• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/88

Click to flip

88 Cards in this Set

  • Front
  • Back
What is the purpose of CAMs?
CAMs hold our tissues together and enable leukocytes to move by extravasation.
What cells express CAMs?
Endothelial cells lining the walls of blood vessels express leukocyte-specific CAMs.
Are the leukocyte specific CAMs expressed by the endothelial cells lining the walls of blood vessels constituitive or induced?
Some are constitutive and some are expressed only in response to cytokines produced during inflammation. (so can be either)
What does 'CAMs' stand for?
"Cell Adhesion Molecules"
What cells have receptors to bind to CAMs on vascular endothelium? Why?
Lymphocytes, Monocytes, and Granulocytes have receptors that bind to CAMs. This is so they can extravagate from the blood to the tissue, where the infection is.
CAMs belong to ? families of proteins. List them.
CAMs belong to 4 families of proteins.

1. Selectin Family

2. Mucin-like family

3. Integrin family

4. Ig superfamily CAMs

(There are actually many more, but these are the important ones)
Describe the general structure of Selectins?
Has an extracellular lectin domain (this is carbohydrate like)and enables binding to CHO groups (salicylated carbohydrate groups: "sialyl lewis groups").
Describe the general structure of Mucins?
Ser, Thr rich proteins. Present to sialyl-lewis and other sulfated CHO groups.
Describe the general structure of integrins?
Has heterodimeric alpha and beta chains. Only type in the family that is a dimer. Can only bind a ligand after it has been activated. Widely found and provides cell matrix interactions throughout the body.
Describe the Ig superfamily CAMs structure?
MadCAM has both Ig (immunoglobulin) and mucin qualities.
Which two of the CAM families like carbohydrates?
Mucin-like and Selectin.
What is LAD?
A disorder involving the CAM families. It is "leukocyte adhesion deficiency". There are two types.

LAD-1 and LAD-2
What is similar about LAD-1 and LAD-2? What distinguishes them from one another?
Both are autosomal recessive disorders that cause recurrent bacterial infections and low extravasation (so very poor wound healing).

LAD-1 is caused by a deficiency in all 4 families. LAD-2 is specifically caused by a deficiency in the Selectin family (and extravasation may be slightly better).
Chemokines are major regulators of ? trafficking.
Chemokines are major regulators of leukocyte trafficking.
Chemokines are ? polypeptides.
Chemokines are small polypeptides (90-130 a.a.).
Chemokines have how many members?
43
Chemokines possess 4 ? cysteine residues. Explain.
Chemokines possess 4 conserved cysteine residues. (whenever you see something conserved it's usually cysteine).
Chemokines possess 4 conserved cysteine residues. List the 2 subgroups.
1. CC subgroup (conserved cysteines are continous, one after another)

2. CXC subgroup (conserved cysteines are separated by some a.a.)
Chemokines selectively control ?, ?, and activation of ?.
Chemokines selectively control adhesion, chemotaxis, and activation of many types of leukocytes.
Some chemokines are actively involved in ?. Some have ? or ? roles.
Some chemokines are actively involved in inflammation. Some have homeostatic or developmental roles in utero.
Chemokines are ? expressed by the thymus.
They are constituitively expressed by the thymus because they play a role in trafficking white T-cells out of here.
Chemokines signal through ?.
Chemokines signal through G-proteins.
What is a CCR? What does it recognize?
"Continous Chemokine Receptors". They recognize CC chemokines.
CXCRs recognize ? chemokines.
CXCRs recognize CXC chemokines.
Interaction between chemokines and their receptors is ? and ? ?.
Interaction between chemokines and their receptors is strong and highly specific.
What is the rate constant for the interactions between chemokines and their receptors?
Kd = 10^-9 (So pretty strong)(the interaction is tight and specific)
Chemokine receptors mediate ? activity.
Chemokine receptors mediate leukocyte activity.
What kind of chemokine receptors do basophils have?
CXCRs and CCR4
What kind of chemokine receptors do neutrophils have?
CXCR2, CXCR1, and CXCR4
Different WBCs have ? chemokine receptors.
Different WBCs have different chemokine receptors.
A cell can respone to a chemokine only if it has what?
Only if it has a receptor that recognizes it.
List 4 possible effects that the binding of a chemokine receptor can cause?
1. An abrupt change in shape.

