67 Structures, Receptors and Functions of Monocytes and Macrophages Flashcards by Amelie Avenido

The major lineage regulator of nearly all macrophages

Monocyte/macrophage colony-stimulating factor (M-CSF; also termed CSF-1)

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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

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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.

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Monoblast or Promonocyte

Have characteristic deeply indented, irregularly shaped nuclei with condensed chromatin, and numerous cytoplasmic microfilaments

Promonocyte

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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

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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

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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

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Monocyte cytoplasmic granules contain these primary lysosomes:

Acid phosphatase and arylsulfatase

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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.

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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).

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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.

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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

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Primary lysozyme granules of monocytes

Acid phosphatase, arylsulfatase, and peroxidase

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Synovium macrophages

Type A cells

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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

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The fixed macrophages of the spleen

Littoral cells

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The macrophages of the marrow

“nurse cells” of the erythroblastic island

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Hepatic macrophages

Kupffer cells

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Connective tissue macrophages

Histiocytes

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Spleen macrophages

Red pulp macrophages

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Bone macrophages

Osteoclasts

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Surface antigen of macrophages

CD68, also known as macrosialin

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A relatively constant feature of cells engaged in endocytosis

Large number of microvilli at the cell surface

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The most constant and characteristic ultrastructural features of macrophages

Electron-dense membrane-bound lysosomes

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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) ## Footnote 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 ## Footnote 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 ## Footnote 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 ## Footnote 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. ## Footnote 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