Inflammation Flashcards
What are the 5 cardinal signs of inflammation?
Heat, Pain, Swelling, Redness, Loss of Function
The defense reaction of living tissue against damage, aimed at removing the cause of injury and repairing the tissue, is called -?
Inflammation
During acute inflammation, there will be a dominating presence of -?
Neutrophils
During chronic inflammation, there will be a dominating presence of _________ in the tissue.
Macrophages
While the most common causes of inflammation are _______ agents, physical agents (fractures, foreign objects, burns, freezes, etc.) and chemical agents (toxins, gases, acids, bases, etc.) can also be the cause.
Biological
What are some common biological agents that could or are responsible for inflammatory processes?
Bacteria, Viruses, Parasites, Fungi
Which of the following would not be considered an exogenous cause? A) Frostbite B) Stress C) Alcohol D) Urea
D) Urea
How does inflammation lead to heat production, a cardinal sign of inflammation?
Injury leads to vasoconstriction and then vasodilation, leading to an increase in blood to the area (raising metabolic activity = increases heat)
How does inflammation lead to redness, a cardinal sign of inflammation?
The vasodilation of vessels leads to increased blood perfusion (hyperaemia), and this causes redness at the site of injury
How does inflammation lead to edema or swelling, a cardinal sign of inflammation?
Vasodilation and stasis of blood flow, increases capillary hydrostatic pressure (forcing water out of the vessel), and increased pore size allows proteins to escape vessels (lowering the colloid oncotic pressure to return water to the vessel)
How does inflammation lead to both pain and the loss of function, both cardinal signs of inflammation?
As a result of leukocyte extravasation, leukocytes will release mediators through the process of phagocytosis of pathogens. These mediators, along with exudate, will stretch pain receptors, causing pain. Prolonged stretch of these receptors will lead to a disruption of tissues, metaplasia, and a loss of function.
What pro-inflammatory cytokines are associated with mediating the induction of fever and stress hormone production?
TNF alpha, IL-1, IL-6, IL-8
TNF alpha, while activating ________ cells and _________, induces inflammation, fever, and an acute phase response. This cytokine is associated will also kill cells via _________.
Endothelial
Neutrophils
Apoptosis
What cells secrete TNF alpha?
Macrophages and T cells
IL-6 stimulates the ______ to produce mediators of the anti-inflammatory response (acute phase proteins, e.g. c-reactive proteins), as well as proliferation of _________ producing cells of the adaptive immune response.
Liver
Antibody
What cells secrete IL-6?
Macrophages, T lymphocytes, and endothelial cells
IL-_ stimulates the production of neutrophils, as well as inducing fever and an acute phase response. This interleukin also activates the _________ in the inflammatory response.
IL-1
Endothelium
What cells secrete IL-1?
Macrophages and endothelial cells
IL-8 is associated with mediating __________ and lymphocyte infiltration into tissues, as well as producing ___________ for neutrophils.
Neutrophils
Chemoattractants
What cells secrete IL-8?
Macrophages and endothelial cells
TNF alpha and what other interleukin are associated with the synthesis of IL-6, IL-8, and IFN gamma?
IL-1
What roles do IL-1, IL-6, and IL-8 have?
The promotion of chemotaxis, induce extravasation, and neutrophillic degranulation
What processes are activated by the pro-inflammatory cytokines released during inflammation?
Coagulation cascade, release of nitric oxide, platelet-activating factor, prostaglandins, and leukotrienes
What complement proteins are associated with vascular permeability, and the chemotaxis of granulocytes?
C3a and C5a
____________, which are lipid-soluble products of arachidonic acid metabolism, contribute to vasodilation, capillary permeability, pain and fever. To a lesser extent they also lower the _____ pressure.
Prostaglandins
Blood
What roles do PGE1 and PGE2 contribute to?
Increasing the effects of histamine and other mediate inflammatory mediators
What role does Thromboxane 2 have?
