Pathoma - Ch. 3 - Chronic Inflammation

Question 1

simple difference between acute and chronic inflammation?

Answer 1

acute: neutrophile
chronic: lymphocyte

Question 2

what is the stimuli for chronic inflammation?

Answer 2

• persistent infection (most common)
• infection with viruses, mycobacteria, parasites, and fungi
• autoimmune disease
• foreign material
• some cancers

Question 3

what does the activation of T cells require?

Answer 3

1) binding of antigen/MHC complex
2) additional 2nd signal

Question 4

explain the CD4+ T cell activation

Answer 4

• extracellular antigen Is phagocytosed, processed, and presented via MHC class II (APC)
• B7 on APC ::binds:: CD28 on CD4 T cell (second signal) **28 divided by 7 is 4)

Question 5

what do activated CD4+ helper T cells do?

Answer 5

secrete cytokines that “help” inflammation

• divide into two subsets to help either B cells or CD8+ T cells

Question 6

what division helps the CD8+ T cells?

Answer 6

Th1 subset; they secrete:

• IL-2 (T-cell growth factor and CD8+ activator)

- IFN-gamma (macrophage activator)

Question 7

what subset helps the B cells?

Answer 7

Th2 subset, by secreting

• IL-4: class switching to IgG and IgE
• IL-5: eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA
• IL-10: Inhibits Th1 helper phenotype

Question 8

how are CD8+ cytotoxic Tcells activated? what do they recognize?

Answer 8

• they recognize Intracellular antigens, which are processed and presented on MHC class I
• IL-2 from CD4+ Th1 cell provides 2nd activation signal
• now ready to kill

Question 9

how do CD8+ T cells kill?

Answer 9

2 ways:

• they secrete perforins and granzyme; Induce apoptosis (by activating caspases) of the target cell
• they express FasL on their surface (which binds Fas on target cell, activating apoptosis)

Question 10

Describe B lymphocytes

Answer 10

• B lymphocytes are immature B cells produced in bone marrow
• they undergo Ig arrangement to become naive B cells that express surface IgM and IgD

Question 11

how do B cells get activated?

Answer 11

1) antigen binding by surface IgM or IgD (then the B cell becomes a plasma cell, which mass produces the respective Igs)
2) B-cell antigen presentation to CD4+ helper T cell via MHC II; CD40 receptor (on B cell) binds to CD40L on helpter T cell (second signal) = activation of T cell

Question 12

what happens when the helper T cell is activated in this fashion (B cell, CD40)?

Answer 12

the helper T cell then secretes

IL-4 and IL-5 (which mediate B cell isotype switching, hypermutation, and maturation to plasma cells)

• this is the necessary reaction for plasma cells to secrete other Ig’s than IgM and IgG

Question 13

chronic inflammation has two subtypes. what are they?

Answer 13

• granulomatous inflammation
• non-granulomatous inflammation

Question 14

what is the defining characteristic of granuloma?

Answer 14

epitheloid histiocytes (macrophages with abundant pink cytoplasms)

Question 15

what two subtypes can granulomas be divided into?

Answer 15

caseating and noncaseating granulomas

Question 16

what is characteristic of noncaseating granulomas?

Answer 16

they lack central necrosis

• they arise in reaction to foreign material, crohn disease, cat scratch disease

Question 17

what is the key differentials in caseating granulomas?

Answer 17

• exhibit central necrosis
• characteristic of TB and fungal infections

Question 18

how are granulomas formed?

Answer 18

1) macrophages find antigen, present it via MHC II to CD4 helper T cells
2) upon binding, macrophages secrete IL-12, Inducing the CD4 helper cells to differentiate into Th1 subtype
3) Th1 cells then secrete IFN-gamma which converts the macrophages into epithelioid histiocytes and giant cells

key: both caseating and noncaseating granulomas are formed this way