Bacterial and Viral Pathogenicity Understanding infection and relevance in clinical practice

Pathogenic bacteria

Bacterial Virulence Virulence factors- molecules secreted/expressed by pathogens which enable them to do the following: COLONISATION INVASION EVASION OF IMMUNE RESPONSES TISSUE DAMAGE

Bacterial Virulence Pili ‘Fimbrae’ involved in adhesion in colonisation step Envelope proteins Involved in immune evasion Flagellae Motility Capsule Interfere with complement and antibody binding Lipopolysaccharide (LPS) Endotoxin on the outer membrane of Gram negative cells which prevents complemen binding

EVASION OF IMMUNE RESPONSES COLONISATION Adherence (association and adhesion) Nutrient acquisition INVASION EVASION OF IMMUNE RESPONSES Vs complement- capsules, LPS, surface proteins Vs antibodies- capsules, antigenic variation Vs. phagocytes- capsules, toxin production V.s cytokine response- alters immune system TISSUE DAMAGE

Learn this table!!! Exotoxin Endotoxin Bacteria Gram +ve and -ve   Exotoxin Endotoxin Bacteria  Gram +ve and -ve Gram –ve Made of Protein Lipopolysaccaride Location Cytoplasm, secreted by living bacteria  Outer membrane, released on cell lysis (see notes) Heat stability  Heat labile  Heat stable Toxoids  Toxoids No toxoids  Lethality  Potentially lethal  Lethal in higher concentrations Effects  Actions selective for specific biochemical targets e.g. protein synthesis  Activates many biochemical pathways (i.e. not specific), effects are mediated by triggering of cytokine release from mammalian cells Please note, exotoxins are secreted by bacteria which is why they are called exo Endotoxins are the ones released on cell lysis -> endotoxic shock in some cases Sorry for any confusion!

Viruses

2. Entry- fusion (enveloped virus) or endocytosis (non-enveloped) 4. Macromolecular synthesis- viral genome copying, viral protein synthesis 1. Attachment 3. Uncoating 6. Release- budding or cell lysis 5. Assembly

Viral virulence COLONISATION (or entry in/out of cells if an intracellular pathogen) EVASION OF IMMUNE RESPONSES TISSUE DAMAGE

Viral virulence COLONISATION Attachment: e.g. GP120 on HIV envelopes binds CD4 on host TH cells APOPTOSIS PREVENTION AND IMMUNE EVASION -Proteins to prevent cell apoptosis -Prevention of HLA class 1 expression, TC cells and NK cells do not recognise infected cells

Cell Death Acute hep A or E

Chronic infection Chronic Hep B B

Latency CENSORED Herpes simplex Varicella zoster virus-chicken pox and shingles CENSORED

Transformation HPV and cervical cancer Also Hep B and hepatocellular carcinoma EBV and lymphoma

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