4: Cellular innate immunity: neutrophils, macrophages, phagocytosis Flashcards
what is phagocytosis?
the ability of some cells to ingest foreign particles
what are professional phagocytes?
neutrophils and macrophages
List the sequence of events in phagocytosis and describe each:
Chemotaxis- delivers the phagocytes to the site of infection
1. Adherence (phagocytic adherence to the target (receptor))
2. Ingestion (engulfment of the target particle)
3. Destruction (intracellular killing and digestion of the target)
3a. Egestion (ONLY IN MACROPHAGES)
what facilitates adherence and ingestion in phagocytosis?
opsonization
what can neutrophils not bind to>
hydrophilic substances
what is opsonization>
the coating of hydrophilic substances with opsonins (IgG, IgM, C3b)
what are the membrane receptors of neutrophils?
- Fc receptor- bind to antibodies that are bound to an antigen especially, IgG
- C3b receptor- bind to C3b when it is coating bacteria
what is a phagosome?
a membrane-bound vessicle containing an ingested microbe or material
what is a phagolysosome?
a fused vessicle that includes the membrane of the phagosome and the lysosome
what is the process of destruction in neutrophils?
1.bind to opsonized microbes via specific receptors
2. formation of a phagolysosome
3. intracellular killing
what happens inside the phagolysosome?
the killing and digesting of the engulfed microbe
what are the 3 processes by which neutrophils destroy invading pathogens?
- lytic enzymes and antimicrobial peptides from granules
- oxidative metabolism (respiratory burst)
- neutrophil extracellular traps
where are the primary granules of neutrophils and macrophages stored?
lysosome
what are the primary granules of neutrophils and macrophages?
- hydrolases
- lysozymes
- myeloperoxidases
- defensins
what are the function of hydrolases?
break covalent bonds by adding water (important for degrading dead bacteria/tissues)
what are the functions of lysozymes and where are they found?
break down peptidoglycan in gram + bacteria
found in many secretions by the body
what are defensins?
small cationic proteins that kill bacteria (gram +)
what is the other name for defensins?
antimicrobial peptides
what are myeloperoxidases?
an enzyme that has an important role in oxygen mediated killing mechanism
what are the secondary granules of neutrophils and macrophages?
- Lysozymes (like primary)
- Lactoferrin
- Collagenase
what is the function of lactoferrin?
chelates iron (bacteria need iron to survive)
what is the function of collagenase?
degrade connective tissue
what is the most potent killing mechanism of a neutrophil?
oxygen-mediated (respiratory burst)
describe neutophil NETs/Traps:
stimulated by LPS/CXCL8(IL-8) which causes the neutrophil to release its nuclear material and granular material (DNA, histones, granular proteins) extracellularly
what is the first cell to the site of infection?
neutrophils followed by monocytes that differentiate into macrophages
what is the function of macrophages?
-promote inflammation or resolution (M1/M2)
-secrete cytokines and chemokines
-phagocytosis
-secrete chemokines IL-8 that attracts neutrophils
-remove dying neutrophils
macrophages are also ???
APCs they present the MHC in their cell membrane helping initiate the adaptive immune response
what makes up the characteristic properties of pus?
dying neutrophils
if neutrophils fail to bind (respond) to the CD31 receptor on macrophages what happens?
macrophages phagocyte neutrophils
M1 macrophages are also called?
pro-inflammatory (classical activation)
M2 macrophages are also called?
anti-inflammatory (alternative activation)
what is the pathway of activation for M1 macrophages?
- bind to TLRs
- innate activation (upregulate phagocytotic characteristics)
- scretes IFN- gamma
- classical activation (increased size, movement, phagocytosis, bactericidal activity)
NETs catch and kill?
bacterial and fungal cells
what is commonly seen with bacterial infections?
neutrophilia
what is commonly seen with viral infections?
neutropenia
what is cyclic neutropenia?
a disorder in dogs that have a deficiency in the bone marrow that decreases neutrophil production
what is the pathway of activation for M2 macrophages?
- bind to IL-4,10,13
- anti-inflammatory response (increased tissue repair, increased MHC class 2 expression, reduced microbial killing)
what is the lifespan of neutrophils?
1-2 days
what is the percentage of neutrophils in WBC circulation in humans and most animal species?
55-90%
what is the percentage of neutrophils in WBC circulation in cows?
25-30%
what is the percentage of monocytes in WBC circulation?
3-7%
macrophages are found in most tissues and are known as what?
resident cells
what is a sign of chronic infection?
macrophage accumulation at the site of inflammation.
what is a granuloma?
focal aggregate of immune cells (predominantly macrophages) that forms in response to a persistent inflammatory stimulus
what is the lifespan of monocytes/macrophages?
circulate for 1-2 days then migrate to tissue then differentiate into a macrophage
can neutrophils phagocytose multiple times?
no
