Principles of Infectious Disease II Flashcards
<p>What are the most "successful" pathogens?</p>
<p>Often those pathogens that limit host damage = balanced pathogenocity</p>
Whate are “Normal Flora”?
- microbial flora that inhabit various body sites of healthy individuals
- profoundly affect metabolism and host physiology, including immune system development and homeostasis - “prime” the immune system
- help exclude dangerous microbes (this balance can be upset by antibiotic treatment or hygiene practices)
- some normal flora represent a potential reservoir for disease
Fun fact: there are more bacteria in your colon than cells in your body!
Ebola virus vs. Human Cytomegalovirus - which is a more “successful” pathogen?
Human Cytomegalovirus (HCMP, type of herpesvirus) because it infects over 90% of some populations, once you have it it stays. It does not cause much disease, but can be passed on readily.
Rapidly fatal infections tend to be self-limiting in a population (ex: Ebola virus).
Side note: HIV has a long phase with little disease but plenty of virus production. Also “successful.” Good host-pathogen balance.
<p>Steps of scientific proof to identify pathogenicity</p>
<p>1 - ASSOCIATE
2 - ISOLATE
3 - INOCULATE
4 - RE-ISOLATE: the agent must be recoverable from the susceptible host</p>
Whate are the four steps of scientific proof to identify pathogenicity (Koch’s Postulates)?
1 - ASSOCIATE: the infectious agent must be present in every disease case
2 - ISOLATE: the agent must be isolated from the disease case and grown in pure culture (when appropriate)
3 - INOCULATE: the specific disease must be reproduced from pure culture in a healthy susceptible host inoculated with the agent
4 - RE-ISOLATE: the agent must be recoverable from the susceptible host
What are the general features of infection?
Pathogens must: 1 - gain ENTRY into the host 2 - PERSIST in the host 3 - CAUSE DISEASE 4 - DISSEMINATE
- each of these steps require the pathogen to overcome the host defenses
- *collectively - factors that facilitate these steps are called VIRULENCE FACTORS
For host entry, a pathogen must…
Pathogen must colonize host through portal of entry, which are heavily defended:
skin, conjunctiva, oropharynx, URI, lower respiratory tract, stomach, intestinal tract, urinary tract
*in some cases, pathogen may enter tissues directly (ex. blood, mosquito)
Host Entry (Infection-Step 1)
ADHERENCE (of bacteria, viruses) to host cells
- bacteria adhere to host cells or extracellular matrix via adhesins
- viruses use receptors (ex: gp102 binding to CD4 receptor on CD4 T cell, or to macrophage)
<p>Once within the body, what defenses does the invader encounter?
(What are the barriers to persistence of the microbe?)</p>
<p>-macrophages
- phagocytes
- neutrophils
- complement
- type 1 interferon response (for viral infection)
- fever (harder for microbes to replicate?)</p>
Invasion (Infection-Step 2)
- pathogens can invade beyond epithelial surfaces, they can move through or between cells
- can involve initial replication in epithelial cells, followed by release of progeny into circulation to infect other cell types
- “Trojan horse” - transport by immune cells. Macrophages and dendritic cells can become infected and migrate to other sites (such as lymph nodes) to spread infection
Bacteria:
-many bacteria encode INVASINS that promote uptake and survival
-this allows bacteria to live and replicate within host cells, though bacteria are free-living
Ex: molecules that
-cause host cell endocytosis
-prevent phagosome acidification
-cause phagosome rupture for escape to cytosol
-degrade cell-to-cell junctions
*some bacteria inject factors into host cell to make it more permissive to infection
What are methods of persistence (during infection-step 3) against host defenses by pathogen within host?
- anti-phagocytic activity
- antigenic variation
- hideout
- induction or inhibition of apoptosis
What is anti-phagocytic activity?
- bacteria are readily engulfed by neutrophils and macrophages
- many pathogens resist uptake due to the production of the POLYSACCHARIDE CAPSULE
- may also inhibit killing activity of the phagocytes (Mycobacterium)
What is antigenic variation?
- some bacteria (such as N. gonorrhea) have elaborate mechanisms to alter their surface proteins to avoid antibodies
- viruses are masters of antigenic variation through simple natural selection during the course of infection
What is hideout (method of persistence)?
agent may occupy niche to avoid detection and/or elimination (ex: herpesvirus becomes latent - quiescent state with limited replication; HSV latent in neurons)
What is induction or inhibition of apoptosis (method of persistence)?
- some agents may induce host cell apoptosis to prevent killing (macrophages killed by Salmonella, for example)
- for some host cell types, apoptosis is a defensive response, and pathogens actively block it (epithelial cells and N. gonorrhea)
What are bacterial biofilms?
- mechanism for bacteria to adhere to a surface
- typically involves the elaboration of a viscous extracellular polysaccharide layer
- permits tenacious adherence (close adherence) to host tissues or medical devices (catheters, artificial joints and heart valves)
- –>increases virulence by rendering the bacteria less accessible to clearance by the immune system
- –>serves as a focus for persistence/recurrence
Define “tropism”
Different viruses have different cell/tissue preferences
**tropism can also refer to the host range (some viruses can infect many species)
Define “virulence”
the relative ability of a pathogen to cause host damage/disease
What effects tropism?
- determined by expression of cell surface RECEPTORSfor virus
- –>ex: HIV gp120 binds to CD4 molecule on T cells
- ANATOMICAL LOCATION
- –>depending on site of entry, virus is exposed to different cell types
- –>enteroviruses can survive low pH of digestive system to infect gut epithelia; many other viruses cannot
- INTRACELLULAR ENVIRONMENT
- ->some viruses can only replicate in certain cell types that have the right transcription factors to turn on viral genes or required host genes
Define “commensal organisms”
“normal flora” of the host
- largely benign or even beneficial
- some commensals can cause disease when one or more host defense mechanisms is compromised in some way:
- ->immune-compromised individuals
- ->through wounds/surgery
- ->antibiotic treatments altering microbial balance
- ->acquisition of new virulence genes by commensals
- *these are referred to as “opportunistic pathogens”
Define “carrier state”
colonization with a potential pathogen in the absence of disease
**not always easy to differentiate between commensal and carrier state
Define “true” or “primary” pathogens
almost always cause disease when present
What can increase pathogen dissemination (spread)?
Coughing, and other symptoms
What are the mechanisms in which infection causes disease?
- DIRECT CELL DEATH or cell dysregulation by pathogen
- ->HIV depletes T cells
- ->poliovirus can kill neurons
- production of TOXINS that can act systemically
- ->exotoxins (many bacteria produce potent toxins that affect host cells and processes to somehow benefit the pathogen)
- ->endotoxin [lipopolysaccharide (LPS) found in Gr- membrane is a potent stimulator of cytokine secretion by many immune cells]
- IMMUNE PATHOLOGY
- ->inflammatory response can be very damaging, even lethal. A major cause of symptoms in many infections
