Bacterial Pathogenesis and Host Defense Flashcards
Direct Effects:
Indirect Effects due to immune cells via natural immune mechanisms:
Indirect Effects via adaptive immune mechanisms (hypersensitivity)
Once virus can affect host in all 3 ways at once. With viruses, need lots of them to have their affect. Some baceria (like gram neg’s that release endotoxins) can cause disease w/o limited #.
Hypersensitivity –> many issues
Important Terms
Pathogen – bacteria capable of causing disease
Virulence – quantitative measure of pathogenicities measured by the number of bacteria required to cause disease
LD50 – number of bacteria necessary to kill half the host
ID50 – number of bacteria necessary to cause infection in half the hosts
Virulence Factors – properties of a bacteria which assist in causing disease ex: pili, capsules, toxins, etc.
Stages of Bacterial Pathogens
- Transmission from an external source into the body
- Evasion of initial host defenses
- Attachment to mucous membranes
- Colonization at attachment site
- Sometimes spread and reattachment
- Disease symptoms caused by toxins or tissue invasion followed by inflammation
- Non specific and specific immune host responses
- Progression or resolution of the disease or resolution
Mechanisms of Bacterial Disease
- Tissue invasion followed by inflammation
- Toxins (exotoxins…enter body from eating food. Don’t have to replicate. and endotoxins also don’t need to replicate, but need enough that endotoxin is sufficient tot cause disease…gram-‘s)
- Immunopathogenesis eg. Rheumatic fever
Transmission Mechanisms I
Human to human
*Direct contact cg infections mono
*Non-direct contact eg. fecal-oral
*Transplacental
*Transferred blood products or contaminated needles
Transmission Mechanisms II
II. Non-human to human
*Contaminated soils eg. Tetanus
*Contaminated water eg. Legionnaires’ disease
*Direct from animals eg. Cat Scratch fever
*Insect vectors eg. Lyme disease
Portals of Entry
Respiratory tract - largest route
GI tract - 2nd largest route
Skin
Genital tract
Virulence Factors I.
I. Bacterial Structures
Pili eg. N. gonorrhea to urinary tract epithelium
Capsules eg. Strep. pneumonia
Glycocalyx eg. Strep. viridans in heart valves
Endotoxin eg. Gram negative bacteria
Biofilms eg. Pseudomonas in cystic fibrosis patients
Bacterial Secretion Systems eg. T3SS in Salmonella typhimurium
Virulence Factors II.
II. Secreted Enzymes
Collagenase & hyaluronidase eg. Strep. pyogenes cellulitis
Coagulase eg. Helps coat Staph. aureus with fibrin to help protect from phagocytosis
Immunoglobulin A protease eg. Degrades IgA (immunoglobulin) allowing Strep. Pneumonia to adhere to mucous membranes
Leukocidins Destroy neutrophilic leukocytes and macrophages eg. Staphylococci and group A Streptococci
Virulence Factors III
III. Other Bacterial Factors
*M protein - antiphagocytic protein produced by Strep. pyogenes
*Protein A - binds to IgG and prevents activation of complement that is necessary to lyse
*Invasins - bacterial molecules which promote bacterial entry or contact with host cells - eg. Heliobacter pylori
*Outer membrane proteins - produced by Yersinia species to inhibit phagocytosis and cytokine production
***Pathogenicity Islands (PAIs) – code for groups of virulence factors particularly in Gram negatives - get rid off pathogenicity island, bacteria can’t cause disease. some islands are located on their chromosomes
IV. Exotoxins
Polypeptides secreted by bacteria
- **Become toxoids when treated with formaldehyde, and/or heat and used for protective vaccines*
- **Frequently have an A-B subunit structure (A portion has toxic activity and B portion is involved in binding to cells)*
- **Are genetically coded on the bacterial chromosome, plasmid or phage*
Have one of five biological effects:
^Alter cellular components
*Are superantigens
^Inhibit protein synthesis
^Increase synthesis of cAMP
^Alter nerve impulse transmissions
Exotoxin Action 2
Type 3 bacteria w/ injectosomes that secrete exotoxin.
Antibody cant prevent these b/c cell injects the endotoxin rather than through receptor (which antibody essentially normally blocks)
Table 2.2 - re-examine this…
Superantigens–> cytokinines –> bad effects
Salmonella - type 3 ctyotoxin
Diptheriea toxin resides on phage. If get phage out of diptheria cell, diptheria can’t cause disease.
Increased synth of cAMP. –> problems for cell
Alterned nerve impulse transmission
Lots of diseases associated with production of exotoxins…
example; superantigens - toxic shock
Virulence Factors V.
