Lung Microbiome - The dysbiosis-inflammation cycle. Inflammation of the airways alters environmental growth conditions of airway microbiota via positive and negative selective pressures. Disordered growth conditions result in a disordered microbiome, which provokes further airway inflammation via pathogen-associated molecular pattern (PAMP)–pattern recognition receptor (PRR) interactions, via microbial metabolite signaling to leukocytes and epithelial cells, and via other pathways. This cascade results in a self-amplifying cycle of airway inflammation and respiratory dysbiosis. #Lung #Microbiome #dysbiosis #inflammation #cycle #pathophysiology #pulmonary

Inflammatory Cascade: Pathogenesis and Clinical Findings Continued Innate Immunity • Phagocytosis: (main mechanism) neutrophils and macrophages engulf foreign pathogens and dead tissue • Complement System: opsonize pathogen (tag for destruction), promote inflammation • Natural Killer Cells: perforin-mediated wall breakdown (puncture holes), enzyme-mediated destruction Acquired Immunity Recruitment • Humoral: (B cell response) production of antibodies, activation of complement system • Cell-mediated: (T cell response) Increased helper cell and cytotoxic cell activity #Inflammatory #Cascade #Inflammation #pathophysiology #immunology

Type IV Hypersensitivity: Pathogenesis and clinical findings Definition: Unique because it is entirely T-Cell mediated; exposure to allergen causes development of allergen-specific T-Cell response. Allergic reaction develops several days after exposure, because T-Cell activation takes time. Initial exposure to allergen (typically a drug) -> Macrophage engulfs antigen -> Antigen presentation on MHC II molecule -> Particular CD4+ Th cells recognize antigen on allergen's surface as potentially harmful -> Th Cells activate macrophages, mast cells or CTLs -> Inflammation and destruction of involved issue => • Stevens-Johnson Syndrome • Contact Dermatitis (Ex. Poison ivy) #TypeIV #Type4 #HypersensitivityReaction #Allergy #Immunology #pathophysiology

Type I Hypersensitivity: Pathogenesis and clinical findings Definition: Production of lgE Antibodies that bind to harmless allergens and induce mast cell degranulation, leading to an allergic reaction. "Sensitization" to Allergen: Initial exposure to allergen (ex. dust, pollen, foods, drugs) -> Patient's immune system mistakenly recognizes allergen as potentially harmful -> Formation of allergen-specific plasma cells that secrete lgE-antibodies -> Allergen-specific lgE Abs persist in body after clearance of allergen Second Exposure to Allergen: Pre-formed lgE binds allergen, creating an allergen-antibody complex -> Allergen-antibody complexes bind to mast cells, causing them to "degranulate": release the pro-inflammatory molecules within them (i.e. histamine) into the blood => • Increased Vascular permeability • Smooth muscle contraction in airways • Mucus secretion • Inflammatory cells recruited Complications: • Acute Asthma • Antibiotic Allergies (ex. penicillin & cephalosporin) • Food Allergies (ex. peanuts) • Hay fever (allergic rhinitis to airborne particles like pollen & dust) • Urticaria (hives) • Allergic conjunctivitis • Anaphylaxis #TypeI #Type1 #HypersensitivityReaction #Allergy #Immunology #pathophysiology