Overview of Pathogenesis(= the manner in which

disease develops.)

1) Transmission2) Portals of Entry3) Adherence4) Multiplication &

Spread • host mechanisms• pathogen invasiveness • pathogen evasiveness

5) Damage to Host6) Outcome

Transmission from a

Reservoir to a New Host

Portals of Entry

Ingress into the Body cavity:

• Mucosal Membranes

- Conjunctiva

- Ear

- Respiratory

- Digestive

- Genitourinary

- Placental

• Skin

• Parenteral Route (mechanical puncture)

Adherence to Host CellsSpecific attachment of pathogen adhesin to host receptor; attachment may also be non-specific.

Multiplication & Spread

• Multiplication - An incubation period is required - time needed for parasite to overcome early host defenses, multiply, & incite disease symptoms.

• Spread - It requires pathogen mobility and/or host transport mechanisms; pathogen may also produce “virulence factors” that enables evasion of host defenses and invasion of tissues.

– Contributing mechanical factors of host:• Tissue type fluid vs solid• Physical anatomy of infected host site (e.g.: eustachian tube; digestive track)

– Contributing virulence factors of the pathogen:• Evasive Factors• Invasive Factors

– Host Defense Evasive Factors of Pathogen:

• Tolerance to physiological barriers (acidic pH of urine & stomach).

• Capsule or cell wall components (M protein)– weak antigenicity (do not stimulate immune system to make antibodies).– avoid/resists phagocytosis (being eaten by white blood cells).

• Microbes vary surface antigens to avoid host immune responses.

– Invasive Factors of Pathogen:

• IgA proteases: Surface enzyme capable of cleaving secretory IgA antibodies released at the mucosal membrane surface.

• Extracellular enzymes of pathogen sometimes aid in spread by destroying tissues or cell components.

• Surface enzymes called invasins rearrange host cytoskeleton filaments for entry and transport to other side of epithelial cells.

Invasive Factors(Extracellular

Enzymes) Activity

HyaluronidaseDegrades hyaluronic acid between cells

Collagenase Splits collagen protein

LecithinaseSplits lecithin of membrane

Coagulase Clots fibrin

Fibrinolysin Lysis of fibrin clots

Proteases, Nucleases, Lipases

Degrades proteins, nucleic acids and fats

Hemolysin Lysis of RBC's

Leukocidin Lysis of Leukocytes

 

Extracellular enzymes of pathogen can aid spread:

Salmonella’s invasin

Damage to Hostdirect host cell damage; hypersensitivity;

pathogenic toxins

Exotoxins• Polypeptides released by Gram+ bacteria; plasmid or prophage encoded.

• Relatively unstable (heat, acid, proteases).

• Highly antigenic (stimulates production of antibodies, called antitoxins).

• Highly toxic! (1 oz. diphtheria toxin could kill all of NYC if effectively administered)

• Three classes of specific host site AB exotoxins (Active/Binding):– Cyto: (kills or effects cell functions like protein synthesis (diptheria and Shiga

toxins).– Neuro: disrupts neural transmission (clostridial & botulinum toxins).– Entero: interrupt gastrointestinal lining function (cholera toxin causes release of

fluids and electrolytes).

• Various membrane disrupting exotoxins.

• Superantigens: over stimulates T-cells of immune system; hypersensitivity.

AB Exotoxins:

Dimeric exotoxin

B= binding

A= enzyme action

Endocytic entry →

Or entry via membrane protein.

Membrane Disrupting Exotoxins:

• Enzymatic toxins dismantle membrane lipid components.

• Toxic porins that assemble in host membrane creating leaking of cytoplasm.

Endotoxin • Fragments of outer membrane from Gram – bacteria

• Lipopolysaccharide (LPS): polysaccharide responsible for antigenicity; lipid toxicity.

• Although less potent than endotoxins they can be:• Pyogenic (inflammation response induced and results in pus)• Pyrogenic (induces Interluekon-1 (IL-1) by macrophage; fever results)

• Shock (Gram– bacteremia; induces tumor necrosis factor (TNF) release;

results in hypotension, capillary fluid loss, and major organ damage)

• Relatively stable; can cause problems even if cells are dead! (Limulus amoebocyte lyase (LAL) assay; a clotting assay.

Summary of Pathogensis