The promotion of the platelet aggregation and vasoconstriction
Leukotrienes, produced from the oxidation of ____________ ____, are slow-reacting substances of __________ (LTC4, LTD4, LTE4), which induce smooth muscle ___________.
Arachidonic acid
Anaphylaxis (SRS-A)
Contraction
What leukotrienes are associated with the inflammatory response?
LTB4, LTC4, LTD4, and LTE4
What role does LTB4 have following diapedesis?
LTB4 acts as a chemoattractant of neutrophils
Vasoactive amines, are found in _____ concentrations in platelets, basophils, and mast cells. This leads to _________, which ________ permeability. These substance act through H_ and _-HT receptors.
High Vasodilation Increases H1 5-HT
PAF, also known as _______-_________ ______, which induces platelet aggregation and activates ________, and as an _________ chemoattractant. This leads to an _____ of plasma proteins from capillaries.
Platelet Aggregation Factor
Neutrophils
Eosinophil
Efflux
Kinins, such as bradykinin, are both associated with pain and vascular permeability. These _____ _________ are associated as well with _________ _______, through the production of fibrin peptides.
Plasma proteases
Clotting factors
What two stages, or responses, are associated with inflammation?
Vascular and then cellular
What phases are associated with the vascular phase of inflammation?
I: Vasoconstriction, lasts a few mins
II: Active vasodilation, redness and heat
III: Passive vasodilation, edema, pain, loss of function
What phases are associated with the cellular response
Chemotaxis, Rolling, Migration/ Diapedesis, Phagocytosis
When an infection occurs, the first cells to arrive are neutrophils, then -?
Macrophages and NK cells
In order for immune cells to move into the interstitium they need to use ___ _________ _________, as endothelial cells also produce these molecules, though some of these responses can only be produced during __________.
Cell Adhesion Molecules (CAM)
Inflammation
What four families of proteins are associated with cell adhesion molecules?
Selectins, Mucin-like CAM’s, Integrins, and Ig-Superfamily CAM
If selectin binds to _____, then what do integrins bind to -?
Selectin = Mucin-like CAM's Integrin = Ig-Superfamily CAM's
What is present on selectins that allow them to bind to mucin-like CAMs?
Cell surface glycoproteins, which bind to carbohydrate chains of mucin-like CAM’s
Which selectins are expressed on leukocytes and endothelial cells?
Leukocytes = Selectin L
Endothelial cells = Selecting P and E
How do endothelial cells express Selectin P and E receptors on their luminal surface?
Selectin P receptors are stored in granules and expressed upon stimulation, whereas Selectin E is synthesized as needed by pro-inflammatory cytokines
Selectins would be associated with the which inflammatory response or stage?
Vascular
While serine and threonine-rich proteins, that bind to selectins, mucins that are found on leukocytes include ______, which binds to ____ or GlyCAM-1 on endothelial cells.
CD62L
CD34 or GlyCAM-1
The selectins P and E on endothelial cells can bind to the ____-_ on neutrophils to aid in initial contact between cells (rolling/ tethering).
PSGL-1
Integrins present on leukocytes, have two chains, an ______ and a ____, which will bind to Ig-Superfamily domains expressed on ________ cells during the cellular phase
Alpha
Beta
Endothelial
An example of a cell adhesion molecule that can bind to either selectins and integrins, is primarily responsible for the migration of leukocytes into the mucosa, and contains features of both Ig-Superfamily and Mucins, is called -?
MAdCAM-1
What causes the increase in CAM’s along endothelial cells?
Cytokines and other proinflammatory mediators
Why do leukocytes exhibit rolling along endothelial cells due to their mucin CAM’s?
They only loosely bind to selectins P and E along endothelial cells
How does the activation of leukocytes, due to IL-8 and MIP-1 beta, following increased chemokine secretion from endothelial cells, lead to adhesion?
