Bacterial Pathogenicies and Host Interactions Lecture Sep 10 Flashcards
What is the LD50?
WHat is the ID50?
LD50 – number of bacteria necessary to kill half the host
ID50 – number of bacteria necessary to cause infection in half the hosts
WHat are the 8 stages of bacterial pathogenicity?
- TRansmission from an external source into the body
- Evasion of initial host defense
- Attachment to mucous membranes
- Colonization at attachment site
- Sometimes spread and reattach in new locations
- Disease symptoms cuased by toxins or tissue invasion followed by inflammation
- Nonspecific and specific immune host repsonses
- Progression or resolution of the disease
What are the three general mechanisms of bacterial disease?
- tissue invasion followed by inflammation
- toxins (exotoxin and endtoxin)
- Immunopathogenesis (like rheumatic fever)
GIve an example of disease caused by toxin only–the bacteria doesn’t even need to multiply in the body.
This is the case in food poisoning where the bacteria replicated in the food and secreted toxin. We eat the toxin-containing food and develope disease.
What are the main branches of transmission mechanisms?
Human to human
Direct contact (like infectious mono)
Non-direct contact (fecal oral)
Transplacental
Transferred blood products or contaminated needles
Non-human to human
Contaminated soil (tetanus)
Contaminated water (legionnaries’ disease)
Direct from animals (cat scratch fever)
Insect vectors (lyme disease)
WHat are the 4 main portals of entry in the order of most common to less common?
- Respiratory tract
- GI tract
- Skin
- Genital tract
What are 6 examples of bacterial STRUCTURAL virulence factors?
- Pili for attachment (N. gonorrhea to urinary tract epithelium(
- Capsule (strep pneumonia)
- Glycocalyx (strep viridans on heart valves)
- Endotoxin (gram negative bacteria)
- Biofilms (pseudomonas in cystic fibrosis patients)
- Bacterial Secretion Systems (T3SS in Salmonella typhimurium)
What are 4 examples of secrete enzymes as virulence factors?
- Coallagenase and hyaluronidase (strep pyogenes cellulitis)
- Coagulase (helps coat staph aureus with fibrin to help protect from phagocytosis)
- Immunoglobulin A protease (degrades IgA allowing strep pneumonia to adhere to mucous membranes)
- Leukocidins (destroy neutrophilic leukocytes and macrophages in staphylococci and group A streptoccocci)
WHat does M-protein do for a bacteria?
It is an antiphagocytic proteins produced by strep pyogenes
What does protein A do for a bacteria?
It binds to IgG and prevents activation of complement
What do invasins do for a bacteria?
Invasins are bacterial proteins which promtoe bacterial entry or contact with host cells (e.g. heliobacter pylori)
What are pathogenicity islands?
PAIs code for groups of virulence factors.
THis is often in gram negative bacteria.
In gram negative bacteria that have PAIs, all of their virulence factors tend to be on the PAI except for the endotoxin.
So if you find a way to get rid of the PAI, the bacteria loses its ability to cause disease
What are toxoids? How are they made?
A toxoid is an exotoxin that has been treated with formaldehyde and/or heat to be used in protective vaccines
What is the general composition of exotosin?
Where are they encoded?
Exotoxins are polypeptides secreted by bacteria
They frequently have an A-B subunit structure with A having the toxic activity and the B protion involved in binding to cells
Exotoxins are coded for on the bacterial chromosome, plasmid, or a phage in the host cell
What are the five biological efects of exotoxin?
ALl exotoxins have at least one of the following effects:
- alter cellular components (clostridium perfringens produces alpha toxin which is a PLP to hydrolyse phosphorylchlorine in the membrane so the membrane breaks down and the cell lyses, causing death. Staph aureus produces an alpha toxin that causes potassium pores leading to a loss of nutrients and cell death)
- are superantigens
- inhibit protein synthesis (c. diphtheriae produce an AB toxin that inactivates elongation factor 2 to prevent protein synthesis by the ribosome)
- increase synthesis of cAMP (vibrio cholerae has a multiunit toxin that increases adenylate cyclase activity leading to an increase in cAMP which triggers the excretion of ions into the lumen the gu leading to diarrhea)
- Alter nerve impulse transmission (clostridium tetani produce a toxin that blocks inhibitory transmitter release, so you get continuous stimulation by an excitatory transmitter) (Clostridium botulinum blocks the release of ACh from vessicles)
For what types of bacteria/toxins would antibodies specific for a toxin NOT be effective?
