Bacterial Resistance and Toxins Flashcards
What is the best known of the nutritional defenses associated with?
the derivation of iron from host tissues
How do pathogenic bacteria derive iron from the host?
- producing iron chelating compounds that scavenge iron by competing directly with transferrin and lactoferrin of the host 2. directly removing iron from iron-binding proteins via receptors on the bacterial surface 3. bacteria can obtain iron through degradation of iron-binding and heme-containing proteins
What are the specific bacterial resistance mechanisms?
toxins, avoidance of phagocytosis, inconspicours adherence, parasitism of nonprofessional phagocytes. walling off
How do bacteria survive and grow inside phagocytes?
disrupt phagosome or phagolysosome
prevent phagosome-lysosome fusion
abrogate the oxidative burst
destroy oxygen radicals
modify effects of antibacterial peptides in the phagolysosome
What is the role of toxins in bacteria?
interfere with cell membrane function
interfere with chemotaxis
leukotoxins or cytotoxins that have direct toxic effects on specific cell types (….?)
How do capsular polysaccharides avoid phagocytosis?
they cement organisms together to prevent opsonization by antibody, complement, or other serum proteins and they make organisms less hydrophobic
The mycoplasmas lack a ____ ______ and have a cell membrane that essentially mimics the _____ _______ of the _______.
cell wall, plasma membrane, phagocyte
How do bacteria avoid professional phagocytes?
some bacteria enter cells other than phagocytes (intestinal epithelial cells, bone marrow, etc.) and are thereby shielded from the professional phagocytes
How do abscesses become walled off?
some bacteria stimulate the host to form a wall around them so that they are not exposed
How can bacteria circumvent the cellular immune response?
- changing the antigens on their surfaces or 2. suppression of the immune response (chronically infected macrophages may produce prostaglandin E2 and other factors that suppress lymphocyte proliferation)
Are T-cells required for simple polysaccharides to stimulate an immune response?
no
For a t-independent immune response, what is the ontogeny of the response?
late
Is there induction of memory in the T-independent response?
no
Is there isotype restriction in the T-independent response?
yes
Is there affinity maturation in the T-independent response?
no
For complex polysaccharide and protein antigens, are T cells needed for an immune response?
yes
What is the ontogeny of response for T-dependent response?
early
Is there induction of memory in the T-dependent response?
yes
Is there isotype restriction for the T-dependent response?
no
Is there affinity maturation in the T-dependent response?
yes
How can simple polysaccharides be converted to T-cell dependent antigens?
by complexing them with protein or some other more antigenically complex material that increases the immunogenicity of the bacterial polysaccharide
What are the steps of the exogenous pathway?
- organism or protein is phagocytosed or endocytosed 2. organism or protein is broken down into antigenic peptides in the phagosome 3. antigenic peptides associate with MHC Class II molecules 4. antigenic peptides are presented to CD4+ T-cells 5. CD4+ T-cells produce cytokines. The end results are either a cytotoxic response or the stimulation of B-cells to produce antibody
What are the steps of the endogenous pathway?
- organism replicates in the cytoplasm of the host cell 2. organism is degraded into antigenic peptides by cytoplasmic enzymes 3. antigenic peptides associate with MHC Class I molecules 4. antigenic peptides are presented to CD8+ T-cells 5. CD8+ T-cells kill host cells that are infected with viruses, bacteria, or parasites
Where does the toxic effect reside in bacterial toxins?
lipid A
How does endotoxin act on cells?
it binds to CD14 with the help of lipopolysaccharide binding protein (LBP)
What immunological effects does LPS have?
it acts as an adjuvant, it is a T-independent mitogen that produces polyclonal B-cell activation and a predominantly IgM response, and it activates complement via both the classical and alternate pathways
What is the majority of the immune response directed towards in regards to endotoxins?
The O-antigen because it is exposed on the surface of bacteria
Draw an endotoxin.
Should look like this
What are exotoxins?
soluble proteins produced and excreted by both gram-positive and gram-negative bacteria
Are endotoxins or exotoxins more toxic?
exotoxins
Are exotoxins heat labile or heat stable?
heat labile
What can exotoxins be converted into?
toxoids
How are exotoxins chategorized?
based on their mechanism of action
What are the categories of exotoxins?
