Immunology - Tolerance Flashcards

(75 cards)

1
Q

After stem cells “choose” to become lymphoid progenitors, those progenitors divide under the influence of

A

IL-7

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2
Q

Unlike B-cells, T-cells undergo very little maturation in the bone marrow. They Need to travel to the ? to develop functional T-cell receptors

A

thymus

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3
Q

the thymus is located where?

A

superior to the heart, anterior to the great vessels

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4
Q

the thymus is largest when?

A

largest prior to puberty, shrinks afterwards

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5
Q

the thymus is divided into ?

A

cortex and medulla

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6
Q

T-cells with TCRs that can bind to antigen presented via HLA WILL survive ->

A

positive selection

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7
Q

T-cells with TCRs that bind self-antigen with high affinity WON’T survive ->

A

negative selection

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8
Q

what is the structure of the TCR?

A

2 chains: 1 alpha and 1 beta - each with a variable region and a constant region

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9
Q

the T-cell receptor is never what? (think location)

A

never secreted - it always stays attached to the membrane

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10
Q

T-cell precursors from the bone marrow enter the thymus from vessels at where?

A

the junction of the cortex and medulla

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11
Q

initially, when the T-cell precursors enters the thymus, they don’t express CD8 or CD4, they are known as ?

A

double negative (DN)

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12
Q

DN cells commit to a T-cell lineage and is known as ?

A

DN3 cells

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13
Q

DN3 cells are mostly found where?

A

in the cortex of the thymus

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14
Q

what do DN3 cells do before turning DN4?

A

genetically shuffle their TCRs

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15
Q

DN cells first rearrange what part of the TCR?

A

beta chain of the TCR

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16
Q

if the rearrangement of the beta chain of the TCR is done correctly, then proliferation continues and they become what?

A

DN4 cells

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17
Q

if the rearrangement of the beta chain of the TCR is done incorrectly, then proliferation continues and they become what?

A

the cell dies

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18
Q

what happens when DN3 cells turn to DN4

A

the alpha chain of the TCR is shuffled

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19
Q

after both TCR chains have been recombined, the developing T-cell expresses what?

A

both CD4 and CD8

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20
Q

what is it called when the T cell precursors expresses both CD4 and CD8?

A

double positive (DP)

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21
Q

what does DP cells do after recombined TCR do?

A

sample thymic epithelial cells HLA (with self-antigens expressed)

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22
Q

if the DP cells have a very low affinity interactions with HLA what happens?

A

death of the DP T-cell

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23
Q

if the DP cells have a medium-low affinity interactions with HLA what happens?

A

survival of the DP T-cell

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24
Q

if the DP cells have a high affinity interactions with HLA what happens?

