L 16 - Types of Immune Response 1 and 2 PDF

16 Types of immune response: Type I & II hypersensitivity reactions ILOs By the end of this lecture, students will be able to  Distinguish etiology, morphology and pathogenesis of types I and II of hypersensitivity reactions.  Apply types I and II reactions to corresp...

16 Types of immune response: Type I & II hypersensitivity reactions ILOs By the end of this lecture, students will be able to  Distinguish etiology, morphology and pathogenesis of types I and II of hypersensitivity reactions.  Apply types I and II reactions to corresponding clinical conditions as anaphylaxis, allergy, and blood groups incompatibility. Introduction; Abnormal immunological responses comprise the following; o Hypersensitivity Reactions o Autoimmune reaction o Immunodeficiency Hypersensitivity Reactions, A “hyper” or exaggerated response to what should be considered harmless antigens.  Hypersensitivity implies an excessive or harmful reaction to an antigen attributable to imbalance between effector and regulatory mechanisms. It affects individuals who have been previously exposed to an antigen and manifest detectable reaction to that antigen and are therefore said to be sensitized.  Hypersensitivity reactions can be elicited by exogenous environmental antigens (microbial and nonmicrobial) or endogenous self-antigens. The development of hypersensitivity diseases (both allergic and autoimmune) is often associated with the inheritance of particular susceptibility genes.  Hypersensitivity reaction Types I, II, and III are immediate \chemical reactions occurring within 24 hours, whereas, Type IV\ cellular reaction develops over several days.  Classification of Hypersensitivity Reactions Type I hypersensitivity reaction (atopy/ Allergy): - It is a rapidly developing [ immediate type] immunologic reaction occurring after the combination of an antigen with immunoglobulin E (Ig E) bound to mast cells in individuals previously sensitized to the antigen. It is also known as anaphylactic reaction or allergy. - (Allergy): an abnormal adaptive immune response that may or may not involve antigen-specific IgE. 1 - Genetically determined susceptibility to allergic reaction, is called (Atopy), affected patients show increased titer of serum IgE and increased IL-4 secreting TH2 lymphocytes. Patient is usually susceptible to allergic diseases such as allergic rhinitis, asthma, atopic dermatitis and others. Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens. It also has familial association. - Antigen; Exogenous environmental antigens(allergens) present on the outer surface of epithelial surfaces or skin, such as pollen grains, dandruff, dusts, food components etc. - Antibody; Immunoglobulin E, which is dependent upon the Th-2 helper cells stimuli. - Effector cells; Mast cells in the tissue and basophil in the blood. - Effector chemical mediators; histamine, leukotrienes, prostaglandins, eosinophils and platelets activating factors. Mechanism of Type I hypersensitivity reaction: the reaction occurs in an early and a late phases. Early phase reaction; develop 5–30 minutes after exposure to antigens, initiated by the introduction of an allergen, which stimulates T helper-2 and IgE production in genetically susceptible individuals. IgE binds to Fc receptors on mast cells, this reaction has no clinical manifestation. On subsequent exposure to the allergen, binding of antigen to IgE activates the mast cells to degranulate and secrete the primary mediators [shown in the figure] that are responsible for the pathologic clinical manifestations of immediate hypersensitivity as redness, swelling, edema, increased secretion and smooth muscle contractions. Late-phase reaction; develop 4–12 hours after the early phase and are mediated by eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells. TH2 cytokine IL-5 is the most potent eosinophil-activating cytokine. They cause tissue damage and late- phase inflammatory reaction. Clinical examples: 2  i. Systemic anaphylactic reaction; Anaphylactic shock: a fatal state. Occur in sensitized individuals following injection of foreign proteins (e.g., antisera), hormones, enzymes, polysaccharides, and drugs (e.g., the antibiotic penicillin), exposure to food allergens (e.g., peanuts, shellfish) or insect toxins (e.g., those in bee venom) - Clinically presentation; Itching, hives, and skin erythema, followed shortly by a striking contraction of respiratory bronchioles and respiratory distress, Laryngeal edema results in hoarseness and further compromises breathing. ii. Localized hypersensitivity: often involving epithelial surface at the site of allergen entry; Hay fever (Allergic rhinitis; redness, sneezing, runny nose), bronchial asthma and bronchospasm (allergic or intrinsic), Food allergy (colic and diarrhea), and atopic dermatitis (eczema, urticaria), and allergic conjunctivitis (redness, itching and tearing. N.B; type I reaction plays a defensive role against parasitic infestations. Type II Hypersensitivity Reaction\ cytotoxic hypersensitivity; Antibodies react with antigens present on cell surfaces or in the extracellular matrix cause disease by destroying these cells, triggering inflammation, or interfering with normal functions. Antigen may be: 1. Exogenous : Microbes, parasites, drugs. 2. Endogenous: Autoimmune diseases, and these are self-Ag. Antibody: This is mainly IgG and occasionally IgM. The effector cells are macrophages, neutrophils, eosinophils, and NK (natural killer) cells. Mechanism of Type II hypersensitivity reaction: Binding of antibody (IgM or IgG) to the antigen on the cell surface or other tissue component leading to either 1) cell destruction or 2) altered function Three mechanisms are involved: 1. Opsonization and phagocytosis 2. Complement- and Fc receptor-mediated inflammation 3. Antibody-mediated cellular dysfunction A-Opsonization and phagocytosis; Antibodies coat exogenous\endogenous cell-surface molecules such as antigens associated with blood typing found on red blood cells (RBCs). Coating of the RBCs by antibodies (opsonization), lead to activation of the complement cascade, and complement-mediated lysis of RBCs, as well as opsonization of RBCs for phagocytosis. 3 Clinical Examples; 1. Hemolytic transfusion reaction associated with mismatched blood transfusion reaction. 2. Hemolytic disease of the newborn (erythroblastosis fetalis), in which there is an antigenic difference between the mother (RH -ve) and the fetus (RH+), and IgG anti-erythrocyte antibodies from the mother cross the placenta and cause destruction and hemolysis of fetal red cells. 3. Autoimmune anemia (against RBCs). 4. Drug reaction B- Complement- and Fc receptor-mediated inflammation; antigen-antibody binding leads to activation of complements, recruitment of neutrophils and macrophages mediating an acute inflammatory reaction through the release of proteases and reactive oxygen species. Clinical Examples; transplant organ rejection reaction, skin rash due to drug reaction. C-Antibody-mediated cellular dysfunction; Autoantibodies bind to cell-surface receptors [ recognized as foreign by immune system] to produce an abnormal activation/blockade of the signaling process. Clinical Examples; abnormal activation (Grave’s disease), abnormal blokage : Myasthenia Gravis. 4