Lecture 6 Flashcards
2 types of virulence factors?
colonization of the host and damage to the host
3 things that damage the host
ability to produce PAMPs, harmful exotoxins, and inducing autoimmune response
what do pamps recognition promote?
synthesize and secrete inflammatory cytokines and chemokines
what does the complement pathway lead to?
inflammation, opsonization of bacteria, chemotaxis of phagocytes
what does the coagulation pathway lead to?
clotting of blood to stop bleeding, more inflammation, and localization of infection
what do PAMPs activate?
toll like receptors (TLR’s)
what are the three importances of nf-kb?
pro inflammatory response, anti-apoptopic function, cellular growth
what is nf-kb before dimerization?
it is a transcription factor resting in the cytoplasm in complex with Ikb then its stimulated and released lkb and nfkb forms to go to nucleus and binds kb sites to activate target genes
how do different heterodimers vary?
preference for kb binding sites, kinetics of nuclear translocation, and abundance in different cells
what happens when TLR4 and LPS binding receptors together recognize LPS?
NF-kb is activated and induction of cytokines and other anti microbial genes
what happens once nfkb releases cytokines?
activation of coagulation pathway, prostaglandins, leukotriens, and activation of complement pathways
what specifically does the damage to the capillary walls?
chemokines cause neutrophils that are adhered to the capillary walls to release proteases and toxic oxygen radicals that harm
what factors lead to acidosis?
combination of hypotension, hypovolemia, DIC, loss of perfusion and ARDS. all these lead to decreased cardiac output
what factors lead to heart failure?
cytokine induced overproduction of Nitric Oxide by cardiac muscle
prolonged vasodilation and increased capillary permeability do what?
plasma leaves the bloodstream and enter the tissue, decreased vascular resistance results in drop of BP and reduced perfusion of blood through tissues and organs, decreased volume of circulating blood
activation of blood coagulation pathway and concurrent down regulation of anticoagulation does what?
clots form within the blood vessels throughout the body called disseminated intravascular coagulation, further drop in blood and oxygen supply through tissues and organs
increased capillary permeability and injury to capillaries in the alveoli of the lungs does what
pulmonary edema and loss of gas exchange leads to acute respiratory distress syndrome
what does reduced perfusion and capillary damage do?
impaired liver function and a failure to maintain normal blood glucose levels and kidney and bowel injury meningitis
what are the percentages of responsibility for septicemia?
45% from gram positive, 45 from negative and 10 from fungi
what are the direct enzymatic mechanisms that affect target cells from toxins?
facilitate spread through tissues, damage cell membranes, immunomodulatory, inhibit protein synthesis, inhibit release of neurotransmitters
what does each subunit in subunit toxins do?
a subunit does enzymatic toxic activity, protein synthesis inhibitors, and adenylate cyclases
B unit mediates binding to host cell receptor, facilitates translocation of A sub unit
what do proteolytic toxins do?
zinc metalloendoproteases inhibit release of neurotransmitters
IgA proteases- made from pathogens that colonize mucosal surface, can autosecrete, cleaves secretory IgA1
what do pore forming toxins do?
rtx family is produced by many gram negative, induce cytolytic effects
sulfhydryl activated family is produced by gram positive, mediates escape from macrophage vacuole and activity is triggered by low pH
what do cytoskeletal modulator toxins do?
alter host cell actin filament polymerization state, antiphagocytic and necrotic effects
what do pyrogenic exotoxins do?
they are potent activators of T cells and T lymphocytes, suppress B cell responses, enhance susceptibility to LPS, and stimulate strong cytokine production
what are some characteristics of SEB?
easily soluble in water, very resistant to temperature fluctuations
what are the steps required for intoxication of cells by Dip toxin?
binding to the cell surface, activation by proteolytic cleavage by FURIN, receptor mediated endocytosis, conformational change within endosomes, translocation across the endosome membrane into cytosol, ADP-ribosylation of EF-2 (causes protein inhibition)
when do autoimmune responses happen?
production of cross reacting antibodies, auto reactive cytotoxic t lymphocytes or CTLs which is further stimulated by the classical complement pathway what
what are immune complexes and how do they cause problems?
formed when high levels of circulating antibodies react with certain bacterial antigens, they can lodge in filtering units such as the kidneys where they activate the complement pathway and destroy kidneys
what are the gram negative type 1 secreted proteins?
RTX toxin, E. coli hemolysin, bacteriocins, metalloproteases
what are the gram negative type 2 secreted proteins?
proteases, cellulases, pectinases, lipases, phospholipases, and AB toxins
what bacteria use the type 4 gram negative secretion?
B pertussis- pertussis toxin, H pylori-CagA and L pneumophila
what are the types of gram negative secretion systems? (just 1-3)
type 1- ATP binding cassette ABC transporter
type 2- general pathway (sec dependent) major secretory pathway
type 3- contact dependent translocation into eukaryotic cells
types 4-5 and tat and srp secretion systems?
type 4- sec like dependent, translocation of DNA/protein complex
type 5- auto transporter (sec dependent) includes b-pore forming domain
Tat (twin arginine transport)- moves folded proteins across CM
SRP-(signal recognition particle)- sec dependent used for CM proteins
what are the differences for gram positive secretion systems?
for type 3 it is instead oligolysin dependent translocation
there is no type 4
