lec 2: innate and inflammation Flashcards
(36 cards)
Describe what happens during phagocytosis by a macrophage?
Start out with macrophage and pathogen
Pathogen binds to TLR
Membrane surrounds pathogen
Pathogen is internalized into a phagosome
Macrophage has a lysosome and phagosome fuses with a lysosome
Since lysosome is filled with all the enzymes it can break bacteria into bits
New compartment formed is phago-lysosome
Lysosomal enzymes now digest bacteria and breaks them into peptide bits that bind MHC (hotdog bun)
MHC activates a T-cell response (when absent, Natural Killer Cells respond)
This whole process can happen with or without TLR’s present (+ or – TLR’s)
TLR’s
Toll-Like-Receptors, found on macrophages (though not needed by them to eat things) and all sorts of cell types
act to recognize different chemical structures on foreign cells (such as lipopolysaccharides or cilia or bacterial DNA)
stimulates DANGER signal- there’s a microbe here!
tells macrophage what kind of microbe it is (worm, bacteria, virus, parasite, food)
phago-lysosome
after a microbe has been phagocytosed by a macrophage, a lysosome merges with the phagosome to form a phago-lysosome, in which the microbe is digested
What else is released after entry/infection by a microbe?
Cytokines, lipid mediators, chemokines, co-stimulatory molecules, ROS
What are cytokines?
- Small proteins (less that 25 kd) that are released in response to a stimuli that can induce responses in other cells
- Initially named interleukins (IL) because they mediated communication between WBC
- Other cytokines were named on their function I.e. TNF – tumor necrosis factor–named on ability to kill tumors but can kill any cell that has tumor necrosis receptor on it
What does IL-1 do?
Interleukin-1 gives you a fever, and neurologically, results in malaise, depression, fatique
IL-6?
fever, neurologically- anxiety
TNF a (alpha)?
“Tumor necrosis factor”– kills tumors, makes you more hostile, Increases endothelium adhesion molecules (so neutrophils can “stop” at site of infection)
Changes cell junctions
TGF b (beta)?
“transforming growth factor”– allows tumors to grow, shuts down immune system in response to food, for example
INF y (gamma)?
“Interferon”– interferes with the growth of viruses
IL-8
is a chemokine, moves neutrophils to the site of infection/causes chemotaxis
what are cytokines produced by adipocytes called?
adipokines
chemotaxis
chemically prompted movement, as spurred by chemokines like IL-8
Macrophages and DC attract other WBC to go from place with lower concentration to place with increased concentration and come help (positive chemotaxis)
ex: bugs bunny and pie, clapping by audience at a blazers game to move person toward fridge
What is sickness behavior?
caused by IL-1, IL-6, and TNFa, malaise, fatigue, depression, anxiety, hostility associated with inflammatory responses to antigens
complement proteins do what?
within the 1st 4 hours of an infection, a cascade of proteins called complement proteins will go poke holes in bacteria using a “MAC” attack, or Membrane Attack Complex
these proteins circulate in your blood to mediate inflammation
what cells respond to infection first?
macrophages and dendritic cells
when/where do neutrophils act?
neutrophils hang out in blood vessels, tethered to the wall, and await a signal from an acute phase protein, then their let go and head to site of infection
STOP (still to adhesion proteins at infection site), DROP (squeeze through vessel wall), ROLL(move to site of infection)
once they’ve killed what’s at the site of infection, they die and make PUS
macrophages eat your pus
gross.
awesome.
what are macrophages called in your blood, tissue, and brain?
monocytes, macrophages, and astrocytes
after a macrophage has been signaled that danger is imminent, what does it do?
it stimulate teh T cells to create teh correct immune response for that particular microbe
What are other innate acute phase protein or cells involved in the response to infection?
Kinins, CRP’s (complement reactive proteins used to measure inflammation in blood test), complement, neutrophils, macrophages, dendritic cells
what are some ways a microbe can prevent getting eaten by a macrophage?
Block uptake (ex: salmonella) Block fusion with lysosome (ex: tuberculosis) Poke holes in the phago-lysosome to escape into the cytoplasm of the cell (ex: listeria)
Name 3 products of signaling through a TLR, or, what are some danger signals?
ROS, Prostaglandins, Leukotrienes Cytokines, adhesion molecules, Costimulatory molecules, Chemokines, lipid mediators
What are co-stimulatory molecules?
“Proteins on the surface of cells that give a “second signal” to T cells or B cells”
mechanism of tolerance if CD86 is not there–
CD28 does not bind to it then, because there is no second signal that a pathogen is present
(I am a bit confused here, because the T cell can still have bound to something the macrophage has presented on its surface, so this seems redundant and/or contradictory)
ROS refers to what
Reactive Oxygen species, or FREE RADICALS
O2/Super oxide (converted to hydrogen peroxide when acted upon by super oxide dismutase)
H2O2/Hydrogen Peroxide (+ metal makes hydroxide=very damaging)
both above act on lipids
O2+ NO= ONOO!= peryoxynitrite
ONOO! +CO2= damages proteins
