Week 3 - Microbiology - Bacterial Pathogenesis and Host Defense Flashcards
Endotoxin
only in gram negative bacteria
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.
What are the 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
**What types of viruses to know about
influenza.. retroviruses.. What he spent a lot of time on. Learning objectives**
What are the three mechanisms of bacterial disease?
- Tissue invasion followed by inflammation
- Toxins (exotoxins (can be toxins that enter by food but no bacterial present.. bacteria produce tosxin in food then eat it.. food poisoning) and endotoxins (gram neg))
- Immunopathogenesis eg. Rheumatic fever caused by specific bacteria
What are transmission mechanisms
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Human to human transmission
Direct contact eg infections mono
Non-direct contact eg. fecal-oral
Transplacental
Transferred blood products or contaminated needles
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
What are the four portals of entry
Respiratory tract (biggest portal!)
GI tract
Skin
Genital tract
Bacterial structures (virulence factors)
Pili Capsules Glycocalyx Endotoxin Biofilms Bacterial Secretion Systems
Secreted Enzymes (virulence factors)
Collagenase & hyaluronidase
Coagulase
Immunoglobulin A Protease
Leukocidins
Other bacterial factors of virulence
M Protein
Protein A - binds to IgG adn prevents activation of complement
Invasions
Outer membrane proteins
Pathogenicity Islands (PAIs)* - in gram neg bacterial there are PAI of genetic material which code for virulence factors. If get rid of PAI - bacteria cant cause disease…
Exotoxins
Polypeptides secreted by bacteria
If you can isolate the exotoxin and treat it with formaldyhol it can be used as vaccine - called a toxoid.
Two components A (toxic) & B (binding structure)
Exotoxins are coded on bacterial chromosom, plasmid, or phage
What are 5 effects of exotoxins?
Alter cellular components Are superantigens Inhibit protein synthesis Increase synthesis of cAMP Alter nerve impulse transmissions
Type III cytotoxins
Some bacteria have a type III cytotoxin
The bacterial use an injectosome to directly inject exotoxin into cell..
Normally, bodily antibodies inhibit B part of exotoxin so it cant get into cell.. however, in this case there is no B part adn body has difficulty fighting it.
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Increase in cytokines has very bad effect on body..
Diptheria toxin
If doesnt get on phage and to make cornebacterium diphtheria it wont cause disease.. if it does get to sit on phage, it will cause adp ribosylase elongation factor 2.. ?? idk anymore
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
What are biological effects of endotoxins?
Induce the release of endogenous pyogenes
Increase vascular permeability
Imitate complement and blood coagulation cascades
Cause fever, hypotension, disseminated intracellular coagulation and shock
Lipid A porting important.. ppl die from endotoxic shock.
Components of host defenses
Acquired immunity - only occur after we get a foreign stimulus from pathogen
Antibodies
- cytoloytic
- neutralizing*
- opsonins
Cytotoxic T cells
-kill antibody coated bacteria and virus infected cells
Innate Immunity
Macrophages - phagocytize and digest bacteria
Complement - assist host immune cells and antibody in lysis of bacteria and virus infected cells
What are two types of immunity
Innate and acquired
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
Passive vs Active Immunity
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Some diseases have both passive and active
Some only active immunity
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Ways for bacteria to avoid 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 IIR?
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).
Avoiding engulfment (IIR)
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
Intracellular survival of bacteira
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.
Bacteria can avoid being killed ***
Other methods of phogocytic or compliment avoidance by bacteria
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Immunological Disguise
Bacteria coat themselves with host proteins
Disguised by “self” proteins – camouflage!
E.g. proteins produced by some bacteria bind Antibodies – BACKWARDS!* - the body doesnt recognize the cell because its covered in its own antibodies
Protein A
Staphylococcal virulence factor..
Staph synthesies proten A. Protein A binds IgG (immunoglobin) on the surface of the cell.. the immune system just sees IgG but not bact so it is disguised..
read pseudomonas paper..
concept questions
Case questions
most difficult.. does a certain bacterial have a toxoid..
