Test 3 Flashcards
What cell type is the critical portal for lymphocytes to extravasate into lymph nodes?
Endothelial cells that line the blood vessels make it possible for lymphocytes to extravasate
into lymph nodes.
List the four steps (and molecules) involved in leukocyte extravasation.
1. Rolling: Selectins expressed by endothelial cells allow for leuokocyte attachment to
the endothelium as they are expressed in an inflammatory response, binding to
carbohydrates on the leukocytes. This causes temporary binding, so the leukocyte
rolls along the endothelium.
2. Activation: As the leukocyte’s rate of rolling decreases, chemokines are detected by
the leukocytes on the endothelial surface. These chemokines help recruit
leukocytes to the site of infection and cause conformational changes on the surface
of the leukocyte so integrins start to gather together to begin adhesion.
3. Arrest and adhesion: the clustered integrins help the leukocyte to stop rolling and
adhere to the endothelial tissue. They bind to Ig-superfamily CAMs on vascular
endothelial cells, strengthening the leukocyte’s bond to the endothelial cells so it is
not as likely to be swept away by the sheer force of blood running through the blood
vessel.
4. Migration: the platelet-endothelial-cell adhesion molecule-1 (PECAM-1), expressed
on both the leukocyte and vascular endothelial cells, is used to allow the leukocyte
to squeeze between the endothelial cells and into the inflamed tissue. By both
binding to PECAM-1, as well as other integrins, the structural integrity of the blood
vessel is saved so no blood or anything else leaks out as they leave the blood vessel.
Describe the different locations T and B cells traffic to upon entering the lymph nodes.
B cells enter the B-cell follicles in the cortex of the lymph node, while T cells enter the
paracortex (T-cell zone) of the lymph node.
Fibroblast reticular cells are found in the T cell-zone, upon which T lymphocytes browse for matching antigen. Follicular dendritic cells are found in the B-cell follicle, which B lymphocytes browse to bind matching antigen.
Why are fibroblast reticular cells and follicular DCs important for immune responses?
Fibroblast reticular cells provide “roads” for lymphocytes to travel on when traversing the
lymph node, facilitating the possibility of these lymphocytes to find antigen.
Both B and T lymphocytes use fibroblast reticular cells, but B lymphocytes switch over to follicular DCs to provide “roads” for them. This is because T lymphocytes bear CCR7, which bind to CCL21 and CCL19 on fibroblastic reticular cells; B lymphocytes, in contrast, bear CXCR5 which binds to CDCL13 on follicular DCs.
How does processed and unprocessed antigen get to T and B cells in the lymph nodes?
Processed antigen is picked up and processed by antigen-presenting cells, especially dendritic cells, which migrate to the closest lymph nodes to present the processed antigen to naïve T and B cells in the lymph node.
Unprocessed antigen can travel to the lymph node via blood if it is small and soluble enough; if larger, they can bind to APCs and be carried to the lymph node that way.
What is the role of CD169+ macrophages in the lymph node?
CD169+ macrophages reside in the subcapsular sinus and are responsible for transferring
opsonized antigen to the interior of the lymph node. Nonantigen-specific B cells pick up the antigen from there by binding them to complement receptors, then deliver the antigen to follicular dendritic cells.
After being activated, how do B cells traffic to find T cell help and how is help provided?
When B cells are activated by antigen, they need help from a T cell in order to be fully activated and differentiate. The T cell provides cytokines to help with B cell differentiation and interact with CD40 to further stimulate the B cell.
When B cells bind to antigen, CCR7 is upregulated which helps them move toward the border between the follicle and the T-cell zone. When the B cell finds its antigen-matching T cell, they bind, forming an immunological synapse between them. They migrate together, with the T cell following along while it gives cytokines to the B cell to stimulate its differentiation. CD40 interaction also occurs and helps the B cell further differentiate and proliferate.
How do CD4 T cells provide help to CD8 T cells when they do not directly interact?
CD4+ T cells provide help by first interacting with DCs which presents both class I and class II MHC. Antigen on class I MHC is presented to CD8+ T cells, while the class II MHC
presents antigen to the CD4+ helper T cells.
This brings them in close enough proximity that the CD4+ T cells can provide the cytokines that CD8+ T cells need. The DC attracts the CD8+ cell by producing CCL3, CCL4, and CCL5 upon contact with the CD4+ helper T cell, thereby recruiting the CD8+ T cell with CCR4 and CCR5 receptors.
Describe how effector cells leave the lymph node and home to specific tissue sites.
Depending on the type of antibody they produce, B cells will migrate to different regions of
the body.
IgM typically stays in the medulla of the lymph node;
IgG goes to the bone
marrow;
and IgA goes to MALT in the gut.
CD8+ T cells follow chemokines released by
innate immune cells to specific sites of infection.
CD4+ T cells vary on their destination by subtype; many stay in the lymph node to stimulate differentiation of other cells or travel to infection sites to help phagocytes take care of opsonized pathogen.
The key for effector cell migration is their chemokine and adhesion receptors and the chemokines being secreted by other cells.
What was learned using two photon imaging technology about the origin and function
of the APCs that cause immune rejection of MHC mismatched skin grafts?
The researchers learned that host DCs infiltrated the graft and process antigens from the graft and present them to CD8+ T cells, which initiates skin graft rejection.
What causes the type I hypersensitivy reactions?
Type I hypersensivity reactions are mediated by IgE antibodies and include many of the most
common respiratory allergens such as pollen and dust mites.
What causes the type II hypersensitivy reactions?
Type II hypersensivity reactions are caused by IgG or IgM antibodies binding to host cells
that are destroyed by complement or cell mediated mechanisms
What causes the type III hypersensitivy reactions?
Type III hypersensivity reactions are due to antigen-antibody complexes depositing on host
cells and inducing complement fixation and inflammation
What causes the type IV hypersensitivy reactions?
Type IV hypersensivity reactions (Delayed type hypersensitivity - DTH) result from
inappropriate T cell activation.
How does IgE function to cause type I symptoms?
IgE antibodies act by cross-linking Fcε receptors on the surfaces of innate immune cells.
The binding of IgE to FceRs activates granulocytes and causes degranulation.
Granule contents released include histamine, heparin, proteases, leukotrienes, prostaglandins, and
chemokines which act on surrounding tissues/cells to cause symptoms.
How do the high and low affinity Fc receptors on mast cells regulate the response?
Mast cells express both FcεR1 (activating) and FcγRIIB (inhibiting) Ig receptors.
If a cell binds IgE and IgG, the inhibiting signal induced by IgG binding wins out. This is partially why inducing IgG in atopic individuals (usually through “allergy shots”) helps treat their allergies.
What is the purpose and mechanism for allergy skin testing?
Skin testing is commonly used and is an inexpensive and relatively safe way to screen a wide range of antigens at once.
Small quantities of known allergens are introduced by injection or applying to a scratch at specific skin sites on the forearm or back. 30 minutes later the sites are reexamined and swelling and redness (resulting from local mast cell degranulation) indicate allergic response.