2. Promotes adhesion.

3. These cells have granules (So when you bind the receptor you see an increase in Calcium so the Calcium channels open and pkgs of granule are released)

4. O2 bursting thru cascade.
List the 4 steps of Leukocyte extravasation.
1. Rolling

2. Activation

3. Arrest/Adhesion

4. Transendothelial Migration
Where does leukocyte extravasation occur?
Occurs only on inflamed vascular endothelium.
The rolling stage of leukocyte extravasation is mediated by what?
Rolling is mediated by selectins.
The activation stage of leukocyte extravasation is stimulated by what?
Activation is by chemoattractant stimulus released by damaged tissue and other cells.
The arrest and adhesion stages of leukocyte extravasation is mediated by what?
Arrest and adhesion are mediated by integrins binding to Ig family members.
Resting, Non-inflamed endothelium has how many adhesion molecules?
Resting, Non-inflamed endothelium has few adhesion molecules.
When do neutrophils not bind to endothelium?
Neutrophils do not bind to non-inflamed endothelium and do not exit the bloodstream when no infection is present. (No E- and P- selectin)
Up-regulation of adhesion molecules occurs during ?.
Up-regulation of adhesion molecules occurs during inflammation.
P-selectin is released by what?
P-selectin is released by Weibel-Palade bodies.
What are the two chemokines involved in activation/up-regulation of adhesion molecules during inflammation?
1. IL-8

2. MIP-1beta
What cells are the first to the site of infection?
Neutrophils are the first to the site.
Monocytes are ? than neutrophils to arrive/adhere to the site of inflammation. Why?
Monocytes are slower than neutrophils. This is because monocytes require ICAM and VCAM to become activated in the plasma membrane.
Once endothelium cells become inflamed and cytokines bind what do they do?
They release chemokines to target neutrophils and cause changes. This facilitates binding.
What does lymphocyte circulation allow for? How long can a complete trip take?
Continual lymphocyte recirculation allows maximal numbers of antigenically committed lymphocytes to encounter Ag. A complete trip can take 1-2 X a day. (This is a carefully controlled and highly regulated process)
What is a HEV?
High-Endothelial Venules. They are extravasation sites. They are "specialized cuboidal cells" located in the post capillary venule of various lymphoid organs EXCEPT THE SPLEEN.
How many lymphocytes are extravasated every second thru HEVs?
A huge amount, (1.4 X 10^4) lymphocytes.
HEVs express a wide variety of ?.
HEVs express a wide variety of CAMs.
When are CAMs referred to by the term VAs instead?
They are called VAs (vascular addressins) when they are distributed in a tissue specific manner.
Explain luekocyte extravasation thru an HEV.
It is basically the same sequence of steps as neutrophil extravasation with some differences. They differ by some adhesion molecules and rolling is less pronounced.
Extravasation thru an HEV is activated by what?
Activation is by integrin LFA-1 induced by chemokine binding to lymphocyte.
When different subsets of lymphocytes migrate the process is called ? or ?.
Process of migration is called trafficking or homing.
The different patterns of the different subsets of lymphocytes when they migrate into tissues is mediated by what?
Different patterns are mediated by unique combinations of adhesion molecules and chemokines.
What directs the circulation of various populations of lymphocytes to particular lymphoid and inflammatory tissues.
Homing receptors direct the circulation of various populations of lymphocytes to particular lymphoid and inflammatory tissues.
Naive cells have no preference for what?
Naive cells have no preference for a particular type of secondary lymphoid-tissue.
Naive lymphocytes circulate ?.
Naive lymphocytes circulate indiscriminately.
Naive lymphocytes initial attachment to HEV is mediated by what?
Naive lymphocytes initial attachment to HEV is mediated by the binding of L-selectin to GlyCAM-1 and CD34 (to name a few)
What promotes tight adhesion to HEV and attracts lymphocyte subpopulations to their zones within the lymph node?
Chemokines promote tight adhesion to HEV and attract lymphocyte subpopulations to their zones within the lymph node.
T-cell activation occurs in the ? region of a lymph node.
T-cell activation occurs in the paracortical region of a lymph node.
T-cell activation takes about how long?
T-cell activation takes about 48 hours.
During T-cell activation Blast cells, once activated, are retained in the cortical region of ? ? tissue.
During T-cell activation Blast cells, once activated, are retained in the cortical region of secondary lymphoid tissue.
When does the shutdown phase occur after T-cell activation?
Shutdown phase is when no Ag-specific lymphocytes can be detected in the circulation. Effector and memory cells then leave in the efferent lymph.
Effector and memory cells have ? homing patterns.
Effector and memory cell have different Homing patterns.
Effector cells home to what?
Effector cells home to regions of infection.
Memory cells home to what?
Memory cells home selectively to the type of tissue in which they first encountered Ag.
Tissue specificity is imparted by what?
Tissue specificity is imparted by repertoire of chemokine receptors. So different affinity for different chemokines.
List 3 important inflammatory mediators.
1. Activation of the Kinin System is by tissue injury