A

death of the DP T-cell

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25
what is the rationale behind the DP T-cell that survives because it has a "low-medium" affinity for a thymic epithelial cell's (TEC) HLA bound to self-antigen
the TCR is capable of interacting with an HLA molecule, but is unlikely to recognize self
26
what is the rationale behind the DP T-cell that dies because it has "high" affinity for a TEC HLA bound to self-antigen
this is T cell with a TCR that recognizes self – it should not be allowed to survive
27
DP cells that have been positively selected and have survived negative selection then what?
"make a choice"
28
The DP cell with its useful TCR will "test" to see if what?
the CD8 or CD4 co-receptor interacts better with the medullary TECs
29
what is central tolerance?
in primary lymphoid organs with negative selection - also consider it including thymus generated Treg cells
30
what is peripheral tolerance?
Treg polarization in SLOs or peripheral tissue
31
what is AIRE?
transcription factor-like protein that binds with a wide range of other transcription factors and activates them
32
Defects in AIRE are rare – they result in an ?
autoimmune polyendocrinopathy syndrome (APS)
33
what is autoimmune polyendocrinopathy syndrome (APS)?
Immune system attacks a wide range of endocrine glands, including the parathyroid glands, the adrenal glands, the pancreas, and the ovaries
34
Treg cells are Polarized by interaction with an APC and presence of high circulating levels of what?
TGF-beta
35
TGF-beta tends to be expressed in higher concentrations by APCs and other cells in ? environments 
"non-inflammatory"
36
CTLA-4 – expressed by helper T-cells, binds to ? with higher affinity than ?
B7 (CD80/86) CD28
37
Binding of CTLA-4 to B7 (CD80/86) molecules on APCs usually renders the ?
CD4+ cell anergic
38
CD4+ Treg cells express high levels of what? as well as ?
IL-2 receptor FoxP3
39
what happens when CTLA-4 bins to CD80/86?
Downregulation of APC presenting antigen : - Reduction in pro-inflammatory cytokines - Production of kynurenic acid (anti-inflammatory)
40
How do Treg cells inhibit APCs through CTLA-4?
Treg cells signal through CD80/86 (B7) on APCs using CTLA-4, leading to APC inhibition.
41
What receptor on APCs does CTLA-4 from Treg cells bind to?
CD80/86 (also known as B7).
42
What happens to CD80/86 expression in APCs after CTLA-4 engagement?
CD80/86 expression is decreased.
43
What enzyme is activated in APCs upon CTLA-4 binding by Tregs?
Indoleamine-2,3-dioxygenase (IDO).
44
What does IDO do in the immune response?
Converts tryptophan to kynurenine, creating an immunoinhibitory microenvironment.
45
How does CTLA-4 signaling affect cytokine expression in APCs?
Leads to decreased IL-6 and TNF-alpha expression.
46
What role does IL-2 receptor expression on Treg cells play in immune suppression?
High IL-2R expression allows Tregs to "soak up" IL-2, preventing effector T cell activation.
47
Why doesn't the immune system attack commensal microbes at mucosal surfaces?
Peripheral tolerance develops early in life, and immune responses are regulated to prevent unnecessary inflammation.
48
What is the role of secreted IgA in response to commensal bacteria?
IgA recognizes but doesn’t kill commensals—it reduces their invasion without triggering inflammation.
49
What cytokine predominates in healthy mucosal environments without tissue damage?
TGF-beta
50
What promotes class-switching to IgA in B-cells at mucosal barriers?
TGF-beta and retinoic acid.
51
What happens if a pathogen causes tissue damage at the mucosal barrier?
PRRs are activated, TGF-beta levels drop, and inflammatory Th responses (Th1, Th2, Th17) develop.
52
what are the key genes implicated in decreased tolerance and autoimmunity?
- IL-2R-alpha - CTLA4
53
what are the diseases associated to defects in IL-2R alpha genes?
multiple sclerosis and Type 1 DM
54
what are the diseases associated to defects in CTLA-4 genes?
Type 1 DM, RA
55
B-cells that travel to the spleen to mature further are known as ?
T1-transitional-1 – B cells
56
what are the roles of the spleen?
- Immune responses to antigens in the bloodstream - Maturation of T1 B cells to T2 B-cells 
57
what are the structures of the spleen
- white pulp - red pulp - capsule
58
the white pulp surrounds what?
the arterioles
59
what is in the inner layer of white pulp?
peri-arteriolar sheath, site containing many T-cells
60
what is in the middle layer of white pulp?
B-cell rich lymphoid follicles
61
what is in the outer layer of white pulp?
specialized B-cells and macrophages here
62
what is the main role of red pulp?
elimination of dysfunctional RBCs
63
during negative selection in the spleen, if T1 B-cells encounter self-antigen what happens?
undergo apoptosis
64
what are the cells called when they survive negative selection?
T2 B-cells
65
what are the requirements for T2 B cells to become mature B cells?
- their BCRs tonically deliver a stimulatory survival signal - up-regulate their BAFF receptors and bind BAFF, also contributing to survival
66
many B-cells in the marginal zone that produce somewhat non-specific, somewhat low-affinity IgM that recognize a number of different microbes, these B-cells are called ?
T cell-independent B-cells (TI)
67
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 - Once lymph enters, the external pressure dissipates - Cells close again and the lymph is pushed forward
68
What provides the driving force for lymph to circulate in the larger lymphatic vessels?
Contraction of skeletal muscle surrounding the lymphatic vessels - Skeletal muscle "squeezes" the vessels -> movement of fluid forwards since there are one-way valves AND Pressure created through breathing
69
One-way valves prevent what?
backflow
70
After exiting lymph nodes, vessels combine to form
trunks
71
Trunks combine to form one of two lymphatic ducts that drain into the blood system, they are called?
- right lymphatic duct - thoracic duct
72
right lymphatic duct drains what?
Drains the right arm, thoracic region, and right head/neck
73
right lymphatic duct drains into what?
into the juncture of the right subclavian vein and right internal jugular
74
thoracic duct drains what?
Drains the rest of the body
75
thoracic duct drains into what?
into the juncture of the left subclavian vein and left internal jugular