Leukocyte Circulation And Migration Into Tissue Flashcards
In the lymph nodes, Ag-activated B cells seek help of what type of cells?
T helper cells.
B cells present antigens to T helper cells. This is important for antibody responses to protein antigens.
What do Ag-activated B cells mature into?
Memory cells or plasma cells.
What are plasma cells?
Terminally differentiated B cells which produce and secrete larg abouts of Abs.
In the spleen, Ag-activated B cells primarily produce Abs against what type of microbe?
Microbial polysaccharides.
What type of cells are found in the periarteolar lymphoid sheath of the spleen?
T cells
What type of cells are found in lymphoid follicles?
B cells.
In search of forein Ags, where do naive T cells migrate into?
Secondary lymphoid organs, such as lymph nodes.
If a T cell is activated by Ags, what does it differentiate into?
Effector or memory T cells.
Where do effector and memory T cell migrate back into?
Peripheral sites of infection.
Where do some activated and differentiated T cells do?
The remain in the LNs and help Ag-activated B cells to become an “Ab factory”
Once effector B cells secrete Abs, where do the Abs go?
They enter the blood and are delivered to sites of infection.
In the absence of Ag stimulation, what type of follicles are found in the LN?
Primary follices.
When is a primary follicle converted into a secondary follicle?
With Ag stimulation. This converts the primary follicle into a secondary follicle or germinal center.
The activation of T cells requires what type of cells?
Professional Ag-presenting cells.
These include:
DCs
Tissue macrophages
B cells.
What are antigen-presenting cells (APCs)?
Cells that capture and process Ags to lymphocytes and provide signals that stimulate the proliferation and differentiation of the lymphocytes.
What cells display Ag to T cells? Are they required for B cells?
APC. They are not required for B cells.
What are the only cells capable of activating naive T cells in the LNs?
Dendritic cells
Naive B cells migrate into what type of lymphoid tissues?
Secondary lymphoid tissues.
DCs and macrophages are cells of innate immunity. What is also of significance of the two?
They provide a link between innate and adaptive immunity.
What is the primary role of dendritic cells?
They activate naive T cells.
How do DCs acquire Ags?
They use phagocytosis, receptor-mediated endocytosis and pinocytosis.
What do activated DCs secrete?
Cytokines
Where do classical DCs reside?
Skin
Mucosa
Organ parenchyma
When classical DCs are activated, where do they migrate to?
LNs where they display microbial protein Ags to T lymphocytes.
Plasmacytoid DCs are early responders to what type of infections?
Viral infections.
During inflammatory responses in tissues, dendritic cells may also be derived from what molecule?
Monocytes
FDCs reside in the lymphoid follices of what organs?
Lymph nodes
Spleen
Mucosal lymphoid tissues
FDCs bind and display Ags on their surfaces for recognition by what molecules?
B lymphocytes
What is migration/recruitment?
The general process of leukocyte movement from blood into tissues.
What is recirculation?
The ability of lymphocytes to repeatedly:
Home to secondary lymphoid organs
Reside there transiently
Return to the blood.
What is leukocyte homing?
Cell migration out of the blood and into peripheral tissues, or to a site of an infection or injury.
The recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury is a major part of what process?
Inflammation.
What is inflammation triggered by?
Recognition of microbes and dead tissues in innate immunen responses.
Inflammation is refined and prolonged during adaptive immune responses.
What is the funciton of an inflammatory response?
It delivers the cells and molecules of host defense to the sites where offending agents need to be combated.
Circulating leukocytes move hrough what mechanisms?
Tethering
Rolling
Adhesion and stop
Transmigration in the tissue.
How does tethering occur?
Through transient interactions of selectins and integrin with their ligands.
What is the purpose of leukocytes rolling?
It allows chemokine receptors on leukocytes to bind chemokines expressed on endothelium.
How do leukocytes adhere to the endothelium?
Receptors signal and activate integrins on leukocytes which interact with ligands expresssed on the endothelium.
As leukocytes migrate, they follow a gradient established by what molecule?
Chemokines
Are adhesion molecules found on healthy or unhealthy endothelial cells?
Unhealthy
Would you expect endothelial cells at sites of injection and tissue injury to express adhesion molecules?
Yes
Leukocyte/lymphocyte homing and recruitemnt require the temporary adhesion of the leukocyte to the endothelial cells of blood vessels.
:)
What are addressins?
A set of several adhesion molecules on the surface of endothelial cells.
What type of selectin is found on endothelium activated by histamine or thrombin?
P-selectin
What type of selectin is found on the endothelium activated by cytokines?
E-selectin
What type of selectin is associated with neutrophils, monocytes, T cells and B cells?
L-selectin
Which selectins are found on endothelial cells?
P selectin and E selectin.
Where is L-selectin expressed only?
On leukocytes and lymphocytes
What is L-selectin activated by?
IL-1 and TNF.
What is L-selectin important for?
Naive T and B lymphocytes for homing into LNs by interacting with high endothelial venules.
What is the function of an integrin?
