MBM - Cell Adhesion and the ECM III

What kind of adhesion must leukocytes have as they migrate to the site of infection or injury?
What are the two phases of Leukocyte adhesion?
1. Selectin Phase
2. Integrin Phase
What is the first CAM that Leukocytes interact with?
What is the second CAM that Leukocytes interact with?
What does cell adhesion regulate?
Cell Proliferation
What do normal epithelial cells exhibit?
What type of dependence do transformed cells exhibit?
What helps regulate proliferation of cells attached to the ECM?
What does ERK do?
1. Enters the Nucleus.

2. If cells in suspension, ERK stays inside cytoplasm.
What do cells from ECM undergo?
What is an example of epithelium that undergoes Anoikis?
Mammary Gland Epithelium
What cells can avoid Anoikis?
Transformed Cells
What are the Major CAM Families?
1. Cadherin
2. Ig Family
3. Selecting
4. Integrin
What do Cadherin CAM's contain?
1. Ca++
2. Cadherin Repeats
3. Cytoplasmic Domain
What do Ig Family CAM's contain?
1. Disulfide Bonds
2. Ig Domains
What do Selectin CAM's contain?
1. Ca++ 2.Lectin-like domain that binds to CARBOHYDRATES.
3. CRP Repeats
*P-Selectin 9
*E-Selectin 6
*L-Selectin 2
What do Integrin CAM's contain?
1. Ligand
2. Divalent Cations
3. EGF-like repeat
4. Alpha Transmembrane
5. Beta Transmembrane
What are the main purposes of CAMs?
1. Epithelial Barrier
2. Cell Polarity
3. Adhesion of normally non-adherent leukocytes to fight infection and remedy injury.
4. Regulation of Cell Proliferation.
5. Embryonic development.
What is important about apical surfaces?

What are the layers of stratified epithelium?
1. Apical Surface
2. Intermediate or Suprabasal surfaces
3. Other Layer
4. Basal Layer
5. Basement Membrane
What would you find in the apical surface?
Cells specialized for barrier function. Lateral adhesion important.
What do you find in the intermediate of suprabasal layers?
Cells that are adhesive all around such as:
1. Desmosomes
2. Adherens Junctions
Upper cells express Tight Junctions. Gap Junctions may also be present.
What do you find in the apical surface (nonadhesive) of the basal layer?
Specialized cells for absorption, secretion and bearing cells.
What do you find in the Lateral Surface (adhesive) of the basal layer?
Tight Junctions - occlude paracellular channels.
1. Adherens Junctions --> Adhesion
2. Desmosomes --> Adhesion
3. Gap Junction --> Intercellular Communication
Why do platelets adhere?
Form Blood Clots
What are platelets essential for?
What form of platelet always circulating?
What activates platelets?
Break in Endothelium
What does PLA2 form?
Thromboxane A2
What does Thromboxane A2 do?
Activates Platelets
What is secreted with platelet activation?
What does vWF promote?
Adhesion to each other, other cells, and ECM molecules such as:

1. Collagen
2. vWF
3. Fibrin
4. Fibrinogen
5. Fibronectin
What adhesion receptors are expressed?
1. alpha2beta1 integrins
2. glycoproteins receptors (GPIb)
What do we know has happened when collagen is present in the blood?
Basement Membrane has been exposed.
What must gets flipped?
Phosphatidyl Serine
What is involved in helping platelets clump up?
What acts as the glue?
What are support cells?
1. WBCs
2. RBCs
What can you get from inappropriate platelet binding?

*plaque (lipids, Ca++) disruption --> platelet activation --> THROMOBUS FORMATION
What is Bernard - Soulier Syndrome?
Hereditary Bleeding Disorder
What is defected in Bernard Soulier Syndrome?
Glycoprotein Complex that binds to vWF (which binds to collagen of basal membrane)
What is presented in patients with Bernard Soulier Syndrome?
1. Thrombocytopenia
2. GIANT platelets
What is Glanzmann's Thrombasthenia?
Hereditary Bleeding Disorder
What is defected in Glanzmann's Thrombasthenia?
Integrin that binds to vWF, which binds to fibrinogen (needed for platelet aggregation)
What is presented in patients with Glanzmanns Thrombasthenia?
Normal Platelet Count as opposed to thrombocytopenia in Bernards Soulier's Syndrome.
Extracellular Matrix is secreted by what?
What maintains most of the ECM and are dispersed within?
What are the functions of the ECM?
Shape, strength,
elasticity to tissues, acts as
substratum for adhesion. Signal transduction.
The ECM is a reservoir for what?
Growth Factors
What is the most abundant protein?
Collagen Family
What does Collagen provide?
1. Tensile Strength and Stability to tissues that must change size or position (tendons).

2. Impart structure to bone, cartilage, tendons, and skin.
How many types of Collagen are found in humans?
28 Types
What CAM is Collagen associated with?
What is BP180?
Collagen Type XVII
What do you get when you have a problem with BP180?
Bullous Pemphigoid
What syndromes can you get with collagen defects?
1. Osteogenesis Imperfecta
2. Alport Syndrome
3. Ehlers-Danlos Syndrome
4. Dystrophic EB

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