Immunology 8 Flashcards
Unlike B-cells, T-cells undergo very little maturation in the ?
bone marrow
After stem cells “choose” to become lymphoid progenitors, those progenitors divide under the influence of
IL-7
T cells need to travel to the ? to develop function T-cell receptors (TCR)
thymus
where is the thymus located
superior to the heart and anterior to the great vessels
thymus is largest or smallest prior to puberty?
largest
the thymus is divided into ?
cortex and medulla
what does double negative mean?
the T-cell precursors do not express CD8 or CD4
when DN cells commit to a T-cell lineagethey are known as ?, these cells are mostly found in the ?
DN3 cells
cortex of the thymus
DN cells first rearrange the ? of the TCR, If this is done correctly, then proliferation continues known as ?. If the beta chain is useless, the ?
beta chain
DN4
cell dies
After the beta chain is rearranged and done correctly, the ? of the TCR is then shuffled.
alpha chain
After both TCR chains have been recombined, the developing T-cell expresses both CD4 AND CD8 -> ?
double positive (DP)
DP cells will recombined with TCRs sample…
thymic epithelial cells HLA
If DP cells has very low affinity interactions to thymic epithelial cells HLA ->
death of the DP T-cell
If DP cells has medium-low affinity interactions to thymic epithelial cells HLA ->
survival of the DP T-cell
If DP cells has very high affinity interactions to thymic epithelial cells HLA ->
death of the DP T-cell
DP cells that have been positively selected and have survived negative selection then ?
“make a choice”
The DP cell with its useful TCR will ? to see if the CD8 or CD4 co-receptor interacts better with the medullary TECs
“test”
ultimately, at the end of T cell development, T cells express only ? or ?
CD4 or CD8
what is the rationale for positive selection when TCR has a “low-medium” affinity for a thymic epithelial cell’s (TEC) HLA bound to self-antigen, it is allowed to survive
the TCR is capable of interacting with an HLA molecule, but is unlikely to recognize self
what is the rationale for negative selection when TCR has a “high” affinity for a thymic epithelial cell’s (TEC) HLA bound to self-antigen, it is allowed to survive
this is T cell with a TCR that recognizes self – it should not be allowed to survive
what is a transcription factor-like protein that binds with a wide range of other transcription factors and activates them for central tolerance
AIRE
CD4+ Treg cells polarized by ?
interaction with an APC and presence of high circulating levels of TGF-B
what is expressed by helper T-cells, binds to B7 with higher affinity than CD28
CTLA-4
Binding of CTLA-4 to B7 (CD80/CD86) molecules on APCs usually renders the CD4+ cell ?
anergic
As well, T-reg cells often express CTLA-4 and can shut down ? expression on the APC.Net result – if you knock out CTLA-4 in a mouse, it always gets very ?
CD80/86
severe autoimmune disease
CTLA-4 binds to CD80/86 ->
downregulation of APC presenting antigen
TREG can inhibit APCs by signaling through the CD80/CD86 (B7) receptor. This engagement results in :
- Decreased expression of CD80/86
- Activation of indoleamine-2,3-dioxygenase (IDO)
- Changes in transcription leading to decreased expression of IL-6 and TNF-alpha
Treg cells also express high levels of ?-> ? IL-2 and preventing it from activating an effector cell
IL-2 receptor
“soaking up”
When the barrier is healthy, with no tissue damage, then ? predominates in the mucosa
TGF-beta
TGF-beta and retinoic acid promotes class-switching to ? by B-cells
IgA
what are some situations that seem to increase the likelihood of developing Tregs and overall tolerance?
○ Exposure to constant antigen levels for long periods of time
○ Exposure to antigen early in life
○ Exposure to antigen in tissue that “looks” healthy
what are the key genes implicated in decreased tolerance and autoimmunity
IL-2R-alpha
CTLA4
In the bone marrow, B-cells that encounter self-antigen have their ?
receptor shuffled
In the spleen, B-cells that encounter self-antigen they ?
undergo apoptosis
what are B cells that have survived negative selection in the spleen
T2 B-cells
What provides the driving force for lymph to enter lymph capillaries?
Interstitial fluid build-up on the outside of the capillaries puts pressure on the capillary cells and forces them apart
What provides the driving force for lymph to circulate in the larger lymphatic vessels?
- Contraction of skeletal muscle surrounding the lymphatic vessels
- Pressure created through breathing
After exiting lymph nodes, lymph vessels combine to form
trunks
Trunks combine to form one of two lymphatic ducts that drain into the blood system:
right lymphatic duct and thoracic duct
The right lymphatic duct drains ?
the right arm, thoracic region, and right head/neck
the right lymphatic duct drains into the
juncture of the right subclavian vein and right internal jugular
the thoracic duct drains?
- Drains the rest of the body
the thoracic duct drains into ?
the juncture of the left subclavian vein and left internal jugular