Host Pathogen Interaction

A generalised sequence applicable across bacterial, viral, fungal, and parasitic infection, though the specific mechanisms at each stage vary by organism (developed in full in the organism-specific sections of this Atlas).

1. Exposure: the host encounters the organism via a specific transmission route.
2. Entry: the organism crosses a host barrier via a specific portal of entry.
3. Adherence: the organism attaches to host cell or tissue surfaces, typically via adhesins.
4. Colonisation: the organism establishes itself at the entry site and begins multiplying.
5. Invasion: the organism penetrates beyond the initial colonisation site into deeper tissue.
6. Multiplication: the organism replicates within the host, increasing in number.
7. Immune evasion: the organism employs strategies to resist or subvert host immune clearance.
8. Tissue damage: direct organism-mediated damage (toxins, enzymes) or host-mediated damage (excessive or misdirected immune response) produces the clinical manifestations of disease.
9. Exit and transmission: the organism leaves the host via a portal of exit, completing the cycle by reaching a new susceptible host.

• Skin: an intact, keratinised, mechanically tough physical barrier, also maintains an acidic surface pH and produces antimicrobial peptides.
• Mucous membranes: a physical barrier at moist body surfaces, coated in mucus that traps organisms and contains secretory IgA and antimicrobial proteins (lysozyme, lactoferrin).
• Mucociliary clearance: coordinated ciliary beating in the respiratory tract continuously moves the overlying mucus layer, and any trapped organisms, upward and out of the airway; impaired in smokers and in ciliary dysfunction syndromes, predisposing to respiratory infection.
• Gastric acid: the highly acidic gastric environment (pH 1-2) kills most ingested organisms before they reach the intestine; acid-suppressing medication (proton pump inhibitors, H2 antagonists) measurably increases susceptibility to enteric infection, including C. difficile and Salmonella.
• Normal microbiota: provides colonisation resistance against incoming pathogens.
• Innate immune responses: rapid, nonspecific defences activated immediately on organism entry, phagocytosis, complement activation, antimicrobial peptides, inflammatory cytokine release, and natural killer cell activity (full detail in Immunology for Microbiology).

• Adhesion: specific adhesin-receptor interactions allow the organism to resist mechanical clearance (mucociliary flow, urine flow, peristalsis) at the point of entry.
• Intracellular survival: organisms that survive within phagocytes (e.g. Mycobacterium tuberculosis, Salmonella species, Listeria monocytogenes) or within nonphagocytic cells evade extracellular antibody and complement surveillance entirely.
• Capsule formation: physically impedes phagocytic engulfment and masks underlying antigens from complement and antibody recognition.
• Antigenic variation: periodic alteration of surface antigens outpaces the adaptive immune response, which is generated against a specific, now-outdated antigenic form (e.g. Neisseria gonorrhoeae pilin variation, Trypanosoma brucei variant surface glycoprotein switching, influenza antigenic drift and shift).
• IgA proteases: enzymes secreted by some mucosal pathogens (Neisseria gonorrhoeae, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae) that cleave secretory IgA, the dominant antibody class at mucosal surfaces, removing a key first-line adaptive defence.
• Complement resistance: mechanisms that prevent complement deposition or downstream membrane attack complex formation on the organism surface (capsule interference, surface protein-mediated complement inactivation, sialic acid mimicry of host cell surfaces).