Upgrade to remove ads
Microbiology Chapter 9: Damage by Microbial Toxins
Terms in this set (56)
damage from infection is caused by:
1. direct action of microbial pathogen
2. host response to infection
1. cell lysis
lysis of host cells
1. microorganism produces toxin that disrupts cell membrane. i.e. anaerobic clostridia causing gas gangrene
2. microbe multiplies within host --> lysis from the inside i.e. rickettsiae causing Rocky motion spotted fever
3. microbes multiply within host cell but are eradicated by cytotoxic lymphocytes or NK cells. i.e. mycobacteria
apoptosis. Microbes have different effects?
- shigella stops apoptosis
- herpes simplex and HIV cause premature apoptosis
-Epstein-Barr virus block apoptosis
How do tetanus, botulism, cholera, and whooping cough carry out their disease?
Don't kill cells directly. Toxins alters key part of metabolism and resembles the action of a hormone or other effector
mechanical causes of damage
-obstruct vital passages: roundworm Ascaris can occlude intestinal lumen or bile duct
- inflammatory response of host: filariae cause elephantiasis- swelling because of tissue reaction that occludes vessels and result sin tissue hypertrophy
-any duct/tube-like organ can be obstructed during infection: cerebral ventricles, prostate, liver, etc.
host responses to infection leading to harmful outcomes (4)
1. accentuated inflammatory response (brain abscess)
2. overwhelming activation of complement system (septicemia)
3. autoimmune response (rheumatic fever)
4. cell-mediated immunity (chronic tuberculosis)
bacterial toxins modulating intracellular targets: (3)
- type III cytotoxins
- type IV to VII cytotoxins
remember: Ex34 inside
bacterial toxins acting on cell surface: (3)
- membrane-damaging toxins
bacterial toxins modulating targets in the extracellular matrix: (1)
remember: exo, outside and within the matrix so must be tough like an enzyme
proteins secreted by bacterium by type I or II secretion, attach to receptors on sensitive cells and are internalized.
where are toxins often encoded?
on plasmids and temperate bacteriophages (b/c not necessary for survival)
when are toxins synthesized?
-either continuously or during the stationary phase (theory is toxins are used to obtain scarce nutrients)
-also during spore formation when cells lyse (i.e. Clostridium organisms that cause botulism, gas gangrene, and tetanus and the Bacillus organism causing anthrax)
what are the two domains of exotoxins?
which helps transport the other into the host cell?
A and B. B
inds to cell membrane and helps deliver A domain into the cell which has enzymatic activity; are
which toxins covalently transfer ADP ribose from nicotinamide adenine dinucleotide (NAD) to target proteins?
-diphtheria toxin, cholera toxin, and exotoxin A of Pseudomonas aeruginosa
-enzyme is ADP ribosyltransferases
organization of exotoxins
- single AB protein covalently bound (diphtheria)
- complex of 6 proteins AB5 noncovalently bound (cholera)
-2A + B are single proteins that associate on host membrane (for anthrax one A is adenylate cyclase, the other is a protease)
-botulinum toxin blocks muscle contraction --> flaccid paralysis. acts at peripheral nerve ending inhibiting stimulatory NT release (ACh)
-tetanus toxin causes irreversible muscle contractions --> spastic paralysis. migrates up axon, across interneuronal junction into inhibitory neurons where A inactivates vesicle fusion of inhibitory NTs
-composed of single proteins w/ A and B domains. bind to neurons and target host proteins within. A is a protease and cleaves proteins responsible for fusion of synaptic vesicles w/ plasma membrane
-made as protoxins that are activated when they bind to host membranes
-internalized via receptor mediated endocytosis
-A domain blocks host protein synthesis by ADP-ribosylation of EF2
-B domain binds to the host cell membrane receptor, aids in transport into endosome, and helps translocate A into the cytosol.
-modulates cell function by elevating levels of cAMP in the epithelium of the small intestine
-1 A and 5 B domains (AB5)
-A domain ADP-ribosylates a G protein (keeping it in its active conformation) up-regulating adenylate cyclase
-tons of ions and water move into the lumen causing watery diarrhea
-activation of adenylate cyclase is also used by heat-labile enterotoxin of E. coli and pertussis toxin of Bordetella pertussis (causes whooping cough by targeting leukocytes)
-diphtheria toxin --> target is EF2 protein
-Cholera toxin, heat labile enterotoxin (E. coli), and pertussis toxin --> target is G protein
botulinum toxin vs tetanus toxin: paralysis
flaccid paralysis vs spastic paralysis
how do type III cytotoxins enter host cells?
-secreted via injectisome (type III secretion system T3SS). when host cell is contacted, T3SS apparatus creates a pore and the toxins are injected directly into host cytosol
-b/c of this mechanism they are unlikely to contact neutralizing antibodies
bacteria using injectisome/ type III cytotoxins
Salmonella, Shigella, Pseudomonas, cholera bacilli, and plague bacilli
type IV secretion system
protein complex that transports DNA between bacteria via conjugation and cytotoxins into host
- Legionella, Brucella, Coxiella
type V secretion system
autotransport features and IgA1 protease (cleaves mammalian IgA) is secreted by this system
type VI secretion system (microbes only; book doesn't describe mechanism)
Vibrio cholerae and Pseudomonas aeruginosa
type VII secretion system
mycobacteria and some Gram-positive bacteria
which cell type have endotoxin?
