Host Damage by Microbes | Chapter 8 | ROBBINS PATHOLOGY Based Audio Podcast
ROBBINS PATHOLOGY CHAPTER 8 - Infectious Diseases Host Damage by Microbes - Microbes damage host tissues through three principal mechanisms: direct interaction causing cell death or transformation, the release of toxins and enzymes, and the provocation of host immune responses that inadvertently injure tissue. Mechanisms of Viral Injury Viral pathogenesis relies on tropism, the specificity for certain cells determined by viral surface proteins binding to host receptors (e.g., HIV gp120 binding CD4) and physical factors like temperature,. Once inside, viruses exert direct cytopathic effects by inhibiting critical host macromolecule synthesis (DNA, RNA, proteins), producing toxic viral proteins, or triggering apoptosis,. Conversely, some viruses prevent apoptosis to ensure their own replication. Crucially, the host's attempt to clear the virus can cause significant damage; viral proteins displayed on cell surfaces mark the cell for destruction by cytotoxic T lymphocytes (CTLs). Furthermore, oncogenic viruses may transform cells into malignant neoplasms by expressing viral oncogenes or inactivating host tumor suppressors. Mechanisms of Bacterial Injury Bacterial damage is driven by virulence genes, often clustered in "pathogenicity islands" or transmitted via mobile plasmids,. • Adherence and Invasion: Bacteria attach to host cells using surface proteins called adhesins and filamentous pili,. Intracellular bacteria have evolved to survive phagocytosis: Mycobacterium tuberculosis blocks phagosome-lysosome fusion to replicate within macrophages, while Listeria monocytogenes escapes the phagosome to multiply in the cytoplasm and spread directly to neighboring cells. • Toxins: Bacterial toxins are classified as endotoxins or exotoxins. ◦ Endotoxin: The Lipid A component of lipopolysaccharide (LPS) in the outer membrane of gram-negative bacteria acts as an endotoxin. It binds to CD14 and Toll-like receptor 4 (TLR4) on host immune cells, inducing the release of high levels of cytokines (TNF, IL-6) which can lead to septic shock and organ failure,. ◦ Exotoxins: These secreted proteins include enzymes that degrade tissue (e.g., proteases causing scalded skin syndrome), A-B toxins that alter intracellular signaling (e.g., neurotoxins causing paralysis), and superantigens that nonspecifically activate massive numbers of T lymphocytes, causing systemic inflammation,. • Quorum Sensing and Biofilms: Bacteria regulate virulence gene expression based on population density (quorum sensing), allowing them to coordinate toxin production or biofilm formation. Biofilms protect bacteria from immune effectors and antibiotics, complicating infections like endocarditis. Injurious Effects of Host Immunity The immune response is often a major source of tissue injury. The granulomatous reaction required to sequester M. tuberculosis can destroy lung parenchyma and cause fibrosis. Cross-reactive antibodies (molecular mimicry) can lead to post-streptococcal rheumatic heart disease, while immune complex deposition causes glomerulonephritis. Finally, chronic inflammation driven by persistent infections (e.g., H. pylori, Hepatitis B) promotes the development of cancer. Analogy: One might view host damage by microbes like a bank robbery. The damage comes from the robbers themselves breaking vaults (direct cytopathic effects/enzymes), the explosives they bring to breach defenses (toxins), and the collateral damage caused by the police shootout trying to stop them (injurious host immunity).
