10/27 Immunology Intro Flashcards
what is the central lymphoid organ located in the superior mediastinum?
the Thymus
what happens to insure that our T cells work properly? that the TCR of T cells does see MHC
development in the thymus that includes two selective steps
what is MHC?
major histo-compatability complex
what type of organ is the thymus?
it is a lympho-epithelial organ
what is a lympho-epithelial organ?
epithelial reticular cells make a cellular reticulum that induces lymphocyte progenitor cells to beome pre-T cells and supports the development of T cells. (no extracellular fibers!)
what is in the thymic cortex?
no extracellular fibers but macrophages and related bone marrow cells are present.
why would it be difficult to find the thymus in an elderly patient?
The thymus is well developed at birth but then involutes and shrinks after the first year of life.
what if you remove the thymus of an adult?
there is no serious consequences.
Outer skin of the thymus
the thymus is covered with a thin capsule which runs into organ forming septae (not trabeculae) and divides the organ into lobes and lobules.
how is the organization of the kidney and the adrenal similar to the thymus?
It is organized into a cortex and a medulla.
How can a microscope section of the thymus be divided into the cortex and medulla?
the cortex is just under the capsule and is darker staining cells that are closer together than in the medulla. The dense is the cortex and the not so dense is the medulla
describe the cells of the thymic cortex!
small little lymphocytes (T cell lineage); spidery epithelial reticular cells; large vaculoe filled macrophages.
the prominate corpuscle in the thymic medulla
small hassall’s corpuscle
the invaginations of the capsule in the thymus
septum!
specialized endothelial cells..that are vessels that are easy for lymphocytes to get in and out of from the blood.
High endothelial venule (HEV)
how can we identify the thymus based on the contents of the medulla (esp. old thymus)?
they have very large hassels corpuscles!
how do we have a blood-thymus barrier
epithelial reticular cell that is wrapped around the capillary. This is found in the Cortex!!!
why do we have a blood-thymus barrier
keep antigens out of the cortex
describe the T cell development
the progenitor stem cells come from the bone marrow and circulate and come in by the HEV and into the medulla and move to the cortex, encounter epithelia cells and become thymocytes, or Pre-T cells. the TCR gene rearrangements occur and TCR is selected and expressed as well as both CD4 and CD8 - move towards medulla and contact with reticular cells, dendritic cells, and macrophages, antigen presenting cells that only present self and if they interact not so strong and not too weak with either a CD4 or CD8 they become that CD4 or CD8. (positive selection) Then into the medulla, it will interact with self antigen presenting cells and if they interact strong they are destroyed (negative selection) then they are successful naive cells and they leave again via the HEVs in the medulla
Does the pre-T cells’ TCR bind properly (moderate afffinity) to host MHC expressed on epithelial reticular cells.?
if no: the cell apoptosis and die; If yes: cell recieves supportive cytokine signals, and becomes a single positive cell (CD4 or CD*) and lives
what is a double positive T cells?
they hvae both CD8 and CD4
what is single positive?
have just one of CD4 or CD8
what if the pre-T cell encounter epithelial reticular cells, macrophages, thymic dendritic cells and see self-antigens on host MHC with high affinity?
then it is told to die (deaht cytokine) – this is negative selection
AIRE
autoimmune regulator – a transcriptional factor that allows low level of many genes in the thymus, increasing the self-proteins that are expressed for negative selection of the T-cells.
what are the two steps that must be passed as you educate a T-cell
Positive selection (bind but not too tight to self). Negative selection (not bind tight to self)
How can many T-cells with self-reactive receptors die or become anergic?
peripheral tolerance!
what is peripheral tolerance?
cells will incounter antigens without benifit of proper “double handshake” and without cenessary cytokine stimulation.
they suppress the activation of effector cells with self-reactive receptors…not clear how
Treg cells
Zones that are characterized by a uniform cell distribution of T-cells
Thymus-dependent areas and are seen i the lymph nodes and spleen
the thymus does not develp properly and thymus dependent sites are poorly populated
DiGeorge syndrome
where are pre-B cells born ?
the bone marrow
what could provide positive selection for B-cells?
adventitial reticular (fibroblast-like) cells may provide positive selection.
what could be important if the B-cells don’t have a thymus to “school” them?
peripheral tolerance
how is the attrition in B and T cell school?
very high! some like 95% die!
the fraction of plasma that escapes from blood vessels
Lymph
how is lymph returned to the circulatory?
returned in endothelial lined vessels that are interspersed by the lymph nodes.
filter the lymph and can react with antigens carried by dendritic cells or arriving in afferent lymphatics form upstream
Lymph nodes
All packed together in the lymph nodes ready to react to antigens
APCs, T and B cells and the antigens!
how are lymph nodes for wet vs. dry different
Dry: make IgG Wet: tend to make IgA
what is the histo presentation of a lymph-node?
capsule with some space under it and the capsule invaginates in trabecula into a cortex which surrounds a medulla
where are the T and B cells in the lymphocytes?
T cell: far away from the capsule. B cell: close to the capsule
what is the flow of lymph in the lymph nodes?
subcapsule sinus to the trabechula down the cortical sinus down to the medula.
describe the flow of an antigen from the skin to the activation of the activation of the T / B cells
bacteria and antigens in skin stimulate the toll like receptors and langerham cells goble up stuff and flows down a lymph duct to a node and then present as a dendritic cell to T cells with the B7 second handshake. and the B cells see the antigen on the FDC and then gets a second handshake in the form of CD40/CD40L with an activated T helper cell. and then B and T are active and you get cellular and Anti-body response!
where are antigens presented in the lymph nodes and by what?
presented in the sinuses which slow down lymph flow and presented by dendritic cells.
what are the first antibodies secreted?
IgM
what if you have continued immune response (secondary response or late primary response).
Isotype switching to IgA, IgE, or IgG results in the appearance of germinal centers in secondary nodules
what is contained in the germinal centers in secondary nodules?
B cells in several developmental stages (some cells are large), follicular dendritic cells, Th cells, and B memory cells.
where does isotype switching occur
in secondary nodule with germinal center – circular clumps of memory cells, folliculardendritic cells B cells etc.
leave the cortex of the lymph nodes and form “cords” in the medulla of the lymph nodes.
Plasma cells!
how do T cells and B cells succeed in scanning the cells of the body?
they recirculate and leave nodes, via lymph, return to the blood stream and reenter nodes again! they come and go from nodes from HEVs
why would we see specific lymphocytes in specific types of nodes?
homing receptors and cytokines: cells are attracted to enter through HEVs, this gives IgG in dry and IgA in wet nodes
when would a swollen lymph node be tender?
when it is an immune response
when would a swollen lymph node be non-tender?
when it is a tumor growth.
