Faculty: Dr. Alvin Fox

Faculty: Dr. Alvin Fox 1

Key Words Pathogen

Transmission

Outbreak, Epidemic, Pandemic

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 Bioterrorism 2

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

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Pathogens • The “usual” rate • • •

Oubreak - local Epidemic - regional/national Pandemic – widespread (international) – infections “beyond the norm”

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Koch's postulates •

isolated –

•

growth –

•

pure culture

induce disease –

•

diseased not healthy people

susceptible animals

re-isolated –

susceptible animals

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Opportunistic infections • compromised people – normal flora – environment

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Opportunists - normal flora • Skin – Staphylococcus aureus, – S. epidermidis – Propionibacterium acnes

• Intestine – Bacteroides * high numbers

– Enterobacteriaceae * low number

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Opportunists - environment • • • •

air water soil food

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Opportunists in hospital • nosocomial

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Transmission • airborne droplets • food • water • sexual contact

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Host defenses • Gut – peristalsis – defecation • respiratory tract – ciliary action – coughing – sneezing • urogenital tract – urination

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Adhesion BACTERIUM

adhesin receptor

EPITHELIUM

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S. pyogenes F-protein lipoteichoic acid

fibronectin

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E. coli

Fimbriae

Flagella

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E. coli fimbriae Type 1 mannose

P

galactose – glycolipids – glycoproteins 15

Penetration and spread Epithelium

Blood stream Salmonella typhi

Salmonella enteritidis

Vibrio cholerae Gut lumen

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Connective tissue destrction • Helps bacterial dissemination – collagenase – hyaluronidase

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

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Protein A inhibits phagocytosis

Fc receptor immunoglobulin

PHAGOCYTE Protein A BACTERIUM

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M protein inhibits phagocytosis

Complement

fibrinogen

M protein r

peptidoglycan

r

r

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Intracellular parasite Lysozome

Bacteria

Macrophage or neutrophil

Phagosome

No fusion

Fusion

Enter cytoplasm 21

Killing of intracellular parasite • Cell mediated immunity

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Tissue Injury • exotoxins • endotoxins and non-specific immunity - no antigen • specific immunity - antigen

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

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A-B toxins Cell surface

Active

Binding

A

B

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• Diphtheria toxin and Pseudomonas exotoxin A – ADP-ribosylates elongation factor (EF2) – inhibits protein synthesis – kills cells, destroys tissues

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Cholera toxin and E. coli labile toxin • ADP-ribosylation of regulator • adenylate cyclase activation • cyclic AMP • active ion and water secretion • diarrhea 27

Shiga toxin - shigellosis Shiga-like toxin – entero hemorrhagic E. coli • lyses 28S rRNA in ribosome • death of epithelial cells • poor water absorption • diarrhea

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• Botulinum toxin – inhibits acetylcholine release – inhibits nerve impulses – muscles inactive –flacid paralysis • Tetanus toxin – inhibits glycine release – inactivates inhibitory neurons – muscles over-active – rigid paralysis 29

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

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Membrane damaging exotoxins • Proteases • Phospholipases • Detergent-like action

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

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Exotoxins • Antibodies (anti-toxins) neutralize – vaccination

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Endotoxin • Lipopolysaccharide • peptidoglycan -endotoxin-like action • cell envelope components • not proteins/enzymes 34

Septic shock • hypotension (tissue pooling of fluids) • disseminated intravascular coagulation • fever • lack of effective oxygenation • overall system failure 35

Endotoxins • • • • • •

non-specific inflammation cytokine release complement activation B cell mitogens polyclonal B cell activators adjuvants 36

Specific immunity and immunopathology • chronic infection • • •

tuberculosis leprosy syphilis

• persisting bacterial remnants • autoimmunity

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

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Bioterrorism • air – most common

• no previous exposure – zoonoses

• manifest initially – colds/flu-like – death

• recognition – – –

clinically (e.g. common source clusters) clinical microbiology biodetection (environment) • future 39