Term
What does inflammation respond to?
What is required during inflammation via leukocytes? |
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Definition
a) Inflammation responds to local injury and trauma
b) controlled migration of leukocytes are required during inflammation |
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Term
a) What are the routes of lymphocyte recirculation?
b) How many circuits per day?
c)What type of route is used? |
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Definition
a) Begins at the blood lymphocyte pool and circulates in the spleen, lymph nodes, tertiary extralymphoid, bone marrow, epithelial surfaces.
b) 1-2 times/day
c) Extravasion: passage of circulating lymphocytes through endothelial cells lining blood vessels. |
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Term
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Definition
| Extravasion is the movement of blood cells through an unruptured vessel wall into the surrounding tissue, particularly at sites of inflammation. |
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Term
| What is the process of extravasion in neutrophil? |
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Definition
1. Rolling: E selectin of endothelium attaches to the mucin of a neutrophil (PSGL-1)
2. Activation: chemokine induces changes in the integrin on neutrophil
3. Arrest/adhesion:- IL-8 will signal transformation for integrin (LFA-1) to change conformation and will attach to ICAM of endothelium.
4. Transendothelial migration: via the chemoattract gradient towards the site of inflammation. |
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Term
| What are the steps of recruiting macrophages to tissue damage site? |
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Definition
1. Tissue damage causes release of chemotactic and vasactive factor that triggers local increase blood flow and capillary permeability.
2. permeable capillaries allow an influx of fluid and cells.
3. Phagocytes migrate to site of inflammation (chemotaxis)
4. Phagocytes and antibacterial exudate destroy bacteria. |
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Term
| What are the two related surface molecules for endothelial cells and leukocytes? |
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Definition
| Selectins are found on endothelial and they bind to mucin-like proteins found on leukocytes. |
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Term
| What two related adhesion molecules that allow for arrest and adhesion? |
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Definition
| Integrin is found on leukocytes and once activated can bind to ICAM before transendothelial migration. |
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Term
| What is the "gate keeper" function of the vascular epithelium? |
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Definition
| The gate keeper are the CAMs that are necessary to allow for transendothelium migration. |
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Term
| Why are chemokines essential? |
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Definition
1. Involved in leukocyte activation.
2. induce cell adhesion to vascular endothelium
3. Act as chemoattractants (for chemotaxis) |
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Term
| Where is L selectin found? What mucin-like came does L selectin attach to? |
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Definition
a) Leukocyte
b) CD34 and GlyCAM1 is the mucin-like protein that l selectin binds to. |
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Term
| Where is E and P selectins found? What mucin-like protein do they bind to? |
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Definition
a) Endothelium
b) They bind to PSGL-1 on neutrophils. |
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Term
| What increases the level of expression of adhesion molecules? |
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Definition
| Inflammation increases the expression on endothelium CAMs. |
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Term
| What is the purpose of lymphocytes circulating? |
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Definition
| To increase the chance of encountering antigen. |
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Term
| Does lymphocyte extravasation undergo directed of undirected extravasation and why? |
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Definition
| Directed extravasation, because lymphocytes have to come out of High-endothelial Venules (HEVs) |
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Term
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Definition
| In secondary organs (MALT and lymph nodes) except for the spleen |
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Term
| What types of adhesion molecules are expressed on HEVs? What is the function? |
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Definition
Vascular Addressins (mucin-like; GlyCam1, CAMs and CD34) are the adhesion molecules expressed on HEVs Interact with homing receptors (lectins; L selectin) on lymphocytes. VAs bring lymphocytes in to bind to APC.
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Term
| What types of lymphocytes are involved with homing, and what tissues do they migrate to? |
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Definition
Naive lymphocytes: migrate to secondary lymphoid organs through HEV
Effector lymphocytes: home to inflammed vascular endothelium
memory lymphocytes: home to type of tissue where they first encountered the antigen. (goes to where they potential could be, just in case) |
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Term
| How is trafficking mediated during homing of lymphocytes? |
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Definition
| Trafficking is mediated by a unique combination of adhesion molecules and chemokines |
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Term
Name the Receptors on the cells and what ligands does it bind to.
(Also considered Vascular addressins) |
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Definition
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Term
What is the process of lymphocyte damage
from HEV to tertiary extralymphoid tissue? |
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Definition
1. Naive T cells are constantly circulating indiscriminately to secondary lymphoid tissue by recognizing mucin-like CAMs, glycam-1 and CD34 with L selectin.
2. proliferate and differentiate: Once it is stimulated by an antigen and goes into shut down phase, to be developed in the germinal centers of the secondary lymphoid organs to mature.
3. Generates into effector and memory cells that express high levels of particular homing receptors that allow them to enter tertiary extralymohoidal tissue.
4. Effector goes to area of inflammation and lymphoblasts goes to area of where it was first encountered antigen. |
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Term
| Describe the T cell extravasation through an HEV |
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Definition
1. Rolling: L selectin binds to CD34 or glycam-1 on VE (vascular endothelium)
2. chemokine stimulate high affinity integrin activation LFA1 by activating T cell G protein coupled receptors
3. chemokines are retained in the glycocalyx of HEVs
4. Activated integrins bind Ig Cams and begin migration |
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Term
What are the general characteristics of chemokines?
