Term
| For lymphocytes, neutorphils and monocytes to get from the blood to inflamed tissue they cross what |
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Definition
| They cross postcapillary venules in regions called high endothelial venules |
|
|
Term
| What shape does high endothelial venules have that allow for better migration of leukocytes |
|
Definition
| cuboidal shape endothelial cells |
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Term
| For migration of leuokocytes to occur they have to first do what |
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Definition
| ATTACH to the endothelium in the venules and then move between the cells of the endothelium |
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Term
| For migration to occur leuokocytes need to be directed/signaled and also have a way to adhere to the surfaces of the endothelium or lymphoid tissue. What is the general name for what anchors leuokocytes to things and what types of things in the body signal leuokocytes |
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Definition
Cell adhesion molecules are on the surface of cells to help faciliate binding between two cells.
Chemotactic chemicals and other cytokines help direct/signal migration |
|
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Term
| Name some cytokines that contribute to migration and leuokocyte signalling |
|
Definition
1. IL-1
2. IFN-Gamma
3. TNF Alpha |
|
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Term
|
Definition
| CAM= Cell adhesion molecules. They are proteins on cell surfaces that facilitate cell adhesion with other cells. |
|
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Term
| what can increase the affinity of CAMs on cell surfaces. Why is this good? |
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Definition
| Cytokines can increase cell's expression of more adhesion molecules. This is good because increases chances of cells being able to attach and possible migrate across endothlium to areas of inflammation |
|
|
Term
|
Definition
1. leukocytes
2. blood has free floating
3. endothelium
4. lymph tissues |
|
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Term
| What chemicals or mediators stimulate cells to express CAMS |
|
Definition
1. TNF Alpha
2. Interleukin-1 IL-1
3. Interferon Gamma
4. Histamine
5. Thrombin
6. Complement
7. Chemokines |
|
|
Term
| How many types of CAMs are there? |
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Definition
|
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Term
| Name the four major groups of protein CAMs |
|
Definition
1. selectin family proteins
2. Mucin-like family glycoprotein molecules
3. Immunoglobulin Superfamily proteins
4. Integrin Family proteins |
|
|
Term
|
Definition
|
|
Term
| immunoglobulin superfamily molecules bind to |
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Definition
|
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Term
| The inital attachment between leukocyte and endothelial cell is via what CAM |
|
Definition
| selectin family binding to mucin-like ligands |
|
|
Term
| name the three types of selectins |
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Definition
1. E selectin
2. P selectin
3. L Selectin |
|
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Term
| Which selectin proteins are activated on endothelial cells |
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Definition
| E selectin and P selectins |
|
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Term
| which selectin is activated on platelets |
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Definition
|
|
Term
| which selectin is activated on leuockytes such as lymphocytes |
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Definition
|
|
Term
| Which selectin is important for binding to HEV in lymphoid tissue? |
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Definition
|
|
Term
| Which selectin is important for B cell binding |
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Definition
|
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Term
| E-selectins are expressed in response to what mediators |
|
Definition
|
|
Term
| P selectin are expressed in response to what mediators |
|
Definition
thrombin
histamine
complement |
|
|
Term
| Which selectins are expressed continuously |
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Definition
| L-selectins. They are always found on leukocytes even if the leukocyte is not differentiated yet. That way with the leukocyte floating around it is always ready. |
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|
Term
| mucin like family of CAMS bind to |
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Definition
|
|
Term
| Which CAMs type is made up of proteins with carbohydrate chains (glycoproteins) |
|
Definition
|
|
Term
| Give three examples of mucin-like ligands |
|
Definition
1. CD34
2. GlyCAM-1
3. PSGL-1 |
|
|
Term
|
Definition
|
|
Term
| which type of mucin-like family CAM is found on endothelial cells |
|
Definition
|
|
Term
| What type of mucin-like family CAM is found on neutrophils |
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Definition
|
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Term
| The immunoglobuline superfamily CAMs are found on? Bind to? |
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Definition
| expressed on endothelial cells and bind to integrins |
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Term
| Give four examples of immunoglobulin superfamily CAMs and what they stand for |
|
Definition
1. ICAM-1, ICAM-2: Intercellular adhesion molecules
2. VCAM: Vascular Cellular Adhesion Molecules
3. MAdCAM: mucosal addressin Cellular Adhesion Molecules |
|
