Chronic Inflammation

Question 1

What is the molecule released by T-helper cells that activates macrophages? What other role does it have?

Answer 1

Interferon-gamma (INF-gamma) activates macrophages as well as promote B-cell class switching from IgM to IgG

Question 2

What is the macrophage alternate pathway’s goal and what activates it?

Answer 2

Activated by IL-3 and IL-4 from T-cells and acts to promote tissue repair (via activation of fibroblasts, enhance angiogenesis, and collagen synthesis).

Question 3

What is produced by TH1 T lymphocytes? What is produced by TH2 cells?

Answer 3

TH1 produces IFN-gamma (IFN-g activates macrophages)

TH2 produces IL-4, IL-5, and IL-3 (responsible for alternate macrophage pathway, eosinophil chemotaxis, B-cell class switching)

Question 4

What are some chemotactic stimuli for macrophages?

Answer 4

TGF-alpha, MCP-1, C5a (part of the complement system),

Question 5

What cytokine is released by macrophages that is important in depositing connective tissue and fibrosis for healing?

Answer 5

TGF-Beta

Question 6

How do macrophages prevent the breakdown of the extracellular matrix?

Answer 6

Via TIMP (tissue inhibitors of metalloproteinases)

Question 7

What is created that is characteristic of chronic inflammation characterized by collection of epitheliod histiocytes?

Answer 7

Granuloma (macrophages with abundant pink cytoplasm are the epithelid histiocytes); also usually surrounded by giant cells and a rim of lymphocytes

Question 8

What is the difference between TGF-alpha and TGF-beta?

Answer 8

TGF-alpha attracts macrophages

TGF-beta is secreted by macrophages to activate fibroblasts and inhibit breakdown of ECM by TIMPs

Question 9

What two molecules make up the TCR complex for antigen surveillance by T cells?

Answer 9

TCR and CD3

Question 10

What are the two activation signals for CD8 cytotoxic T cell activation?

Answer 10

1. Intracellular antigen presented on MHC class I
2. IL-2 from CD4+ T_H1 cell provides 2nd signal

Question 11

What are the two activation signals for CD4+ helper T cell activation?

Answer 11

1. Extracellular antigen that is phagocytosed, processed, and presented on MHC class II
2. B7 on antigen presenting cells bind CD28 on helper T cells to provide 2nd signal

Question 12

How do cytotoxic T cells kill pathogens?

Answer 12

They secrete perforin which allows secreted granzyme; granzymes activate apoptosis. Also occurs by expression of FasL which binds Fas on target cells and activates apoptosis.

Question 13

What characterizes a granuloma?

Answer 13

Hallmark of chronic inflammation; characterized by epitheliod histiocytes (which are macrophages that resemble epithelial cells)

Question 14

What is the difference between caseating and noncaseating granulomas?

Answer 14

Caseating granulomas have central necrosis, noncaseating granulomas do not have central necrosis

Question 15

What are the etiologies for noncaseating granulomas?

Answer 15

Sarcoidosis, beryllium exposure, Crohns disease, cat scratch disease, reaction to foreign material

Question 16

What are the etiologies for caseating granulomas?

Answer 16

Tuberculosis and fungal infections

Question 17

How do granulomas develop?

Answer 17

1 Macrophages present antigen to CD4+ T helper cells

2 the interaction leads macrophages to secrete IL-12, leading CD4+ T cells to differentiate into the TH1 subtype

3 TH1 secrete IFN-gamma which converts macrophages into epithelioid histiocytes and giant cells

Question 18

Is Wegener’s granlomatosis necrotizing or non-necrotizing?

Answer 18

Necrotizing

Question 19

What genetic defect leads to chronic granulomatous disease?

Answer 19

Defect in formation of reactive oxygen species due to NADPH oxidase deficiencies

Question 20

How is chronic granulomatous disease tested in the lab?

Answer 20

A lack of production of superoxide prevents a color change reaction in a NBT test.

So if the test does NOT change color, CGD may be present

If the test does change color to blue, then superoxide species are forming and NADPH is intact