Acute Inflammation Flashcards
Effusions: Its presence implies that there is an increase in the permeability of small blood vessels triggered by some sort of tissue injury and an ongoing inflammatory reaction.
Exudate
a fluid with low protein content (most of which is albumin), little or no cellular material, and low specific gravity. It is essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability
Transudate
excess of fluid in the interstitial tissue or serous cavities
Edema
an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells and, in many cases, microbes.
Pus/suppurative exudate
Vasodilation is largely induced by ___ in acute inflammation
Histamine
The most common mechanism of vascular leakage . It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators. It is called the immediate transient response because it occurs rapidly after exposure to the mediator and is usually short-lived (15 to 30 minutes
Endothelial cell contraction with resultant interendothelial space increases.
vascular leakage begins after a delay of 2 to 12 hours and lasts for several hours or even days;
Delayed prolonged leakage; late sun burn
Increased transport of fluids and proteins
through a cell
Transcytosis
Normal function of lymphatics
drain the small amount of extravascular fluid that has seeped out of capillaries
red streaks near a skin wound is a telltale sign of
infection in a wound; following the trail of lymphatics = lymphangitis
Important molecules in leukocyte extravasation: ___ in rolling; _____ (usually displayed bound to proteoglycans) in activating the neutrophils to increase avidity of integrins; ____ in firm adhesion; and _____ in transmigration.
selectins
chemokines
integrins
CD31 (PECAM-1)
3 types of selectins:
Bind to leukocytes
Bind to endothelium
Bind to platelets and endothelium
L-selectin
E-selectin
P-selectin
Tissue macrophages, mast cells, and endothelial cells that encounter microbes and dead tissues respond by secreting
TNF and IL1 - function?
Chemokines - function?
Other mediators such as histamine and thrombin stimulate what?
- cause endothelial cells to upregulate E selectin and ligand for L-selectin
- Attract WBC along a concentration gradient
- Luminal relocation of P-selectin in endothelial cells
TNF and IL-1 induce endothelial expression of ligands for integrins, mainly
VCAM-1 and ICAM-1
Endogenous chemoattractants
1) cytokines , particularly those of the chemokine family (e.g., IL-8); (2) components of the complement system, particularly C5a ; and (3) arachidonic acid (AA) metabolites, mainly leukotriene B 4 (LTB 4 )
How is chemotaxis initiated in leukocytes?
Binding of endogenous or exogenous chemoattractants, then activation of second messengers that increase cytosolic calcium and activate small guanosine triphosphatases of the Rac/Rho/cdc42 family as well as numerous kinases
How long does it take for monocytes to become the predominant cell type in an inflammatory response?
24-48 hours
Microbiocidal products derived from superoxide (O2-)
hypochlorite (HOCl − ) and hydroxyl radical ( − OH),
Microbiocidal products derived from NO
peroxynitrite (OONO − ).
mannose and fucose residues of glycoproteins and glycolipids are typically found on ____
microbes
mammalian glycoproteins and glycolipids contain terminal ____ or ____
sialic acid or N-acetylgalactosamine
Which cell has a mannose receptor?
Macrophage
molecules that bind and mediate endocytosis of oxidized or acetylated low-density lipoprotein (LDL) particles that can no longer interact with the conventional LDL receptor
Occurs via scavenger receptors
Mac-1 (CD11b/CD18)
A macrophage integrin, may bind microbes for phagocytosis
Major opsonins
IgG antibodies, the C3b breakdown product of complement, and certain plasma lectins, notably mannose-binding lectin
How are ROS produced?
rapid assembly and activation of a multicomponent oxidase, NADPH oxidase (also called phagocyte oxidase), which oxidizes NADPH (reduced nicotinamide-adenine dinucleotide phosphate) and, in the process, reduces oxygen to superoxide anion.
What is the production of ROS called in neutrophils?
