micro - bacterial pathogenesis and host defense Flashcards
Bacteria cause disease in MANY WAYS
and you don’t necessarily require a large # of cells, because ____ produces a disease.
toxin
bacteria capable of causing disease
pathogen
quantitative measure of pathogenicities measured by the number of bacteria required to cause disease
virulence
of bacteria necessary to kill 1/2 the hose
LD50
of bacteria necessary to cause infection in half the hosts
ID50
properties of bacteria which assist in causing diease (pili, capsules, toxins, etc)
Virulence Factors
8 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
3 Mechanisms of Bacterial Disease
- Tissue invasion followed by inflammation
- Toxins (exotoxins and endotoxins)
- Immunopathogenesis eg. Rheumatic fever
What is Transmission Mech 1?
I. Human to human
Direct contact eg. infections mono
Non-direct contact eg. fecal-oral
Transplacental
Transferred blood products or contaminated needles
What is Transmission Mech 2?
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
Where do bacterial diseases enter body?
Respiratory tract
GI tract
Skin
Genital tract
What are the Virulence Factors?
bacterial structure
secreted enzymes
other bacterial factors
Exotoxin
Endotoxins
Virulence Factors - bacterial structure
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 - secreted enzymes
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 allowing Strep. Pneumonia to adhere to mucous membranes
Leukocidins Destroy neutrophilic leukocytes and macrophages eg. Staphylococci and group A Streptococci
Virulence Factors - other bacterial factors
III. Other Bacterial Factors
M protein - antiphagocytic protein produced by Strep. pyogenes
Protein A - binds to IgG and prevents activation of complement
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
place that doces for virulence factors: PATHOGENICITY ISLANDS. If you can get rid of it, get rid of bacteria’s ability to cause disease
Virulence Factors - Exotoxin
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 - 2nd way
- inject bacterial cytosol directly into host cell - antibodies can’t reach them because they’re never on the outside, unlike normal pathway that invovleds binding to receptors on the outside of the cell
What do bacterial exotoxins affect?
alter cellular compunents
superantigens
inhibition of protein synthesis
increased synthesis of cAMP
altered Nerve Impulse Transmission
- the info to make the toxins that do these are located at various places - if you can get ride of that place, you can get rid of the toxon; will not cause disease
What do superantigens do?
increase cytokines, have negative effect on cell
Virulence Factors: Endotoxins
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:
Induce the release of endogenous pyogenes
Increase vascular permeability
Imitate complement and blood coagulation cascades
Cause fever, hypotension, disseminated intracellular coagulation and shock
What is the difference between Innate and Aquire Immunity?
Innate: Macrophages and Complement (assist host immune cells and antibody in lysis of bacteria and virus-infected cells)
Acquired: Antibodies (cytolytic, neutralizing-lock up Viral Attachment Protein with an antibody, opsonins) and Cytotoxic T Cells (kill antibody-coated bacteria and virus-infected cells).
What is the difference between Passive and Active immunity?
passive = giving preformed antigen-specific antibodies to help protect from disease (like rabies immmune globulin - you don’t have to make your own antibodies)
active = giving antigens to stimulate an individual to develop immunity to help protect from disease (like Flu)
What kind of vaccine is availabe for flu?
shot, inactivated, or whole virus - split vaccine
Are live or dead vaccines better?
live - mimic natural pathway, better response
How do bacteria avoid Innate immune response?
** - avoice 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
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.
survival w/in phagocyte
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.
Capsules can inhibit phagocytosis AND complement activation
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 of ^: * Trypanosome Variant-Specific Glycoprotein (VSG) cassettes. - switch back and forth between different cassettes
Bacteria: B. recurrentis Neisseria
Immunological disguise
Bacteria coat themselves with host proteins
Disguised by “self” proteins – camouflage!
E.g. proteins produced by some bacteria bind Antibodies – BACKWARDS!
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.
What is protein A?
Staph synthesizes protein A - which has ability to bind immunoglobulin (IgG), causing bacteria to look normal to immune system - therefore is not killed.
REMEMBER PROTEIN A - PART OF STAPHYLOCOCCUS.
IS PSEUDOMONAS AERUGINOSA gram - or +?
Gram -
involved in cystic fibrosis patients; forms biofilms
