Microbial Pathogenesis (2)
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An organism that causes disease
Primary Pathogen(aka "Frank Pathogen")
An organism that causes disease in otherwise healthy individuals
An organism that causes disease in immunocompromised individuals or when introduced into an unusual location
The degree of pathogenicity of an organism
Processes/products that contribute to an organism's ability to cause disease
The established association between microbe and host; microbe grows on a body surface
Microbes that routinely colonize healthy individuals without causing disease
*10x as many bacteria than human cells
- *1000's of different species
- *1000x more anaerobes than aerobes
- *Greatest number and variety found in the intestines (gut)
Koch's Postulates (Definition)
Criteria to fulfill in order to establish a causal relationship between a specific microbe and a particular disease
Koch's Postulates #1
The microorganism should be found in all organisms suffering from the disease and should NOT be found in healthy organisms.
Koch's Postulates #2
The microorganism must be isolated from a diseased organism and grown in pure culture.
Koch's Postulates #3
The cultured organism should cause disease when introduced into a healthy organism.
Koch's Postulates #4
When re-isolated from the diseased experimental host, the microorganism must be identical to the original causative agent.
Koch's Postulates (Problems)
- *Some diseases are asymptomatic
- *Polymicrobial infections can't be purified
- *Lack of animal models (humans)
Basic Steps of Pathogenesis
- 1. Acquisition
- 2. Adherence/Invasion
- 3. Proliferation
- 4. Damage
- 5. Evade Host Response*
- 6. Transmission
- Toxin consists of a Beta subunit which binds to the host and an Alpha subunit which carries the biological/enzymatic activity.
- Substance with a specific toxic effect on certain cells.
- ie. Diphtheria toxin (DT)
- Exotoxin tha specifically targets intestinal cells.
- ie. Cholera toxin (CT)
- Exotoxin that targets the genetic material within the cell, causing mutations.
- ie. Cytolethal distending toxin (CDT)
A toxin kept "within" the bacterial cell, to be released only after destruction of the bacterial cell wall.
- Cytotoxins that oligomerize to form pores in the cell membrane.
- ie. S. aureus (alpha toxin)
Immune Response Damage
Indirect damage by pathogen due to inflammatory response in host.
Endotoxin recognized by TLR4 that stimulates cytokine release and induces a cascade of adverse effects.
- Simultaneously bind to TCR and MHC class II molecules on APC. Causes a massive release of cytokines.
- ie. S.aureus (toxic shock syndrome)
Bacteria surrounded by immune cells (macrophages, T Cells, B Cells)
Evade Host Response
To be a good pathogen, bacteria must avoid innate (phagocytosis/complement) and adaptive (Ab/cell-mediated) immune responses.
Methods of Host Response Evasion:
- 1. Intracellular growth ("hide-out")
- 2. Biofilm formation (EPS)
- 3. Capsule (hides PAMPs)
- 4. Alter complement pathway
- 5. Inactivate T Cell Response
- 6. Antigenic variation (avoid Ab)
- 7. Inactivate Ab response (cleave Ig)
Type III Secretion System (T3SS)
- Multi-component virulence factor process that delivers effectors directly from bacteria into host cell cytosol through a needle complex. (Effectors suppress host defenses and /or promote pathogenesis)
- ie. Yersinia, Salmonella, Shigella, Pseudomonas, E.coli (path)
Goal of pathogen is to survive, multiply, and move on to the next host. Some bacterial symptoms aid in transmission(B.pertussis & V.cholerae)
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