Flashcards in Chp. 2 Acute Inflammation Deck (24):
What is the purpose of inflammation? What are the two types of inflammation?
The purpose of inflammation is to allow inflammatory cells, plasma proteins, (i.e. complement), and fluid to exit blood vessels and into the interstitial space.
So point is to get all of this stuff out of the blood vessel and into the tissue space.
Two types are acute and chronic.
What characterizes acute inflammation? What does it arise in response to?
It is characterized by the presence of EDEMA AND NEUTROPHILS IN TISSUE!!!
Arises in response to infection to eliminate a pathogen, or tissue necrosis (neutrophils there to remove necrotic debris).
This is an example of immediate response of the immune sys. Because it so fast, it is innate immunity with limited specificity.
What are the mediators of acute inflammation?
There are 5 mediators:
1. Toll Like Receptors (TLRs)
2. Arachidonic Acid Metabolites
3. Mast Cells
5. Hagemen Factor (Factor 12)
What are Toll Like Receptors (TLRs)? How are they activated?
TLRs are things that can sense pathogen associated molecular patterns or PAMPs. This is basically stuff that does not belong in the human body. They are activated by PAMPs that are commonly shared by microbes.
TLRs are present on the surfaces of innate immunity cells (macrophages, dendritic cells). AS WELL AS LYMPHOCYTES SO THEY HAVE A ROLE IN CHRONIC INFLAMMATION.
For ex, CD14 is a co-receptor for TLR4 on macros that recognize LPS. LPS is a PAMP on gram - bacteria.
What does activation of TLRs result in? What other roles do TLRs play in inflammation?
Activation of TLRs results in:
Upregulation of NF-kB. This is a nuclear transcription factor that activates the immune system by up regulation immune response genes that produce multiple immune mediators.
TLRs are also present on cells of ADAPTIVE IMMUNITY (i.e. lymphocytes) so they are also A MEDIATOR OF CHRONIC INFLAMMATION!!
What is NF-kB? If its activated, what happens?
NF-kB is a transcription factor that causes up regulation of immune response genes to produce mediators. It is activated by TLRs
What is Arachidonic acid and where is it located? How is it liberated from this location? Once its liberated, what enzyme then acts upon it?
Arachidonic acid is a molecule located in phospholipid bilayer of cell membranes. It is released by PHOSPHOLIPASE A2.
Once it is out in the cytosol, one of two enzymes will act on it. Either Cyclooxygenase or 5 Lipoxygenase.
What does cyclooxygenase act upon? What is made and what do these products do?
It acts upon arachidonic acid. This reaction produces prostaglandins (PGs).
The PGs made are: PG I2, E2, D2 and they all mediate vasodilation and increase vascular permeability TOGETHER.
HOWEVER, PGE2 ALSO MEDIATES FEVER AND PAIN!!!
What does PGE2 mediate?
It mediates vasodilation, vascular permeability, fever, and pain
What does 5-Lipoxygenase act upon and what products are made? What do these products do?
It acts upon arachidonic acid and creates the Leukotriennes (LTs):
LTB4, LTC4, LTD4, LTE4.
LTB4 attracts and activates NEUTROPHILS!!
LTC4, D4, & E4 are all slow reacting substances of anaphylaxis. They mediate vasoconstriction, bronchospasm, and vascular permeability.
Where does vasodilation occur? How about vascular permeability?
Vasodilation: at the ARTERIOLE
Vascular Permeability: POSTCAPILLARY VENULE
What are the key mediators that attract neutrophils?
LTB4, C5a, IL-8, bacterial products (i.e. N-formylmethianine)
What are mast cells? Where are they located? How are they activated? (3 ways...high yield, lol)
These are cells of innate immunity that are widely distributed t/o connective tissue.
Activated 3 ways:
1. Tissue Trauma (bc they're in tissues)
2. Complement Proteins C3a & C5a
3. Cross Linking of SURFACE IgE by antigen
What Ab does a mast cell have on its surface?
IgE. If its cross linked by Ag, it can activate the mast cell.
Once a mast cell is activated, what happens?
Mast cell activation has an immediate and a delayed response.
Immediate response releases PREFORMED HISTAMINE GRANULES which mediate vasodilation and increased vascular permeability.
After the immediate response, you get the delayed response where arachidonic metabolites are formed, IN PARTICULAR LEUKOTRIENNES!!
What molecule released by mast cells allows for the continuation of acute inflammation?
Leukotriennes are responsible for an acute inflammation process that can continue hours or even days later.
LTs are the second phase of mast cell response!!
What is complement? What are the 3 ways they are activated?
Complement are pro-inflammatory serum proteins circulating in the blood that when activated "complement" inflammation.
They circulate as inactive precursors in the blood.
1. Classical Pathway
2. Alternative Pathway
3. Mannose Binding Pathway
Describe the 3 activation pathways of complement
Classical: C1 binds IgG or IgM that is bound to Ag
Alternative: Microbial products directly activate complement
Mannose Binding Lectin (MBL): This molecule binds to mannose on pathogens and activates complement
What do all complement activation pathways eventually result in?
All pathways result in production of C3 converses. This enzymes causes C3 to produce C3a and C3b.
C3b then produces C5 convertase which acts upon C5 to produce C5a and C5b.
C3b and IgG are opsonins for phagocytosis
C3a & C5a activates mast cells.
C5a is a neutrophil chemoattractant
C5b then joins C6-C9 to form the MAC complex
MAC is a complex that lyses microbes by creating a hole in their membrane
What is the MAC comprised of?
C5b complexed with C6-C9
What are the anaphylatoxins?
C3a and C5a which trigger mast cell degranulation which results in the release of histamine.
Histamine then mediates vasodilation and increased vascular permeability.
What is Hagemen factor (Factor XII) and where is it located? How is it activated, and what does its activation result in?
Hagemen faactor is an inactive PRO-INFLAMMATORY protein produced in the liver.
It is activated by being exposed to the sub endothelial or tissue collagen (this means endothelium has been damaged for these things to be exposed). When exposed to these things, its activated and then the following happens:
Activation of coagulation and fibrinolytic systems
Activation of complement
Activation of the Kinin System: Kinin cleaves HMWK to BRADYKININ. Bradykinin which mediates vasodilation and increase vascular permeability (like histamine) AND PAIN
Note: Gram- bacteria can activate Hagemen factor causing DIC with infection. Hagemen factor can induce a hyper coagulable state.
What two molecules mediate pain?
Summary of what histamine mediates, and the other two that are the answer to the first question
Bradykinin and PGE2.
So Histamine mediates vasodilation and increased vascular permeability
Bradykinin mediates vasodilation, increased vascular permeability, and PAIN
PGE2 mediates vasodilation, increased vascular permeability, pain AND FEVER