IV. Endotoxins
Are integral parts of the cell wall of Gram negative rods and cocci
Involve the Lipid A component of lipopolysaccharide
Only weakly antigenic; no toxoids made
Induced biological effects focus on fever and shock
Biological Effects of Endotoxin
Induce the release of endogenous pyogenes
Increase vascular permeability
Imitate complement and blood coagulation cascades
Cause fever, hypotension, disseminated intracellular coagulation and shock
Important Components of Host Defenses
_ Innate Immunity_
*Macrophages - Phagocytize and digest bacteria
*Complement - Assist host immune cells and antibody in lysis of bacteria and virus-infected cells
Important components of Host Defenses
Acquired Immunity
-Antibodies
*Cytolytic
****Neutralizing - antibody sits on virus so can’t infect
*Opsonins
-Cytotoxic T Cells
*Kill antibody-coated bacteria and virus-infected cells. See when antibodies interact with pathogen.
Passive vs. Active Immunity
- *Active Immunity**
- Administration of specific antigens to stimulate an individual to develop immunity to help protect from a disease ex. Influenza vaccine
- *Passive Immunity**
- Administration of preformed antigen-specific antibodies to help protect from disease ex. Human rabies immune globulin given to someone suspected to be suffering with disease right now.
Vaccines: live vs killed
Influenza - has live, but less virulent version of virus (get thru nose). Also get inactivated cocktail of killed versions of most likely-to-infect versions of influenza thru shot.
Live are always preferred b/c they go through the natural progression yielding a natural immune response.
Hep B - identified viral attachment gene. Use it to make attachment proteins that are injected. In process, body makes antibodies, too.
Tetanus toxoid & typhoid - ex of bacterial vaccines.
Human Immune Globulins; active v passive
Avoiding the innate immune response
Dealing with phagocytes and complement:
There are essentially three categories of bacterial strategies to deal with phagocytic cells:
*Avoiding contact with phagocytes
*Inhibition of engulfment
*Survival within the phagocyte
Avoiding Contact with Phagocytes:
The bacteria can reside in a niche not patrolled by phagocytes.
The bacteria can suppress inflammation and/or chemotaxis.
The bacterium can coat itself with host proteins (more later).
Inhibition of Engulfment by Phagocytes
Many bacterial capsules are anti-phagocytic.
Some surface polysaccharides (such as those that aid in biofilm structure) are anti-phagocytic.
Some bacteria produce specific anti-phagocytic products.
Capsules can inhibit phagocytosis AND complement activation
Survival within Phagocytes
Intracellular survival is mediated by bacteria in three basic ways:
Escape the phagosome
Shigella, Lysteria
Adapt to the phagosome
Coxiella, Leishmania
Modify the phagosomal compartment
Salmonella, Legionella, Mycobacteria, etc.
Other methods of phagocytic or complement avoidance by bacteria:
LPS O-antigen
Blocks MAC access - keeps at “arm’s length.”
Complement component peptidases
Destroy complement components. This inactivates the components AND stops complement activation.
Antigenic variation
Some bacteria spontaneously change the profile of the surface proteins that they express.
Antibodies are formed in response to specific antigens on the bacteria.
Because of a delay in the immune response (antibody formation), the bacteria can stay one step ahead by producing variants of itself.
Example: Trypanosome Variant-Specific Glycoprotein (VSG) cassettes.
Bacteria: B. recurrentis
Neisseria
3rd type of immunity avoidance:
Immunological disguise
Bacteria coat themselves with host proteins
Disguised by “self” proteins – camouflage!
E.g. proteins produced by some bacteria bind Antibodies – BACKWARDS!
Immunological disguise
E.g. The Treponema pallidum parasite coats itself with host fibronectin.
E.g. S. aureus produces coagulase and clumping factor. This leads to the deposition of host fibrin on the bacterial surface.
Protein A - A Staphylococcal Virulence Factor
Staph synthesizes protein A, which can bind IgG so bacteria looks normal to host immune system. Thus, not killed. Remember this one and others he spent time on.
Look to right of this complicated slide. Note diseases caused and how.
produces toxins. Note this and all things that lead to it’s virulence. Systemic infections, and toxin-mediated infections.
Pseudamonas aeruginosa
Gram-
involved in cystic fibrosis patients
Of its virulence factors, one is formation of biofilm. Hip replacement - good place to crx biofilm.
Quarum sensing - P. aeruginosa and Salmonella. Don’t synthesize full arsenal of virulence factors, but do synth autoinducers that sit out there while bacteria multiply. When cricital mass is reached, autoinducers release whole repitoire of virulence factors.
