Bacterial Pathogenesis Flashcards
What is a pathogen?
organism that has the capacity to cause disease:
- opportunistic
- primary
What are opportunistic pathogens?
- rarely cause disease in healthy hosts regularly cause disease in compromised hosts:
- burn victims susceptible to infection with pseudomonas aeruginosa
- HIV patients more susceptible to intracellular bacteria (mycobacteria)
- hospitalized patients on broad spectrum antibiotics (clostridium difficile)
What are primary pathogens?
cause disease in healthy individuals
- have virulent mechanisms to overcome, mechanical, innate and adaptive immune responses rarely associate with their host except in the case of disease
- bacillus anthracis
Infectious disease?
- damage or loss of tissue or organ function due to infection or host inflammatory response
- symptoms of infections are caused by the microorganism or by the immune response of the host
Contact with organism does not always lead to disease, what could it lead to?
- elimination by host defense
- part of normal flora
- carrier state
- disease
Whether or not disease results depends on what?
- virulence of pathogen
- environmental factors
- host factors
What is virulence determinate?
properties that enable an organism to enter, replicate and persist in a host:
- expression of capsule, LPS, or pili
- elaboration of exotoxins that kill WBCs, proteases, siderophores
- generation of DNA inversions that lead to antigenic and phase variation
How do we determine what properties of an organism are necessary or involved in the disease process?
there are scientific processes that we can go through to determine whether or not a virulence factor is required for that organism to cause disease or whether it facilitates ability to cause disease -some have several factors
Stages of infection?
Transmission
Colonization
Multiplication
Invasion
Dissemination
Damage
Congenital transmission?
transmission from mother to child
Colonization?
- the ability to resist physical removal during infection
- establishment at site of infection can be mediated by specific receptor mediated interactions or biofilm formation
Receptor mediate adhesion?
- adhesion: macromolecules on the surface of bacteria (pili, MSCRAMMs)
- receptor: specific carb or peptide on the surface of host cell that is bound by the adhesion
- bacterial adhesions mediate host specific adherence (E coli 987P only cause diarrhea in young pigs) and tissue specific adherence (E coliP pili mediate adherence to urinary tract)- gram -
Microbial surface components recognizing adhesive matrix molecules?
- MSCRAMMs
- superfamily of surface adhesions that target host extracellular matrix proteins such as fibrinogen, fibronectin, collagen for adhesion
- only been studied in Gram + bacteria (lipoteichoic acid binds fibronectin)
- very specific
Biofilm formation?
- aggregate of bacteria that bind to each other on a surface within a slime layer
- many difficult to treat infections are caused by bacteria in biofilms
- bacteria can communicate with other bacterial species in biofilms
- within biofilms bacteria resist:
- antibiotic attack
- being flushed away
- phagocytosis and complement attack
How can bacteria acquire iron?
- secrete chelator called siderophore that bind ferric ions for transport into cell, can steal iron
- some bacteria have membrane proteins that have more affinity for iron than lactoferrin or transferrin, they take the iron
- multiplication: acquisition of iron
What are exoenzymes?
- allow organisms to degrade certain structures in the body, such as DNA
- facilitate dissemination
- Hyaluronidase- breaks down hyaluronic acid the ground substance of connective tissue
- Deoxyribonuclease (DNase)- thin pus made viscous by DNA released by dead WBC
- Streptokinase- activates plasminogen and converts it to plasmin which attacks fibrin clots allowing spread
What are toll like receptors?
- pattern recognition receptors (PRR)
- many that bind extracellular bacteria (TLR-4 for LPS)
Mechanism that LPS stimulates immune system (lipid A induces cytokines)?
- different than with super antigens
1. lipid A binds to LBP
2. binds to CD14 and TLR-4
3. signal is sent inside cell to stimulate NF-kappaB to release TNF-alpha (coagulation) and IL-1 (fever)
4. could cause septic shock
What is diphtheria toxin?
- blocks protein synthesis
- A is the active unit, B is binding unit
- only cells with a receptor B, will be affected by A
- toxin expressed on a prophage, only diphtheria strains with phage are pathogenic
- toxin converted to toxoid -part of DTap vaccine
What does cholera toxin result in?
- massive loss of water from intestinal epithelial cells
- AB toxin
- get it through drinking water, bacteria gets into gut -enterotoxin
- causes increased adenylate cyclase, increased cAMP
- watery diarrhea, rice water stools (vibrio cholera)
What are super antigens?
- powerful polyclonal T cell mitogens, get more activation, more aggravation, more cytokines
- stimulates nonspecific T cell responses
- binds to MHC class 2 molecule and T cell receptor outside of antigen binding sites (outside of cleft)
- leads to improper immune response and a toxic cascade of cytokines (toxic shock syndrome)
- increase TNF-alpha
Mechanisms microbes use to prevent harmful effects of complement?
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