Establishment of Infection

1. Establishment of Infection • In order to cause disease pathogen must follow a series of steps • Gain entrance to host • Adherence • Colonization • Avoid Host Defenses • Cause host damage

2. Portals of entry 1. Mucus membranes • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Placenta 2. Skin 3. Parenteral route • Bite, puncture, injection, wound

3. Most microbes have a preferred portal of entry • Streptococci when inhaled may cause pneumonia; when ingested they do not • A few microbes cause illness no matter how they enter • May cause different illness based on portal • Plague has 2 forms; bubonic and pneumonic • Anthrax has 3 forms

4. Adherence (adhesion) • Critical Step • Bacteria use adhesins (ligands) • Viruses has surface attachment proteins • Binding to host cells receptors is highly specific

5. Colonization • Organism must multiply in order to colonize • New organisms must compete with established organisms for nutrients and space • May form biofilms

6. Virulence factors • Structural or physiological characteristics that aid in penetrating or avoiding host defenses

7. Capsules • Avoid phagocytosis; Prevents dessication; aids attachment • Incomplete phagocytosis • Escape the phagosome • Prevent fusion with lysozome • Survive inside phagolysozome

8. Fimbrae • Attachment • Components of cell wall • M proteins of Streptococcus • Mycolic acid of Mycobacteria and Norcardia • Outer membrane of Gram- bacteria

9. Extra-cellular enzymes (exoenzymes) • Coagulases • Kinases • Hyaluronidase • Dissolves hyaluronic acid • Collagenase

10. IgA proteases • Leukocidins • Antigenic variation • Avoid antibodies by altering surface antigens • Neisseria varies pili type

11. Penetration into host cytoskeleton • Manipulate actin to penetrate cells and to move between cells • Some pathogens induce non-phagocytic cells into endocytosis • Disruption of cytoskeleton may cause membrane ruffling

12. Damage to the Host • In order to cause disease pathogen must cause damage • Damage facilitates dispersal of organisms • Vibrio cholerae causes diarrhea • Bordetella pertussis causes coughing • Damage can be direct result of pathogen such as toxin production or indirect via immune response

13. Bacterial Damage to Host Cells • Use host cell’s nutrients • Binding to and invading host cells • Induce hypersensitivity reactions (allergies) • Production of toxins (Toxigenicity) • May be exotoxins or endotoxins

14. Exotoxins • Produced by G+ bacteria • Produced as part of their metabolism • Secreted externally or released following cell lysis • Proteins • Enzymatic nature • Highly soluble • Heat Liable

15. Among most lethal substances • Toxoids • Inactivated exotoxins • Induce antitoxins that provide immunity • Antibodies against a specific toxin • Passive immunity in form of antitoxin can be given as treatment

16. Grouped into functional categories • Neurotoxins • Enterotoxins • Cytotoxins

17. Staphylococcus aureus • enterotoxin – may be heat stable • exofoliatin toxin • Scalded skin syndrome • Toxic Shock Syndrome (cytotoxin) • Vibrio cholera • cholera enterotoxin

18. Clostridium botulinum • botulinum neurotoxin • Clostridium perfringens • Gas gangrene • Clostridium tetani • tetanus neurotoxin

19. Endotoxins • part of the outer portion of the G- cell wall • lipopolysaccharides (LPS) • lipid portion (lipid A) • Released when cells die and cell walls lyse • Antibiotics used to treat diseases can lyse cells • May cause an immediate worsening of symptoms

20. All endotoxins produce the same symptoms • Chills, fever, weakness, aches • May activate blood clotting proteins • May cause septic shock that can be fatal • Heat stable; not suitable for use as toxoids • Do not cause formation of antitoxins • Antibodies may enhance action of toxins • Salmonella typhi, Proteus spp. and Neisseria meningitidis

22. Mechanisms of Viral Pathogenesis • Cytopathic effects • Avoiding immune responses • Antibodies interact with extracellular viruses only • Viruses can remain intracellular by forcing neighboring cells to fuse in the formation of syncytium • Viruses can outpace body’s capacity to produce antibody

23. Some virus-infected cells release interferons to warn neighbor cells • Anti-viral proteins • Helps limit viral replication • Some viruses encode specific proteins to interrupt activity of interferons

24. Mechanisms of Eukaryotic Pathogenesis • Fungi • Generally opportunistic • Most serious fungal infections caused by dimorphic fungi • Some produce mycotoxins • Claviceps; Ergot toxin • Aspergillus; Aflatoxin • Amanita; Neurotoxins

25. Parasites • Most live within intestinal tract or enter body via bite of an arthropod • Use host nutrients • Presence of parasite interferes with host function • Parasite's metabolic waste can cause symptoms

26. Algae • A few species produce neurotoxins • Alexandrium produces toxin that causes paralytic shellfish poisoning • Produces symptoms similar to botulism

27. Portals of Exit • Respiratory and gastrointestinal tracts • Most common • Genitourinary tract • Skin/wounds • Biting insects • Contaminated needles and syringes