2.1 acute inflammation, part 2 Flashcards
What are the three major, general phases of inflammation?
- Fluid phase
- PMN phase
- Macrophage phase
What is the peak time of the PMN phase of inflammation?
24 hours
What is the peak time of the macrophage phase of inflammation?
2-3 days
Where in the blood stream to heavy particles sit? What happens to them with vasodilation?
- Center
- Move toward the periphery with vasodilation
What is the first step of PMN arrival? What is involved in this step?
Margination
- Vasodilation slows blood flow
- Cells marginate from center of flow to the periphery
Where do PMNs marginate at?
Post capillary venule
What is the second step in PMN migration, and what occurs with this?
Rolling
-Selectins (speed bumps) slow down the rolling marginated PMNs
What are the “speed bumps” that cause the rolling phase of PMN migration? What cells do these come from?
P-selectin
-Weibel-Palade bodies
E-selectin induced by TNF and IL-1
What are the chemokines that induce E-selectin upregulation?
TNF and IL-1
What are the two proteins contained within Weibel-Palade bodies?
P-selectin
vWF
What chemokine induces WP bodies to release P-selectin?
Histamine
What is the molecule on leukocytes that bind selectins? What does this interaction cause?
- Sialyl Lewis X
- Interaction results in rolling of leukocytes along the vessel wall
What is Sialyl Lewis X, and what does it do?
Molecule on leukocyte that binds to selectins on endothelium that results in rolling
What is the third step of PMN migration? What occurs with this?
Adhesion:
-Cellular adhesion molecules upregulated on endothelium
What are the cytokine that upregulate adhesion molecules on the endothelium?
TNF and IL-1
What are the cytokines that upregulate integrins on leukocytes, to facilitate bind to ICAMs and VCAMs on the endothelium?
C5a and LTB4
What is the pathophysiology of leukocyte adhesion deficiency? Inheritance pattern?
AR defect of integrins (CD18 subunit)
What are the clinical findings of leukocyte adhesion deficiency? (3)
- Delayed separation of the umbilical cord
- Increased circulating PMNs
- Recurrent bacterial infections that lack pus formation
Delayed separation of the umbilical cord = ? Why?
- Leukocyte adhesion deficiency
- No PMNs to cause inflammation to necrotic umbilical cord
Recurrent bacterial infections that lack pus = ?
Leukocyte adhesion deficiency
Why is there an increase in the circulating PMNs with leukocyte adhesion deficiency?
Marginated pool shrinks d/t lack of ability to adhere
What, generally, is pus? Why, then, is there no pus with leukocyte adhesion deficiency?
- Dead PMNs sitting in fluid
- No PMNs d/t lack of adhesion
What is the 4th and final step of PMN migration?
Transmigration and chemotaxis
-Leukocytes transmigrate across the endothelium of postcapillary venule
What guides PMNs once they cross the postcapillary venules? (4)
chemoattractants:
- IL-8
- C5a
- LTB4
- Bacterial products
What are the two major opsonins that enhance phagocytosis by PMNs?
IgG
C3b
How does the general process of phagocytosis occur?
Pseudopods from leukocytes extend to form phagosomes, which then internalize and merge with lysosomes to form phagolysosomes
What is Chediak-Higashi syndrome? Inheritance pattern?
AR Protein trafficking defect, characterized by impaired phagolysosome formation
What are the components of the BAILIN mnemonic for Chediak-Higashi syndrome?
- Bleeding disorders
- Albinism
- Infections
- Leukopenia
- Infiltrative lymphohistiocytosis
- Neuropathy
Why is there neutropenia in Chediak-Higashi syndrome?
No way to separate cells d/t defective microtubules
Why are there giant granules in leukocytes in Chediak-Higashi syndrome?
Inability to distribute granules produced by the golgi
Why is there defective primary hemostasis with Chediak-Higashi syndrome?
Loss of platelets d/t loss of movement out of megakaryocytes
Why is there peripheral neuropathy with Chediak-Higashi syndrome?
Inability to traffic nutrients to the periphery
Why is there albinism with Chediak-Higashi syndrome?
Melanocyte cannot transfer melanin to the keratinocytes d/t crappy microtubules
