Faculty: Dr. Alvin Fox

Key Words Pathogen/Epidemic Adhesion Normal flora Penetration Infection Invasiveness/spread Infectious diseases Extra/intra cellular pathogen Compromised host Exotoxin Opportunistic infection Endotoxin (non-specific immunity) Nosocomial Specific immunity Koch’s postulates Autoimmunity TransmissionBioterrorism

Pathogenicity virulence factors virulence factors number of initial organisms number of initial organisms immune status immune status

Pathogens EpidemicsEpidemics –healthy people

Koch's postulates isolatedisolated –diseased not healthy people growthgrowth –pure culture induce diseaseinduce disease –susceptible animals re-isolatedre-isolated –susceptible animals

Opportunistic infections compromised people –normal flora –environment

Opportunists - normal flora Skin – Staphylococcus aureus, – S. epidermidis – Propionibacterium acnes Intestine –Bacteroides *high numbers – Enterobacteriaceae *low number

Opportunists - environment air water soil food

Opportunists in hospital nosocomialnosocomial

Transmission airborne droplets airborne droplets food food water water sexual contact sexual contact

Host defenses GutGut –peristalsis – defecation respiratory tractrespiratory tract –ciliary action –coughing –sneezing urogenital tracturogenital tract –urination

Adhesion adhesin EPITHELIUM receptor BACTERIUM

S. pyogenes fibronectin F-protein lipoteichoic acid

E. coli with fimbriae

E. coli fimbriae mannose Type 1 galactose galactose – glycolipids – glycoproteins P

Penetration and spread Vibrio cholerae Salmonella enteritidis Salmonella typhi Epithelium

Connective tissue destrction Helps bacterial disseminationHelps bacterial dissemination –collagenase –hyaluronidase

Extracellular pathogens resistant to extra-cellular killing resistant to extra-cellular killing killed on phagocytosis killed on phagocytosis resist killing resist killing –by avoiding internalization

Protein A inhibits phagocytosis Protein A immunoglobulin Fc receptor BACTERIUM PHAGOCYTE

M protein inhibits phagocytosis M protein rr r peptidoglycan Complement fibrinogen

Intracellular parasite No fusion lysozome phagosome Fusion Enter cytoplasm

Killing of intracellular parasite Cell mediated immunityCell mediated immunity

Tissue Injury exotoxinsexotoxins endotoxins and non-specific immunityendotoxins and non-specific immunity - no antigen specific immunityspecific immunity - antigen

Exotoxins proteins proteins usually enzymes destroy cellular structures destroy cellular structures destroy extracellular matrix destroy extracellular matrix

A-B toxins Active Binding A Cell surface B

Diphtheria toxin and Pseudomonas exotoxin A – ADP-ribosylates elongation factor (EF2) – inhibits protein synthesis

Cholera toxin and E. coli labile toxin ADP-ribosylation of regulator adenylate cyclase activation cyclic AMP active ion and water secretion diarrhea

Shiga toxin - shigellosis Shiga-like toxin - enterohemorraghic E. coli lyses rRNA in ribosome lyses rRNA in ribosome death of epithelial cells death of epithelial cells poor water absorption poor water absorption diarrhea diarrhea

Botulinum toxin Botulinum toxin – inhibits acetylcholine release – inhibits nerve impulses – muscles inactive –flacid paralysis Tetanus toxin Tetanus toxin – inhibits glycine release – inactivates inhibitory neurons – muscles over-active rigid paralysis – rigid paralysis

Clostridium perfringensClostridium perfringens -collagenase Staphylococcus aureusStaphylococcus aureus - hyaluronidase Exotoxins - extracellular matrix of connective tissue

ProteasesProteases PhospholipasesPhospholipases Detergent-like actionDetergent-like action Membrane damaging exotoxins

destroys blood vessels destroys blood vessels stops influx inflammatory cells stops influx inflammatory cells creates anaerobic environment creates anaerobic environment allows growth of this strict anaerobe. allows growth of this strict anaerobe. C. perfringens phospholipase

Exotoxins Antibodies (anti-toxins)Antibodies (anti-toxins) neutralize –vaccination

Endotoxin LipopolysaccharideLipopolysaccharide peptidoglycan -endotoxin-like actionpeptidoglycan -endotoxin-like action cell envelope componentscell envelope components not proteins/enzymesnot proteins/enzymes

hypotension (tissue pooling of fluids) hypotension (tissue pooling of fluids) disseminated intravascular coagulation disseminated intravascular coagulation fever fever lack of effective oxygenation lack of effective oxygenation overall system failure overall system failure Septic shock

Endotoxins non-specific inflammationnon-specific inflammation cytokine releasecytokine release complement activationcomplement activation B cell mitogensB cell mitogens polyclonal B cell activatorspolyclonal B cell activators adjuvantsadjuvants

Specific immunity and immunopathology chronic infectionchronic infection tuberculosistuberculosis leprosyleprosy syphilissyphilis persisting bacterial remnantspersisting bacterial remnants autoimmunityautoimmunity

help survival on external surfaceshelp survival on external surfaces –H. influenzae –S. pneumoniae –N. gonorrhoeae –N. meningitidis IgA proteases

Bioterrorism airair –most common no previous exposureno previous exposure –zoonoses manifest initiallymanifest initially –colds/flu-like recognitionrecognition –clinically (e.g. common source clusters) –clinical microbiology –biodetection (environment) futurefuture