General principles of microbiology

ACEM Primary

Table of Contents

Routes of Entry

Site	Local defences	Basis for failure	Pathogens
Skin	Epidermal barrier	Mechanical defects Needlestick Bites Direct penetration	S aureus, Candida, P aeruginosa HIV, hepatitis virus Yellow fever, Plague, Lyme disease, Malaria, Rabies Schistosoma
GIT	Epithelial barrier Acidic secretions Bile and pancreatic enzymes Normal protective flora	Attachment and local proliferation/ invasion of microbes Uptake through M cells Acid resistant eggs/ cysts Resistant microbial external coats Broad spectrum Abx use	Vibrio cholera, Giardia, Shigella, Salmonella, Campylobacter Poliovirus Protozoa, helminths Hepatitis A, rotavirus, norovirus Clostridium difficile
Resp tract	Mucociliary clearance Resident alveolar macrophages	Attachment and local proliferation of microbes Ciliary paralysis by toxins Resistance to killing by phagocytes	Influenza viruses H influenzae, M pneumoniae, Bordtella pertussis M tuberculosis
Urogenital tract	Urination Normal vaginal flora Intact epidermal/ epithelial barrier	Obstruction, microbial attachment, local proliferation Antibiotic use Direct infection/ local invasion Local trauma	E Coli, N gonococcus Candida Herpes virus, syphilis Various STI (HPV)

Transmission of infection can occur by contact (direct/ indirect), respiratory route, faecal- oral route, sexual/ vertical transmission and insect/ arthropod vectors
Pathogen can establish infection if it possesses virulence factors that overcome normal host defences or if defences are compromised
Host defences:
- Skin = tough keratinised barrier, low pH, fatty acids
- Resp = alveolar macrophages, mucociliary clearance, Ig A
- GI = acidic gastric pH, viscous mucous, pancreatic enzymes + bile, defensins, IgA and normal flora
- Urogenital = repeated flushing, acidic environment created by commensal flora
Pathogens can spread locally or systemically by transport in lymphatics, blood or nerves

Viral

Direct damage by entering host cells and replicating at hosts expense
Tropism = predilection for viruses to infect certain cells, determined by
- Expression host cell R
- Presence of cellular transcription factors that recognise viral enhancer and promoter regions
- Anatomic barriers
- Local temperature, pH and host cell defences
Direct cytopathic effects
- Prevent synthesis of host macromolecules (DNA, RNA, proteins)
- Produce degrading enzymes
- Induce apoptosis
Host lymphocytes attack virus infected cells Transformation of infected cells into benign or malignant tumour cells

Bacterial

Bacterial adherence to host cells
- Via adhesin proteins and pili
Interactions with host cell
- Inhibit protein synthesis
- Replication
- Host cell lysis
Bacterial toxins:
- Endotoxin = lipopolysaccharide (large component of outer cell membrane of G-ve bacteria)
- Exotoxins = secrete enzymes
  - Can alter signalling pathways
  - Inhibit release of neurotransmitters (C tetani)
  - Superantigens stimulate T cells -> cytokine release -> capillary leak and shock (TSS)

Growth in niches that are inaccessible to host immune system
- Intestinal lumen (C difficile) or gallbladder – escape cell mediated immunity
Antigenic variation
- High mutation rate (influenza)
- Genetic rearrangement (Borrelia burgdorferi -> Lyme disease)
- Large diversity of serotypes (Strep pneumoniae)
Resistance to innate immune defences
- Carbohydrate capsule on bacteria that cause pneumonia or meningitis (pneumococcus, meningococcus, H influenzae) -> shield bacterial antigens and prevent phagocytosis
- Viruses produce proteins that block complement activation
Impairment of effective T cell antimicrobial responses
- DNA viruses (HSV, CMV, EBV) bind or alter MHC I proteins thus impairing peptide presentation to CD8+ cells

Suppurative (purulent)	Mononuclear, granulomatous	Cytopathic- Cytoproliferative Reaction	Tissue necrosis	Chronic inflammation and scarring
Acute tissue damage: – Increased vascular permeability – Neutrophil infiltrate Caused by “pyogenic” bacteria = G+ve cocci and G-ve rods Neutrophils + liquefactive necrosis = pus	Chronic response Plasma cells or macrophages Caused by viral, intracellular bacteria or parasites, spirochetes and helminth infections = Syphilis, HBV	Viruses à Cell necrosis/ proliferation with sparse inflammatory cells. Inclusions (viral aggregates) may be visible = herpesviruses, adenoviruses Fused cells = polykaryons Epithelial cell proliferation = umbilicated papules of molluscum contagiosum (poxvirus)	Gangrenous necrosis C perfringens -> toxins to induce this	Chronic HBV

Last Updated on August 20, 2021 by Andrew Crofton