Lecture 5 - Phagocytosis Flashcards
What is phagocytosis
ability of some cells to ingest foreign particles
What are phagocytes
class of cells which are capable of ingestion and
killing of microorganisms that incite inflammatory response
What cells are the first to accumulate around invaders and initiate phagocytosis
neutrophils
What are the second cells to migrate to the tissue site and intiate phagocytosis
local and blood-borne macrophages
Neutrophils and macrophages are sometimes referred to as _____ for their roles in phagocytosis
professional phagocytes
What are the 2 professional phagocytes
neutrophils and macrophages
What are the 4 steps of phagocytosis
- chemotaxis
- adherance
- ingestion
- destruction
What is chemotaxis (in regards to phagocytosis)
delivery of phagocytic cells to the infection site
What is adherance (in regards to phagocytosis)
phagocytic adherance to the target
What is ingestion (in regards to phagocytosis)
engulfment of the target particle
What is destruction (in regards to phagocytosis)
intracellular killing and digestion of the target
What part of phagocytosis is only in the case of macrophages
egestion
What can neutrophils phagocytose
anything more HYDROPHOBIC than itself
What is opsonization
coating of a hydrophilic material
with opsonins that include IgG, IgM, C3b, etc
What happens after opsonization of a hydrophilic substance
allows neutrophils to bind it
What bacteria can neutrophils NOT phagocytose until they are opsonized
bacteria with HYDROPHILIC capsules (Staphylococcus, Streptococcus, Klebsiella)
Why are mycobacteria sp. easily phagocytosed by neutrophils
have hydrophobic capsules
What 2 neutrophil membrane receptors are important for phagocytosis
Fc and C3b
What do Fc receptors bind
antibody that is bound to an antigen, especially IgG antibody
What do C3b receptors bind
to C3b when it is coating bacteria, ect.
What happens once neutrophils bind to opsonized material
it is readily engulfed, forming phagosome
What is a phagosome
membrane bound vesicle containing the ingested microbe or material
What happens when a phagosome migrates into the cytoplasm and collides with lysosomal granules
lysosomal granules explosively discharge their contents into the membrane-enclosed vesicle (phagosome)
What is formed when membranes of the phagosome and lysosome fuse
digestive vacuole called phagolysosome
What can fuse with the phagolysosomes
other lysosomes
What occurs within the phagolysosome
killing and digesting of the engulfed microbe
What does it mean when the killing process is confined to the phagolysosome?
none of the toxic substances and lethal activities of the phagocytes are turned against themselves
What is the first detectable effect on bacterial physiology after phagolysosome formation; and how fast does it occur after engulfment
loss of viability; within a few minutes
What happens 10-30 minutes after ingestion
many pathogenic and nonpathogenic bacteria are killed followed by lysis and digestion of the bacteria by lysosomal enzymes
What are the 3 killing processes
- lytic enzymes and antimicrobial peptides from granules
- oxidative metabolism (respiratory burst)
- neutrophil extracellular traps
What are stored in primary and secondary granules
lytic enzyme and antimicrobila peptides
Where are lytic enzymes and antimicrobial peptides stored
primary and secondary granules
What are the 4 primary granules?
- hydrolases
- lysozyme
- defensins
- myeloperoxidase
What are hydrolases
breaks covalent bonds by adding water, important
for degrading dead bacteria or dead tissues
What are lysozymes
breaks down peptidoglycan in Gram-positive bacteria. Found in many secretions in the body
What are defensins
small cationic proteins that kill bacteria, especially
Gram-positive bacteria; 29-42 amino acids long; hydrophobic outside and hydrophilic interior and insert into a membrane and form a pore
What is another name for defensins
antimicrobial peptides
What is a myeloperoxidase
enzyme that has an important role in the oxygen mediated killing mechanism
What are the 3 secondayr granules
- lysozymes
- lactoferrin
- collagenase
What is lactoferrin
chelates iron- bacteria need iron for survival
What is collagenase
degrades connective tissue, so it can move through to the site of inflammation
What is the most potent killing mechanism of a neutrophil
oxygen mediated killing mechanism
Where does oxygen mediated killing occur
phagolysosome
What are the killing products of the respiratory burst
- hypochlorite
- hydrogen peroxide
- aldehydes
- oxygen radicals (superoxide anion and hydroxyl radical)
What s chronic granulomatous disease
fatal disease causes by defective oxidative enzyme
What are neutrophil extracellular traps (NETs)
Stimulated neutrophils release nuclear material and granular proteins extracellularly
What are NETs neutrophils stimulated by
CXCL8 or LPS
What nuclear material and granular proteins do NETs release extracellular
DNA, histones, granular proteins
What does the extracellular degranulation in NETs creat
mesh that traps bacteria and the antimicrobial proteins kill the bacteria
NET is NOT a result of neutrophil death but an active response to _____
inflammatory stimuli called as NETosis
What is the fate of neutrophils after extended phagocytosis, killing, and digestion of baterial cells AND what does this form
die and lyse; forms pus
What is the fate of macrophages
egest digested debris and allow insertion of microbial antigenic components into the plasma membrane for presentation to lymphocytes in the immunological response
What are the major surface receptors of macrophages
- complement receptors
- antibody receptors
How are macrophages innately activated
TLRs and related receptors
What does IL-4, IL-13, and IL-10 do to macrophages
alternate activation- M2 cells (tissue repair and less microbial killing)
What does IFN-y do to macrohages
classical activation-M1 cells
How does arginine cells activate macrophages
- converted to ornithine, activates M2 cells
- NOS2 activates M1 cells
What is the role of macrophages in chronic infections
prolonged tissue irritation->M2 macrophages accumulate->IL-1, TGFB, fibroblast GF, angiogenic factors->fibrosis->granuloma formation
how do macophages remove dying neutrophils
when CD31 fails to reply, neutrophil is phagocytosed
What cells begin the healing process in damaged tissues?
macrophages
