Bacterial Pathogenesis Flashcards
What is the difference between an infection and a disease?
Infection is the presence of a micro-organism in/on host tissue while disease is the pathological + clinical consequence of an infection
What is an opportunistic pathogen compared to a true pathogen?
Opportunistic pathogens are usually commensal/environmental while the mere presence of a true pathogen can initiate disease
What is the normal function of a commensal bacterium?
Metabolism
Immune system development
Colonisation resistance
Protection
What are some aseptic sites?
Lower resp tract
Upper urogenital tract
Blood, CSF, Synovial fluid
Internal organs and tissues
Define pathogenesis
Mechanisms by which an infectious agent induces symptoms or pathology
What are the different sources of disease?
A. Endogenous
B. Animals within a group
-epidemic
-endemic
C. Animals of other species
D. Environment
What are direct methods of transmission?
Mucosal or droplets: oral, respiratory, urogenital
What are methods of indirect tranmission?
A. Food and water (fecal oral)
B. Fomites
C. Arthropods - biol and mech
D. Iatrogenic
E. Nosocomial
Why are arthropod infections considered invasive/systemic?
There is direct entry into the vascular system
Why are the Outer Surface Proteins of Borrelia burdorferi important to their pathogenicity?
OspA and OspB are the most abundant
Contribue to phase and antigenic variation
Manipulate their expression for survival in different body temps/pH of hosts
What allows pathogenic bacteria to overcome normal microflora?
Large inoculum
Abx
Host factors - immune suppression, reduced peristalsis
Physical destruction
What are some of the mechanisms of persistence in Borrelia burgdorferi?
Active immune suppression
-Innate and adaptive: C’ inhibition, induce anti-inflammatory cytokines, tolerization of MAC and lymphocytes, sequester AB
Immune evasion
-Phase and antigenic variation: gene conversion/mutn/recomb, variable Ag expression
-Physical seclusion
What are the symptoms of canine lyme disease?
Long incubation - arthritis after weeks/months
Rare neurological issues
May cause glomerulonephritis due to immune complexes -> blood in urine
Does Coxiella burnetti require ticks as a vector for transmission to humans?
No, not tick dependent
What disease does Coxiella burnetii cause?
Q fever in humans
Ruminant infections usually asymptomatic
Ovine - abortions
What is Tularemia?
Bacteria septicemia caused by Francisella tularensis - highly virulent, bacterial weapon
List some potential sites of entry for bacteria
- Inhalation - Resp Tracts
- Ingestion - GI tract
- Coitus - Urogenital
- Mucous membranes
- Wounds, bites, injections
- Transplacental
Whats the difference between the challenge dose and the infective dose, and when does infection occur?
Challenge dose is the number of bacteria that are actually encountered while the infective done is the minimum number of bacteria that are required to initiate infection. When challenge dose >/ inf dose, infection may occur
Why are flagella important in motility and chemotaxis?
Movement to invasion/attachment site or away from negative stimuli, can function as adhesin
How does the flagella contribute to entry and establishment of Borrelia burgdorferi?
Endoflagella
Spirochete moves as a corkscrew
Hidden from immune recognition
Allows mobility even in viscous environmnet
What are the steps of actin polymerisation motility of Listeria?
Internalized in primary vacuole
Secretion of bacterial escape proteins
Vacuole membrane disrupted
Free cytoplasmic bacteria recruit and polymerize host’s actin
Propel bacteria and allows intrusion into adjacent cell
What receptors to fimbriae adhesins tend to bind to?
Host glycolipid or glycoproteins such as:
Mannose
Sialic acid
Galactose
Glucosamines
What receptors do non-fimrial adhesins tend to bind to?
Host glycoproteins or glycan
ECM glycoproteins such as fibronectin, E-cahderin, Integrins
Form cross bridges that confer robust adherence
What does invasion refer to?
Breach of epithelial barriers
Can be into or between euk, cells.
Utilize invasins and proteases
What are invasins?
Pathogen surface factors that drive invasion and can function as adhesins. Can manipulate rearrangement of cell cytoskeleton to promote uptake.
Briefly outline salmonella invasion
Induce membrane ruffling and consequent pseudopoda uptake of bacteria.
Remain within phagosome and replicate there while cell surface returns to normal
List some non-specific host defence mechanisms
Physical barriers - skin, mucus +mucociliary elevator, pH, degradative enzymes, dessication
Nutrient sequestering
Commensal microbes
Innate immune response - complement, inflammatory response, PRRs, fever
How do pathogens get the nutrients for proliferation?
Intracellular path - compete with host for nutrients available to the cell itself
Extracellular - enxzymes to degrade proteins and obtain short peptides for bacterial growth
What are some Iron Acquisition mechanisms?
Haeme/Tf/Lf binding proteins ->Streptococci, Pasteurella
Binding proteins - siderophores, transport mechanisms for Hg, Heme, etc
What proteins are currently being investigated as a vaccine candidate?
Iron binding proteins
How do pathogens overcome host defences?
Rapid replication
Low immunogenicity
Anti-opsonic activity
Intracellular survival
Concealment
Antigenic variation
Extracellular products
What are some methods that bacteria use to lower their immunogenicity?
Reduce antigenicity with capsules/LPS Oantigen
How do polysaccharide capsules reduce the antigenicity of bacteria?
Composed of polysaccharides such as Hyaluronic acid + scialic acid present in human and animal tissue that is not recognized as pathogenic
Expressed in infection, used as vx
Give an example of a capsule forming bacteria
Pasteurella multocida
Has 6 different capsular antigens that contribute to differentiating strains
16 serotypes identified based on LPS
What is the potential role of hyaluronidase in pathogenesis?
