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. 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 Mechanisms of Viral Pathogenesis

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