant patients. Treatment Cancer treatment is Immunotherapies are anti cancer treatment known as that are geared at boosting immune immunotherapies defenses. Therapeutic: treats existing cancer Prophylactic: treats to prevent cancer Gardasil: vaccine that prevents HPV strains that causes cervical cancer Monoclonal antibody treatment, interleukin, interferon treatments Investigational T cell therapy aim to train T cells and destroy cancer cells  Autoimmune system disorders Lack of self tolerance Autoimmunity: specific immune system attack Autoimmune disorders with possible against healthy self infectious agents association tissues Immune system Type I diabetes attacks insulin Autoimmune disorders: Coxsackievirus B producing cells of the pancreas chronic conditions that develop due to damaged Rheumatoid heart disease Inflammation and scarring of the heart Streptococcus pyogenes self tissues that were attacked. Multiple sclerosis Loss of insulating sheath Why? HSV 6, Epstein barre and 20 more Exposure to possible infectious agents Guillain barre syndrome Peripheral nerves are attacked T and B cell also lack self tolerance Campylobacter jejuni and causes muscle weakness. Systemic vs. localized Systemic affects tissues and organs throughout the body. Localized is towards a specific tissue or organ. E.g. lupus is systemic E.g. rheumatoid arthritis is localized Women make up 80% of inflicted damage and autoimmune disorders. Etiology Can be due to super antigens that activate T cells against self factors. Pathogen may have antigens similar to the host that causes overproduction of antibodies that cross reach with host tissues Inappropriate self antigen presentation  Immune system disorder Introduction to hypersensitivity Hypersensitivity: inappropriate response of the secondary immune response Mediated by antibodies or T cells E.g. allergy and autoimmune disorders Can be localized or systemic Response of the secondary but uses primary immune response factors (coated antigens with antibodies, granulocytes) Uses the cell and comb classification system Type I, II, III mediated by antibodies Type IV mediated by T cells Type is allergies and the rest are associated with autoimmunity Class Type I Type II Type III Type IV Description Allergies Cytotoxic cells Immune complexes Delayed hypersensitivity T cells IgG or IgM interacting IgG or IgM with non soluble interacting with Driven by IgE interacting with soluble or cell antigens on cell surface or extracellular soluble matrix-bound antigens antigens antigens Drugs trigger the response Yes Yes Yes Yes Associated with autoimmunity No Yes Yes Yes Hemolytic disease Serum sickness, Nickel, latex, poison Localized or of newborn, blood autoimmune ivy, tuberculin skin Selected examples systemic transfusion disorders like test reaction, chronic allergies reaction, good lupus, rheumatoid graft rejection, pasture disease arthritis certain autoimmune disorders like MS and hashimoto thyroiditis  Immune system disorder Type I hypersensitivity Type I Includes Allergies and not related to autoimmunity. Type I Hypersensitivity explained Allergen: any antigen that triggers Learning the threat IgE production and leads to allergy 1 Sensitization stage Allergy: immune system fights Antigen/allergen: exposure to the substance triggers off the perceived threat that antigen that trigger IgE production would be harmless Plasma B cells are activated (antibodies) IgE binds to the surface of the mast cells/basophils Examples Atopic asthma 2 postsensitization stage Big react. All allergies Atopic dermatitis (Atopic asthma or A person exposed to the allergen after allergy based eczema) sensitization. The allergen binds to IgE on Allergen exposure mast cell/basophil surface that triggers Body first must encounter the antigen to degranulation trigger the production of antibodies. The allergen exposure that triggers Sensitization heightens immune sensitivity the IgE production is known as Post sensitization is when the immune system sensitizing exposure react to the substance after it has been sensitized. Sensitizing exposure Allergen exposure is when the person comes Degranulation into contact with any substance that triggers Post sensitization allows allergens to the immune system to see it as a threat, even bind to the previous made IgE though it may be harmless. antibodies that are anchored to the mast cell. IgE allergen interaction Can occur on the very first exposure to the antigen causes antibody coated mast cells or surprisingly after many years. and basophils to release Triggers the production of IgE by the immune system proinflammatory factors (histamines, leukotrienes) from their cytoplasmic Risk factors granules Family history of allergies, asthma, or atopic eczema  Immune system disorder Type I hypersensitivity Route of exposure to the allergen can impact allergy symptoms Inhaled allergen = respiratory issues, swollen airways and coughing Ingested and injected food, drugs = skin manifestation(hives), digestive system distress, respiratory distress Type I categories Seasonal allergies Cold like symptoms, ear congestion, sinuses, itchy water eyes Atopic dermatitis Eczema that is itchy, flaky and scaly Atopic asthma Dyspnia, shortness of breath, cough, wheezing, chest tightness Food/drugs allergy Diarrhea, odd taste in mouth, itchy throat, stomach pain, skin rash, hives, swelling, sneezing, coughing The more IgE the body