Activation of endothelial cells and leukocytes leads to conformational changes altering the integrins of leukocytes into high affinity states for binding to endothelial Ig-Superfamily CAMs.
Following strict binding of the leukocyte to the endothelium, they will use what receptors to migrate paracellularly into the interstitium?
PECAM-1 aka CD131
Selectin L receptors on neutrophils are associated with their rolling, as they are being bound to ____-_ along activated endothelial cells.
PSGL-1
True or False: Without inflammation, there will be no expression of selectin P, selectin E, and other cell adhesion molecules along endothelial cells.
True
ICAM expression will occur on ________ cells, while expression of _____ and _____ on neutrophils for firm adhesion.
Endothelial = ICAM
CD11a, CD11b aka CD18 aka LFA-1 and MAC-1 = Neutro.
While monocytes arrive slightly later than neutrophils, what ligands do they recognize with their CD11 and CD18 receptors?
VCAM-1 and ICAM-1 along endothelial cells
While monocytes use the same receptor for diapedesis as neutrophils, they utilize the binding of _____ for rolling, and are activated by ___-_.
Rolling = CD62L
Activation = MCP-1
Diapedesis - PECAM-1
What adhesion molecules can be utilized for monocytic extravasation?
Bacterial peptides, CR3, and CR4
True or False: The extravasation of lymphocytes is similar to that of monocytes.
False, similar to that of neutrophils
What do lymphocytes pass through to exit venules?
HEVs or high endothelial venules
What chemokines are needed for activation of lymphocytes in circulation to exit through high end venules?
CCL19, CCL21, and CXCL12
What leads to systemic manifestation of inflammation in the body?
The release of pro-inflammatory mediators into circulation
What responses occur due to systemic inflammation?
Acute phase response, WBC alterations, febrile temperature, and sepsis/ septic shock
What organs or glands are associated with the systemic acute phase response?
Bone marrow, Brain, Adrenal gland, Liver
Why are some complement proteins and CRP’s, or c-reactive proteins, considered acute phase proteins?
They alter their concentrations in response to proinflammatory mediators (TNF alpha, IL-1, IL-6, IL-8), as they are synthesized by the liver
In dogs, what are examples of acute phase proteins?
CRP or c-reactive protein, SAA or serum amyloid A, Hp or haptoglobin, AGP, or Cp
What are the ligands for CRP’s?
Pneumococcal polysaccharides and phosphorylcholine
How is MBL considered an APP, or acute phase protein?
It recognizes mannose present on the microbes
Effects of systemic inflammation leads to -?
Anorexia, altered sleep patterns, lethargy, cachexia (muscle loss due to loss of anorexia), metabolic acidosis (increased cellular metabolism)
What anti-inflammatory factors are synthesized for the termination of inflammation?
TNF beta, IL-4 and IL-10, as anti-inflammatory mediators are lead to neutrophil apoptosis and macrophage departure.
What role does IL-4 have?
Secreted by CD4+ Th2 cells and Mast cells, it promotes growth and survival of lymphocytes and mast cells and as an anti-inflammatory mediator
What role does IL-10 have?
Secreted by macrophages, it inhibits activated macrophages, dendritic cells, and Th1 cells
What roles do IL-4 and IL-10 have in regards to the concentrations of pro-inflammatory mediators?
Down regulates them
Omega 3 FA’s are associated with synthesizing _______ and ______ to initiate neutrophil apoptosis.
Resolvins and fixins
Lipoxins, which are needed to ________ inflammatory processes, is produced from _________ _____.
Terminate
Arachidonic acid
IL-1 antagonists and soluble tumor necrosis factors receptors are upregulated during -?
Anti-inflammatory processes
What are the outcomes associated with inflammation?
Resolution = restoration of inflamed tissues
Fibrosis = vast tissue destruct., scar formation, impaired
Abscess formation = pus cavity
Chronic inflam. = prolonged, macrophages present
