The Immune Cell Flashcards
Give some special macrophage-like cells in specific tissues?
Microglia in the brain and kupffer cells in the liver.
What are tissue macrophages derived from?
Monocytes that circulate the bloodstream
What is phagocytosis?
A special from of endocytosis also used by macrophages to internalise large particles, eg. Microorganisms.
Give the steps of phagocytosis in macrophages?
- Surrounded by a membrane derived from the plasma membrane
- Phagosome vesicle is formed
- Membrane fusion delivers the antimicrobial molecules to the phagosome- maturation
- Phagolysosome is formed and kills
How do macrophage receptors on the cell surface recognise microorganisms?
Either bind directly (pattern recognition receptors) or bind to the molecules that have optimised the microorganism (opsonic receptors).
How is a phagosome formed?
The actin skeleton has a role in pushing the pseudopods out from the plasma membrane which envelope the microorganism.
During maturation of a phagosome to produce a phagolysosome what happens?
Its contents becomes more acidic and it moves along the microtubules towards the nucleus
How do phagolysosomes kill microorganisms?
Nutrient deprivation, eg. Lactoferrin
Membrane permeabilisation, eg. Defensins
Hydrolases, eg. Lysozyme, phospholipases and proteases
Acidification
Production of reactive oxygen and nitrogen species.
How is tuberculosis is adapted to survive within macrophages?
It arrests maturation by blocking it at an early stage and not allowing other proteins, except for Rab5, to be recruited.
SapM hydrolysis PIP3 which would usually promote fusion of phagosomes containing M.tuberculosis with early endosomes
How does listeria manage to modify and escape from phagosomes?
Listeriolysin O is a toxin secreted by the bacterium which creates pores in the phagosome which allows for calcium and hydrogen ions to escape which blocks fusion as these are required.
Phospholipases are also produced which cause breakdown of the phagosome and the escape of the bacterium.
What are cytotoxic T lymphocytes?
Cytotoxic cells that kill other cells that are abnormal.
What does the receptor on cytotoxic T lymphocytes recognise and what happens?
Peptides presented by MHC class 1 molecules on aberrant cells. This triggers exocytosis of secretory lysosomes which contain perforin (and granzymes) which facilitates the granzymes entry into target cell where they induce apoptosis.
What are secretory lysosomes?
Combine degradative function with exocytosis, they contain lysosomal hydrolyses, transporters and are of an acidic pH but they also store the perforin and granzyme enzymes for exocytosis.
What are membrane fusion reactions catalysed by?
SNARE proteins.
They form a trans-SNARE complex that drives the fusion of the two membranes. Important in exocytosis.
What is FHL-2 and 3?
FHL-2: an immunological disorder in which cytotoxic T lymphocytes are impaired in their ability to kill the viruses infecting cells, it’s caused by mutation in pore forming protein perforin
FHL-3: a mutation in Munc13-4, causes the secretory lysosomes to dock but not fuse to the plasma membrane.
