16.7 Innate/Adaptive Immunity, Pathology/Infection/Disease, Microorganisms & Human Disease, Environmental Microbiology

Innate & Adaptive Immunity, Infection/Disease, and Environmental Microbiology

Quick Answer: The Bulletin's "interaction between microbe and host" group ends with immunity (innate vs. adaptive), the infection-disease distinction, common microorganisms and human disease by organ system, and environmental microbiology including normal flora. Expect questions that link a pathogen to the immune mechanism that clears it and to the clinical syndrome it produces.

Innate Immunity

Innate immunity is the first line of defense — rapid, non-specific, and without immunologic memory.

• Physical barriers: skin, mucociliary escalator of the respiratory tract, mucus, gastric acid, urinary flow.
• Chemical barriers: lysozyme in tears/saliva (cleaves bacterial peptidoglycan), defensins (antimicrobial peptides), low pH of skin and stomach.
• Complement system: a cascade of plasma proteins activated by three pathways — classical (antibody-antigen complex), alternative (spontaneous hydrolysis of C3 on microbial surfaces), and lectin (mannose-binding lectin). The common endpoint is the C3 convertase, leading to opsonization (C3b), inflammation (C3a/C5a), and membrane attack complex (C5b-9) lysis of Gram-negative bacteria.
• Phagocytes: neutrophils (first responders, short-lived, pus-forming) and macrophages (tissue-resident, antigen presentation) ingest and kill microbes via reactive oxygen species (respiratory burst, NADPH oxidase — deficient in chronic granulomatous disease) and lysosomal enzymes. Dendritic cells bridge innate and adaptive immunity by presenting antigen to T cells.
• Natural killer (NK) cells kill virus-infected and tumor cells lacking MHC class I, regulated by activating and inhibitory receptors.
• Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) detect pathogen-associated molecular patterns (PAMPs): TLR4 recognizes LPS, TLR2 recognizes lipoteichoic acid, TLR3 recognizes dsRNA, TLR7/8 recognize ssRNA, TLR9 recognizes unmethylated CpG DNA.

Adaptive Immunity

Adaptive immunity is specific, slower (days), and generates memory.

B cells mature in the bone marrow and produce antibodies (immunoglobulins):

• IgM — first produced, pentamer, primary response, efficient complement activator.
• IgG — most abundant serum antibody, crosses placenta (passive neonatal immunity), opsonization and complement fixation.
• IgA — dimer with secretory component, protects mucosal surfaces; found in breast milk, saliva, tears, gut.
• IgE — binds mast cells and basophils; mediates type I hypersensitivity and defense against helminths.
• IgD — B cell receptor function.

B cell responses are T-dependent (protein antigens, germinal center class switching and affinity maturation, memory) or T-independent (polysaccharide antigens like pneumococcal capsule, weaker memory — reason for conjugate vaccines that convert polysaccharide to T-dependent).

T cells mature in the thymus, where positive and negative selection establish self-tolerance. CD8+ cytotoxic T cells kill virus-infected cells via perforin/granzyme and Fas-FasL. CD4+ helper T cells coordinate responses: Th1 (intracellular pathogens, IFN-γ, macrophage activation), Th2 (helminths and allergy, IL-4/IL-5, eosinophils and IgE), Th17 (extracellular bacteria and fungi, IL-17, neutrophil recruitment), and Treg (FoxP3, immune tolerance, IL-10/TGF-β).

Antigen presentation: MHC class I presents endogenous peptides (viral, tumor) to CD8+ T cells; MHC class II presents exogenous peptides (phagocytosed pathogens) to CD4+ T cells. Hypersensitivity types I–IV (Gell and Coombs) connect to disease: type I (IgE, anaphylaxis), type II (IgG antibody to cell, hemolytic anemia), type III (immune complexes, glomerulonephritis, SLE), type IV (delayed T cell–mediated, TB skin test, contact dermatitis).

Infection, Colonization, and Disease

• Colonization: microbe present without harm (e.g., S. aureus in nares).
• Infection: microbe established and possibly causing immune response but not always symptoms (latent TB).
• Disease: clinically apparent damage (active TB with cough, fever, weight loss).
• Pathogenicity: capacity to cause disease; virulence: degree of that capacity.
• Carrier state: host harbors pathogen asymptomatically and can transmit (typhoid Mary, HBV chronic carriers).

Microorganisms and Human Disease — Organ System Map

Environmental Microbiology

Normal (resident) flora colonize skin, oral cavity, GI tract, and vagina without causing disease and compete with pathogens via microbial antagonism (competition for receptors and nutrients, bacteriocin production, low pH). Disruption (broad-spectrum antibiotics) allows overgrowth of pathogens like Clostridioides difficile (pseudomembranous colitis) and Candida. The gut microbiome synthesizes vitamin K and short-chain fatty acids and educates the immune system.

Environmental microbes drive biogeochemical cycles: nitrogen-fixing bacteria (Rhizobium), nitrifiers, denitrifiers; carbon cycling via decomposers; sulfur cycling. Extremophiles inhabit hot springs, deep-sea vents, and salt flats. Water microbiology uses indicator organisms (E. coli, coliforms) to assess fecal contamination. Food microbiology includes fermentation (lactobacilli in yogurt, Saccharomyces in bread/beer) and food spoilage. In healthcare, environmental reservoirs (water systems, medical devices) are sources of Legionella and Pseudomonas outbreaks.

This microbe-host-environment triangle is the organizing frame PA-CAT uses: a microbe's structural identity, its virulence and transmission, the host immune response it triggers, the clinical syndrome it produces, and its environmental reservoir all feed into the same diagnostic reasoning.