Virulence

Infection

colonization w/o definite symptoms

Disease

ill effects to host

Virulence Factors

Factors produced by pathogens that are specifically involved in disease production

• What they do

  • promote colonization of pathogen

  • allow pathogen to evade host defenses

  • cause damage to host

• Virulence is multifactorial

Characteristics of Streptococcus pyogenes

• Gram+ cocci, grow in chains

• Nutritionally fastidious

• Aerotolerant anaerobes

• Normal residents of mouth, rose, skin, stomach & vagina

• Extracellular pathogen

Degradation of Complement Factors

• Two Serum Proteins (B & H)

  • C3b + B - activates complement cascade

  • C3b + H - then C3b degraded by I protein

• M protein

  • binds H factor from serum which recruits C3b & the serum protein I degrades it

  • No opsonization

• C5a protease

  • Degrades C5a

  • No chemotaxis

  • Immune cells are not being called to infection as quickly

Mimicking Host

Capsule of S. pyogenes

• Composed of hyaluronic acid

• Hyaluronic acid is found in human connective tissue

• Mimics host so it doesn’t emit a strong immune response

Overstimulate Immune System

Spe (streptococcus pyogenes)

• 7 variants are superantigens

• SpeA

  • Found in Strains TSLS & necrotizing fasciitis

  • Located on T12 bacteriophage

Characteristics of Vibrio cholerae

• Gram^- rod

• Transmitted fecal-oral

• Causes extensive diarrhea

  • loss of H₂O & electrolytes

• often fatal if not treated

• Produces an exotoxin

• Extracellular pathogen

Exotoxins

• Secreted proteins from bacteria

• Activate at low concentration

• Very immunogenic

AB Toxins

Two subunits

• A - catalytic subunit → catalyzes some damaging event inside host cell

• B - binding subunit → gives toxin host cell specificity

• Many are ADPR toxins (ADP-ribosylating)

Cholera Toxin

• binds to GM₁ ganglioside on epithelial cells in small intestine

• cAMP levels increase

• Ions released from cell

• H₂O flows out of cell - diarrheha

Stimulatory G Proteins

• A₁ attaches ADPR to G₅

• GTP is locked into place

• Adenylate cyclase not turned off in absence of hormone

• cAMP levels increase

Characteristics of Listeria monocytogenes

• Gram⁺ rod

• Food borne pathogen

• Opportunistic infection

• Intracellular pathogen

PrfA

is a transcription factor that upregulates transcription of virulence genes at body temperature

Listeriolysin O (LLO)

• Pore forming toxin

• Activity activated at low pH

• Allows escape from phagosome to cytoplasm

ActA

• Polymerizes / depolymerizes actin cytoskeleton of host cell

• Allows bacterium to move through host cell & invade neighboring cells

Influenza Transmission

• Incubation: 2 days (range 1-4 days)

• Communicability: shortly before onset of symptoms to 4-5 days of illness

• Transmission (human to human):

  • Primary: Aerosol → Direct contact

  • Secondary: Indirect contact

• Age-related mortality (very young & elderly)

  • Often due to secondary infections

  • Pneumonia & meningitis

Influenza A Virus

• 8 - ssRNA segments

• Two surface spikes

  • H → hemagglutinin (18 subtypes)

  • N → neuraminidase (11 subtypes)

Hemagglutinin

attaches virus to specific receptor on host cell (sticky)

Neuraminidase

cleaves the virus from the cell surface as it buds

Antigenic Variation

alteration of pathogen surface that leads to ability to evade the immune system

• Antigenic drift → minor changes

• Antigenic shift → major changes

Antigenic Drift

• RNA replication processes error prone

• Immune system not as effective

• May lead to illness

  • depends on how different antigen is

  • yearly vaccine boosts specific immunity

Antigenic Shift

• Due to genetic reassortment

• Causes MAJOR change in virus

• Typically little immunity in population

• Often leads to pandemics