Breaks down Hyaluronic Acid
Contributes to invatsion and dissemination - degrading ground substance in ECM
Tightly regulated - production where capsule loss may be beneficial
Give examples of 2 bacteria species that produce hyaluronidase?
Pasteurella multiocida
Staphylococcus aureus
What is an important bacteria species that forms sialic acid capsules?
Neisseria meningitidis -> sepsis and meningitis in humans
Bleb formation of capsule
Group C - unique bacerial sxr that can be a successful vaccine
Group B - homologous to human cell molecules, non immunogenic
Define immune tolerance
The process in which host immune system does not attack an antigen
Self tolerance
Acquired/Induced tolerance - can be created to external antigens
What are some potential problems with immune tolerance?
Tolerance of infection in pregnancy
High persistent doses of circulating Ag
How does LPS work as an anti-opsonic factor?
Binds complement away from cell surface
Sugar side chains not well recognized by complement
How do M-like proteins function as anti-opsonic factors?
Factor-H (complement blocker) binds to M protein, C3b binds to Factor H and blocks opsonization
How does Protein A function as anti-opsonic factors?
Non-specifically bind to Fc region of IgG, no recognition by phagocytes
How do bacteria survive intracellularly and inhibit inflammation?
Stimulate secretion of anti-inflammatory signalling
Block chemotaxis
Kill phagocytes
How do extracellular enzymes prevent oposinisation?
Break down AB/Complement and prevent opsonization
How do mycobacteria inhibit inflammation?
Infect macrophages
Produce:
IL-6 -> Inhibit TCell activation
IL-10 -> Immunosuppressant
TGF-B -> antiinflammatory
How do bacteria inhibit chemotaxis and give an example
Formylated peptides secreted by growing bacteria are highly recognized by PMN
S. aureus produces CHIPS that binds to PMN receptor and blocks major ligand recognition -> no chemotaxis
How do bacteria survive intracellularly and inhibit inflammation?
Stimulate secretion of anti-inflammatory signalling
Block chemotaxis
Kill phagocytes
How do bacteria, such as M. haemolytica and salmonella, kill phagocytes?
Toxins + induce apoptosis.
M. haemolytica
Secrete leukotoxin which:
Impairs phagocytosis
As well as:
Reduces lymphocyte proliferation
Cytotoxic
Lyses platelets
How do bacteria survive intracellularly?
Resist killing and multiply in phagocyte
Inhibit fusion of phagocytic lysosome with the phagosome
Give examples of how bacteria inhibit phagosome fusion with phagocytic lysosome
M. tuberculosis - cell wall components released that modify lysosomal mem and inhibit fusion
Chlamydia - cell wall component modify phagosome mem
Listeria - escape proteins disrupt phagosome mem
How do bacteria conceal themselves from the immune response?
Acquisition of host molecules
-ie. Fc bidning protein: binding Fc of IgG so it cannot be recognized
-ie. Fibrinogen binding protein: limit Ab detection
Intracellular locations
‘Privileged’ locations
How do bacteria demonstrate antigenic variation?
Phase variation
-ie. salmonella flagella subunit
Antigenic drift
-changes in epitopes due to immune selection acting on aa sequences
What are some extracellular products bacteria have to overcome host defences?
Secreted antigens - bind opsonins/ab and prevent interaction with pathogen
Toxins - compromise host defence
Modulins - modulate host response via cytokines
What are 3 types of bacterial toxins?
Exotoxins
Endotoxins
Superantigens
What are some classes of bacterial exotoxin?
Membrane damaging”
-enzymatic
-poreforming
Cellular modification of:
-regulatory proteins
-ion channels
-protein synthesis
-neurotransmitter release
Give an example of bacteria with enzymatic lysis
C. perfringens alpha toxin
Targets phospholipid bilayer
Hydrolyses cell membrane lipids
Eyrthrocyte lysis important species tropism
Give an example of pore formation exotoxin
S. aureus alpha toxin forms a pore in the membrane
Disrupts ion balance, lysis
What is an example of a cellular modifying toxin?
Tend to be A-B toxins
E.Coli
The labile toxin- increase adenylate cyclase activity
Verotoxin or shiga-like toxin - blocks protein synthesis
C. diptheriae
Diptheria toxin - inactivate aa transfer and prevent protein synthesis
C. tetani
Tetanospasmin - block inhibitory trasnmitter release
What is an example of bacterial endotoxins?
Primarily lipid A component of LPS of Gram-ve bac
interact with humoral and cellular factors and lead to inflammatory mediator release
High levels can lead to significant effects (fever, DIC, shock)
How do superantigens confer toxic effects?
Non specific Tcell activation by binding to MHC class II mol
Excessive lymphokine production
Eg. Staph Toxic Shock Syndrome Toxin
How do fungal exotoxins cause damage?
Hepatotoxicity
Mucosal haemorrhage
Immunosuppression
Carcinogenesis
What is toxicosis intoxication?
Toxin presence can damage host even in absence of pathogen
What are the possible outcomes of infection?
Acute or chronic disease
-infective agent excreted
-spontaneous recovery
Asymptomatic carriers
-include convalescent carriers
Latency
-dormant phase
What influences the outcomes of infection?
Immune status
Bacterial factors - virulence
Host factors -stress, age, diet, general health, existing infections, genetic susceptibility
Environmental factor - hygiene, crowding, weather
What are the possible ways infection can resolve?
Complete recovery
Recovery with persistent damage
Persistence and carriage
Death
Why is understanding the pathogenic cycle critical?
Disease control:
-management and husbandry
-anti-microbial therapy
-immunotherapy
-preventative vaccines
-quarantine/culling