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Term
| Which CAM has the ability to bind to integrins and selectins? What family does it belong to? |
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Definition
| MAdCAM can bind to integrins and selectins since it contains domains similar to immunoglobulin and mucin like domains. |
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|
Term
| Where are integrin Family CAMs expressed on? What do they like binding to |
|
Definition
| expressed on leukocytes and binds to immunoglobulin superfamily. |
|
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Term
| Integrin family will bind leukocytes to? 2x |
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Definition
| Binds leukocytes to endothelial cells or other cells in the immune response via its integrin-immunoglobulin connection. |
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|
Term
| Integrins are made up of? |
|
Definition
| two polypeptide chains. Alpha and beta |
|
|
Term
| give two examples of a Beta-2 Integrin subfamily CAM |
|
Definition
|
|
Term
| leukocytes will first attach to endothelium via selectins and mucin-like ligands. Then what CAM begins to work after this initial attachment |
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Definition
| Integrin CAMs begin to work after this as result to increase exposure to cytokines which have a stronger influence on the leuokocyte since its been slowed down by the rolling phase and weak bonding with selectins on the endothelium and mucin-like ligands on the leukocyte |
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|
Term
| The main point of CAMs is |
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Definition
| Main point of CAMs is to have a way for adhesion of leukocytes to the endothelium wall. Although CAMs can also do other things such as binding lymphocytes to lymphoid tissue for differentiation or even for cell to cell adhesion. Their main goal is leukocyte adhesion to endothelial walls for migration to occur. |
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|
Term
|
Definition
| migration of cells to an area of inflammation in response to chemotactic factors. |
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|
Term
| Cells will migrate towards higher or lower concentrations of chemotactic factors |
|
Definition
| Towards HIGHER CONCENTRATIONS |
|
|
Term
| Where area chemotactic molecules releases from |
|
Definition
1. Sites of inflammation
2. leukocytes
3. lypmhatic organs
4. skin |
|
|
Term
| Chemotactic molecules will bind to leuokcytes and signal them to |
|
Definition
| increase production and affinity of their integrins on their walls so that they will have a more likely chance of adhering to endothelial cells to go aid in the fight against pathogens. |
|
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Term
| If chemotactic molecules are responsible for luring in more reinforcements for pathogenic invasion then give some examples of chemotactic molecules and their source of production |
|
Definition
1. f,Met-Leu-Phe: small peptide from bacteria
2. C5a, C3a: complement system
3. LTB4: from metabolism in arachidonic acid in the lipoxygenase pathway
4. Platelet activating factor (PAF) from breakdown of membrane phospholipids
5. Fibrinopeptides: from fibrinolysis and thrombinolysis
6. Chemokines |
|
|
Term
| do all chemokines have chemotactic properties ? |
|
Definition
|
|
Term
| to be a chemokine you most have what properties |
|
Definition
| low molecular weight polypeptide with 2-6 cysteines |
|
|
Term
| often chemokines are made by 2x |
|
Definition
1. leukocytes
2. endothelial cells |
|
|
Term
| how are chemokines classified? What are the groups they then fall under with this classification system |
|
Definition
based on the position of two of the four cysteine residues
Two groups they can fall under:
1. CC
2. CXC |
|
|
Term
| Give three examples of CC type Chemokines |
|
Definition
1. MIP-Alpha (Macrophage Inflammatory Protein)
2. MIP-Beta
3. RANTES (Regulated upon Activation Normal T-cell Expressed and Secreted |
|
|
Term
| Give the main example of a CXC subgroup of chemokines |
|
Definition
| 1. IL-8 - A chemokine in the subgroup CXC |
|
|
Term
| IL-8 is a chemokine part of what sub-group? What does it attract |
|
Definition
| CXC subgroup of chemokines and attracts neutrophils for anaphylaxis |
|
|
Term
| Chemokine receptors on leuokocytes and other cells are iniated and result in what |
|
Definition
1 intracellular signalling
2. pasage of peptide chains
3. can bind to more tha njust one specific chemokine |
|
|
Term
| first leukocyte to migrate during acute inflammation |
|
Definition
|
|
Term
| In chronic inflammation what leukocytes migrate |
|
Definition
| lymphocytes and macrophages predominantly |
|
|
Term
| Name the four steps of migration for neutrophils |
|
Definition
1. Rolling
2. Activation
3. Arrest and Adhesion
4. Transendothelial migration |
|
|
Term
| initially during the rolling phase of neutrophil migration what happens |
|
Definition
| The neutrophil needs to get slowed down and adhere to the endothelium. To do this there needs to be anchors which come in the shape of mucin-like ligands on the neutrophil surface. More of these are expressed and given more affinity by signals from TNF alpha and IL-1 from macrophages. (macrophages) are already on the front lines and calling for help) By having more mucin-like ligands the neutrophil has a higher chance of snagging a E or P Selectin on the endothelial surface. This will help slow the neutrophil and possible adhere it. But this first step and bond is weak. |
|
|
Term
| What happens during the activation phase of migration |
|
Definition
