Chp. 2 Acute Inflammation

Question 1

What is the purpose of inflammation? What are the two types of inflammation?

Answer 1

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.

Question 2

What characterizes acute inflammation? What does it arise in response to?

Answer 2

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.

Question 3

What are the mediators of acute inflammation?

Answer 3

There are 5 mediators:

1. Toll Like Receptors (TLRs)
2. Arachidonic Acid Metabolites
3. Mast Cells
4. Complement
5. Hagemen Factor (Factor 12)

Question 4

What are Toll Like Receptors (TLRs)? How are they activated?

Answer 4

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.

Question 5

What does activation of TLRs result in? What other roles do TLRs play in inflammation?

Answer 5

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!!

Question 6

What is NF-kB? If its activated, what happens?

Answer 6

NF-kB is a transcription factor that causes up regulation of immune response genes to produce mediators. It is activated by TLRs

Question 7

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?

Answer 7

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.

Question 8

What does cyclooxygenase act upon? What is made and what do these products do?

Answer 8

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!!!

Question 9

What does PGE2 mediate?

Answer 9

It mediates vasodilation, vascular permeability, fever, and pain

Question 10

What does 5-Lipoxygenase act upon and what products are made? What do these products do?

Answer 10

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.

Question 11

Where does vasodilation occur? How about vascular permeability?

Answer 11

Vasodilation: at the ARTERIOLE

Vascular Permeability: POSTCAPILLARY VENULE

Question 12

What are the key mediators that attract neutrophils?

Answer 12

LTB4, C5a, IL-8, bacterial products (i.e. N-formylmethianine)

Question 13

What are mast cells? Where are they located? How are they activated? (3 ways…high yield, lol)

Answer 13

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

Question 14

What Ab does a mast cell have on its surface?

Answer 14

IgE. If its cross linked by Ag, it can activate the mast cell.

Question 15

Once a mast cell is activated, what happens?

Answer 15

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!!

Question 16

What molecule released by mast cells allows for the continuation of acute inflammation?

Answer 16

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!!

Question 17

What is complement? What are the 3 ways they are activated?

Answer 17

Complement are pro-inflammatory serum proteins circulating in the blood that when activated “complement” inflammation.

They circulate as inactive precursors in the blood.

Activated via

1. Classical Pathway
2. Alternative Pathway
3. Mannose Binding Pathway

Question 18

Describe the 3 activation pathways of complement

Answer 18

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

Question 19

What do all complement activation pathways eventually result in?

Answer 19

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

Question 20

What is the MAC comprised of?

Answer 20

C5b complexed with C6-C9

Question 21

What are the anaphylatoxins?

Answer 21

C3a and C5a which trigger mast cell degranulation which results in the release of histamine.

Histamine then mediates vasodilation and increased vascular permeability.

Question 22

What is Hagemen factor (Factor XII) and where is it located? How is it activated, and what does its activation result in?

Answer 22

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.

Question 23

What two molecules mediate pain?

Summary of what histamine mediates, and the other two that are the answer to the first question

Answer 23

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

Question 24

Describe the Mannose Binding Lectin Pathway of activating complement.

Where is it found and what is it complexed with? What happens when MBL is activated? What are the products made?

Answer 24

MBL recognizes and binds to Carbohydrates on pathogens, ie bacteria, fungi, viruses, protozoa.
It is a protein complexed to another protein called a MASP (which is a serine protease) in the blood. When MBL binds to its target on a pathogen, the MASP cleaves C4 into C4a and C4b.

C4b binds to the bacterium and then initiates the formation of C3 convertase. This eventually leads to the MAC.