Chapter 2.1 Acute Inflammation (Part 2)

Question 1

What are the three phases of acute inflammation? When does each phase peak? Describe.

Answer 1

Fluid phase (goal of initial phase is to bring fluid and edema important activating proteins like complement into tissue space)

neutrophil phase (peaks 24 hours)

macrophage phase (peaks at about 2-3 days)

Question 2

Describe the first step of neutrophil arrival.

Answer 2

particles that were running in center of flow (heavier) will now come to edge of the blood flow = margination

margination is first step of neutrophil arrival.

Question 3

Where do neutrophils come in?

Answer 3

same place that fluid comes in from… post capillary venules

Question 4

Describe how vasodilation changes the speed of blood flow. In what vessels does this take place?

How does position of cells change? Why?

Answer 4

slows blood flow in postcapillary venules

cells marginate from center of flow to periphery

Question 5

Describe the mechanism of the second step in neutrophil arrival “rolling”.

Answer 5

Cells that have marginated to periphery have to slow down - hit these “selectin speed bumps” which are upregulated on endothelial cells (which line the blood vessels)

endothelial cells begin to express selectins which will cause neutrophils to slow down along blood vessel periphery = “rolling” (roll slowly along selectin speed bumps)

Question 6

Selectin “speed bumps” are upregulated on endothelial cells during neutrophil activation.

What are the two subtypes of selectins and where do they come from?

Answer 6

P-selectin is released from Weibel-Palade bodies; mediated by histamine

E-selectin is induced by TNF and IL1

Question 7

Where does P-selectin come from? What mediates its release?

Answer 7

Weibel-Palade bodies (has proteins necessary for survival of endothelial cells…

W- Von Willibrand factor
P- P selectin

mediated by histamine

Question 8

What two things induce E-selectin?

Answer 8

TNF and IL-1

Question 9

What do selectins bind? What does this interaction result in?

Answer 9

Bind sialyl Lewis X on leukocytes (this allows for rolling of neutrophils)

interaction results in rolling of leukocytes along the vessel wall

(leukocytes =WBC, neutrophils and macrophages use this mechanism)

Question 10

Define “adhesion” and describe what factors upregulate adhesion molecules.

Answer 10

binding of leukocyte to vessel wall

cellular adhesion molecules (I CAM and V CAM) are upregulated on endothelium by TNF and IL-1

Question 11

What will upregulate integrins on leukocytes?

Answer 11

C5a and LTB4 (same molecules that draw in the neutrophils)

interaction results in firm adhesion to vessel wall

(integrins on neutrophils bind cellular adhesion molecules on endothelial cells which will allow the neutrophil to come across blood vessel into the tissue space

Question 12

What causes Leukocyte Adhesion Deficiency? How is it inherited?

Describe the mechanism/implication.

Answer 12

autosomal recessive defect of integrins (CD18 subunit)

(integrins are necessary for neutrophil to bind cellular adhesion molecules on endothelium.. no integrin… neutrophils cannot get into tissue)

Question 13

What might delayed separation of umbilical cord indicate? Describe disease and mechanism.

Answer 13

Leukocyte Adhesion Deficiency

Delayed separation of umbilical cord (when baby born, umbilical cord which had blood flowing through it is sealed when no longer connected to placenta, so undergoes necrosis, then acute inflammation so tissue can be destroyed so it can be healed, when blood supply of umbilical cord is cut off, tissue will tie, and cord will fall off…neutrophils coming in to destroy tissue help it fall off

if neutrophils cannot come in, that separation of umbilical cord from baby skin will be delayed

Question 14

What do increased circulating neutrophils indicate?

Describe.

Answer 14

Leukocyte Adhesion deficiency

Normally:
neutrophils circulating in the blood (50 percent)
neutrophils hanging out in blood vessels of lung (50 percent) =marginated pool (adhesion necessary)

if adhesion defected marginal pool can’t hang out, those neutrophils will be released into blood so patients have increased circulating neutrophils

Question 15

What do recurrent bacterial infections that lack pus formation indicate?

Answer 15

Leukocyte Adhesion deficiency

Question 16

Define transmigration and chemotaxis (Step 4).

Answer 16

Leukocytes transmigrate across endothelium of postcapillary venules

move toward chemical attractants (bacterial products, IL8, C5a, LTB4)

Question 17

What 4 products attract neutrophils?

Answer 17

bacterial products
IL-8
C5a
LTB4

Question 18

Define phagocytosis.

Answer 18

consumption of pathogens of necrotic tissue by neutrophils

enhanced by opsonins (IgG and C3b)

Question 19

What are two opsonins that enhance phagocytosis by neutrophils?

Answer 19

IgG and C3b

Question 20

How does phagocytosis occur?

Answer 20

pseudopods (long arms) from leukocytes extend to form phagosomes

phagosome is internalized and merges with lysosomes to form phagolysosomes

Question 21

What is Chediak-Higashi Syndrome? How is it inherited?

Answer 21

protein trafficking defect (autosomal recessive)

(railroad system of microtubules that guide the phagosome to the lysosome)

if microtubules out, railroad out, then can’t traffick phagosome to lysosome

Question 22

What are 6 clinical features of Chediak-Higashi Syndrome?

Answer 22

Increased risk of pyrogenic infections

Neutropenia

Giant granules in leukocytes

Defective primary hemostasis

Albinism

Peripheral neuropathy

Question 23

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have increased risk of pyrogenic infections.

Answer 23

Increased risk of pyogenic infections (phagosome created but can’t merge with lysosome bc they cannot destroy organisms that neutophils consume)

Question 24

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have neutropenia.

Answer 24

neutropenia (neutrophils in bone marrow when dividing ..moving DNA and cellular components, but if cannot move things around properly, cannot divide properly, so defect in generation of neutorphils)

Question 25

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have giant granules in leukocytes.

Answer 25

Giant granules in leukocytes (granules produced in golgi go along railroad system to get distributed across neutrophils, if defect in trafficking and granules cannot be sent to periphery and distribute to cell, they pile up around golgi and appear as giant granules around leukocyte)

Question 26

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have defective primary hemostasis.

Answer 26

Defective primary hemostasis (hemostasis is dep. on platelets and platelets contain granules …if not properly distributed and not properly functioning, defect in hemostasis)

Question 27

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have albinism.

Answer 27

Albinism (pigment of skin occurs via melanocytes… multiple keratinocytes make up skin, 1 melanocyte prod. pigment for 25 keratinocytes, prod pigment then hands off to keratinocytes, melanocytes can prod. pigment but cannot pass along rail system to keratinocytes so can’t get proper pigment of skin)

Question 28

Describe the mechanism/explain why patients affected with Chediak-Higashi Syndrome have peripheral neuropathy.

Answer 28

Peripheral neuropathy (if we have nerve at periphery… cell body for nerve of toe is near spinal cord, so the actual nerve can be up to 2 feet or longer, nucleus and key proteins prod by cord, need railroad system to keep the bottom of nerve or distal nerve healthy and alive, if patients have protein trafficking defect they can’t keep alive peripheral nerves)