First Aid, Chapter 2 Cells Involved in Immune Responses, Monocytes, Macrophages, and Dendritic Cells

Question 1

What are monocytes?

Answer 1

WBCs that replenish macrophages and dendritic cells in teh periphery.

Question 2

What is the shape of monocytes nucleas? How big is the monocyte? What receptors do they express on their surface?

Answer 2

• Monocytes are cells with one, kidney-shaped nucleus and are 10–15 μm in size.
• Express surface receptors for IgG, IgA, and IgE.

Question 3

Where do monocytes originate? What do they express after further maturation? Where do they go and what do they become?

Answer 3

• Originate from monoblasts (Figure 2-3).
• Highly express CD14 and CD16 after further maturation.
• Migrate to peripheral tissue and become macrophages and dendritic cells.

Question 4

How big are macrophages? How many nuclei do they have? What type of movement do they move in? What do they capture particles with? What do they express?

Answer 4

• Mononuclear cells with a diameter of 21 μm (Figure 2-4).
• Move in tissue via amoeboid movement and capture particles with pseudopodia.
• Express CD14, CD11b/CD18 (Mac-1), and CD36.

Question 5

What are the macrophage subtypes named? Where are they located?

Answer 5

Have several subtypes named by location, including Kupffer cells (liver), histiocytes (tissue), osteoclasts (bone), mesangial cells (kidney), and alveolar macrophages (lung).

Question 6

What causes macrophages to differentiate? How long do they survive?

Answer 6

• Develop in response to granulocytemonocyte colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF).
• Can survive weeks in tissue.

Question 7

What are the functions of macrophages?

Answer 7

• Clear cellular debris as well as bacterial invaders.
• Can be activated by signals, such as IFNy and LPS (which binds CD14).
• Present pathogens to helper T cells via MHCII molecules.
• Secrete cytokines, such as TNFα, IL-12, IL-18, IL-1, IL-6 (CXCL-8).

Question 8

Where is CD14 expressed? What is it a component of?

Answer 8

CD14 is a highly expressed receptor on monocytes and macrophages, which binds lipopolysaccharide and activates an immune response. It is a component of Toll-like receptor 4 (TLR4)

Question 9

What do the common myeloid and lymphoid progenitors come from? What cells directly come from the common myeloid progenitor? lymphoid progenitor? (FIgure 2-3)

Answer 9

Common myeloid ->
Megakaryocyte
Erythrocyte
Mast cell
Myeloblast

Common lymphoid ->
Natural killer cell (large Granular lymphocyte)
Small lymphocyte

Question 10

What cell does the megakaryocyte differentiate into?

Answer 10

Thrombocytes

Question 11

What cells do myeloblasts differentiate into?

Answer 11

Basophil
Neutrophil
Eosinophil
Monocyte

Question 12

What cells does the monocyte differentiate into?

Answer 12

Macrophage

Dendritic cells

Question 13

What do macrophages do when they cannot clear a pathogen?

Answer 13

Many macrophages (see Figure 2-4) fuse to form granulomas in order to wall off a pathogen when they are unable to clear it

Question 14

What infections are granulomas characteristic of?

Answer 14

sarcoidosis (noncaseating granulomas) and tuberculosis (caseating granulomas).

Question 15

What cytokine promotes granuloma formation? What is the cytokine secreted by?

Answer 15

TNFα, which is secreted by macrophages, promotes granuloma formation.

Question 16

What causes HLH?

Answer 16

Hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (when secondary to chronic rheumatoid disease) is uncontrolled activation of macrophages with a marked increase in circulating cytokines.

Question 17

What is HLH characterized by? What is seen on bone marrow biopsy? What is the diagnosis made by?

Answer 17

This potentially life-threatening syndrome is characterized by high fever, hepatosplenomegaly, high ferritin and triglyceride levels, and low fibrinogen and circulating NK levels. Hemophagocytosis can often be seen on bone marrow biopsy. The diagnosis is made when five of the eight following criteria are met: fever, splenomegaly, cytopenia involving two or more cell lines, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, hepatitis, low or absent NK cell activity, ferritin level >500 µg/L, and soluble CD25 (sIL-2 receptor) >2400 U/mL.

Question 18

What does EBV infection in boys with XLP (x-linked lymphoproliferative syndrome) lead to?

Answer 18

HLH is often a fatal consequence of Epstein-Barr virus (EBV) infection in boys with Xlinked lymphoproliferative (XLP) syndrome, which is due to mutations in the SH2D1A gene (encodes SAP protein

Question 19

What are the subsets of dendritic cells?

Answer 19

Myeloid (DC1) conventional DCs, plasmacytoid (DC2), langherans, interstitial

Question 20

What markers are found on myeloid DC1? What is the precursor? What are the functions?

Answer 20

Markers: CD1, CD11b/c, CD13, CD14
Precursor: Myeloid
Primarily act in phagocytosis and antigen presentation

Question 21

What is the precursor of plasmacytoid (DC2) dendritic cells? What do they secrete? What types of infections is it associated with?

Answer 21

Precursor: Lymphoid

Secrete large amounts of IFNα and associated with viral infections

Question 22

What markers are found on langerhans cells? What is the precursor? What cells do they prime?

Answer 22

Markers: CD11c, CD207 Birbeck granules
Precursor: Myeloid (CLA+)
Prime CD8 T cells

Question 23

What markers are found on interstitial dendritic cells? What is the precursor? What cells do they activate?

Answer 23

Markers: CD2, CD99, CD68
Precursor: Myeloid (CLA-)
Activate B cells

Question 24

What do dendritic cells form in response to?

Answer 24

GM-CSF and IL-4 from the common myeloid or lymphoid progenitor

Question 25

What is the function of dendritic cells? What form are they in the tissue? IN the lymphoid organs? What do they do at each site? What do they express?

Answer 25

-The major antigen presenting cells (APCs) and are critical in starting germinal center reaction.
o Are immature in the tissue (where they specialize in antigen uptake) and mature in the lymphoid organs (where they specialize in antigen presentation; increased MHC II expression).
-Express B7.1 and B7.2 (CD80/CD86) which interacts with CD28 on T cells to provide costimulation.

Question 26

Which subset of dendritic cells produces type I IFN during viral infections?

Answer 26

plasmacytoid dendritic cells

Question 27

What are CD1 isoforms? What do they do? Where do they map with respect to the MHC locus?

Answer 27

CD1 isoforms (CD1a– CD1e) are class I MHC like molecules that present nonpeptide (lipid and glycolipid) antigens to T cells. CD1 maps outside the MHC locus on chromosome 15.