damage by bacterial pathogens Flashcards
Mechanisms that damage the host during infections
cell death
damage by host responses
toxins
host cell death caused by?
growth of pathogen in cells
cell mediated immunity
membrane damaging toxins
growth of pathogen within host cells and damage to host cell
Cell membrane damage causes cell death (free radicalinduced lipid peroxidation).
• Damage is proportional to number of bacteria inside cell.
cell-mediated immunity and cell death
indirectly caused by pathogen, infection recognized via CD8 and MHC= cell killed
Membrane-damaging toxins
lead to apoptosis
Damage caused by host responses
Uncontrolled inflammation
Inflammation – healthy response
- increased blood supply (redness)
- increased vascular permeability (edema)
- chemotaxis (infiltration by phagocytes and lymphocytes
due to exaggerated adaptive immune response = hypersensitivities
type I hypersensitivity, can lead to?
Th2, IgE, mast cells
allergy but can lead to anaphylaxis and shock
Type II hypersensitivity
bound antibodies leading to complement and leukocyte activation against cell surfaces/ extracellular matrix
Type III hypersensitivity
bound antibodies leading to complement and leukocyte activation to soluble molecules, then immune complex deposition into vascular membrane
Type IV hypersensitivity
inflammation by purely CMI responses (not antibodies)
Toxins
Microbial product or component that can injure another cell or organism at low concentrations usually altering host metabolism
mechanisms of toxin action (where they can operate?)
Modulation of targets inside a host cell
Action in the extracellular matrix
Action on surface of a host cell
variation in toxin production and disease conseuqnces
Toxin production and disease consequences vary widely
among pathogenic bacteria
transfer of toxin genes
Like transposons, many toxin-encoding genes are carried
on plasmids or temperate bacteriophage genomes (easy to
transfer to other, non-toxigenic bacteria).
CTXφ (a bacteriophage) and Vibrio cholerae
ctxA and ctxB encode the
proteins that comprise
cholera toxin
types of toxins causing Modulation of targets inside a host cell
Exotoxins
Type III cytotoxins
exotoxins
secreted by pathogen via type I and II systems
Type III cytotoxins
injected into host cells contact-dependent
Common features of exotoxins
- A-B toxins (2 components)
- Require activation (proteolysis or reduction of disulfides)
- Many are ADP-ribosyltransferases
ADP-ribosyltransferases
take the ADP ribose from NAD and add to a target protein in the host cell thus inactivating it
AB exotoxins
B domain is the binding domain
A is the enzymatic (active) domain
B domain also mediates the entry of the A domain into the host cell
• only A enters cell for some toxins
• A and B enter cell for other toxins
Action of diphtheria toxin (an exotoxin)
toxins with Action on surface of a host cell
membrane damaging toxins
super Ag
endotoxins
types of Membrane-damaging toxins
lipases, pore-forming toxins, hemolysins
Endotoxin example
LPS, specifically lipid A
endotoxin in small vs large amounts
toxins with Action in the extracellular matrix
Exoenzymes:
collagenases
hyaluronidases
DNases: break down viscous DNA left by dead cells
streptokinase (Streptococcus pyogenes): activates plasminogen (converts to plasmin) help microbes spread
Protection against exotoxins
A. Immunization with toxoids
B. Treatment with antitoxins passive immunization
