67 Structures, Receptors and Functions of Monocytes and Macrophages Flashcards
The major lineage regulator of nearly all macrophages
Monocyte/macrophage colony-stimulating factor (M-CSF; also termed CSF-1)
The functions of mononuclear phagocytes
- Phagocytosis, killing, and digestion of microorganisms, particulate material, or tissue debris;
- Secretion of chemical mediators and regulators of the inflammatory response;
- Interaction (as dendritic cells) with antigen and lymphocytes in the generation of the immune response;
- Cytotoxicity, such as killing of some tumor cells; and
- Other functions specific for macrophages of particular tissues
In the presence of endothelial cells grown on an extracellular matrix, monocytes differentiate along two distinct pathways: toward ______________ or__________________
Dendritic cells OR Macrophages
Monocytes that migrate across endothelium in an abluminal to luminal direction differentiate into dendritic cells. In contrast, monocytes that remain in the subendothelial matrix differentiate into macrophages.
Monoblast or Promonocyte
Have characteristic deeply indented, irregularly shaped nuclei with condensed chromatin, and numerous cytoplasmic microfilaments
Promonocyte
Promonocyte or Monocyte
Nucleus occupies approximately half the area of the cell and usually is eccentrically placed, chromatin net with fine strands bridging small chromatin clumps, cytoplasm is spread out, stains grayish-blue
Has clear cytoplasmic vacuoles
Monocyte
Characteristic of monocyte in phase microscopy
- Nucleus has a distinct chromatin pattern on a cloudy background
- The cytoplasm is clear gray.
- Reniform nucleus with a juxtanuclear depression filled by a centrosome and its active undulating movement similar to that of other leukocytes
A striking feature on phase-contrast microscopy that differentiates a small monocyte from a large lymphocyte
The ruffled plasma membrane that forms prominent phase-dense folds at the cell surface and edge
Monocyte cytoplasmic granules contain these primary lysosomes:
Acid phosphatase and arylsulfatase
TRUE OR FALSE
Most lysozyme produced by mononuclear phagocytes is secreted rather than stored intracellularly.
TRUE
Most lysozyme produced by mononuclear phagocytes is secreted rather than stored intracellularly.
TRUE OR FALSE
Monocytes also give a weak but positive periodic acid–Schiff reaction (for polysaccharides) and a Sudan black reaction (for lipids).
TRUE
Monocytes also give a weak but positive periodic acid–Schiff reaction (for polysaccharides) and a Sudan black reaction (for lipids).
Frequently used as a marker for monocytes
Nonspecific esterase
Monocyte esterases are inhibited by sodium fluoride, whereas the esterases of the granulocytic series are not.
Monocyte esterases are inhibited by _________
Sodium fluoride
Monocyte esterases are inhibited by sodium fluoride, whereas the esterases of the granulocytic series are not.
Distinguish marrow monocytes from early myelocytes
Primary lysozyme granules of monocytes
Acid phosphatase, arylsulfatase, and peroxidase
Synovium macrophages
Type A cells
Human marrow promonocytes and blood monocytes contain granules that comprise two functionally distinct populations
- Those with the enzymes acid phosphatase, arylsulfatase, and peroxidase (analogous to the azurophil granules of the neutrophil)
- Those that lacks alkaline phosphatase
The fixed macrophages of the spleen
Littoral cells
The macrophages of the marrow
“nurse cells” of the erythroblastic island
Hepatic macrophages
Kupffer cells
Connective tissue macrophages
Histiocytes
Spleen macrophages
Red pulp macrophages
Bone macrophages
Osteoclasts
Surface antigen of macrophages
CD68, also known as macrosialin
A relatively constant feature of cells engaged in endocytosis
Large number of microvilli at the cell surface
The most constant and characteristic ultrastructural features of macrophages
Electron-dense membrane-bound lysosomes
Markers of classical monocytes which comprise 90% to 95% of total circulating monocytes
CD14+-bright/CD16-negative cells
When dendritic cells (DCs) mature into ______________________, they have reduced uptake capacity and induce an adaptive immune response or tolerance.
Antigen-presenting cells (APCs)
FcRs are divided into three distinct classes:
FcRI /CD64
FcRII/ CD32
FcRIII/ CD16
FcR that found on monocytes, macrophages, and activated neutrophils, binds MONOMERIC IgG and can play a role in granulocyte-mediated antibody-dependent cytotoxicity
FcRI /CD64
FcR that is present on many cell types, bind COMPLEXED IgG (rather than monomeric), regulates B-cell function and can induce mediator release from myeloid cells and phagocytosis of Ig-coated particles
FcRII/ CD32
FcR that is expressed by neutrophils, natural killer (NK) cells, and tissue macrophages, bind Ig in IMMUNE COMPLEXES and Ig BOUND TO CELL-SURFACE MEMBRANES
Responsible for antibody-dependent cellular cytotoxicity.
FcRIII/ CD16
All three FcRs specifically bind the human IgG subclasses _______
IgG1 and IgG3
Complement receptor that binds dimeric C3bi and is found on both monocytes and macrophages.
(CR) 1 (or CD35)
Complement receptor that binds the complement fragment C3b.
CR3 (or CD11b)
Leukocyte integrin (β2) subfamily
Lymphocyte function–associated antigen (CD11a)
CR3 (or CD11b)
α-X integrin chain (CD11c)
Share a common β subunit (CD18)
Are key molecules responsible for alerting the innate immune system to the presence of microbial infections.
