Chronic Inflammation, Macrophages, and Granuloma Pathophysiology

50 vocabulary flashcards covering key concepts from the lecture notes on chronic inflammation and granulomatous diseases.

Chronic inflammation

A prolonged inflammatory response dominated by monocytes/macrophages rather than neutrophils, caused by persistent infection, toxins, or autoimmune diseases.

Monocytes

Circulating precursors that migrate into tissues and differentiate into tissue‑type macrophages within 48 hours.

Macrophages

Matured monocytes in tissues that can cause tissue destruction or promote fibrosis depending on stimuli.

Mononuclear cell infiltration

Infiltration of monocytes and lymphocytes characteristic of chronic inflammation.

Lymphotaxin

Chemokine that recruits lymphocytes to sites of inflammation.

MIP-1α

chemokine that recruits monocytes from the bloodstream.

CD8+ T cells, B cells, and neutrophils

MIP-1β

chemokine that recruits monocytes.

CD4+

sialyl-Lewis X (sLex)

Carbohydrate ligand expressed on leukocytes that binds endothelial E- and P-selectins to promote rolling.

E-selectin

Endothelial adhesion molecule that binds leukocyte ligands like sLex to mediate rolling.

P-selectin

Endothelial adhesion molecule involved in leukocyte rolling and early adhesion.

LFA-1

integrin on leukocytes that binds ICAM‑1 for firm adhesion.

ICAM-1

endothelial receptor for LFA‑1.

VCAM-1

binds integrins to promote leukocyte adhesion.

PECAM-1

mediates diapedesis across endothelium.

Tissue destruction

A hallmark of chronic inflammation due to macrophage/mediator activity.

Healing attempts

Attempts at healing include connective tissue replacement to restore function and may lead to fibrosis.

Fibrosis

Scar formation resulting from loss of normally functioning cells and tissue remodeling.

Angiogenesis

Formation of new blood vessels during healing and granulomatous responses.

Growth factors

Mediators that promote fibrosis and tissue repair (e.g., macrophage‑derived growth factors).

Coagulation factors

Proteins that promote clotting and fibrin deposition within the inflammatory milieu.

TNF-α

pro‑inflammatory cytokine that activates macrophages and supports granuloma maintenance.

IFN-γ

Th1 cytokine that activates macrophages and promotes epithelioid differentiation.

Degradative enzymes

Macrophage‑secreted enzymes that degrade extracellular matrix and tissue.

Plasminogen activator

Enzyme converting plasminogen to plasmin, part of the fibrinolytic system.

Plasmin

Active protease that dissolves fibrin clots and aids tissue remodeling.

Fibrinolytic system

Pathway that dissolves clots, facilitating cell recruitment and tissue remodeling.

Complement (C1-C5)

cascade components that promote inflammation and opsonization.

ROS (reactive oxygen species)

Reactive molecules produced by macrophages that kill pathogens but can damage host tissue.

NO (nitric oxide)

Reactive species with antimicrobial effects and vasodilation; produced by macrophages.

Prostaglandins

Eicosanoids involved in vasodilation, edema, pain, and inflammation.

Leukotrienes

Eicosanoids that promote chemotaxis and vascular permeability in inflammation.

HETE

products of the lipoxygenase pathway of arachidonic acid.

Lipoxins

Eicosanoids that promote resolution of inflammation.

Thromboxane

Eicosanoid involved in platelet aggregation and vasoconstriction.

TGF-β

a potent fibrogenic cytokine promoting collagen deposition and fibrosis.

Fibrogenic cytokines

Cytokines that promote fibrogenesis and remodeling of connective tissue.

Collagenases

Enzymes that remodel collagen during tissue repair.

Granuloma

A structured collection of macrophages (epithelioid cells and possibly giant cells) forming a granulomatous lesion.

Granulomatous hypersensitivity

Delayed-type hypersensitivity driven by persistent T-cell activation by macrophages.

Epithelioid cell

Activated macrophage with epithelial‑like appearance within a granuloma.

Multinucleated giant cell

Fusion of macrophages forming a multinucleated cell within granulomas.

Mycobacterium tuberculosis

Bacterium that causes tuberculosis, a classic granulomatous disease.

Leprosy

Mycobacterial disease causing granulomatous inflammation.

Sarcoidosis

Noncaseating granulomatous disease affecting multiple organs.

Crohn’s disease

Inflammatory bowel disease characterized by granuloma formation and transmural inflammation.

Glucocorticoids

Steroid anti-inflammatory agents that suppress IL‑1/IL‑6, chemotaxis, phospholipase, COX, iNOS, and CD4 activation of macrophages.

Infliximab

Monoclonal antibody that neutralizes TNF‑α, reducing inflammation.

Etanercept

Recombinant TNF receptor fusion protein that binds TNF‑α, preventing its activity.

Pentoxifylline

Drug that, with Thalidomide, reduces TNF‑α release by phagocytes.

Thalidomide

Drug that, with Pentoxifylline, stops TNF‑α release by phagocytes.