Chapter 9
Macrophages, Microglia and Dendritic Cells
Anuja Ghorpade, Howard E. Gendelman and Jonathan Kipnis
QUESTIONS
True or False
1.
Microglia are solely neuroprotective cells
2.
Microglia are solely neurodestructive cells
3.
Microglial activation is always associated with impaired neurogenesis
4.
Microglia are not found in the retina but only in the optic nerve
5.
Retinal detachment associated with vitreoretinopathy as a result of complication of ocular trauma is mediated
solely by microglia
6.
Microglia could be a source of IGF-1 in the brain
7.
Microglia can clear amyloid plaques, but not very efficiently
8.
Th1 soluble products enhance the production of chemokines and cytokines (CXCL10/IP10, TNF and IL-6) by
microglia
9.
T cells in combination with anti-MOG antibodies induce demyelination
10. Astrocytes are the major cells of interest in the mechanically injured CNS
Multiple Choice
11. Which of the following describe the shared functions of mononuclear phagocytes?
a. Phagocytosis
b. Intracellular killing of microbes and elimination of tissue debris
c. Secretion of bioactive factors
d. Antigen presentation
e. All of the above
12. Mononuclear phagocytes are a family of terminally differentiated cells with shared innate immune functions
and include all of the following with the exception of?
a. Monocytes
b. Macrophages
c. Dendritic Cells
d. Histiocytes
e. CD4+ T lymphocytes
f. Microglia
13. The ontogeny of tissue macrophages includes the following in order of development?
a. Monoblasts to promonocytes to monocytes to tissue macrophages
b. Promonocytes to monoblasts to monocytes to tissue macrophages
c. Monoblasts to monocytes to histiocytes to Kupffer cells
d. Monocytes to promonocytes to tissue macrophages
9.
Macrophages, Microglia and Dendritic Cells
Anuja Ghorpade, Howard E. Gendelman and Jonathan Kipnis
2
14. All are histological features of monocytes and macrophages except?
a. Large, irregularly shaped cells with a kidney-shaped or round nucleus.
b. Ample cytoplasm in contrast to lymphocytes
c. Smooth surface
d. Differentiated cells commonly bear microvilli that are visualized with localization of vimentin.
e. After activation cells revert to an activated state and appear amoeboid in nature.
15. Macrophages express a number of surface markers that can be classified broadly into family of receptors that
include all of the following except?
a. Adhesion molecules
b. Chemokines
c. Lectins
d. Advanced glycation endproducts
e. TCR
Essay Questions
16. Describe the neuroinflammatory theory of Alzheimer’s disease
17. How can microglial responses be modulated during neurodegenerative conditions?
18. Is there a dual role of microglia in health and disease? How does this occur?
ANSWERS
1.
False
2.
False
3.
False
4.
False
5.
False
6.
True
7.
True
8.
True
9.
True
10.
False
11.
e
12.
e
13.
a
9.
Macrophages, Microglia and Dendritic Cells
Anuja Ghorpade, Howard E. Gendelman and Jonathan Kipnis
14.
c
15.
e
3
16. Describe the neuroinflammatory theory of Alzheimer’s disease
The accumulation of amyloid plagues affects microglial immune responses and secretion of a broad range of proinflammatory factors. Parallel with this response is increased phagocytic and clearance mechanisms of both microglia
and blood-borne macrophages. What is not known is the relative contribution of the microglia responses to the actual
disease process and whether it is reactive or participatory. Macrophage and microglial activation positively affects cell
mobility and mobility and can also increase inflammatory responses in brain tissues.
17. How can microglial responses be modulated during neurodegenerative conditions?
There are four possible ways a microglial response can be affected in disease. First, it is to remove the inciting made of
cell activation. This could include clearance of aggregated and/or oxidized proteins (amyloid beta or synuclein for
Alzheimer’s and Parkinson’s disease respectfully) or elimination of microbe (human immunodeficiency virus, HIV) in
case of HIV dementia. Second, it is to deactivate the microglia through anti-inflammatory drugs that can pass the
through the blood-brain barrier and be delivered selectively to sites of injury or disease. Third, is to modulate a
microglia phenotype by changing its microenvironment through induction of adaptive immune responses or delivery on
delivery of cytokines. Fourth, is to target the destruction of the activated or neurotoxin-producing cell.
18. Is there a dual role of microglia in health and disease? How does this occur?
Microglia are known to regulate innate and adaptive immune responses in the central nervous system (CNS). These
same cells also play important functional roles for neurons and neighboring glia through their production of trophic
factors. In response to injury, infection, ischemia, and inflammatory cues, microglia cells become activated and
become highly mobile enabling the cells to migrate to sites of injury. When they reach diseased or injured CNS tissues,
they phagocytose and clear (ingest and destroy) cellular debris as well as secrete neurotoxic and neurotrophic factors
serving to affect the disease course. It is likely that modulation of microglial function towards a trophic phenotype can
provide therapeutic benefit for CNS disease. Thus, extracellular signals that activate microglia as the actual cell
responses to environmental cues determine disease outcomes or describe ways the CNS can combat degenerative
events. The means by which activation triggers secretion of molecules that affects the function of the brain and spinal
cord as well as altering immune responses in the CNS are critical determinants for microglial function in health and
disease.