produce, the more severe the symptoms are  Immune system disorder Type I hypersensitivity Anaphylaxis Term used to describe allergic response to an antigen Diagnosing allergies Can be localized or systemic Can be done by looking at signs and Localized anaphylaxis: isolated symptoms through skin and blood test symptoms such as runny nose, watery eyes, sneezing Solutions Confined rash that may Eliminating a single food group and monitor how they feel occur with contact or Can be difficult to track due to multiple seasonal allergy ingredients and potential allergens. Allergen share Systemic anaphylaxis is antigenic features and can generate cross caused by ingested/ reactivity to other allergens inhaled allergens such as E.g. eating pecans but also allergic to walnuts, foods, drugs, insect almonds, cashews though never having them before venoms Use air purifiers, implement house Can be fatal and lead to anaphylactic shock ** cleaning, getting rid of pets Treatment includes EpiPen (auto injector) Blood and skin test Blood test - look for IgE levels, tigers against variety of allergens and how severe the allergen is. Allows to monitor escalation or remission Skin test - screen allergies against food, airborne, contact allergies Fast but itchy and cause lesions Scratch/pricking the skin, patch Wheal and flare is when the test, intradermal tests that lesion is raised, flare is allows patient to be exposed flattened and reddened area to the allergen, waiting and forms checking for skin lesion at Extent of the wheal (flared exposure site. lesion) and flare is measured Desensitization: shifting immune response to allergen by moving from T helper 2 dominated immune response to T helper 1 dominated immune response. Shift in T cells alter the antibodies made to the allergen from IgE to IgG (Least effective against food)  Immune system disorders Type II Type II involves IgG or IgM interacting with nonsoluble antigens on the surface or extracellular environment. E.g. extracellular collagen on connective tissues How Type II reaction causes harm Cytotoxic reactions: cell lysis Complement cascade activation lyses cell and recruits phagocytes to destroy target cell Antibodies directly recruit cells (especially natural killer cells) to lyse tagged extracellular substances/cells **Cytotoxic reactions can be a normal response to foreign antigens E.g. hemolytic disease of newborn, good pasture syndrome, blood transfusion reaction Can also be autoimmune based (rheumatic heart disease, autoimmune hemolytic anemia Complement proteins are made in the liver and are sent to the blood where they are floating around and waiting to be triggered to be active E.g. c2, c4, c9 Complement dependent Complement independent ** Relies on the activation of ** Does not require complement complement proteins to destroy proteins instead cytotoxic target cell immune cells that directly mediate destruction  Complement cascade independent and dependent Immune system disorder Type II Complement cascade activation Recruits phagocytes to destroy target cells and lyse cells. Complement dependent cytolysis Antibodies tag the target cells (antibodies bind on to the target cell surface) Complement proteins are activated due to trigger of antibodies Two possible outcomes: Formation of the membrane attack complex (MAC) MAC is pore that allows water and ions to flow causing cell lysis Or Complement proteins coat the target cells, marking it for destruction by phagocytic cells Combines antibodies (adaptive immunity) with complement proteins (innate immunity) Complement independent cytolysis Antibodies tag the target cells(binds to the target cell surface) Recruitment of immune cells (such as NK cells) that recognize the antibody coated cell through Fc receptors (antibody-binding receptors) Cell lysis NK cells release cytotoxic molecules (perforins, granzymes), leading to apoptosis or lysis of the tagged cell Relies on the collaboration of antibodies and cytotoxic immune cells  Immune system disorder Type II The third way of inflicting damage occurs without cytolysis Antibodies react with cell surface receptor on self cells Antibody-receptor interaction Causes receptor inactivation or overactivation Myasthenia gravis occurs due to Graves’ disease occurs due receptor inactivation to over activation Causes muscle weakness and fatigue Causes overly active thyroid (hyperthyroidism) Nerve ending releases acetylcholine Antibody binding stimulates receptor Antibody blocks acetylcholine from Cell produces too much thyroid hormone binding to its receptor; muscle does not contract  Blood group incompatibility Immune system disorder Type II Blood group incompatibility may lead to a transfusion reaction Blood type Antigens found on the surface of transfused red blood cells If antigens are foreign, a transfusion reaction may occur A, B, O are considered carbohydrates Rh(rhesus factor) is considered a protein Denotion of blood type Find the presence of an carbohydrate followed by presence of an Rh that is a superscript negative or positive sign Those who don’t have A, B, Rh have O antigens AB+ is a universal recipient O- is a universal donor Most common blood types is o+ and A+ A and B is common A and B antigens are common through environment, contact and food. So anyone’s immune system that recognizes the A and B antigens are foreign develops antibodies. Exposure to Rh is not routine so a Rh- negative person