B3: neutrophils, macrophages, NK cells, interferon (innate immune system)

what are granulocytes?

class of white blood cells that posses granules in their cytoplasm

why are neutrophils called granulocytes?

neutrophils have granules

what’s in the granules (generally speaking)?

packed with toxic chemicals and enzymes

• defensins

• hydrogen peroxide

• hypochlorous acid (bleach)

where are neutrophils normally?

roam in blood and lymph

how do neutrophils respond to signs of an infection?

recognize sites of inflammation and move into tissues by squeezing though the gaps in the blood vessels

what do neutrophils use to find the site of cell damage?

move by chemotaxis to site of cell damage

hunt bacteria in the tissue

usually first immune cells to arrive at the scene

what are the 3 stages of phagocytosis?

attachment/adherence

ingestion

digestion

phagocytosis: what happens in attachment/adherence

neutrophils are usually looking for a signal/target

what are the receptors of a neutrophil recognize?

bacterial molecules

• LPS

• peptidoglycan

• teichoic acid

• flagella

will also recognize antibody-bound objects (adaptive)

phagocytosis: what happens in ingestion?

neutrophils extend their cell membrane (pseudopods) so that it wraps the bacterium, bringing it into the cytoplasm

phagocytosis: what happens in digestion?

phagosome fuses with granules

granule contents destroy/degrade bacteria

what are the consequences to surrounding tissues when neutrophils respond?

tissue damage from granules contents

release chemicals that attract more immune cells

• as long as they find PAMPs → they’re going to send out more signals for inflammation

• more neutrophils will come → more damage

what are macrophages?

agranulocytes: no visible granules under the microscope

• actually have similar structures, lysosomes

where are macrophages normally found?

everywhere:

• alveolar macrophages (lungs)

• splenic macrophages (spleen)

• microglial cells (nervous system)

• also some patrolling in the blood

how is macrophage’s respond to an infection similar to a neutrophil?

recognize bacteria via receptors to conserved proteins

adhere/ingest/digest bacteria, signal for inflammation

how is a macrophage’s respond to an infection not similar to a neutrophil?

fuse phagosome with a lysosome

lysosome kills bacterium

what are lysosomes?

normal digestive compartment that all cells have

how are lysosomes different from granules?

lysosomal chemicals are relatively gentle

little or no tissue damage

what other cells do macrophages consume other than bacteria?

clearance of dead/dying “self” cells

ex: RBCs → macrophages engulf, digest, and recycle the parts

do macrophages generally cause tissue damage as they act?

no! which is why they are found everywhere

what is the same with macrophages and neutrophils?

both are phagocytic cells that can recognize PAMPs

what is different with macrophages and neutrophils?

neutrophils are the FIRST to arrive

• potent granules, great at killing bacteria

• also causes some collateral damage to tissues

macrophages arrive LATER

• clean up remaining bacteria

• clear out damaged cells by the neutrophils

in sensitive tissues, would you find neutrophils, macrophages, or both?

usually only macrophages

limits of phagocytosis

some pathogens are too small and numerous → viruses

some pathogens are too large → helminths

what are natural killer cells?

non-phagocytic immune cells

carry granules loaded with toxic chemicals

what do natural killer cells do?

probe cells looking for abnormal proteins

how do NK cells sense that an infection may be occurring?

absence of “normal” proteins = kills cell

presence of “abnormal” proteins (PAMPs) = kills cell

presence of bound antibodies = kills cell

what does it mean that a NK cell looks for the absence of “normal” proteins?

is the cell displaying proteins that are supposed to be displayed?

give an example when a cell would not be displaying its normal cells?

if a cell was infected a virus

• stop producing normal proteins

• NK cells eliminate the source of the virus to slow down/eliminate the rate of the virus

how do they attempt to stop the infection? what’s the effect on the infected cell?

infuse with the cell and injects its contents into the cell

cell dies

what infectious agents are NK cells better at attacking than either neutrophils or macrophages?

one of the only innate defenses against viruses

• helps infected cells kill themselves before too much harm is done

plays a role in clearing developing tumor cells

• a cell would stop producing proteins if it is becoming cancerous

• NK cells with spot and kill them

what kinds of microbial assault is interferon designed to combat?

secreted molecules that warn cells to put up antiviral defenses

recognize viral molecules, trigger interferon production

describe how an interferon response works

an infected cell can recognize they’re infected

trigger interferon response: produce interferons and secrete them

interferons float around and hit receptors on neighboring cells

neighboring cells respond by turning on the production of antiviral proteins

antiviral proteins make the cell more resistant to infection

does interferon help the original infected cell defend itself? who does it help?

does nothing to help the infected cell (immune system may clear infected cell (NK cells))

interferon acts locally, warning nearby cells to defend themselves

why aren’t the interferon-based defenses simply on all the time?

interferon response is costly → causes problems with how our body normally functions