WHen the bacteria has a type III cytotoxin that is being injected into the cell through an injectosome. The antibodies never have access because the toxin is never in the extracellular space.
What to superantigens trigger? WHat is the result?
Superantigens cause the massive release of cytokines, resulting in systematic inflammation, hypotension and shock.
Describe endotoxin.
Where are they located? on what bacteria?
Can toxoids be maid?
Endotoxins are integral parts of the cell wall of gram negative rods and cocci.
This is the lipid A component of LPS
It cannot be made into toxoids for vaccines because it is only weakly antigenic (just very toxic)
What are the biological effects of endotoxin?
- Induce the release of endogenous pyrogens–fever
- increase vascular permeability
- imitate complement and blood coagulation cascades
- cause fever, hypotension, disseminated intracellular coagulation and shock
What is the difference between innate immunity and adaptive/acquired immunity?
Innate immunity is the macrophages (for phagocytosis) and complement (for lysis) which are in our systems all the time–they’re innate.
Acquired immunity is immunity our body learns. It involves antibodies that learn to recognize specific antigens (cytolytic, neutralizing, opsonins) and cytotoxic T cells to kill antibody-coated bacteria and virus-infected cells.
What is the difference between passive and active immunity?
Passive immunity is when the body doesn’t have to learn its own response. It coems from administration of preformed antigen-specific antibodies to help protect from disease (like the human rabies immune globulin)
Active immunity is when the body still has to learn its own repsonse even though it’s helped a long a bit. This is the administration of specific antigens to stimulate an individual tod evelop immunity to help protect from a disease (like the influenza vaccine).
What are some main live vaccines?
What are some main killed vaccines?
Which tends to be more effective?
Live/attenuated:
HPV vaccine, MMR, polio, varicella, yellow fever, small pos, influenza (cold adapted–in the nose spread)
Killed:
Hepatitis A, Influenca (whole virus injected), polio (salk), rabies, japanese encephalitis, cholera (diptheria toxoid), pertussis, plague, typhoid
Live vaccines are more effective
What are some main diseases we can provide immunoglobulins for (either human Ig or horse Ig)?
CMV, HepB, Rabies, Tetanus, Smallpox, Varicella-zoster,
Botulism, Dipheria (from horses)
What are the three general bacterial strategies tod eal with phagocytic cells?
- Avoid contact with phagocytes
- Inhibition of engulfment
- Survival within the phagocyte
What are three ways a bacteria can avoid contact with phagocytes?
- reside in a niche not patrolled by phagocytes
- suppress inflammation and/or chemotaxis so the phagocytes don’t even come
- coat itself with host proteins to camouflage
WHat are three ways bacteria can inhibit engulfment by phagocytes?
- Many bacterial capsules are anti-phagocytic
- Some surface polysaccharides (such as those that aid in biofilm structure) are antiphagocytic
- Some bacteria produce specific antiphagocytic products
What two things can capulses inhibit?
Phagocytosis and complement activation.
The combination fo the two is what’s necessary to lyse the cells.
What three ways can bacteria deal with the phagosome after being engulfed?
- escape the phagosome (shigella, lysteria)
- Adapt to the phagosome (coxiella, leishmania)
- Modify the phagosomal compartment (Salmonella, legionella, mycobacteria)
How does LPS block phacotytosis?
The LPS O-antigen blocks macrophage access
What do complement component peptidases do for a bacteria?
Destroys the complement components which inactivates the components AND stops complement activation
What does antigenic variation do for a bacteria?
Some bacteria are able to spontaneously change the profile of the surface proteins that they express.
Antibodies are formed inr esponse to specific antigens on the bacteria
After a while, the bacteria is able to use a different cassette and present different surface proteins that the antibodies won’t recognize, thus allowing the bacteria to stay one step ahead of the immune response
Trypanosome variant specific glycoprotein (VSG) cassettes in B. recurrentis and neisseria are examples of this
What are two things a bacteria can coat itself in to use as camouflage? What proteins are required for this?
Some will use coagulase and clumpting factor (staph auerus) to coat themselves with fibrin on the bacterial surface.
The treponema pallidum parasite does something similar
Staphyloccoci with protein A are able to bind IgG antibiodies backwards to camouflage themselves.
What issue does pseudomonas cause in cystic fibrosis patients?
They create biofilm infections in the lungs
