Chronic Inflammation

Question 1

Chronic Inflammation

Answer 1

Histologically characterized by Lymphocytes & Plasma Cells

Delayed Response
More specific (Adaptive Immunity)

Question 2

Plasma Cells on Histo

Answer 2

Nucleus on the side of the cell

Area of glassy clearing between nucleus & cytoplasm

Question 3

Stimuli for Chronic Inflammation

Answer 3

Persistent Infection (most common)
Viral Infections
Mycobacterial Infections
Parasite Infections
Fungal Infections
Autoimmune Disease
Foreign Material
Some Cancers

Question 4

T Lymphocytes

Answer 4

Born as Progenitor T Cells in bone marrow

Educated in the Thymus

Question 5

T Lymphocytes in the Thymus

Answer 5

Undergo TCR rearrangement into CD4 or CD8

Question 6

TCR Complex Recognizes

Answer 6

Antigens presented on MHC

CD4+ recognize Ag on MHC - II
CD8+ recognize Ag on MHC - I

Question 7

MHC predominantly expressed on APCs

Answer 7

MHC - II

Question 8

T Cell Activation (General)

Answer 8

Bind Ag-MHC Complex

2nd Signal

Question 9

CD4 Activation

Answer 9

APC presents Ag on MHC - II
B7 on APC binds CD28 on CD4 cell (2nd signal)

CD4 differentiates into Th1 or Th2
Secretes cytokines helping inflammation

Question 10

Th1 Cells Secrete

Answer 10

IL-2 (CD8 Activator, T Cell Growth Factor)

IFN-γ (Macrophage Activator)

Question 11

Th2 Cells Secrete

Answer 11

IL-4 (Class Switcher to IgG & IgE)
IL-5 (Eosinophil attractant & activator, B-Cell → Plasma Cell inducer, class switcher to IgA)
IL-10 (Th1 Inhibitor, Induces Inflammation Resolution)

Question 12

IL-2

Answer 12

Activates CD8+ T Cells
T Cell Growth Factor

Secreted by Th1 CD4 Cells

Question 13

IFN-γ

Answer 13

Macrophage Activator

Secreted by Th1 CD4 Cells

Question 14

IL-4

Answer 14

Facilitates class switching to IgG & IgE

Secreted by Th2 CD4 Cells
Involved in maturation of B Cells

Question 15

IL-5

Answer 15

Facilitates Eosinophil Chemotaxis
Facilitates Eosinophil Activation
Facilitates B Cell Maturation into Plasma Cells
Facilitates Class Switching to IgA

Secreted by Th2 CD4 Cells

Question 16

IL-10

Answer 16

Inhibits Th1 Cells
Induces resolution of inflamation

Secreted by Th2 CD4 Cells

Question 17

MCH-I Ag Loading

Answer 17

Intracellular Ag loaded

Question 18

CD8 Activation

Answer 18

1st Signal: Intracellular Ag Presented on MHC-I

2nd Signal: IL-2 from Th1 CD4 Cell

Question 19

Cytotoxic CD8 Killing Mechanism

Answer 19

Method 1:
Perforins secreted
Granzyme secreted
Caspase Cascade Activated
Apoptosis

Method 2:
FAS-L binds FAS-R (CD95) on target
Caspase Cascade Activated
Apoptosis

Question 20

3 ways to activate Caspases

Answer 20

Intrinsic Mitochondrial Pathway (Cytochrome C Leak)
Extrinsic Receptor Pathway (FAS - FASL or TNF)
CD8+ T Cell (Granzyme)

Question 21

B Lymphocytes

Answer 21

Immature B cells produced in the bone marrow
Undergo Ig Rearrangement
Naive B Cells express IgM & IgD

Question 22

B Cell Activation

Answer 22

Ag binds IgM or IgD → Becomes IgM or IgD-secreting Plasma Cell

OR

B Cell consumes Ag
B Cell presents Ag to Th2 via MHC-II
CD40R on B Cell binds to CD40L on Th2
Th2 secretes IL-4 & IL-5
IgM or IgD switches to IgG, IgE & IgA
Hypermutation
B Cell matures into Plasma Cell

Question 23

Granulomatous Inflammation

Answer 23

Characterized by Granuloma
Epithelioid Histiocyte Aggregation
Giant Cells surround it
Rim of Lymphocytes around all else

Caseating (w/ central necrosis) or Non-Caseating

Question 24

Key Cell defining Granulomatous Inflammation

Answer 24

Epithelioid Histiocyte

Macrophage w/ pink cytoplasm

Question 25

Normal Macrophages have

Answer 25

Foamy clear cytoplasm

Question 26

Caseating Granuloma DDX

Answer 26

``` TB (Perform AFB) Fungal Infections (Perform GMS) ```

Question 27

Non-Caseating Granuloma DDX

Answer 27

Foreign Material Reaction (Breast Implants) Sacroidosis (usually see granulomas in multiple sites of the body, especially lung) Beryllium Exposure (appears very similar to sarcoid) Crohn's Disease Cat Scratch Disease (usually see stellate-shaepd granulomas in the neck)

Question 28

Histologic Hallmark of Crohn's Disease

Answer 28

Non-Caseating Granulomas

Question 29

Histologic Hallmark of Ulcerative Colitis

Answer 29

Crypt Abscesses

Question 30

IL-12

Answer 30

Induces CD4 → Th1

Question 31

Steps in Granuloma Formation (both caseating and non-caseating)

Answer 31

Interaction between Macrophages & Th1 Cells Macrophages present Ag via MHC-II to CD4 cells Macrophages secrete IL-12 CD4 → Th1 Th1 secretes IFN-γ Macrophage → Eipthelioid histiocytes & Giant Cells