Lecture No.7

Bacterial Evasion of the Immune ResponseBacterial Evasion of the Immune Response

Bacterial Evasion of the Immune ResponseBacterial Evasion of the Immune Response

• Physical barriers.Physical barriers.• Innate immunity.Innate immunity.• Humoral immunity.Humoral immunity.• Cell-mediated immunity.Cell-mediated immunity.

Physical BarriersPhysical Barriers

• Epithelium. Epithelium. • Toxins. (Toxins. (E. coliE. coli))• Adherence. (Adherence. (E. coliE. coli))• Invasion.Invasion. ((ShigellaShigella))

• Mucous.Mucous.• Proteases. (Proteases. (PseudomonasPseudomonas))• Adherence. (Adherence. (HaemophilusHaemophilus))• Invasion. (Invasion. (ListeriaListeria))• Motility. (Motility. (CampylobacterCampylobacter))

• Cilia.Cilia.• Toxins. (Toxins. (BordetellaBordetella))• Adherence. (Adherence. (StreptococcusStreptococcus))• Invasion. (Invasion. (MycobacteriumMycobacterium))• Motility. (Motility. (PseudomonasPseudomonas))

Innate ImmunityInnate Immunity

• Phagocytes. Phagocytes. • Toxins. (Toxins. (YersiniaYersinia))• Invasion.Invasion. ((LegionellaLegionella))

• Complement.Complement.• Interference. (Interference. (MycobacteriumMycobacterium))• Resistance. (Resistance. (StreptococcusStreptococcus))

• Surfactant.Surfactant.• Proteases. (Proteases. (PseudomonasPseudomonas))• Commandeer. (Commandeer. (MycobacteriumMycobacterium))

Humoral ImmunityHumoral Immunity

• IgA. IgA. • Ab binding. (Ab binding. (StaphylococcusStaphylococcus))• Proteases. (Proteases. (PseudomonasPseudomonas))• Antigenic variation. (Antigenic variation. (NeisseriaNeisseria))• Invasion. (Invasion. (SalmonellaSalmonella))

• Serum Ab.Serum Ab.• Ab binding. (Ab binding. (StreptococcusStreptococcus))• Antigenic variation. (Antigenic variation. (BorreliaBorrelia))• Proteases. (Proteases. (NeisseriaNeisseria))• B cell toxins. (B cell toxins. (ActinobacillusActinobacillus))

• Complement + Ab.Complement + Ab.• Resistance. (Resistance. (StreptococcusStreptococcus))• Proteases. (Proteases. (PseudomonasPseudomonas))• Invasion. (Invasion. (LegionellaLegionella))

Cell-mediated ImmunityCell-mediated Immunity

• T cells (helper or cytotoxic). T cells (helper or cytotoxic). • Prevent antigen presentation. (Prevent antigen presentation. (ListeriaListeria))• Interfere with cytokines. (Interfere with cytokines. (PseudomonasPseudomonas))• Toxins. (Toxins. (ActinobacillusActinobacillus))

• Activation of macrophages.Activation of macrophages.• Prevent antigen presentation. (Prevent antigen presentation. (LegionellaLegionella))• Interfere with cytokines. (Interfere with cytokines. (MycobacteriumMycobacterium))• Avoid lysosomes. (Avoid lysosomes. (SalmonellaSalmonella))

Bacterial Motility and AdherenceBacterial Motility and Adherence

Adherence MechanismsAdherence Mechanisms

Extracellular vs. IntracellularExtracellular vs. Intracellular

Extracellular PathogensExtracellular Pathogens

Transmission.Immune avoidance. (physical, innate)Colonization. (physical, innate, humoral)Survival. (innate, humoral, cell)Replication. (innate, humoral, cell)

Streptococcus pneumoniaeStreptococcus pneumoniae

Streptococcus pyogenesStreptococcus pyogenes

Type III Secretion and Type III Secretion and YersiniaYersinia

Antigenic Variation in Antigenic Variation in NeisseriaNeisseria

Relapsing FeverRelapsing Fever

Antigenic VariationAntigenic Variation

Mechanisms of Variation in Mechanisms of Variation in BorreliaBorrelia

TreponemaTreponema (Syphilis) (Syphilis)

Intracellular PathogensIntracellular Pathogens

• Transmission.Transmission.• Immune avoidance. (physical, innate)Immune avoidance. (physical, innate)• Invasion. (innate, humoral)Invasion. (innate, humoral)• Survival. (innate, cell)Survival. (innate, cell)• Intracellular replication. (cell)Intracellular replication. (cell)• Cell-cell spread. (physical, innate, Cell-cell spread. (physical, innate,

humoral)humoral)

Intracellular Life-CycleIntracellular Life-Cycle

Invasion. Initial regulatory signals triggering developmental cycle.

Initial Survival. Stress response, trafficking and other intracellular survival genes on. Extracellular growth genes off.

Intracellular Compartment. Biosynthetic, metabolic and transport genes on. Stress response and trafficking genes down..

Replication. DNA replication, cell replication, biosynthetic, metabolic and transport genes on. Intracellular survival genes down..

Host Cell Death/Lysis. Starvation response, microaerophilic, chemotaxis, motility, adherenceand invasion genes on. Replication, biosynthetic, transport and metabolic genes down..

Mechanisms of EntryMechanisms of Entry

Standard phagocytic events.lysosomal fusion?acidification?

killing?

Coiling phagocytic events.ribosome lined vesicle

bacterial replication

Mycobacterial Entry MechanismsMycobacterial Entry Mechanisms

Immune Avoidance by LatencyImmune Avoidance by Latency

Proteases and CytokinesProteases and Cytokines

ListeriaListeria Stays Intracellular Stays Intracellular

Some Evasion StrategiesSome Evasion Strategies

Immune Response: Good or Bad?Immune Response: Good or Bad?