2. Enzymatic cascade beginning with Hagemann Factor (XII) (This is the RATE LIMITING STEP)

3. Bradykinin is a potent peptide. Upon release, it causes increased vascular permeability, vasodilation, pain, smooth muscle, and contraction.) (This is also released during asthma)
Describe lipids as inflammatory mediators.
Following membrane perturbation, phospholipids of macrophages, monocytes, neutrophils and mast cells degrade to arachidonic acid and lyso-platelet-activating factor.
IL-12 and INF-gamma also contribute to ?.
IL-12 and INF-gamma also contribute inflammation.
How does INF-gamma play a role in inflammation?
INF-gamma plays an important role in chronic inflammation by attracting and activating macrophages.
How does IL-12 play a role in inflammation?
IL-12 induces differentiation of proinflammatory Th1.
C3a and C5a are ?.
Anaphylotoxins (inflammatory mediators)
What is chronic inflammation due to?
Chronic inflammation is due to presistent Ag or when Self-Ags continually activate T-cells.
How do some micororganisms/bacteria evade immune system surveillance?
Because they possess cell wall components that are phagocytosis resistant. (so they become persistent Ags)
What is the hallmark of chronic inflammation? What is key?
The hallmark of chronic inflammation is the accumulation and activation of macrophages. INF-gamma and TNF is key.
When the release of cytokines stimulates fibroblast and collagen production what is the result?
The release of cytokines stimulates fibroblast and collagen production resulting in fibrosis and granulomas.
INF-gamma and TNF-alpha play a central role in the development of what?
INF-gamma and TNF-alpha play a central role in development of chronic inflammation.
TNF-alpha is secreted by what? What is it referred to as? What does it contribute to?
TNF-alpha is secreted by activated macrophages. Referred to as "cooley's toxin". This contributes to tissue wasting seen in chronic inflammation.
INF-gamma has ? activities.
INF-gamma has pleiotropic activities.
What does pleiotropic mean?
Multiple effects
INF-gamma is produced exclusively by what? What do they act on?
INF-gamma is produced exclusively by NK cells and T-cells and they act on macrophages.
What is kikexia?
It is tissue waste due to TNF-alpha from loss of appetite.
HEV-like structures appear in chronic ? disease.
HEV-like structures appear in chronic inflammatory disease.
Where do HEV-like structure appear?
They appear along vasculature in tertiary extralymphoid sites of chronic inflammation.
What may play a role in the induction of HEV-like structures?
INF-gamma and TNF-alpha may play a role in their induction. They may be a target for new therapies.
All NSAIDS are currently under scrutiny for ? issues.
All NSAIDS are currently under scrutiny for cardiovascular issues.
The latest findings concerning the pharmacotherapy of inflammation indicate what?
They indicate that narcotics are superior in controlling pain of osteoarthritis.