Inflammatory Cells, Chemical Mediators, and Systemic Effects of Inflammation

Comprehensive vocabulary flashcards covering the cellular components, chemical mediators, pathways, and systemic manifestations of acute and chronic inflammation based on lecture notes by Dr. Tin Nwe Oo.

Inflammation

A protective response of vascularized tissues that delivers leukocytes and host defense molecules from the circulation to sites of infection and tissue damage to eliminate pathogens, clear debris, and repair tissue.

Neutrophils

The hallmark primary responder cells of acute inflammation that predominate in inflammatory infiltrates during the first $6\text{ to }24\text{ hours}$, respond rapidly to chemokines, and undergo apoptosis after $24\text{ to }48\text{ hours}$.

Monocytes

Circulating blood leukocytes that replace neutrophils in inflammatory infiltrates after $24\text{ to }48\text{ hours}$ and extravasate into tissues to mature into longer-lived macrophages.

Macrophages

The dominant mononuclear phagocytic cells in chronic inflammation, derived from bone marrow hematopoietic stem cells or embryonic precursors, that ingest debris, initiate scar formation, secrete mediators, and present antigens.

Kupffer cells

Specialized, long-lived tissue-resident macrophages residing in the liver that are seeded by embryonic precursors from the yolk sac and fetal liver during early development.

Microglia

Tissue-resident macrophages located within the central nervous system (brain) that arise from embryonic precursors during early embryonic development.

Alveolar macrophages

Tissue-resident mononuclear phagocytes located in the pulmonary alveoli of the lungs that provide primary immune defense against inhaled pathogens.

Lymphocytes

Adaptive immune cells (T and B cells) that dominate chronic inflammation and autoimmune diseases, generating long-lived memory cells and reciprocal activation loops with macrophages.

$$\text{Th1 cells}$$

A subset of $\text{CD4}^+$ T helper cells induced by $\text{IL-12}$ and $\text{IL-18}$ that secrete $\text{IFN-}\gamma$ and $\text{TNF-}\beta$ to mediate cell-mediated immunity and activate macrophages.

$$\text{Th2 cells}$$

A subset of $\text{CD4}^+$ T helper cells induced by $\text{IL-4}$ that secrete $\text{IL-4}$, $\text{IL-5}$, and $\text{IL-13}$ to stimulate allergic responses and anti-parasitic defense.

$$\text{Th17 cells}$$

A subset of $\text{CD4}^+$ T helper cells induced by $\text{IL-6}$, $\text{IL-23}$, and $\text{TGF-}\beta$ that secrete $\text{IL-17A}$, $\text{IL-17F}$, $\text{IL-22}$, and $\text{IL-26}$ to recruit neutrophils and monocytes in autoimmune responses and inflammation.

Eosinophils

Leukocytes characterized by bi-lobed nuclei and prominent granules containing major basic protein, recruited in parasitic helminth infections and allergic hypersensitivity reactions.

Major basic protein (MBP)

A specialized cytotoxic constituent of eosinophil granules that is directly lethal to parasitic worms (helminths) but also capable of causing collateral injury to host epithelial cells.

Mast cells

Connective tissue-resident sentinel cells armed with surface receptors that degranulate to release preformed histamine and prostaglandins during immediate hypersensitivity and secrete pro-inflammatory cytokines in chronic inflammation.

Histamine

A vasoactive amine stored mainly in mast cells, basophils, and platelets that induces arteriolar vasodilation and increased post-capillary venular permeability via endothelial contraction.

Serotonin

A preformed vasoactive amine released by platelets and enterochromaffin cells that exhibits vascular actions similar to histamine, causing vasodilation and increased vascular permeability.

Anaphylatoxins ($\text{C3a}$ and $\text{C5a}$)

Complement cleavage fragments that promote acute inflammation by stimulating leukocyte recruitment, leukocyte activation, and histamine liberation from mast cells to increase vascular permeability.

$$\text{C3b}$$

A complement cleavage product that acts as a potent opsonin by depositing onto microbial surfaces, enabling recognition and ingestion by phagocytes bearing $\text{C3b}$ receptors.

Membrane attack complex (MAC)

A lytic assembly of terminal complement proteins ($\text{C5b--9}$) that embeds into microbial cell membranes to form transmembrane pores, causing osmotic cell lysis.

Bradykinin

A liver-derived vasoactive peptide of the kinin system that mediates vasodilation, increased vascular permeability, extravascular smooth muscle contraction, and pain.