What is the function?
What are the effects? |
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Definition
a. Superfamily of small polypeptide 90-130 aa's
- CC group-conserved cysteines are contiguous
- CXC group-conserved cysteins are divided by another amino acid
b. Selective and specific control of adhesion chemotaxis and activation of leukocytes
- important for homeostasis and inflammatory repsonse
c. Wide reaching effects
- development of brain and heart
- proper wound healing. |
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Term
| What are the characteristics of chemokine receptors? |
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Definition
1. 7 transmembrane polypeptide chain bind chemokines with high affinity (Ka > 109)
2. two subgroups: CC or CXC
3. can bind to more than one chemokine
4. activate small G protein signaling pathways with multiple cellular effects. |
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Term
| What results from the signaling pathway when the chemokine receptor is activated? |
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Definition
1. multiple celluar effects result to chemotaxis. |
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Term
What the subgroups of chemokine receptors on
a. neutrophil
b. basophil
c. eosinophil
d. monocyte
e. resting t lymphocyte
f. activated t lymphocyte |
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Definition
a. Neutrophil: CXR1, CXR4, CXR2 (Nx-1,2,4)
b. Basophil: CCR1, CCR2, CCR3 (Bc- 1, 2, 3)
c. Eosinophil: CCR1 and CCR3 (Ec- 1,3)
d. Monocyte: CCR1, CCR2, CCR4, CXR4 (Mc: 1,2,4)
e. Resting t lymphocyte: CXR4 (Cx- 4)
f. activated t lymphocyte: CCR1, CCR2, CCR3, CCR4, CXR3, CXR4 (Acx: 1,2,3,4,3,4) |
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Term
What happens from phospholipid
degradation of membranes?
[image] |
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Definition
With Phospholipase, it releases arachidonic acid and lyso-PAF.
Lyso-PAF leads to Platlet Activating factor -> platelet aggregation.
Arachidonic acids leads to prostalandins and thromboxane from one pathway and the other pathway leads to leukotrienes. |
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Term
| What does IFN-gamma and IL-12 do in chronic inflammatory repsonses? |
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Definition
IFN-gamma: Macrophage activation and chronic inflammation
IL-12: differentiation of pro inflammatory t helper cell 1. |
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Term
| What is the local acute inflammatory repsonse? |
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Definition
1. Tissue damage causing activation of complement system then the inflammation will have C3a and C4a attach to mast cell causing degranulation to release histamine, prostaglandins and leukotrienes and causing extravasation of moocyte then calling neutrophil and lymphocyte to site of inflammation. |
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Term
| What are the multiple local acute inflammatory response? |
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Definition
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Term
Explain what is expressed and relatively at what level before and after cytokine exposure to the liver hepatocytes.
Which is the regulator? |
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Definition
Before Cytokine: C/EPB expressed constitutitively
After Cytokine: Increased level of NF-IL6, decreased level of C/EPB.
The regulator is NF-IL6. |
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Term
| What are some chronic inflammatory responses? |
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Definition
Inadequate clearance of microorganisms can cause
- autoimmune disease
- tissue damage and wasting of types of cancer
- hallmark: accumulation and activation of macrophages
- macrophage activation of fibroblats and development of fibrosis
- formation of granulomas.
- development of chronic inflammatory disease and the role of HEVs
- IFN gamma and TNF alpha and chronic inflammation |
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Term
Which cells release Interferon gamma (IFN-gamma)?
Which cells do IFN gamma bind to and what is the result of the effects? |
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Definition
1) release IFN gamma
a) CD4+/TH1 cell; NK Cell; CD8+/Tc Cell
2) IFN gamma bing to these cells
a) CD4+/TH2 cell -> decrease proliferation, decrease production of IL4 and IL5 (which inhibited by IFN gamma that is released by TH1, so cannot produce IGE which is a class switch of B cells)
b) Macrophage -> increase expression of class II MHC and increase the microbicidal activity
c) Dendritic cell -> increase the expression of class II MHC molecules
d) NK cell -> increase cytotoxic activity
e) B cell -> increase differentiation and increase Ab production (increase IgG2a and decrease IgE and IgG1) |
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Term
| What is the function of anti-inflammatory agents? |
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Definition
| Due to over active stimulation due to allergies, anti-inflammatory agents can reduce inflammation of a response. |
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Term
| What are some anti-inflammatory agents? |
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Definition
1. Antibody therapies: blocking leukocyte extravasation with antibodies to CAMs (e.g LFA-1, ICAM-1)
2. Corticosteroids:
- choleterol derivatives
- decrease the # of circulating lymphocytes through lypholysis or alternations in circulation patterns
- reduce phagocytic and killing activity of
macrophages and neutrophils.
- stabilize the lysosomal membrane and reduce release
of lysosomal enzymes in lymphocytes. (reduce
degranulation)
3. Nonsteroidal anti-inflammatory drugs
- ex. aspirin, tylenol
- inhibitions of cyclooxygenase pathway.(inhibit fever
pathway)
- cox1 and cox2 |
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