Gram-negative bacteria in their outer membrane
another name for endotoxin
lipopolysaccharide (of gram - bacteria)
low concentrations of endotoxin
alarm reactions: fever, activation of complement (alternative path), activation of macrophages, stimulating of B lymphoytes
high concentrations of endotoxin
shock and death
How do structural components of microbes stimulate rapid innate immunity response?
it stimulates our innate immune system via pattern recognition receptors which provides a rapid response to infection and helps activate our adaptive immune system (handles long term resistance)
pattern recognition receptors recognize:
1. endotoxin- Gram-negative bacteria
2. lipoteichoic acid- Gram-positive bacteria
3. lipoglycans- mycobacteria
4. mannans- yeast
3 parts of endotoxin
1. glycolipid: Lipid A (contains uniquely short FAs, active component)
2. core of sugars, ethanolamine, and phosphate
3. O Antigen, long side chain of species specific sugars (antigenic component)
biologically active component?
targets for endotoxin posses specific endotoxin receptors --> toll-like receptors (TLRs) and are present on:
mononuclear phagocytes, neutrophils, platlets, and B lymphocytes. when the pattern recognition receptors bind TLRs they start a signal cascade in the cell which leads to cytokine production and the "alarm reactions"
how does endotoxin cause fever?
mononuclear phagocytes release cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) which set of events known as acute phase response.
Lipoteichoic acid of Gram-positive bacteria causes same progression
what cells cause vasodilation as a result of a small amount of endotoxin? what is the signal?
what cells cause increased antibody synthesis as a result of small amount of endotoxin? what is the signal?
what causes inflammation as a result of small amounts of endotoxin? what causes it?
activation by alternate pathway
effects of low endotoxin concentration
-Membrane attack complex (MAC) is produced and phagocyte chemotaxis and opsonization occur
-neutrophils are activates and C3b opsonization aids phagocytosis
- anaphylatoxins (C3a and C5A) increase capillary permeability and release lysosomal enzymes from neutrophils
what effect does macrophage activation have?
increased production of lysosomal enzymes
enhance rate of phagocytosis
secretion of hydrolases
**limits growth of cancer and potential anticancer agents called biological response modifiers are endotoxin derivatives
IL-1 release induced by endotoxin causes B lymphocytes to divide. Endotoxin is considered what, in this case?
they mature to produce antibodies and aid in long term resistance to infection. Endotoxin is known as a immunological adjuvant
bacterial sepsis and endotoxic shock
Seen in high levels of endotoxin
bacteria overwhelm the body and endotoxic shock occurs causing hypotension and disseminated intravascular coagulation (DIC)
-hypotension mediators: cytokines, nitric oxide, and eicosanoids
-DIC can cause infarction in tissues when blood supply is cut off from thrombi. Waterhouse-Friderichsen syndrome (meningococcal infection) occurs when infarction causes adrenal insufficiency and death is the result
-endotoxin aids coagulation by activating factor XII and setting off the intrinsice clotting cascade, platelets are degranulated, and neutrophils release proteins that stabilize fibrin clots
toxins that harm host cell by damaging membrane
often called hemolysis and include: lipases or pore forming toxins
lipase toxin produced by Clostridium perfringens causing gas gangrene
main substrate is phosphatidylcholine (AKA lecithin) and causes indiscriminate cell lysis
homogenous pore former .Example?
each pore has same number of protein molecules
example is alpha-toxin of Staphylococcus aureus
heterogeneous pore forming toxins. Example?
pores vary in size and number of monomer toxin molecules
prototype is streptolysin O produced by certain streptococci. is oxygen labile and binds to cholesterol lyses RBCs also favors membranes of lysosomes releasing hydrolytic enzymes leading to apoptosis of WBCs
stimulate production of large amounts of antibodies not directed against itself. they complex MHC molecules of antigen-presneting cells with T-cell receptor on lymphocytes to stimulate antigen-independent activation of lymphocytes
toxins that act in the extracellular matrix of the cell
-degradative enzymes that are spreading factors which disperse pathogen
-gram+ release hyaluronidase breaks down hyaluronic acid the ground substance of CT
-gram+ release deoxyribonuclease (DNase) thins pus made viscous by the DNA released from dead white blood cells
-streptokinase from Streptococcus progenies activates plasminogen to plasmin that attacks fibrin clots
-collagenases and elastases
Spreading factors, hyaluronidase, streptokinase, collagenases, elastases, and deoxyribonuclease are examples of what kind of toxin? Where do these toxins act?
Exoenzymes; act in the extracellular matrix of the cell
have been used successfully as treatment/vaccination of diseases like tetanus that produce such small amounts of toxin that an effective response does not occur on its own
chemically inactivated toxins (used for tetanus and diphtheria vaccines)
antitoxins are administered to people who have been exposed to toxin producing pathogens.
side effect is serum sickness (immune reaction against foreign proteins)
What constitutes an effective cholera vaccine? Why do current approved vaccines have limited efficacy?
Need to stimulate large amounts of intestinal IgA antibodies. Current vaccines don't stimulate enough production. Oral vaccines made of disarmed pathogen create enough and are being developed for approval
You might also like...
clinical microbiology lecture 18
Microbiology Chapter 15 Troy University
Bacterial Pathogenesis: Virulence Factors
Exam 3 Ch 15
Other sets by this creator
Micro 17: Invasive and Tissue- Damaging Enteric Ba…
Micro 16: Enteric Bacteria- Secretory Di…
Path 19: The Pancreas
Path 14 Red Blood Cell and Bleeding Diso…