Infectious disease

Question 1

What are the routes of entry of microbes in the body?

Answer 1

1. Skin - with direct breach (e.g. schistosomiasis) or skin damage allowing access of less virulent organisms (e.g. burns, IV lines, bites)
2. GIT - with low gastric acidity, antibiotics that alter normal flora, loss of pancreatic function or diminished bowel motility
3. Resp tract - with disrupted mucociliary clearance (e.g. smoking) or ineffective macrophage clearance (e.g. TB)
4. Urogenital tract - with bladder atonia, flow obstruction or reflux, antibiotics which kill lactobacilli and render vagina susceptible to candidate infection

Question 2

How are microbes transmitted?

Answer 2

• Person-to-person: respiratory, faecal-oral, sexual or transplacental
• Animal-to-human: direct contact or ingestion
• Insect or arthropod vectors: passive infection or as host for pathogen replication

Release of microbes from the body - skin shedding, coughing, sneezing, urinary or faecal voiding, sexual contact, or insect or animal vectors

STIs - risk groups, sexual practices, co-infection by other agents, pregnancy (maternal-to-foetal spread in utero or at delivery)

Nosocomial infections - more likely to be drug-resistant, commonly via hands or contaminated surfaces, blood transfusion and organ transplantation rare

Question 3

How do micro-organisms cause damage to host tissues?

Answer 3

• Entering cells and directly causing cell death
• Releasing toxins that kill cells
• Releasing enzymes that degrade tissue components
• Damaging blood vessels, causing ischaemic necrosis
• Inducing host inflammatory cell responses that directly/indirectly injure tissues

Question 4

What are the mechanisms of viral injury?

Answer 4

Viral tropism (predilection for infecting specific cell types) influences what tissues will be injured, e.g.

• Binding to specific cell surface proteins
• Cell-type-specific proteases to enable binding
• Cell-type-specific transcription factors
• Physical barriers, local temperature, and pH

Once inside cells, viruses damage or kill host cells by:
• Direct cytopathic effects
• Inducing an anti-viral host immune response
• Transformation of infected cells

Question 5

What are the mechanisms of bacterial injury?

Answer 5

1. Bacterial adherence to host cells: often first step is binding to specific host cells or matrix via surface adhesins, or pili
2. Virulence of intracellular bacteria: can kill host cells by rapid replication and lysis (e.g. Shigella, E. Coli), or maintain host cell viability while evading intracellular defences and proliferating within endosomes (M. tuberculosis) or cytoplasm (L. monocytogenes)
3. Bacterial toxins:
   a) Endotoxin - LPS is a cell wall component of G -ve bacteria composed of lipid A and O Ag. High doses of lipid A contribute to septic shock, DIC and ARDS
   b) Exotoxins - secreted by the bacteria damage host tissues by:
   • Enzymes destroy tissue integrity by digesting structural proteins
   • Exotoxins alter intracellular signaling, e.g. diphtheria, cholera
   • Neurotoxins block neurotransmitter release and cause paralysis, e.g. botulism, tetanus
   • Superantigens stimulate massive T-cell proliferation and cytokine release, e.g. Staph aureus TSS

Question 6

How do host immune responses to microbes cause injury?

Answer 6

• Granulomatous responses can cause secondary tissue damage and fibrosis, e.g. M. tuberculosis
• Immune destruction of infected hepatocytes following HBV infection
• Abs directed against bacterial Ags may cross-react with host molecules (e.g. rheumatic heart disease), or may form immune complexes that lodge in vascular beds (e.g. post-strep GN)
• Chronic inflammation and epithelial injury may lead to malignancy (e.g. H. pylori and gastric ca)

Question 7

How do microbes evade host immunity?

Answer 7

• Replication in sites inaccessible to host immune response (e.g. Cl. difficile replicates in SB lumen), or rapid invasion of host cells immune responses become effective (e.g. malaria sporozoites entering hepatocytes)
• Constantly changing surface Ags (e.g. HIV)
• Escaping phagocytosis or complement-mediated lysis (e.g. pneumococcus)
• Inhibiting innate immune mechanisms
• Decreased recognition of infected cells by T-cells, or compromising lymphocyte function