13: Inflammation and Cytokines Flashcards
What is Platelet-activating factor (PAF) chemotactic for?
Inflammatory cells
[It increases adhesion molecules]
Which cell type is the largest producer of IL-1?
Macrophages
Which substance causes vascular smooth muscle constriction, opposing the effects to nitric oxide?
Endothelin
For how long do platelets last?
7-10 days
What decreases inflammation by inhibiting phospholipase from converting phospholipids to arachidonic acid?
Steroids
Which amino acid is a precursor to nitric oxide?
Arginine
[It is the substrate for nitric oxide synthase]
Which leukotriene is chemotactic for inflammatory cells?
LTB4
Which cytokine increases hepatic acute phase proteins (C-reactive protein, amyloid A)?
IL-6
What generates Platelet-activating factor (PAF)?
Phospholipase in the endothelium
Which cell type is the main source of histamine in the tissues?
Mast cells
Which complement factors combine to form the membrane attack complex that causes cell lysis by creating a hole in the cell membrane?
- C5b
- C6
- C7
- C8
- C9 (10-16 molecules of C9)
What causes peripheral vasodilation, increased permeability, pain, and pulmonary vasoconstriction?
Bradykinin
Where are L,-, E-, and P-Selectins located?
- L-Selectin = leukocytes
- E-Selectin = Endothelial cells
- P-Selectin = Platelets and endothelial cells
[Involved in rolling adhesion]
Which cell type has a dominant role in wound healing?
Macrophages
[Macrophages release important growth factors]
Which 2 prostaglandins inhibit platelets and cause vasodilation, bronchodilation, increased vessel permeability?
- PGI2
- PGE2
[Produced from arachidonic precusors]
Platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) are all involved in which 2 processes?
- Angiogenesis
- Epithelialization
[IL-8 and hypoxia are also angiogenesis factors, but they do not induce epithelialization.]
Which cell type is the primary mediator of reperfusion injury?
PMNs
[Wikipedia: Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN, PML, or PMNL) because of the varying shapes of the nucleus, which is usually lobed into three segments. This distinguishes them from the mononuclear agranulocytes. In common parlance, the term polymorphonuclear leukocyte often refers specifically to neutrophil granulocytes, the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow.]
What are the two main hepatic acute phase response proteins?
- C-reactive protein (an opsonin, activates complement)
- Amyloid A
[IL-6 increases hepatic acute phase proteins]
For how long do PMNs last in the blood vs the tissues?
- Blood 7 days
- Tissues 1-2 days
Which two complement factors are chemotactic for inflammatory cells?
- C3a
- C5a
Which cell type is the largest producer of TNF?
Macrophages
How does atelectasis cause fever?
Alveolar macrophages release IL-1
How does nitric oxide cause vascular smooth muscle dilation?
It activates guanylate cyclase and increases cGMP
What gets released by lymphocytes in response to viral infection or other stimulants?
Interferons
[They activate macrophages, natural killer cells, and cytotoxic T cells. They inhibit viral replication.]
Platelet-derived growth factor (PDGF) is chemotactic and activates which 2 cell types?
- Inflammatory cells (PMNs and macrophages)
- Fibroblasts (collagen and ECM proteins)
[PDGF has been shown to accelerate wound healing.]
Which factors are only components of the classic complement pathway?
C1, C2, and C4
[The classic pathway is activated by antigen-antibody complexes]
Which disease is characterized by NADPH-oxidase system enzyme defect in PMNs that results in a decrease in superoxide radical formation?
Chronic granulomatous disease
Which 3 leukotrienes are the slow-reacting substances of anaphylaxis, causing bronchoconstriction and vasoconstriction followed by increased permeability (Wheal and flare)?
- LTC4
- LTD4
- LTE4
[Produced from arachidonic precursors]
Eosinophils are increased during what kind of infection?
Parasitic infections
Which two complement factors are opsonins?
- C3b
- C4b
What is located in the lungs and inactivates bradykinin?
Angiotensin-converting enzyme (ACE)
Which 3 growth factors do macrophages release when responding to endothelial injury?
- Platelet-derived growth factor (PDGF)
- IL-1 (Cytokine)
- TNF-alpha (Cytokine)
Which two cytokines compose the main initial cytokine response to injury and infection?
- TNF-alpha
- IL-1
Which cell type releases major basic protein?
Eosinophils
[Major basic protein stimulates basophils and mast cells to release histamine]
Which molecule is the primary effector in type I hypersensitivity reactions?
Histamine
[Causes vasodilation, tissue edema, postcapillary leakage]
What is the primary cell type in type I hypersensitivity reactions?
Mast cells
Which 3 factors produced during the complement cascade are anaphylatoxins that increase vascular permeability, bronchoconstriction, and activate mast cells and basophils?
- C3a
- C4a
- C5a
How does IL-1 cause fever?
PGE2 mediated in the hypothalamus
[NSAIDs decrease fever by reducing PGE2 synthesis]
Beta-2 integrins (CD11/18) located on leukocytes bind to what in anchoring adhesion?
ICAM, VCAM, PECAM, ELAM on endothelial cells
[Also involved in transendothelial migration]
Where do the classic and alternative complement pathways converge?
Factor C3
[Mg is required for both pathways]
When do catecholamines peak after an injury?
24-48 hours
[Norepinephrine is released from sympathetic posganglionic neurons and both epinephrine and norepinephrine are released from the adrenal medulla]
Fibroblast growth factor (FGF) and Epidermal growth factor (EGF) are chemotactic and activate which cell type?
Fibroblasts
Which cell type is the main source of histamine in the blood?
Basophils
[Basophils are not found in tissue and so the main source of histamine in the tissue is mast cells.]
Endothelial injury resulting in exposed collagen causes release of which two factors?
- Platelet-activating factor
- Tissue factor
Which factors are only components of the alternative complement pathway?
B, D, and P (properdin)
[Activated by endotoxin, bacteria, and other stimuli]
Following endothelial injury, platelets bind to exposed collagen and release growth factors such as platelet-derived growth factor (PDGF) that lead to what?
PMN and macrophage recruitment
[Wikipedia: PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal. Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)[12][13] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.
PDGF plays a role in embryonic development, cell proliferation, cell migration, and angiogenesis. Over-expression of PDGF has been linked to several diseases such as atherosclerosis, fibrotic disorders and malignancies. Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.
PDGF is a required element in cellular division for fibroblasts, a type of connective tissue cell that is especially prevalent in wound healing. In essence, the PDGFs allow a cell to skip the G1 checkpoints in order to divide. It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.]
