Ch 14 Allergy and Parasites PDF

Ch 14: Allergy and Parasites Immune reactions activated by non-pathogen antigens. Occur on second or subsequent Hypersensitivity Reactions exposures by a sensitized individual. Allergies and immune condi...

Ch 14: Allergy and Parasites Immune reactions activated by non-pathogen antigens. Occur on second or subsequent Hypersensitivity Reactions exposures by a sensitized individual. Allergies and immune conditions cause excessive side effects that destroy host tissues (inflammation) Type I hypersensitivities Drive allergic or atopic responses; not autoimmune Adaptive immune responses directed at Autoimmunity healthy host cells and tissues (type II, III, and IV) Type I: IgE on FceRI receptors bind soluble antigens (allergens) and cause degranulation of mast cells, basophils, and eosinophils. Histamine leads to inflammation. Type II: IgG binds to cell-associated antigens or cell-surface receptors, Hypersensitivity Differences activating complement or altering signaling. Type III: IgG binds to soluble foreign proteins and forms an immune complex that is deposited and tissues. Type IV: CD4 Th1 cells and CD8 Cytotoxic T cells respond to the epitopes of foreign antigens or modified self-proteins. Antigens that elicit an allergic/atopic response Allergens (type I). Small, soluble, dried up proteins that are rehydrated when they contact mucus and release antigens. Mast Cells Primary responders: When IgE binds to FceRI, release histamine and TNF-a to induce allergic inflammation (leaky capillaries → recruit effector cells).  Granulocytes found in mucosal and epithelial tissues. Long-lived and retain memory for antigens. Secondary responders: In late effector phase, release toxic granules Reside in connective tissues of the Eosinophils respiratory, GI, and GU tracts. Found in low numbers due to toxicity Stimulated by IL-5 produced by mast cells and Th2 cells Secondary responders: In late effector phase, recruited to inflamed tissue Basophils and activated via TLRs IL-4 and IL-13 secretion biases T cell differentiation to Th2 and B cell isotype switching to IgE Receptor with very high-affinity for IgE present FceRI on mast cells and basophils. Cross-linking results in degranulation. 1. Sensitization Phases of Type I Hypersensitivity 2. Early Effector 3. Late Effector Initial allergen exposure: Allergens are taken up by dendritic cells and processed, presented to T cells in lymph nodes. Induces differentiation into Th2 cell, Sensitization Phase which activates B cells to isotype switch and produce allergen-specific IgE IgE binds to FceRI on mast cells, priming the site for the secondary response Immediate Effector Phase Re-exposure to allergen causes cross- linking of IgE on mast cells and immediate degranulation. Pre-formed factors like Histamine/TNF-a induce smooth  muscle contractions and inflammation (wheal and flare, recruit more cells) Mast cells secrete IL-4 to recruit Th2 cells and IL-5 to recruit eosinophils. Mast Cells release Lipid Factors (PAF, Leukotrienes, and Prostaglandins), which are more potent and cause mucus secretion. More Th2 cells are activated by antigen-presenting cells with allergen Late Effector Phase bound to FceRI (IL-4 cytokine). Th2 Cells proliferate and secrete IL-5 cytokines, which recruits eosinophils and basophils. IgE binds and activates degranulation of eosinophils, which release toxic proteins. GI tract: Fluid secretion/peristalsis → diarrhea and vomiting Airways: Constriction/mucus Allergic Reaction Effects production → expulsion via coughing, sneezing, etc. Blood vessels: Permeability → edema and inflammation Allergy: IgE mediated response Allergy vs Intolerance (anaphylaxis, urticaria, etc.) Intolerance: Not IgE-mediated (asthma) Allergic Rhinitis Atopic/Allergic Asthma Type I Diagnoses Urticaria Angioedema Atopic dermatitis (eczema) Systemic Anaphylaxis Inhaled allergens activate mucosal mast cells, Allergic Rhinitis causing blood vessel permeability, inflammation, swelling, mucus secretion, etc. Atopic Asthma IgE-mediated response, allergen activates mucosal mast cells, resulting in smooth muscle  contraction and swelling/constriction of airways Urticaria: hives induced by subcutaneous antigen → localized swelling Skin Conditions Angioedema: Activation of mast cells in deeper subcutaneous tissue leads to more diffuse swelling Atopic dermatitis (eczema): Prolonged allergic response of the skin Allergen/antigen enters the bloodstream, spreading to tissues and activating mast cells throughout the body. Heart and circulatory system: vascular Systemic Anaphylaxis permeability, swelling of tissues, anaphylactic shock Respiratory tract: contraction of smooth muscle, constriction of airways, difficulty breathing GI tract: contraction of smooth muscle, vomiting, diarrhea A combination of genes (alleles, pro- Predisposing factors inflammatory genes) and environment (exposure, microbiota) leads to clinical atopy CD4 Th2 cells and mast cells are supposed to protect the body against helminths and Purpose of IgE mediated responses parasites that are too large to be phagocytosed. IgE allows for ejection (sneezing, etc.) The idea that developed countries have increased incidence of atopic disorders due to vaccination, antibiotics, and hygiene. Exposure is limited, so the immune system is Hygiene Hypothesis undeveloped and rarely mounts Th1 and Th17 responses to combat intracellular pathogens. Therefore, differentiation is biased towards Th2, which would normally fight parasites, but is instead stimulated by allergens. Treatments for Atopic Disorders Prevention: Environment modification / behavior (avoidance)  Pharmacological Immunological: Desensitization with allergy shots - allergen-specific immunotherapy (SIT) Helminthic Therapy: Introducting parasitic infections = rare occurence of allergic disease. Biases the immune system to produce parasite-specific IgE. Antihistamines: block histamine from binding H1 receptors, blocking its effects Monoclonal anti-IgE: blocks IgE from Pharmacological treatments binding to FcRs by binding to its constant region (Fc) Lipoxygenase antagonists: Prevents generation of leukotrienes Corticosteroids and epinephrine