Innate Immunity Part I Flashcards
How do B and T cells migrate to different zones of the LN?
By chemokines that are produced in specific areas.
How do Ag-loaded DCs enter the lymph node?
Though afferent lymphatic vessels that come from sites of Ag entry.
Once DCs are in the lymph node, what regions of the lymph node do they migrate to?
T-cell rich areas of the node.
How do naive T lymphocytes home to lymph nodes?
Via L-selectin binding to peripheral lymph node addressin on the HEV.
Are HEVs present in primary or secondary lymphoid organs?
Secondary.
Which chemokines are displayed on the surface of the HEV?
Chemokines CCL19 and CCL21
What must chemokines bind to in order to activate integrins?
CCR7
What receptor is necessary for effector T cells to exit the LN?
S1PR1. Effector T cells sense a gradient that the receptor produces, which allows them to leave the lymph node.
If an S1P gradient is produced in lymph nodes, what type of T cell will respond to it (and subsequently leave the LN)?
Effector T cells.
How do Ag-activated T cells respond to S1P?
They do not respond to it, and hence stay in the lymph node.
Ag-activated T cells have low levels of S1PR1 and cannot exit the lymph node.
Activated effector T cells home to sites of infection in peripheral tissues. Cell migration into tissue is mediated by what substances?
E-selectin, P-selectin, integrins and chemokine (CXCL10) that are produced at sites of infection.
Many chemokines and chemokine receptors are involved in what process?
They are involved in effector/memory T cell migration.
What ligand on the endothelial cell does L-selectin bind to?
PNAd
What is the function of L-selectin/PNAd?
Initial weak adhesion of naitve T cells to the HEV in the lymph node.
What ligand on the endothelial cell does CCR7 bind to?
CCL19 or CCL21
What is the function of CCR7/CCL19 & CCL21?
Activation of integrins and chemokinessis
What is the function of LFA-1/ICAM-1?
Stable arrest of cells on HEV in the LN.
What do E and P selectin ligands bind do on endothelial cells?
E or P selectin
What is the function of E/P selectin ligands and E/P selectins?
Initial weak adhesion of effector and memory T cells to cytokine activated endothelium at peripheral site of infection.
What is the function of CXCR3/CXCL10?
Activation of integrins and chemokinesis
What is the function of CCR5/CCL4?
Activation of integrins and chemokinesis
What is the function of LFA-1 or VLA-4/I-CAM1 or VCAM-1?
Stable arrest of cytokine-activated endothelium at peripheral sites of infection.
What are the three bonds made during jrolling and arrest of an effector T lymphocyte on endothelial cells?
PSGL-1 & Psel/Esel
CD44 & CD 44
VLA-4 & VCAM
What receptor is important for the mobilization of effector T cells in sites of infection and inflammation?
CD44
What do endothelial cells secrete that facilitate the homing mechanism of effector T lymphocytes?
Chemokines
E & P selectin
Hyaluronic acid
What must vascular endothelial cells express in order for CD44 to mediate rolling interactions?
Hyaluronic acid
Natural ligans
E-selectin
Chemokine signaling via ____ results in increased integrin affinity, such as VLA-4, which enhances adhesiveness.
GPCRs (G protein coupled receptors)
True or false: naive B cells use the same basic mechanisms as do naive T cells to home to secondary lymphoid tissues throughout the body.
True
What is the migration pathway of immature B cells?
Bone marrow -> blood -> red pulp of spleen -> white pulp of spleen.
As B lymphocytes mature, what receptor do they express that promotes their movement into the white pulp?
Chemokine receptor CXCR5.
The migration occurs in response to chemokine CXCL13.
Once maturation of B cells is completed within the white pulp, where do they migrate to?
They reenter circulation and home to lymph nodes and mucosal lymphoid tissues.
What does homing of mature naive B cells from the blood into LNs involve?
Rolling interactionf of HEVs, chemokine activation of integrins, and stable arrest.
Homing of mature naive B cells from the blood into LNs involves what chemokines?
CXCL12 and CCL19/CCL21 on HEV, as well as their chemokine receptors CXCR4 and CCR7 on naive B cells.
In the stroma, B cells migrate into follices driven by what receptor?
CXCL13.
It is recognized by CXCR5 expressed on naive B cells.
What is a process that may occur when B cells enter a follicel?
They may encounter Ag and become activated.
What are the cirulating effector cells involved in innate immunity?
Neutrophils, macrophages and NK cells
What are the circulating effector proteins involved in innate immunity?
Complement
Mannose-binding protein lectin
C-reactive protein
What is the function of complement?
It kills and opsonizes microbes.
It also activates leukocytes.
What is a common function of mannose-binding lectin and C-reactive protein?
Both activate complement.
What is opsonization?
The process by with a pathogen is marked for elimination.
Which cytokine in innate immunity causese inflammation?
TNF, IL-1 cytokines
Which cytokine from innate immuity shows resistance to viral infection?
IFN-alpha, beta
What cytokine from innate immunity activates macrophages?
IFN-gamma