Flashcards in Inflammation #2 (Murnane) Deck (63):
T/F Arthritic disease are the MOST crippling disease in the US, the symptoms are INDIRECTLY related to inflammation
irritation and thickening of the synovium
Synovitis beings _____ in RA and _____ in OA
______ and ______reduces FRICTION between ligaments, muscles, skin, tendons, or bones when they rub together
bursea; tendon sheaths
When the bursea is infected it is known as ______; when the tendon sheaths are infected it is known as _____
The immune system includes what 2 intrinsic pathways?
-innate (nonspecific) immunity
-adaptive (specific) immunity
Innate immunity= _____ and ____ while
_____ and ___
innate: gout and OA
adaptive: lupus (SLE) and RA
What are the 2 most common types of phagocytes?
-neutrophils (common WBC)
macrophages develop from _____ and are stimulated AFTER _____
______ are the most abundant phagocyte, but they die fighting
What cells drive most blood mediated inflammatory responses?
(both are apart of the buffy coat, which is less than 1% of whole blood)
T/F Macrophages take longer to develop than neutrophils, but live far longer
What mechanism does macrophages use to get to the site of inflammation?
the marking of pathogens by complement proteins (innate immunity) OR antibodies (adaptive immunity)
During phagocytosis, the pathogen is engulfed in a vesicle called a ______ which fuses with a _____= ______
During the typical inflammatory response there are FOUR major components?
-sensors that detect the inducers
-inflammatory mediators produced by sensors
-target tissues affected by mediators
PAMPs and DAMPs are considered _______. PAMPs are associated with _______ cells while DAMPs are associated with _____ cells.
inducers; foreign cells (pathogens); damaged
TLR (toll-like receptors) are an example of _________ and are found on which cells?
macrophages, neutrophils, dendritic cells
- expressed in many cells
______ phagocytizes bacteria in about 14 days but lives for only 6 hours to a few days.
What granulocyte releases HISTAMINE and other INFLAMMATORY MEDIATORS and contains ANTICOAGULANTS?
-primarily release histamine
______ develop into macrophages at a lower density than neutrophils.
What is the only granulocyte than can live for years and mounts a direct or immune response?
direct: cell attack
TLR4 agonist can go into the _____ , _____, and ______, where it will bind to toll-like receptors.
Bone, Cartilage, Synovial membrane
What happens when TLR4 agonist bind to TLR in cartilage?
It cause the release of cytokines and prostaglandins
What happens when TLR4 agonist bind to TLR in bone? (2)
-stimulate osteoBLAST to release cytokines
- stimulate osteoCLAST to undergo resorption (break down of bone)
Macrophages contain what ____ and _____ receptors that recognize ____ and _____ respectively.
-Toll-like receptors (TLR): PAMPs and DAMPs
-TNF receptors: selective for TNF
What pathway do PAMPs/DAMPs and TNF stimulate (via receptors) in macrophages?
What happens after the NFkB pathway is stimulated in macrophages?
- macrophage nucleus translocation occurs
-changes transcription and translation
- cause the release of cytokines (TNF, IL-1, IL-6, IL-8) which cause inflammation
Cytokines (TNF, IL-1, IL-6, IL-8), Bradykinin, Histamine, and Eicosanoids (prostaglandins, leukotrienes and thromboxanes) are all considered SENSORS.
Name the 4 major steps involved in ACUTE inflammatory response.
1. Tissue damage
2. Mediator release
3. Response to mediator release
What are the 4 cardinal signs of inflammation?
What 4 responses can occur as a result of the release of mediators of inflammation?
-killing/degradation of stimulus
What causes redness and heat of the inflamed region?
-complement (innate system)
What causes pain and swelling (edema) of inflamed region?
- increased capillary permeability and exudate to tissues
- PGs and kinins
How does increasing capillary permeability EXACERBATE inflammatory cells?
By delivering clotting proteins and complement.
4 steps to phagocyte mobilization.
- Diapedesis (transmigration)
- ________ releases neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells.
-during ________ neutrophils cling to walls of capillaries in inflamed area in response to cell adhesion molecules
- ________ is the mechanism by which neutrophils get out the blood vessels into the tissues.
-What is it considered when chemotactic agents promote (+) chemotaxis of neutrophils
____ play a role in Margination and Rolling while ______ play a role in Adhesion & Spreading and Diapedesis.
Where does the process of leukocyte recruitment occur?
The initial step of the leukocyte emigration occurs with ______ molecules.
- selections (slow WBCs down) and interns (allow for adhesion)
What activates selectins ligands? (3)
- cytokines (TNF, IL-1), histamine,
-selectin expression is regulated by cytokines produced in response to infection and injury
-once activated, the rolling and migration process begins
What are the 2 main ligands for integrins?
ICAM-1 and VCAM-1
(unregulated by cytokines)
SELECTINS are responsible for FIRM ADHERENCE of leukocytes to the endothelium.
(converted to a high affinity state by chemokine)
CCL2 (MCP-1) and CCL5 (Rantes) are examples of chemokine released from(3)
monocytes, macrophages, t cells
CXCL8 (IL-8) are examples of chemokine released from
IL-8 released primarily during inflammation
bind certain substances found on the stimulus (microbe, antigen)
T/F Microtubules play a role in the formation of phagolysosomes
What are the requirements to be a mediator of inflammation ? (3)
-produce inflammation alone
-shown to increase in levels at site of inflammation
-drugs that inhibit activity must reduce inflammation
Activation of Hageman factor (XIIa) initiates what other 4 systems?
What are the vitamin K dependent pathways?
2, 7, 9, 10
What are important properties of eicosanoids? (5)
-very broad range of physiological action
-synthesized in all tissues
-converted to inactive metabolite and transported to liver
-very short half-life
What cytokines can induce COX-2? (3)
What can inhibit COX-2?
What are the most important cytokines in acute inflammation? (2)
TNF and IL-1
T/F TNF causes inflammation and organ damage, so it is an excellent pharmacological target