Respiratory burst
an enzyme complex consisting of at least seven proteins. In resting neutrophils, different components of the enzyme are located in the plasma membrane and the cytoplasm.
Phagocyte oxidase
Where are ROS produced in the cell?
lysosome and phagolysosome
What happens to hydrogen peroxide after it is produced in the cell?
the azurophilic granules of neutrophils contain the enzyme myeloperoxidase (MPO), which, in the presence of a halide such as Cl −, converts H2O2 to hypochlorite (the active ingredient in household bleach).
How does hypochlorite destroy microbes?
destroys microbes by halogenation (in which the halide is bound covalently to cellular constituents) or by oxidation of proteins and lipids (lipid peroxidation).
Endogenous antioxidants
(1) the enzyme superoxide dismutase , which is found in or can be activated in a variety of cell types; (2) the enzyme catalase , which detoxifies H2O2 ; (3) glutathione peroxidase, another powerful H2O2 detoxifier; (4) the copper-containing serum protein ceruloplasmin ; and (5) the iron-free fraction of serum transferrin .
a soluble gas produced from arginine by the action of nitric oxide synthase (NOS),
Nitric oxide
iNOS, the type that is involved in microbial killing, is induced when…
macrophages and neutrophils are activated by cytokines (e.g., IFN-γ) or microbial products
In macrophages, ___ reacts with ___ to generate the highly reactive free radical peroxynitrite (ONOO −).
NO; superoxide
Are phagocyte oxidase or iNOS mutations severe?
No - there is overlap - mild immunodeficiencies result
What do specific granules of neutrophils contain?
lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase
What do azurophil granules of neutrophils contain?
myeloperoxidase, bactericidal factors (lysozyme, defensins), acid hydrolases, and a variety of neutral proteases (elastase, cathepsin G, nonspecific collagenases, proteinase 3).
What do acid proteases do?
degrade bacteria and debris within the phagolysosomes , which are acidified by membrane-bound proton pumps
What do neutral proteases do?
various extracellular components, such as collagen, basement membrane, fibrin, elastin, and cartilage, resulting in the tissue destruction that accompanies inflammatory processes. can also cleave C3 and C5 complement proteins directly, yielding anaphylatoxins, and release a kinin-like peptide from kininogen
What is α 1-antitrypsin?
the major inhibitor of neutrophil elastase. A deficiency of these inhibitors may lead to sustained action of leukocyte proteases, as is the case in patients with α 1-antitrypsin deficiency
Defensins
cationic arginine-rich granule peptides that are toxic to microbes
Cathelicidins
antimicrobial proteins found in neutrophils and other cells;
Lysozyme
hydrolyzes the muramic acid- N -acetylglucosamine bond, found in the glycopeptide coat of all bacteria
an iron-binding protein present in specific granules
Lactoferrin
a cationic protein of eosinophils, which has limited bactericidal activity but is cytotoxic to many parasites
Major basic protein
extracellular fibrillar networks that provide a high concentration of antimicrobial substances at sites of infection and prevent the spread of the microbes by trapping them in the fibrils
Neutrophil Extracellular Traps (NETs)
NET formation in circulation is dependent on ____ activation.
Platelet
The inability of the leukocytes to surround and ingest some substances, such as immune complexes
Frustrated phagocytosis
IL-17 induces the secretion of ____
Chemokines that recruit other leukocytes
In the absence of effective T H 17 responses, individuals are susceptible to fungal and bacterial infections, and the skin abscesses that develop are “______,” lacking the classic features of acute inflammation, such as warmth and redness.
Cold abscesses
Where do plasma-derived mediators come from?
i.e. complement - are produced mainly in the liver and are present in the circulation as inactive precursors that must be activated, usually by a series of proteolytic cleavages, to acquire their biologic properties
a preformed vasoactive mediator present in platelets and certain neuroendocrine cells, such as in the gastrointestinal tract, and in mast cells in rodents but not humans.
Serotonin