- cytotoxic toxins 2. toxins with intracellular activity 3. others (includes those with unknown mechanisms)
What is the role of hemolysis in disease?
hemolysis is RBC damage - too much RBC damage can cause death
What is the function of cytolytic toxins?
they may lyse cells or merely produce membrane effects that result in permeability changes
What are phospholipases and what do they do?
they are major components of the plasma membranes of mammalian cells that hydrolyse glycerophospholipids and sphingolipids
What are cholesterol-binding cytolysins and what do they do?
thiol or sulfhydryl activated cytolysisns, otherwise knwon as oxygen-labile hemolysins, that bind and sequester cholesterol in cell membranes leading to cell lysis
What type of bacteria produce cholesterol-binding cytolysins?
gram-positive bacteria
What do RTX toxins do?
form pores in cell membranes that either inhibit the function of the cells or kill them
What does the S. aureus leukocidin do?
it affects PMN’s and macrophages from rabbits and humans and causes marked granulocytopenia followed by granulocytosis
What are toxins with intracellular activity frequently composed of?
two polypeptide chains
What is the role of the B subunit in toxins with intracellular activity?
it is responsible for binding the toxin to receptors on the target cell
What is the role of the A subunit in toxins with intracellular activity?
it enters the cell
In order for the intracellular toxin to have a toxic effect, what must happen?
the A chain or fragments of it need to be split off from the toxin
How is the A chain split from the toxin?
proteolysis or reduction of disulfide bonds
Some of these bacterial toxins that have intracellular effects mimic hormones. What is the role of the A and B subunits?
the B subunit is responsible for binding and the A subunit is responsible for increasing intracellular cyclic AMP
Which toxins activate adenylate cyclase?
LT toxin of E. coli, cholera toxin, pertussis toxin, and anthrax toxin
How does LT toxin activate adenylate cyclase?
it binds to GM1 ganglioside on the cell membrane, trypsin cleaves the two subunits, and the A subunit is transported into the cell
How does pertussis toxin activate adenylate cyclase?
it affects a regulatory inhibitor subunit of cAMP in islet cells in the pancreas leading to increased insulin production
How does anthrax toxin activate adenylate cyclase?
It acts as an A-B structure toxin. The toxin has three subunits (1 B and 2 A subunits). One of the A subunits causes increased cAMP levels and the other is a proteolytic enzyme that cleaves MAPK-ERK kinase and interferes with the immune response
Which toxins inhibit protein synthesis?
exotoxin A (in C. diptheriae and pseudomonas aeruginosa) and shiga toxin
How does exotoxin A and shiga toxin inhibit protein synthesis?
it uncouples protein synthesis by NAD-dependent ADP ribosylation of elongation factor 2
What is a superantigen?
a protein antigen that is able to bind directly to the variable beta region of the T-cell and stimulate large numbers of T-cells to release interleukins 2 and 4
What is an example of a superantigen toxin?
toxic shock syndrome toxin
What are examples of toxins in the ‘other’ category?
tetanus neurotoxin and neurotoxins of Clostridium botulinum
What is a Type 1 bacterial secretion system?
a chaperone-dependent secretion system that utilizes the Hly and TolC gene clusters to move ions, drugs, proteins, and some polysaccharide compounds out of the bacterium
What are examples of toxins that are secreted by the type 1 bacterial secretion system?
RTX toxins and lipases
How does the type 2 secretion system work?
the system uses one system to move substances to the periplasm and then uses a complex of pore forming secretin proteins to span the outer membrane
How does the type 3 secretion system work?
the system is homologous to the basal body of bacterial flagella and basically acts like a molecular syringe to inject proteins directly into eukaryotic cells
What triggers the type 3 secretion system?
the low calcium concentration in the cytosol triggers the secretion mechanism
What are some examples toxins secreted via the type III secretion system?
Salmonella, Yersinia, and Vibrio
How does the type 4 secretion system work?
the system is homologous to conjugation systems of bacteria and is capable of transporting both DNA and proteins into and out of the bacteria cell
What are some examples of toxins that use the type 4 secretion system?
Bordatella pertussis, legionella pneumophila, and helicobacter pylori