Toll-like receptors
Toll-like receptors implicated in viral nucleic acid recognition
TLRs 3, 7, and 9
Elimination of the integrin β2 subunit causes
Leukocyte adhesion deficiency type I
Non–Toll-Like, Nonopsonic Receptors
Scavange receptors (SR-A I/II, MARCO, CD36)
Lectins (Dectin-1, DC-SIGN, Mannose receptor,C-type lectin domains, Cysteine-rich domain, Fibronectin type II domain)
Non–Toll-Like, Nonopsonic Receptors: mainly involved in endocytosis, with a predominant intracellular localization.
Mannose receptor
Non–Toll-Like, Nonopsonic Receptors: a lectin-like receptor that is widely expressed on myeloid cells, with a single immunoreceptor tyrosine-based activation motif (ITAM)–like motif in its cytoplasmic tail
It recognizes β glucans, abundant in fungal walls, including bioactive zymosan particles, and has been implicated in innate resistance to fungal infection.
Dectin-1
Non–Toll-Like, Nonopsonic Receptors: implicated in mycobacterial recognition as well as in the uptake and exchange of lipids
Class B SRs, such as CD36 and SR-BI
Non–Toll-Like, Nonopsonic Receptors: plays a role in apoptotic cell uptake and has been implicated in macrophage fusion
CD36, thrombospondin
Class II MHCs
Human leukocyte antigen (HLA)-DR, HLA-DP, and HLA-DQ
Induce macrophages to express higher levels of MHC class II antigens
IFN-γ
Downregulate HLA-DR antigen expression on macrophages
Prostaglandin E, α-fetoprotein, and glucocorticoids
Type of CD11 expressed on more than 95% of fresh human monocytes and macrophages
CD11b
Whereas CD11a is expressed on all leukocytes, CD11b and CD11c are expressed predominantly on monocytes and macrophages, a minor subset of B lymphocytes, and most polymorphonuclear leukocytes.
Antibodies specific for CD11b, may block this CR’s ability to bind to CD3bi
It strongly inhibit CR-mediated rosetting of erythrocyte–IgM antibody– complement complexes.
OKM1 or Mo1
CD11b is expressed on more than _____% of fresh human monocytes and macrophages
More than 95%
Protein that is expressed on the outer leaflet of apoptotic cells, contributes to apoptotic cell recognition
Phosphatidylserine (PS)
Pathogenic mechanisms of different organisms on monocyte/macrophage phagocytosis
- Inhibit acidification and fusion (Mycobacterium)
- Multiply within secondary lysosomes (Leishmania)
- Escape free into the cytosol (Listeria)
- Translocate their genomes into the cytoplasm by fusion (enveloped viruses)
A major myelomonocytic product of macrophages that is constitutively expressed in vitro but is upregulated in granulomata in vivo
Lysozyme
Has function in priming of biosynthetic and functional responses associated with cytotoxicity and inflammation in cell-mediated immunity
IFN-γ
The initial name of IFN-γ was macrophage activating factor
Monocytes differentiate along two distinct pathways:
Dendritic cells or macrophages
Precursors of monocytes
Monoblasts and promonocytes
A striking feature on phase-contrast microscopy of monocytes
ruffled plasma membrane
Elimination of the integrin β2 subunit causes
Leukocyte adhesion deficiency type I
Receptor thaht is mainly involved in endocytosis, with a predominant intracellular localization
Mannose receptor
Receptor that displays dual functions, contributing to the clearance of mannose-terminal lysosomal hydrolases and of neutrophil granule glycoproteins such as myeloperoxidase (MPO), as well as of hormones (eg, thyroglobulin) and exocrine secretion products (eg, amylase)
Multilectin mannose receptor
Splenic macrophages contain a high percentage of HLA-____–positive cells (50%), whereas peritoneal macrophages have relatively few (10–20%)
HLA-DR
IFN-γ: (induce or downregulate) higher levels of MHC class II antigens
induce
Prostaglandin E, α-fetoprotein, and glucocorticoids (induce or downregulate) HLA-DR antigen expression
Downregulate
Circulating half-life of classical or CD14 high monocytes
1- to 2-days
Subset of monocyte that resemble alveolar but not peripheral macrophages and are dramatically expanded in pathologic conditions, such as sepsis, HIV infection, and cancer
CD14+CD16+ monocytes
The surface antigen ______ is expressed primarily in T-helper lymphocytes and can act as receptors for HIV type 1 (HIV-1)
CD4
Chemokine receptor that has been the major coreceptor on monocytes/ macrophages for M-tropic HIV-1 infection
CCR5
When in the homozygous state, CCR5Δ32 homozygous individuals are highly protected against acquisition of HIV
TRUE OR FALSE
When activated monocytes express a greater potential for cytotoxicity and antimicrobial functions than resident tissue macrophages
TRUE
When activated monocytes express a greater potential for cytotoxicity and antimicrobial functions than resident tissue macrophages
Central nervous system macrophages
Microglia
TRUE OR FALSE
Monocytes are not resistant to virus infection, compared with more differentiated macrophages.
FALSE
Monocytes are relatively resistant to virus infection, compared with more differentiated macrophages.
These cells selectively adhere to lipid- and platelet-activated endothelium, a precursor to atherogenesis.
TRUE OR FALSE
Activated macrophages express a greater potential for cytotoxicity and antimicrobial functions than monocytes
FALSE
Activated monocytes express a greater potential for cytotoxicity and antimicrobial functions than resident tissue macrophages
Macrophages are rich in lysosomal digestive enzymes, activated by falling pH of approximately _____ within the mature vacuole.
6.5
