MICROB 3200 1nd Edition Lecture 7 Outline of Current Lecture • Describe hypersensitivities and the classification system used for the four types of hypersensitivity reactions – discuss the immune mechanisms involved in each type• Discuss autoimmune diseases that target individual tissues vs. systemic responses and how hypersensitivity reactions contribute to autoimmune responses• To discuss how immunodeficiencies can affect various aspects of immune responsivenessHypersensitivityDef: A pathological immune response upon repeat exposure to an antigen.Common general features:Antigens can be exogenous (pathoghens, dust, food, pollen, drugs,etc…)Antigens can be endogenous tissue antigens (autoimmune responses)Can be linked to inheritance of genetic susceptibility ( for example: MHC, cytokine receptors, estrogen and others) Result from an imbalance of effector and regulatory immune responseThe Characteristics of the Four Types of Hypersensitivity ReactionsType I (Immediate) HypersensitivityLocalized or systemic reactions that results from the release of inflammatory molecules in response to an antigenDevelop within seconds or minutes following exposure to an antigenCommonly called allergies and the antigens that stimulate them are called allergensThese 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.Type I: AllergyDoubled in US since 197054% of people tested were positive to at least one of 10 allergens27.5% responded to dust mite8.6% responded to peanuts20% of US residents have allergies or hay fever8-10% have asthmaCauses:Genetic susceptibility.Atopic individuals have higher serum IgE and more IL-4 producing TH2 cells.These have been linked to cytokine and MHC loci.Other causes:Hygiene hypothesis Lack of vitamin D Age related dietary consideration2ND Exposure Results in DegranulationType II (antibody mediated) HypersensitivityResults when cells are destroyed by an immune response, often due to the combined activities of complement and antibodiesIs a component of many autoimmune diseases2 significant examples non autoimmune examples:Destruction of blood cells following an incompatible blood transfusionDestruction of fetal red blood cells in hemolytic disease of the newbornABO Blood Group Characteristics and Donor/Recipient MatchesRH System and Hemolytic Disease of the NewbornBased on the rhesus, or Rh, antigenAntigen that is common to the red blood cells of humans and rhesus monkeysTransports anions and glucose across the cytoplasmic membraneRh positive (Rh+) individuals have the Rh antigen on their red blood cells while Rh- individuals do notPreexisting antibodies against Rh antigen do not occur in Rh- individualsRisk of hemolytic disease of the newbornDrug-Induced Type II ReactionsSome drug molecules can spontaneously bind to blood cells or platelets, modify ‘self’ and stimulate the production of antibodies.Can produce various diseases Immune thrombocytopenic purpuraAgranulocytosisHemolytic anemiaType III (Immune-Complex Mediated) HypersensitivityDue to the formation of antigen-antibody complexes, also called immune-complexesCan cause systemic or localized reactionsSystemicSystemic lupus erythematosusRheumatoid arthritisLocalizedHypersensitivity pneumonitisGlomerulonephritisType III HypersensitivityExamples of immune complex mediated disease: target antigen; pathologySLE: (autoimmune) ANA antibodies; nephritis, skin lesions arthritis, others.Polyarteritis nodosa: e.g., Hepatitis B antigens; systemic vasculitis.Reactive arthritis: bacterial antigens (e.g., Yersinia toxins), acute athritis.Type IV (Delayed or Cell-Mediated) HypersensitivityInflammation due to contact with certain antigens. Results from the interactions of antigen, antigen-presenting cells, and T cellsDelay in the response reflects the time required to allow for macrophages and T cells to migrate and proliferate at the site of the antigenAllergic Contact DermatitisA cell-mediated immune response resulting in an intense irritating skin rashResponse triggered by chemically modified skin proteins that the body regards as foreignCan happen when a hapten, such as the oil from poison ivy and related plants, binds to proteins on the skinIn severe cases, CTL cells destroy so many skin cells that acellular, fluid-filled blisters developOther haptens include formaldehyde, cosmetics, and chemicals used to produce latexExamples: T cell target; pathologyContact sensitivity: various environmental antigens, such as the oil from poison ivy and related plants, binds to proteins on the skin; skin inflammation and blisters.Type I diabetes (autoimmune): pancreatic islet β cell antigens; insulitis, destruction of islet cells and diabetesMultiple sclerosis (autoimmune): CNS myelin proteins; demyelination, paralysis ocular lesions.Rheumatoid arthritis (autoimmune): unknown antigen; chronic arthritis with inflammation, cartilage and bone destruction.Autoimmune diseases individual tissue vs. systemic responses and how hypersensitivity reactions contribute to autoimmune responsesAutoimmune DiseaseThe phenomenon of autoimmunity - whereby the body produces antibodies, CD4 and cytotoxic CD8 T cells that target normal body cellsMost autoimmune diseases appear to develop spontaneously and at random (…ummm sort of…)Some common features of autoimmune disease have been notedOccur more often in older individualsMore common in women than menCategories of Autoimmune DiseaseTwo major categoriesSingle tissue diseasesSystemic diseasesSingle Tissue Autoimmune DiseaseCan commonly affect various tissuesBlood cellsEndocrine glandsNervous tissueAutoimmunity Affecting Nervous TissueMultiple sclerosis T cells attack and destroy the myelin sheath that insulates the brain and spinal cord neurons andincreases the speed of nerve impulses along the neuronsResults in deficits in vision, speech, and neuromuscular functionMay be triggered by a viral infectionSystemic Lupus Erythematosus (SLE)Generalized immune disorder that results from a loss of control of both humoral and cell-mediated immune responseAutoantibodies against DNA (other nuclear antigens) result in immune complex formationDeposition of complexes in the skin result in a characteristic butterfly-shaped rash for which the disease is namedComplexes deposit in glomeruli and cause glomerulonephritisComplex deposition in the joints results in arthritisImmunodeficiencies are bad for