Chronic Inflammation Flashcards
Chronic Inflammation
Histologically characterized by Lymphocytes & Plasma Cells
Delayed Response More specific (Adaptive Immunity)
Plasma Cells on Histo
Nucleus on the side of the cell
Area of glassy clearing between nucleus & cytoplasm
Stimuli for Chronic Inflammation
Persistent Infection (most common) Viral Infections Mycobacterial Infections Parasite Infections Fungal Infections Autoimmune Disease Foreign Material Some Cancers
T Lymphocytes
Born as Progenitor T Cells in bone marrow
Educated in the Thymus
T Lymphocytes in the Thymus
Undergo TCR rearrangement into CD4 or CD8
TCR Complex Recognizes
Antigens presented on MHC
CD4+ recognize Ag on MHC - II
CD8+ recognize Ag on MHC - I
MHC predominantly expressed on APCs
MHC - II
T Cell Activation (General)
Bind Ag-MHC Complex
2nd Signal
CD4 Activation
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
Th1 Cells Secrete
IL-2 (CD8 Activator, T Cell Growth Factor)
IFN-γ (Macrophage Activator)
Th2 Cells Secrete
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)
IL-2
Activates CD8+ T Cells
T Cell Growth Factor
Secreted by Th1 CD4 Cells
IFN-γ
Macrophage Activator
Secreted by Th1 CD4 Cells
IL-4
Facilitates class switching to IgG & IgE
Secreted by Th2 CD4 Cells
Involved in maturation of B Cells
IL-5
Facilitates Eosinophil Chemotaxis
Facilitates Eosinophil Activation
Facilitates B Cell Maturation into Plasma Cells
Facilitates Class Switching to IgA
Secreted by Th2 CD4 Cells
IL-10
Inhibits Th1 Cells
Induces resolution of inflamation
Secreted by Th2 CD4 Cells
MCH-I Ag Loading
Intracellular Ag loaded
CD8 Activation
1st Signal: Intracellular Ag Presented on MHC-I
2nd Signal: IL-2 from Th1 CD4 Cell
Cytotoxic CD8 Killing Mechanism
Method 1: Perforins secreted Granzyme secreted Caspase Cascade Activated Apoptosis
Method 2:
FAS-L binds FAS-R (CD95) on target
Caspase Cascade Activated
Apoptosis
3 ways to activate Caspases
Intrinsic Mitochondrial Pathway (Cytochrome C Leak)
Extrinsic Receptor Pathway (FAS - FASL or TNF)
CD8+ T Cell (Granzyme)
B Lymphocytes
Immature B cells produced in the bone marrow
Undergo Ig Rearrangement
Naive B Cells express IgM & IgD
B Cell Activation
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
Granulomatous Inflammation
Characterized by Granuloma
Epithelioid Histiocyte Aggregation
Giant Cells surround it
Rim of Lymphocytes around all else
Caseating (w/ central necrosis) or Non-Caseating
Key Cell defining Granulomatous Inflammation
Epithelioid Histiocyte
Macrophage w/ pink cytoplasm
Normal Macrophages have
Foamy clear cytoplasm
Caseating Granuloma DDX
TB (Perform AFB) Fungal Infections (Perform GMS)
Non-Caseating Granuloma DDX
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)
Histologic Hallmark of Crohn’s Disease
Non-Caseating Granulomas
Histologic Hallmark of Ulcerative Colitis
Crypt Abscesses
IL-12
Induces CD4 → Th1
Steps in Granuloma Formation (both caseating and non-caseating)
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
