First Aid, Chapter 2 Cells Involved in Immune Responses, Mast Cells Flashcards

1
Q

What are mast cells? Where are they found? What is their role in immunity?

A

Mast cells (MC) are ubiquitous granulocytes found in skin and mucosal membranes; known primarily for their role in immediate hypersensitivity, but now better known as a regulator of innate immunity.

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2
Q

What is the staining of mast cells? What do mast cells contain? Describe the nuclei? How big are they?

A

Metachromically staining cell. Contain large cytoplasmic granules, which are filled with preformed mediators (e.g., histamine) that can be released quickly. Have peripheral, unsegmented nuclei and are 9–14 μm in size (Figure 2-6).

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3
Q

What are mast cells derived from (what are the markers on it)? Where do mast cells develop their phenotype?

A

Derived from pluripotent, kit+ (CD117+), CD34+ stem cells in the bone marrow.
-Develop phenotype after arrival in the tissue (Table 2-7)—mature in the tissue (unlike basophils and eosinophils).

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4
Q

What is the receptor for the cytokine stem cell factor? What is stem cell factor needed for? What medication is it a target for? What is the gene that encodes for the receptor?

A

Kit is the receptor for the cytokine stem cell factor, the critical growth factor of mast cells and a target of imatinib. The gene that encodes the receptor kit, c-kit, is a proto-oncogene.

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5
Q

What are the mast cell phenotypes?

A

MCt, MCtc, MCc

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6
Q

What are the mediators for MCt? Where are they located? Do they express C5aR? What do they appear like? What cells do they require for their development? Do they respond to opiates, C5a, C3a, and vancomycin?

A

Mediators: Tryptase
Location: Respiratory tract and intestinal mucosa (Mnemonic: For MCT, think Tissue. For MCTC, think Connective Tissue.)
Do not express C5aR (CD88); scroll-like appearance; require T cells for their development; do not respond to opiates, C5a, C3a, and vancomycin

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7
Q

What are the mediators for MCtc? Where are they located? Do they express C5aR? What do they appear like? Do they require T cells for their development? Do they respond to opiates, C5a, C3a, and vancomycin?

A
Mediators: Tryptase, chymase, carboxypeptidase, cathepsin G 
Location: Skin, blood vessels, eyes, synovium, intestinal, and respiratory submucosa (Mnemonic: For MCT, think Tissue. For MCTC, think Connective Tissue.) 
Express C5aR (CD88); whorled appearance;
do not require T cells for their development; respond to opiates, C5a, C3a, and vancomycin
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8
Q

What is the mediator for MCc? Where is it located?

A

Mediator: Chymase
Locations: Lymph nodes, intestinal submucosa, and salivary glands

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9
Q

What is the high affinity IgE receptor?

A

High-Affinity IgE Receptor/FcεRI

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10
Q

Describe the tetrameric form of the high affinity IgE receptor. Where is it found? Describe the alpha, beta, and gamma chains.

A

Tetrameric form: Composed of one α chain, one β chain, and two gamma chains; it is found on mast cells and basophils.

  • The α chain contains two immunoglobulin domains that bind with high affinity to IgE.
  • The β chain contains four transmembrane domains and one immunoreceptor tyrosine-based activation motif (ITAM).
  • The gamma chains are covalently linked, and each contains one ITAM. This is the main signaling component.
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11
Q

Describe the trimeric form of the high affinity IgE receptor. Where is it found?

A

Trimeric form: Composed of one α chain and two γ chains; it is found on dendritic cells, monocytes, and eosinophils.

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12
Q

What is is the low affinity IgE receptor and where is it found?

A

Low-Affinity IgE Receptor/ FcεRII/CD23: C-type lectin; it is found on mature B cells, activated macrophages, eosinophils, dendritic cells, and platelets.

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13
Q

How does the dust mite allergen interact with the low affinity IgE receptor?

A

The allergen responsible in dust mite allergy (Der-p-1) is known to cleave CD23 from the cell surface, increasing the production of allergen-specific IgE.

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14
Q

What cell is IgE signalling of mast cells similar to?

A

IgE binds to FcεRI via the α chain. Signaling of mast cells is similar to that in B cells with Lyn, Fyn, and Syk.

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15
Q

What antibody is seen in urticaria patients that can also be seen in patients without urticaria?

A

Some CIU patients have IgG directed against the α chain of FcεRI, though this is also seen in patients without urticaria. There is no evidence that these antibodies are pathogenic in urticaria.

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16
Q

How do allergens activate mast cells?

A

Cross-linking of the IgE receptor.

Mast cells can also be activated by: IgG via FcRI; bacterial antigens via TLR 2/6 or 4; C3a or C5a (anaphylatoxins)(MCTC only); cytokines; neuropeptides; physical stimuli (e.g., heat, pressure); substance P; and drugs [radiocontrast media; opioids (MCTC only); muscle relaxants].

17
Q

What mediators do mast cells release

A

Release preformed mediators (

18
Q

What mediators do mast cells release 10-30 min after activation?

A

Produce and release lipid-derived mediators (~10–30 minutes) after activation via the arachidonic acid pathway; responsible for late allergic reactions (e.g., PGD2, LTC4, LTB4, PAF).

19
Q

What mediators do mast cells release hours to days after activation?

A

Produce and release cytokines and chemokines (hours to days) after activation (eg, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, GM-CSF, TNFα, MCP-1, MIP1α, and RANTES [CCL-5]).

20
Q

What is the function of histamine? Is it preformed?

A

Smooth muscle contraction; mucus production; vasodilation; gastric acid secretion; and wakefulness.

It is preformed.

21
Q

What is the function of tryptase? Is it preformed?

A

Serine (protease) endopeptidase.

It is preformed.

22
Q

What is the function of carboxypeptidase? Is it preformed?

A

Peptidase for C-terminal end of peptide.

It is preformed.

23
Q

What is the function of chymase? Is it preformed?

A

Serine (protease) endopeptidase.

It is preformed.

24
Q

What is the function of heparin? Is it preformed?

A

Anticoagulant.

Preformed.

25
Q

What is the function of prostoglandin D2? Is it preformed or lipid-derived?

A

Increases vascular permeability; bronchoconstriction; inhibits platelet aggregation; chemoattraction

Lipid-derived.

26
Q

What is the function of leukotriene C4 and B4? Is it preformed or lipid-derived?

A

Increase vascular permeability; bronchoconstriction

Lipid-derived.

27
Q

What is the function of platelet-activating factor? Is it lipid-derived?

A

Bronchoconstriction; vasodilation; and platelet aggregation

28
Q

In what condition are both immature and mature tryptase elevated? In what condition is only mature tryptase elevated?

A

Both α- (mostly immature) and β- (mostly mature) tryptase are elevated in mastocytosis, but only β-tryptase (i.e., mature tryptase) is elevated in anaphylaxis. Mast cells are the major producers of tryptase.

29
Q

Which mast cell mediator is both preformed and produced in the late phase?

A

TNF