Chapter 2.1 Acute Inflammation (Part 1)

Question 1

How does acute and chronic inflammation differ in regards to immune cells simplistically?

Answer 1

inflammation is when cells from vessel come out of vessel and into tissue space - if neutrophils are primary cell that comes into tissue space that is acute inflammation, if leukocytes are the primary cells that come into the tissue space that’s chronic inflammation

Question 2

Define inflammation.

Answer 2

allows inflammatory cells, plasma proteins, and fluids to exit blood vessels and enter the interstitial space

acute/chronic inflammation (acute=neutrophils, chronic=lymphocytes)

Question 3

What two things characterize the presence of acute inflammation?

Answer 3

edema (fluid from blood vessels that accumulates in tissue space- causes swelling)

neutrophils (key inflammatory cell that comes out of vessel into tissue space)

Question 4

What two stimuli induce acute inflammation?

Answer 4

infection

tissue necrosis

Question 5

What is the difference between apoptosis and necrosis?

Answer 5

necrosis is followed by acute inflammation

(apoptosis is not)

necrosis- body will send neutrophils in to destroy tissue then can heal

Question 6

After an MI a patient may have an increase in white count. What type of cell has increased?

Answer 6

neutrophils bc they are generated and pushed up into dead tissue

Question 7

What is the goal of acute inflammation?

Answer 7

neutrophils come in to eliminate the pathogen or clear necrotic debris

Question 8

What does innate immunity include?

Answer 8

Includes the epithelium that protects body surfaces

mucus secreted by cells

complement system (series of proteins present in inactive state in serum but can be activated)

mast cells (widely distributed throughout tissue)

macrophages

neutrophils, eosinophils, basophils

(broad system that is non-specific that defends host against microbes)

Question 9

Acute inflammation is mediated by several factors. Describe TLRs. Where are they present? What do they do?

Answer 9

present on cells of innate immune system (macrophages and dendritic cells)

recognize PAMPS (patterns of molecules present on pathogens, TLR recognize pattern and then let body know invader is present, turn on acute response) 
=commonly shared by microbes

Question 10

What is CD14? Where is it present and what does it do?

Answer 10

CD14 (TLR) present on surface of macrophages

recognizes lipopolysaccharride (LPS) (which is on outer membrane of GN bacteria)

When CD14 sees that PAMP (LPS) it then activates the innate immune system.

Question 11

What happens once a TLR recognizes a PAMP?

Answer 11

upregulates NF-kB (the molecular switch)

TLR activated, results in upregulation of NF-kB, turns on acute inflammatory response, activates immune response genes and leads to production of multiple immune mediators

Question 12

Are TLRs present on cells of adaptive immunity?

Answer 12

Yes, also present on lymphocytes and they mediate chronic inflammation

Question 13

How is Arachidonic Acid released?

Answer 13

released from phospholipid cell membrane by phospholipase A2

-acted on by cyclooxygenase or 5-lipooxygenase pathway

Question 14

What pathway produces PG (prostaglandin)?

Describe action of PG. What type of vessels do they act on?

Answer 14

cyclooxygenase

PGI2, PGD2, PGE2 mediate vasodilation (at level of ARTERIOLE) and increased vascular permeability (at level of POST CAPILLARY VENULE)

PGE2 also mediates fever and pain

Question 15

What does PGE2 mediate?

Answer 15

fever and pain

Question 16

What pathway produces leukotrienes?

Answer 16

5-lipooxygenase pathway

Question 17

What does LTB4 do?

Answer 17

Attracts and activates neutrophils

Question 18

What four mediators activate neutrophils?

Answer 18

C5a, IL8, bacterial products, LTB4

Question 19

What three things do LTC4, LTD4, and LTE4 do?

Answer 19

mediate vasoconstriction, bronchospasm, increased vascular permeability (occurs when pericytes contract increasing opening or space between endothelial cells)

(contract smooth muscle, cause it to contract), arteriole and bronchus are lined by smooth muscle

Question 20

Where are mast cells found?

Answer 20

widely distributed throughout connective tissue

Question 21

How can mast cells be activated (3 ways)?

Answer 21

• tissue trauma
• complement proteins C3a and C5a
• cross-linking of cell-surface IgE by antigen

Question 22

Once mast cell is activated, what immediate response occurs?

Describe effect and where effect takes places.

Answer 22

release of preformed histamine granules

mediate vasodilation of arterioles and increased vascular permeability of post capillary venules

Question 23

What is the delayed response of mast cell activation?

Answer 23

production of arachindonic acid metabolites, particularly leukotrienes (allow for maintenance of acute response)

Question 24

Patient has mast cells which activate the acute inflammatory response and several hours later the acute inflammatory response continues, what is major mechanism by which mast cells will allow for progression of acute inflammatory response?

Answer 24

production of arachidonic acid metabolites, particularly leukotrienes

Question 25

What is complement?

Answer 25

proinflammatory serum proteins

“complement” inflammation

circulate as inactive precursors

Question 26

How does activation of complement occur? What 3 pathways?

Answer 26

classical pathway - C1 binds to IgG or IgM that is bound to antigen (GM makes classical cars)

alternative pathway- microbial products directly activate complent

Mannose binding lectin pathway -MBL binds mannose on microorganisms and activates complement

Question 27

What is the result of activation of complement?

Answer 27

all pathways lead to same result

C3 convertase generated which converts C3a and C3b, C3b helps prod C5 convertase, C5a and C5b produced, C5b complexes with C6-C9 to prod. membrane attack complex (prod hole in membrane to allow for lysis of microorganism)

Question 28

What do the following key products do:

C3a
C5a
C3b
MAC

Answer 28

C3a and C5a- trigger mast cell degranulation

C5a- chemotactic for neutrophils

C3b-opsonin for phagocytosis

MAC- lyses microbes by creating holes in cell membrane

Question 29

What is Hageman factor?

What does this play an important role in?

How is it activated?

Answer 29

inactive proinflammatory protein produced in liver

activated upon exposure to subendothelial or tissue collagen

(important role in DIC, esp severe GN sepsis)

Question 30

Why does Hageman factor play an important role in DIC?

What does Hageman factor do?

Answer 30

it activates coagulation and fibrinolytic systems

activates complement

activates Kinin system- cleaves HMWK to bradykinin, which mediates vasodilation, increased vascular permeability and pain

Question 31

What are the cardinal signs of acute inflammation?

Answer 31

redness (rubor) and warmth (calor)

redness- increasing amount of blood flow, due to vasodilation

occurs via relaxation of arteriolar smooth muscle

key mediators are histamine, PGs, (PGI2, PGE2 and PGD2), and bradykinin

Question 32

Describe swelling (tumor) mechanism. What are the key mediators?

Answer 32

Due to leakage of fluid from postcapillary venules into interstitial space

key mediators 1) histamine, 2) tissue damage

Question 33

Describe mechanism and mediators of pain (dolor).

Answer 33

bradykinin, PGE2, sensitive sensory nerve endings

Question 34

Describe mechanism of fever.

Answer 34

pyrogens cause macrophages to release IL-1 and TNF (get into bloodstream, get into perivascular cells of hypothalamus where temp. regulation of body mediated, they increase cyclooxygenase activity which increases PGE2 which raises temperature set point)

increase cyclooxygenase activity in perivascular cells of hypothalamus

increases PGE2, raises temperature set point