It integrates signals triggered by extracellular ligans with cytoskeleton-dependent motility, shape change and phaogcytic responses.
What is a function of an integrin?
It mediates adhesion of cells to other cells or to extracellular matrix via various specific ligands.
What is a function of integrins?
They mediate adhesion of cells to other cells or to extracellular matrix via various specific ligans.
What is integrin activation?
Integrin activaiton is when integrins are able to respond to intracellular signals by rapidly increasing their affinity.
Integrin activation occurs in all leukocytes in response to what?
Chemokine binding to chemokine receptors.
When does integrin activation occur in T lymphocytes?
When Ag binds to TCRs
What is integrin activation mediated by?
Chemokine-induced conformational changes in the extracellular domains of integrins. It leads to an increased affinity for integrins.
Are integrins normall in a low-affinity or high affinity state?
Low-affinity.
Activation of leukocyte integrins occurs when rolling of leukocytes occurs.
What is a function of chemokines?
They stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues.
Do neutrophils and monocytes require activation to be recruited into tissue sites of infectiono r injury?
No
How do neutrophils and monocytes enter the tissue?
Through post-capillary venules except parencymal tissues (liver, lungs, kidney).
What are the functions of myeloid leukocytes?
They eliminate infectious pathogens, clear dead tissues and repair the damage.
What process occurs during the interaction between P-selectin and ligands on leukocytes?
Rolling
How do naive T cells enter lymph nodes?
Via high endothelial venules
How do dendritic cells bearing Ag enter the lymph nodes?
Through lymphatic vessels.
How do effector and memory T cells get to sites of inflammation?
They leave the blood and enter peripheral tissues through venules.
T and B lymphocytes both express which selectin?
L-selectin.
How do naive lymphocytes enter the LN?
Through high endothelial venules
What is the term for L-selectin ligands expressied on HEV?
Peripheral node addressins
How do B and T cells migrate to different zones of the LN?
By chemokines
Ag-loaded DCs enter the LN through … ?
Lymphatic vessels
HEV is present in what ytpe of lymphoid organ?
Secondary lymphoid organs.
Naive T lymphocytes home to lymph nodes as a result of…?
L-selectin binding to peripheral lymph node addressin on HEV.
Naive T cells that have recently entered a LN cannot sense _____ between the T cell zone of the node and the lymph.
S1P concentration.
Ag-activated T cells have low levels of ____ and the cells stay in the LN.
S1PR1
Where do activated effector T cells home to?
Sites of infection in peripheral tissues.
Cell migration into tissue is mediated by what selectins?
E and P selectins, as well as integrins and chemokines that are produced at sites of infection.
Chemokines and chemokine receptors are involved in what?
Effector/memory T cell migration.
What is the significance of CD44?
It is important for the mobilization of effector T cells in sites of infection and inflammation.
At sites of infection, what is secreted by endothelial cells?
Chemokines.
E and P seletin is expressed here, as well as hyaluronic acid.
CD44 can mediate why type of interactions?
Rolling interactions with vascular endothelial cells that express HA
Chemokine signaling via GPCRs results in what?
Increased integrin affinity.
How do naive B cells home to secondary lymphoid tissues throughout the body?
They use the same basic mechaisms as do naive T cells.
As B cells mature, what chemokine receptor do they express?
CXCR5
Once B cells express chemokine receptor CXCR5, where do they move?
Into the white pulp.
Once maturation of B cells is completed in the white pulp, where do mature naive B cells go?
They reenter the circulation and home to lymph nodes and mucosal lymphoid tissues.
Homing of mature naive B cells from the blood into LNs involves …?
Rolling interactions of HEVs, chemokine activation of integrins, and stable arrest.
What chemokiens are required for the homing process?
CXCL12 and CCL12/CCL21 on HEV and chemokine receptors CXCR4 and CCR7 on naive B cells.
In the stroma, B cells migrate into follices drived by ___ recognized by CXCR5 expressed on naive B cells.
CXCL13
In the follicles, what may B cells encounter that may lead to their activation?
Ag
What is the function of CCL2?
It recruits leukocytes (monocytes).
What is the function of chemokine CCL19?
T cell and dendritic cell migration into parafollicular zones of lymph nodes.
What is the function of CCL21?
T cell and dendritic cell migration into parafollicular zones of lymph nodes.
What is the major function of chemokines CXCL8?
Neutrophil recruitment.
It is also know as IL-8
What is the major function of CXCL10?
Effector T cell recruitment
It is also known as IP-10
What is the function of chemokine CXCL-13?
B cell migration into follicles
T folllicular helper cell migration into follicles.
What is the function of chemokine CXCL12?
Homing naive B cells to lymph nodes.
Its original name is SDF-1 alpha beta
What chemokines are used during activation of luekocytes?
IL-8, MCP-1
What molecules are used during capture and rolling phases of leukocytes?
E-selectin
What adhesion molecules are used to adhere leukocytes to endothelial cells?
VCAM-1, ICAM-1
During transmigration of leukocytes, endothelial cells present what ligand that is recognized by receptors on neutrophils?
CXCL8 (also known as IL-8)
