Watson leukocytes sem 1 Flashcards
What are selectins?
During the tethering/rolling stage of leukocyte migration fast moving leukocytes are tethered to vessel wall. They are guided by specific homing receptors and their ligands.
Selectins are lectin-like adhesion molecules which bind CHO structures weakly.
What selectins are constitutively present?
L-selectins, leukocytes.
P-selectins, platelets.
What selectins require de novo synthesis taking 2-6 hours?
E-selectin: endothelium.
What is L-selectin?
Expressed by leukocytes, binds weakly to CHO structures. Constitutively present.
Leukocyte activation leads to transient avidity increase, rapid shedding by proteolytic cleavage
How do P-selectin and L-selectin differ?
L+S = leukocytes P = Platelets and endothelium, stored in granules and constitutively present.
Rapidly translocated to the cell surface upon cell activation by thrombin, histamine etc.
What selectin is rapidly translocated to the cell surface upon cell activation by thrombin, histamine etc.?
P- selectin.
Why is E selectin slower to appear than P or L?
It is not constitutively expressed and requires de novo synthesis after induction via IL-1 and TNF.
Inhibited by GCs.
What is LADII?
Leukocyte adhesion deficiency II.
Patients will suffer recurrent infections with no pus produced.
Neutrophillia.
Severely impaired neutrophil accumulation in skin inflammation.
What is LADI?
Leukocyte adhesion deficiency I.
Patents suffer recurrent bacterial infections with no pus.
Leukocytes do not adhere to extracellular material or endothelium in vitro.
What are integrins?
Activated following signals from chemokines to endothelial surfaces.
Heterodimeric proteins expressed on surface of leukocytes and most other cells.
Leukocyte activation has what effect on integrins? [2]
- Conformational change - affinity.
2. Clustering of integrins - avidity.
What is the ligand for leukocyte bound integrins?
ICAM.
IntraCellular Adhesion Molecule.
ICAM-2 basally expressed.
ICAM-1 induced by IL-1, TNFa from bacteria/damaged cell or tissues.
Which ICAM is basally expressed?
ICAM-2 basally expressed.
ICAM-1 induced by IL-1, TNFa from bacteria/damaged cell or tissues.
What is VCAM1 and what binds to it?
Vascular adhesion molecule 1.
Integrin alpha4-beta1 binds to it.
Expression of VCAM1 induced by cytokines.
VCAM1 expression is induced by what?
Cytokines.
ICAM1 expression is induced by what?
IL-1/TNFa from bacteria or damaged cells and tissues.
Natalizumab was a treatment for MS.
How was it believed to work?
Monoclonal antibody against alpha-4 integrin which inhibits T lymphocyte interactions with brain endothelium, decreased trafficking of T-cells into the brain.
It led to progressive brain viral infection.
What is the process of chemotaxis?
Directed leukocyte movement stimulated by chemotaxins/chemoattractants.
The source of chemotaxins is the site of inflammation.
Chemotaxins attract leukocytes and activate them, causing integrin activity and avidity change + movement.
What is the difference between a chemokine and a chemotaxin?
All chemokines are chemotaxins but not all chemotaxins are chemokines.
Chemokines are SELECTIVE, most other chemotaxins such as LTB4, C£a, C5a and formylpeptides are not selective.
Which of the following is selective in its actions?
Chemokines
Chemotaxins.
Chemokines are SELECTIVE, most other chemotaxins such as LTB4, C£a, C5a and formylpeptides are not selective.
All chemokines are chemotaxins but not all chemotaxins are chemokines.
What is fMLP?
Bacterial product that is also a chemotaxin.
What lipids are chemotaxins?
LTB4
What are the common chemokines?
CXCL
CCL
What plasma proteins are chemotaxins?
C3a
C5a