CHRONIC INFLAMMATION

Question 1

What is the most common stimulus of chronic inflammation? What are the other stimuli of chronic inflammation?

Answer 1

1. PERSISTENT INFECTION**
2. Infection with viruses, mycobacteria, parasites
3. Cancer
4. Autoimmune conditions
5. Foreign matters

Question 2

What is the TCR complex that recognizes the Ag in context of MHC?

Answer 2

TCR complex = TCR + CD3

Question 3

Which cytokines are produced by CD4+Th1 subset? What do they do?

Answer 3

Th1 - Helps CD8+!

1. IL-2: Tcell growth factor + activates CD8+ Tcells
2. IFN-gamma: Activates macrophages

Question 4

Which cytokines are produced by CD4+ Th2 subset? What do they do?

Answer 4

Th2 - Helps B cells

1. IL-4: IgM class switching to IgG + IgE
2. IL-5: Esoinophil attraction and activation + Promotes maturation of B cells to plasma cells + Class switching to IgA
3. IL-10: Decreases Th1 phenotype

Question 5

What are the two activation signals of CD4+T-cells?

Answer 5

SIGNAL 1: Extracellular Ag presented on MHC Class II (APC) - TCR (CD4+ T-cell)
SIGNAL 2: B7 (APC) - CD28 (CD4+Tcell)

Question 6

What are the two activation signals of CD8+T-cells?

Answer 6

SIGNAL 1: Intracellular Ag presented on MHC Class I (APC) - TCR (CD8+ T-cell)
SIGNAL 2: IL-2 released from CD4+Th1 cell

Question 7

What are 3 ways of activating capases and thus activating APOPTOSIS?

Answer 7

1. INTRINSIC MITOCHONDRIAL PATHWAY - Driven from cytochrome c leaking out from mitochondria
2. EXTRINSIC RECEPTOR PATHWAY - Fas death receptor (CD95) -Fas ligand OR TNF-alpha binding the cells
3. CD8+T-cell dumping granzyme

Question 8

What are the 2 ways that CD8+T-cells mediate killing?

Answer 8

1. Secretion of PERFORIN+GRANZYME

2. Expression of FAS LIGAND to bind to FAS on target cells

Question 9

What are the two mechanisms of B cell activation?

Answer 9

1. Activation into IgM/IgD secreting plasma cells - EXTRACELLULAR Ag binds to surface IgM/IgD -> Activation into IgM/IgD secreting plasma cell
2. Activation into IgG/IgE/IgA secreting plasma cells -
   SIGNAL 1: INTRACELLULAR Ag gets presented on MHC Class II on the B cell (APC) -> Recognized by CD4+Th2 cell
   SIGNAL 2: CD40 (B cell) - CD40L (CD4+Th2 cell)
   RESULT: Release of IL-4 (switching to IgG/IgE) + IL-5 (switching to IgA)

Question 10

***What is the key defining feature of a GRANULOMA? What are some other possible features?

Answer 10

EPITHELIOID HISTIOCYTES
Some other possible features = Multinucleated Giant cells (LANGHANS cells) + Lymphocyte rim

**LANGHANS (granuloma feature) is different from LANGERHANS cells (APC on skin and mucosal membranes)

Question 11

What is the Ddx list of a NON-CASEATING GRANULOMA?

Answer 11

Ddx: Exposure to foreign material, Sarcoidosis, Be exposure, Crohn’s, Cat Scratch Disease

Question 12

Pt has a stellate-shaped granuloma on the neck. What type of granuloma is this?

Answer 12

NON-CASEATING GRANULOMA

Question 13

Pt had breast cancer and had a breast implant procedure. She suddenly feels something in her axilla lymph nodes. What is she at increased risk for within chronic inflammation?

Answer 13

NON-CASEATING GRANULOMA

Question 14

What are the steps to forming BOTH CASEATING + NON-CASEATING GRANULOMAS?

Answer 14

1. Macrophages present Ag in MHC Class II to CD4+ Th cell. Macrophages release IL-12.
2. IL-12 differentiates CD4+ Th cell to Th1 subtype. CD4+ Th1 releases IFN-gamma
3. IFN-gamma converts macrophages to epithelioid histiocytes + giant cells