| The activation phase is also called the triggering phase. B/c by now after the first step of rolling the neutrophil has slowed enough to be exposed to more signals (cytokines). Although there may be some attempts to adhere to the endothelium through the rolling phase and P/E Selectins with the mucin like ligands of teh neutrophil, this is not that strong. So now that ther eis more time for the neutrophil to be exposed to more cytokines, chemokines and chemotactic molecules such as IL8, MIP1Beta, C5a, C3a. THIS RESULTS IN INCREASE AFFINITY OF THE INTEGRIN MOLECULES LFA-1 and CR3 for intracellular adhesion molecules ICAM-1 and VCAM (immunoglobulin superfamily ICAMs) on the endothelium. |
|
|
Term
| Describe the arrest and adhesion phase of migration for neutrophils |
|
Definition
| Here finally STRONG BINDING OCCURS. VIA Beta 2 integrins on neutrophils with ICAM (immunoglobulin superfamily) on endothelial cells |
|
|
Term
| What is the name for what occurs during the transendothelial migraiton phase of neutrophil migration |
|
Definition
|
|
Term
| movement between endothelial cells of leuokocytes during migration is known as |
|
Definition
|
|
Term
| What is the name of lymphocytes that are not specialized that enter lymphoidal tissue |
|
Definition
|
|
Term
| Lymphocytes that travel in and arround secondary lymphoid tissue need something to help them adhere and become mature. so what is that? |
|
Definition
| On the lymphocytes they contain L-selectins and on the HEV (High endothelium venules) there are mucin like ligands. Together the bind and allow for the migration of lymphocytes |
|
|
Term
| What is homing (Trafficking) referring to in regards to lymphocytes and 2nd lymphoidal tissue |
|
Definition
| Lymphocytes migrate differentially. They go to different types of tissues depending on what they are. This is all influenced by chemokines and their signalling of different CAMs they place on lymphoid tissue. |
|
|
Term
| What is the proper name of a lymphocyte which migrates to sites of inflammation |
|
Definition
|
|
Term
| What is the name of lymphocytes that are not specialized that enter lymphoidal tissue |
|
Definition
|
|
Term
| Lymphocytes that travel in and arround secondary lymphoid tissue need something to help them adhere and become mature. so what is that? |
|
Definition
| On the lymphocytes they contain L-selectins and on the HEV (High endothelium venules) there are mucin like ligands. Together the bind and allow for the migration of lymphocytes |
|
|
Term
| What is homing (Trafficking) referring to in regards to lymphocytes and 2nd lymphoidal tissue |
|
Definition
| Lymphocytes migrate differentially. They go to different types of tissues depending on what they are. This is all influenced by chemokines and their signalling of different CAMs they place on lymphoid tissue. |
|
|
Term
| What is the proper name of a lymphocyte which migrates to sites of inflammation |
|
Definition
|
|
Term
| How does the body know or is able to specifically attract effector lymphocytes to inflammed areas and not just to all areas or attract naive lymphocytes? |
|
Definition
| Endothelial cells in areas of inflammation (sites of attack) will increase their levels of CAMs that are specific to lymphocytes. They will have more ICAM-1, VCAM, E and P Selectins |
|
|
Term
| Inflammed tissues will have increase levels of what 4x CAMs to specifically aid in the migration of lymphocytes |
|
Definition
1. ICAM-1
2. VCAM
3. E Selectins
4. P Selectins |
|
|
Term
Effector lymphocytes migrate to:
Memory lymphocytes migrate to: |
|
Definition
Effector cells migrate to areas of attack
Memory cells migrate to areas where they were first exposed to Ag |
|
|
Term
| Whats the difference in the surface of effector and memory lymphocytes compared to naive lymphocytes? Why is this different |
|
Definition
| Effector and memory lymphocytes have HIGHER LEVELS of integrins! More integrins they have then the easier it will be they will come across CAMs on endothelial cells and be able to migrate or for cell-cell communication. Remember these are your differentiated, mature lymphocytes. We want them to interact and respond! Naive cells are useless so we wouldn't want them to have lots of integrins and prematurely respond but have nothing to contribute to the fight. |
|
|
Term
| A naive lymphocyte (NAIVE) has a rolling phase during which what happens |
|
Definition
| Naive lymphocyte has L-selectins on its surface. But less than a mature lymphocyte. It binds to mucin-like ligands on the high endothelial venules of endothelial cells in LYMPHODAL TISSUE! |
|
|
Term
| what happens during the activation phase of lymphocytes in LYMPOIDAL TISSUE |
|
Definition
| Inflammation or antigens in lymphoidal tissue will sitmulate release of CHEMOKINES (like IL-8) which are released from the lymphoidal endothelial cells. This than stimulates the NAIVE lymphocytes to increase expression of their integrins!! |
|
|
Term
| What happens with the arrest and adhesion phase of lymphocytes in lymphoidal tissue |
|
Definition
| Now that there are more integrins on the lymphocyte from the activation phase. These naive lymphocytes can now adhere to lymphoidal tissue. They can now make a more permenant attachment via LFA-a (type of integrin) to immunoglobulin super family CAM on enothelial cell known as ICAM-1. |
|
|
Term
| activated lymphocytes have more LFA-1 and less L-selectin compared to naive lymphocytes. Why so |
|
Definition
| Need LFA-1 for more permenant binding to immunoglobulins superfamily CAMs on endothelium where inflammation is. LFA-1 is a type of integrin. The L-Selectins are needed for naive lymphocytes to bind in Lymphoidal tissue for differentiation. If it is an effector cell thna thats pointless. |
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