Hypersensitivity PDF

Bana What’s Hypersensitivity? What happens in Sensitization/first exposure? Potent immunological reaction, leading to tissue damage 1. APC bind to naïve T cells and it’s seen in autoimmune disease, allergy and other 2. Naïve T cells are activated into TH2...

Bana What’s Hypersensitivity? What happens in Sensitization/first exposure? Potent immunological reaction, leading to tissue damage 1. APC bind to naïve T cells and it’s seen in autoimmune disease, allergy and other 2. Naïve T cells are activated into TH2 cells immunopathology 3. TH2 cells produce IL-4 and IL-5 / 3. IL-4 → activates naïve B cells and makes them An exaggerated response by the immune system to a secrete IgE drug or other substance. 4. IL-5 → stimulates activation of eosinophils 4. IgE bind to Fcε receptors on mast cell What is the classification of hypersensitivity reactions? 5. mast cells secrete histamine, tryptase and other inflammatory mediators and they stimulate leukotrienes and 1. Type I Immediate hypersensitivity (IgE) cytokines 2. Type II Antibody mediated cytotoxicity 3. Type III Immune complex deposition What happens in the Second exposure? 4. Type IV Delayed hypersensitivty (cellular) Early/ acute phase (minutes after exposure): What are the IgE mediated diseases? 1. Antigen binds to IgE on mast cell and cause cross- linking of IgE 1. Rhinitis 2. The cross-linking signals the mast cell to 2. Asthma degranulate and release histamine 3. Urticaria 3. Histamine increases vascular permeability 4. Angioedema Late phase (6-12 hours): 5. Anaphylaxis 1. Leukotrienes and cytokines attract monocytes, 6. (Eczema) eosinophils and T cells to the site of inflammation 2. Eosinophils prolong inflammatory response What is Atopy? Explain hypersensitivity II: the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema), Activation of the complement system (IgM and IgG): and is a predisposition to generate IgE-mediated 1. MAC responses to environmental allergens 1. Complement proteins form Membrane Attac Complex (MAC) what are the common sources of Allergens? 2. MAC will cause cell lysis 2. Activation of macrophages → phagocytosis 1. Inhaled materials No complement system: 2. Injected materials 1. Antibody Dependent Cell mediated Cytotoxicity 3. Ingested materials (ADCC): 4. Contacted materials 1. IgE activate Eosinophils → eosinophils release inflammatory mediators → cell lysis What are the phases of IgE mediated response? 2. IgG activate Neutrophils and Monocytes → they release inflammatory mediators → cell 1. Sensitization/first exposure lysis 2. Second exposure: 2. Antibodies against cell surface receptors 1. Early/Acute phase of response 2. Late phase of response Autoantibodies are antibodies that react with self- antigens Bana What are the diseases related to hypersensitivity II? Serum sickness: 1. Autoimmune cytopenias 2. anti-GBM disease 3. Hashimoto’s thyroiditis → Autoantibodies 4. Rheumatic fever 5. Hyperacute transplant rejection 6. Hemolytic anemia 7. Myaesthenia gravis 8. Graves Disease How can Type II Hypersensitivity block the receptor? Like what happens in Myaesthenia gravis: Antibody to the acetylcholine receptor bind to Ach receptor → ACh cant bind to ACh receptor → Motor nerve cannot signal to muscle to contract. What happens in Graves Disease? Form of hyperthyroidism, Antibody binds to TSH- receptor → which cause thyroid hormone Arthus reaction: overproduction Explain hypersensitivity III: an abnormal immune response is mediated by the formation of antigen-antibody aggregates called "immune complexes" the Complement system is activated e.g. Systemic lupus erythematosus (SLE), Rheumatoid vasculitis, Serum sickness explain what happens in Serum sickness? During serum sickness, the immune system falsely identifies a protein in antiserum as a harmful substance Explain hypersensitivity IV (1 to 4 days → (antigen). The result is an immune system response that delayed): attacks the antiserum 1. Antigen presented to T cells What happens during Arthus reaction? 2. T cell activated 3. They secrete IL-12 An Arthus reaction is the result of a localized 4. IL-12 activate Th1 inflammation of the small vessels (i.e., vasculitis) near 5. Th1 secretes interferon (IFN-) the injection or bite site. 6. IFN- activates macrophages 7. Macrophages form Granuloma e.g. Rheumatoid arthritis cellular rejection Bana