2.1 Acute inflammation, part 1 Flashcards
What are the cells that are present in tissue during acute and chronic inflammation respectively?
Acute = PMNs Chronic = Lymphocytes
What are the two primary hallmarks of acute inflammation?
Edema and PMNs
What are the two major causes of acute inflammation?
Infection and tissue necrosis
What are the cells of the immune system that have TLRs? What is the role of TLRs?
- Macrophages and dendritic cells
- Recognize PAMPs
What is the TLR that is on macrophages, and has the ability to recognize LPS?
CD14
Where is LPS on gram negative bacteria?
Outer membrane
What is the transcription factor that is upregulated with TLR activation? What does this do?
- NF-kappa B
- Leads to the production of multiple immune mediators
True or false: TLRs are not present on lymphocytes, and therefore do have a role in chronic inflammation
False–they are on lymphocytes, and they do play a role in chronic inflammation
Where is Arachidonic acid released from? What is the enzyme that mediates this?
Released from the phospholipid cell membrane by phospholipase A2
What are the two pathways that arachidonic acid can gown down? What are the enzymes that mediate each pathway?
- COX for prostaglandins
- 5-Lipoxygenase for leukotrienes
What are the prostaglandins that are mediate vasodilation, and increased vascular permeability?
PGI2
PGD2
PGE2
(“Help 2 DIE-ilate”)
Which PG, in addition to mediating increased vascular permeability, mediates fever and pain?
PGE2
Where do PG mediate vasodilation and increased vascular permeability respectively?
Vasodilation at the arterioles
Increased vascular permeability in the postcapillary venules
What is the function of LTB4?
Attracts and activates PMNs
What are the leukotrienes that mediate vasoconstriction, bronchospasm, and increased vascular permeability?
LTC4
LTD4
LTE4
Which leukotriene activates PMNs?
LTB4
What are the four primary PMN chemoattractants?
- LTB4
- C5a
- IL-8
- Bacterial products
What are the function of LTC4, LTD4, and LTE4?
Smooth muscle contraction (bronchoconstriction, vasoconstriction)
What is the function of the pericyte in endothelial cells?
Contraction of the vessels, to open up spaces between endothelial cells during edema
Where are mast cells found?
Widely distributed throughout the CT of the body
What are the three main mechanisms of activating mast cells?
- Tissue trauma
- Complement (C3a + C5a)
- Cross linking of surface IgE by antigen
What is the immediate response of mast cell activation?
Release of preformed histamine causes vasodilation of arterioles and increased vascular permeability
What are the components of the delayed response of mast cell activation?
Production of arachidonic acid metabolites (leukotrienes)
How is complement normally found in the blood?
Inactive precursors in the blood
DAF inactivates which complement components?
C4b and C3b
What initiates the classical complement pathway?
C1 binds to IgG or IgM
What initiates the alternative pathway?
C3 directly binds and activates complement
What activates the lectin pathway?
Mannose binding lectin binds mannose on microorganisms, and activates complement
Where do all three of the complement pathways converge? What does this do?
C3 convertase, to generate C3a and C3b
What is the most common complement deficiency?
C2
What is the defect in paroxysmal hemoglobinuria?
-Loss of CD55 (DAF) d/t loss of GP anchor)
How is C5 convertase activated? What does this do?
From C3b
C5 convertase produces C5a and C5B to help produce the MAC
What is the major function of C5a?
Chemotactic factor for PMNs
What is the major function of C3b?
Opsonin for phagocytosis
What is the function of the MAC?
Lyses microbes by creating holes in the cell membrane
Which complement if associated with GMN?
C3
What is Hageman factor? What activates it?
Inactive proinflammatory protein produced in the liver, that is activated upon exposure to subendothelial or tissue collagen
Why does gram - Sepsis lead to DIC?
Gram negative bacteria can activate Hageman factor
What is the function of Hageman factor?
- Activates the coagulation and fibrinolytic systems
- Activates the complement system
- Activates Kinin system
What is the Kinin system that is activated by Hageman factor?
Hageman cleaves HMWK to bradykinin, which mediates vasodilation, pain, and increased vascular permeability
What are the two major inflammatory cytokines that mediate pain? MOA?
PGE2
Bradykinin
Sensitive sensory nerve endings
What are the key mediators of Rubor and calor? (3)
Histamine
PGs
Bradykinin
What are the two major mediators of swelling?
Histamine
Tissue damage
Where does leakage of fluid occur with edema?
Post capillary venule
What are the cells that release IL-1 and TNF to cause fever?
Macrophages
What is the MOA of IL-1 and TNF to produce fever?
Increased COX activity in the perivascular cells of the hypothalamus produces PGE2 to increase set point of hypothalamus