would only develop antibodies after exposure to the Rh positive blood Hemolytic transfusion reaction (Red blood cells are lysed) Blood incompatibility causes hemolytic transfusion reaction Signs and symptoms: Fever, chills, lower back pain, constricting chest pain, rapid heart beat(tachycardia), reduced blood pressure, muscle aches Treatment: No treatment, cure or therapies Refer to table 13.5  Immune system disorders Type II Rh factor incompatibility during pregnancy may lead to hemolytic disease of newborn Does not cause serious problems but can cause jaundice in baby Condition that occurs when bilirubin increases as red blood cells are lysed Can lead to brain damage but are modified by the liver Hemolytic disease of the newborn Rh+ baby red blood cells are lysed in response to mothers anti rh antibodies that cross the placenta Occurs when mother has been sensitized to Rh- usually with the first baby that was Rh+ Can be followed by miscarriage, abortion, or after baby is born placenta separates from uterine wall Subsequent pregnancy: pregnancy that occurs after the first pregnancy If the mother had a subsequent pregnancy, IgG antibodies against the Rh factor cross the placenta and target fetus Rh+ red blood cells. Causes fetal red blood cell lysis and may induce a severe fetal anemia In utero signs Fetal tissue edema, enlargement of liver, heart, spleen and yellowing of amniotic fluid If the baby survives Severe jaundice, enlarged spleen, liver, anemia, difficulty breathing, widespread tissue edema Are there ways to prevent sensitization? No but pregnancy must be closely monitored and interventions such as fetal blood transfusion A Rh- women should be prevented from being sensitized to Rh factor Done through Rh(D) immunoglobulins to pregnant Rh- mother  Immune system disorder Type III Characterized by immune complexes Depositing in tissues Makes excessive antigen antibody complexes Deposition into tissue attract complement factor that triggers inflammation Can be autoimmune or normal response IgG or IgM Insoluble antigen antibody complexes form Deposits into tissues attracting complement factors (inflammation) Activates inflammation and recruits leukocytes to tissues Leukocytes release cytokines and promote inflammation Autoimmune type III hypersensitivities Disease Auto-antibodies General features Systemic; manifests with rash Systemic lupus erythematous DNA, ribosomes across cheeks, nose, fatigues, joint pain. Fever, hair loss Rheumatoid arthritis Rheumatoid factor Severe arthritis Attack on connective tissues and all Scleroderma Enzymes or dna rep. organs may be affected; hardened thick skin Sjogrens syndrome Rheumatoid factor Systemic; dry eyes and mouth and may develop with lupus Post streptococcal Antibodies against May develop after untreated glomerulnephritis streptococci cross react streptococcus pyogenes infection with proteins in kidney and can cause renal failure  Immune system disorders Type III Non autoimmune type III Antivenoms: antibody preparation that neutralizes the effects of venom E.g. snakes, scorpions Antitoxins: made using antibodies against toxins Tetanus, botulism, anthrax Potential risk of antivenom and antitoxins Serum sickness: patients immune system recognizes the substance as foreign As antibodies bind to their targets, immune complexes get lodged in blood vessels or joints causing symptoms Rash, dsypnea, joint ache, abdominal pain, headache Monoclonal antibody treatment can cause serum sickness too  Immune system disorders Type IV Mediated by T cells and result in delayed hypersensitivity Manifest slowly over 12-72 hours after the stimulating antigen is encountered Hypersensitivity occurs if it’s directed at self tissues or aimed at harmless substances If the antigen presents self antigen or resembles self antigen, hypersensitivity reaction can occur Autoimmune type IV hypersensitivity Disorders are marked by destruction of specific tissues rather than systemic inflammation seen in type III Disorders Guillan barre syndrome T cells attack nerves that regulate muscle contraction Result in loss of motor function and paralysis Hashimoto thyroiditis T cell mediated attack on thyroiditis Gland is under active Hypothyroidism Type I diabetes Insulin producing cells in the pancreas are destroyed, can’t regain the blood glucose levels Multiple sclerosis Myelin producing cells are damaged Celiac disease Patient T cells attack the lining of the small intestine within 2-3 days of consuming gluten Triggered by haptens Non autoimmune Contact dermatitis from poison ivy , poison oak rash, latex Secondary exposure causes extremely itchy red rash Latex: patients and healthcare providers are getting it due to increased exposure and can be due to gloves everyday that promote dry, cracked skin Transplant rejection and graft versus host disease GVHD occurs in bone marrow transplant where white blood cells made in the transplanted bone marrow attack new body they find themselves inhabiting In transplant, T cytotoxic cells detect tissue is foreign and reject transplant of the tissue Tuberculin skin test Can’t declare if it’s Detects exposure to mycobacterium tuberculosis vaccination or natural PPD (purified protein derivative) is injected into the forearm exposure If induration (hardened, reddened skin) develops and lesions meet a size criterion, test is declared positive Patient had some exposure to tuberculosis antigens