Kallikrein

An enzymatic component of the kinin cascade that promotes neutrophil chemotaxis and leukocyte aggregation.

Arachidonic acid

A $20$-carbon polyunsaturated fatty acid cleaved from membrane phospholipids by phospholipase $A_2$ and converted into inflammatory eicosanoids via cyclooxygenase and lipoxygenase pathways.

Prostacyclin ($\text{PGI}_2$)

A cyclooxygenase pathway metabolite produced in vascular endothelium that promotes vasodilation and potently inhibits platelet aggregation.

Thromboxane $A_2$ ($\text{TxA}_2$)

A cyclooxygenase metabolite derived predominantly from platelets that stimulates platelet aggregation and induces vasoconstriction.

Leukotriene $B_4$ ($\text{LTB}_4$)

A 5-lipoxygenase pathway product that serves as a potent chemoattractant and activator of neutrophils, stimulating leukocyte adhesion and transmigration.

Cysteinyl leukotrienes ($\text{LTC}_4$, $\text{LTD}_4$, $\text{LTE}_4$)

Lipoxygenase-derived arachidonic acid metabolites that cause severe bronchospasm, vasoconstriction, and marked increases in vascular permeability.

Lipoxins ($\text{LXA}_4$ and $\text{LXB}_4$)

Anti-inflammatory eicosanoids generated via 12-lipoxygenase that inhibit neutrophil adhesion and chemotaxis, functioning to resolve inflammatory reactions.

Chemokines

A large family of small ($8\text{ to }10\,\text{kDa}$) signaling proteins (classified into C-X-C, C-C, C, and $\text{CX}_3\text{C}$ subgroups) that direct the recruitment, adhesion, and chemotaxis of leukocytes.

Platelet-activating factor (PAF)

A phospholipid-derived mediator from leukocytes and mast cells that causes platelet aggregation, degranulation, vasodilation, increased vascular permeability, and oxidative burst.

Substance P

A neuropeptide that transmits pain signals, causes vasodilation, enhances vascular permeability, and increases leukocyte adhesion and chemotaxis.

Pyrogens

Fever-inducing substances classified into exogenous pyrogens (e.g., bacterial lipopolysaccharide) and endogenous pyrogens (e.g., $\text{IL-1}$ and $\text{TNF}$).

Prostaglandin $E_2$ ($\text{PGE}_2$)

A prostaglandin synthesized by perivascular and hypothalamic endothelial cells in response to $\text{IL-1}$ and $\text{TNF}$ that resets the hypothalamic thermostat to an elevated temperature level, causing fever.

Leukocytosis

An elevation in circulating white blood cell count above normal ($4000\text{--}11000\,\text{cells/mL}$), typically reaching $15000\text{ to }20000\,\text{cells/mL}$ in response to $\text{TNF}$ and $\text{IL-1}$-mediated bone marrow release.

Leukemoid reaction

An extreme, non-neoplastic elevation in circulating leukocyte count reaching $40000\text{ to }100000\,\text{cells/mL}$, resembling leukemia, driven by severe infection.

Neutrophilia

An increased number of circulating neutrophils in the peripheral blood, classic for bacterial infections.

Lymphocytosis

A selective increase in the absolute count of circulating lymphocytes, characteristically observed in viral infections such as infectious mononucleosis or mumps.

Eosinophilia

An increase in circulating eosinophils, commonly induced by allergic disorders (e.g., asthma, hay fever) and multicellular parasitic helminth infestations.

Leukopenia

A paradoxical reduction in circulating white blood cells seen in specific infections (e.g., typhoid fever, certain viruses, rickettsiae, and protozoa) caused by leukocyte sequestration in vascular beds.

Acute-phase proteins

Plasma proteins primarily synthesized by hepatocytes in the liver—notably C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA)—whose concentrations rise sharply in response to $\text{IL-6}$, $\text{IL-1}$, and $\text{TNF}$.

Erythrocyte sedimentation rate (ESR)

A laboratory test where elevated plasma fibrinogen causes red blood cells to aggregate into rouleaux and sediment more rapidly, serving as a non-specific clinical marker for systemic inflammation.

Hepcidin

An acute-phase liver protein whose elevated production during chronic inflammation sequesters iron from red cell progenitors, resulting in anemia of chronic disease.

Septic shock

A severe systemic manifestation of sepsis characterized by massive cytokine release (especially $\text{TNF}$ and $\text{IL-1}$) leading to the clinical triad of disseminated intravascular coagulation (DIC), hypotensive shock, and metabolic disturbances (hyperglycemia).