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MIMM 314 > Abadie lecture 2 > Flashcards

Abadie lecture 2 Flashcards

1
Q

presenting T cells in the germinal center leads to …

A

crosstalk and reciprocal activation that allows B cells to be activated and differentiate

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2
Q

what can B cells produce after their interaction with T cells

A

cytokinesssss
-proinflammatory: IL12, IL6 and TNFalpha
-regulatory cytokines like IL-10 and IL35

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3
Q

type 1 cytokines activates what type of b cells and type 2

A

type 1:Be1 cells
Type2: Be2 cells
this will also produce cytokines
same idea as th1 and th2 cells

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4
Q

B regulatory cells produce…

A

IL-10

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5
Q

B cell depletion: SLE lead to….

A

-decreased activation of CD40 cells lead to decreased autoreactive T cells
-increased expression of markers of T regs
-this restaures balance of homeostatic T cell response
-shows that B cells play a role in activation of T cells

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6
Q

true or false: Anti-CD20 does deplete plasma cells and prevents the differentiation of newly formed B cells from becoming plasma cells

A

false
Anti-CD20 does deplete not plasma cells and prevents the differentiation of newly formed B cells from becoming plasma cells

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7
Q

APC and regulation of T cell immunity; break in tolerance; B cells are not seen as….

A

b cells are not seen as primary antigen presenting cells but tend to promote the expansion of the T cell response

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8
Q

APC and regulation of T cell immunity; B and T cell feedforward loop

A

-the break in tolerance in an autoimmune disease leads to huge proliferation of both T and B cells

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9
Q

APC and regulation of T cell immunity; feedforward loop broken; what is the hypothesis

A

the hypothesis is that the removal of these cells breaks the expansion and survival of these cells

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10
Q

APC and regulation of T cell immunity; regulatory T cell expansion

A

removing B cells will lead to regulatory expansion of T cells and cytokines that will further dampen the T cell activation

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11
Q

APC and regulation of T cell immunity; tolerance re-established; regulatory feedforward loop

A

this leads of autoreactive T cells

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12
Q

Be1 cells produce

A

a th1 like response so it secretes infy and il12

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13
Q

Be2 cells produce

A

a th2 like response so it secretes il2, il13 and il2

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14
Q

what is the difference between Be1 and Be2 cells

A

Be2 cells can’t differentiate into antibody secreting cells while the Be1 cells can

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15
Q

what do B regulatory T cells produce

A

Il10 and it can dampen the activation of effector T cells

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16
Q

what can plasma cells produce

A

-antibodies
-beneficial cytokines like il10 and il35

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17
Q

which type of B cells can produce inflammatory cytokines and what are they

A

-memory b cells
-il6, gm-csf and tnf

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18
Q

true or false; plasma and memory b cells do not produce the same type of cytokines

A

true
because they don’t reside in the same tissues

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19
Q

what are the 3 compotents of humoral responses

A

-b cells
-plasma cells
-antibodies

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20
Q

in almost all autoimmune and inflammatory disease you have production….

A

-production of antibodies against self-antigens

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21
Q

true or false: in almost all autoimmune and inflammatory disease you have production of antibodies against self-antigens which are all pathogenic

A

false some of them were proved to not be

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22
Q

what can anti-cd20 do? in terms of b cell depletion therapies for ms

A

-prevents the formation of new inflammatory lesions which shows a clinical improvement and it works
-rituximab is the most popular on the market
-removing the b cells allows for the treatment to work

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23
Q

atacicept treatment; what does it do

A

-reduces circulating B cells aka plasma cells and decreases serum antibody titers

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24
Q

true or false; atacicept treatment slaps for ms and why

A

it lowkey sucks
-in the context of ms b cells produce dangerous cytokines while the plasma cells produce beneficial cytokines
-removing the b cells=the patient will improve
-removing plasma cells=patient will get worse

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25
study if mouse model of ms: they observed an infiltration of mucosal plasma cells (IgA+) into the brain and the spinal cord of the animal treated with excess peptide and they observed that these cells were..... and removing these cells the animal got....
proinflammatory worse
26
true or false: plasma cells have a very beneficial role in case of MS while B cells are more harmful
true
27
true or false: celiacs disease is an autoimmune disease
false autoimmune lack inflammatory disorder due to the production of antibody against tissue (self-antigen)
28
what causes celiacs disease
gluten induced enteropathy reversible on a gluten free diet
29
what happens to some celiacs disease patients that is not a slay
a very small amount of these patients on a gluten free diet can become refractory and get a malignant transformation of T cells in the gut that acquire an activated phenotype with an nk receptor and develop T cell lymphoma
30
celiacs disease only develops in individuals carrying....
-hla-dq2 or hla-dq8
31
which % of the pop carries hla-dq2 or hla-dq8 mutations
40% but only 1% will develop the disease -not everyone will get it because it requires the interaction of genetic, environmental and immune response factors
32
which disease causes villous atrophy with intraepithelial lymphocytosis
celiacs disease
33
where is TG2
in many tissues and is important in many functions
34
in celiacs disease; antibodies directed to...
deaminated gluten peptides and tissue transglutaminase
35
celiacs disease il15 in intestinal mucose
-overexpression of pro inflammatory cytokine -some can have increased expression type 1 inf
36
celiacs disease antigluten cd4+t cells are.... but not ...
required but not sufficient
37
celiacs disease; Gluten gives rise to.....
-proteins called guanidine and glutenin which are long filaments
38
where do guanidine and glutenin go through
-the epithelial barrier where they get into contact with the transglutaminase which daemidates the gluten peptides
39
guanidine and glutenin go through the epithelial barrier where they get into contact with the transglutaminase which daemidates the gluten peptides; this makes.....
this makes the gluten peptide have much higher affinity due to negative charge for binding to hla-dq2 and hla-dq8 on apc
40
celiacts disease: apc migrates to....
the draining lymph node where the peptide is presented to T cells -since this is a very pro inflammatory environment, an inflammatory T cell response will be made (Th1) and the regulatory T cells will be dampened
41
in celiac disease, cd8 t cells that reside between epithelial cells are capable of....
becoming cytotoxic and killing epithelial cells -they will somehow upregulate their cytotoxic components
42
true or false B cells play a role in celiacs
yeah -they produce antibodies against transglutaminase and gluten
43
production of highly celiac disease specific antibodies that reflect that gluten is a substrate for....
TG2\
44
in patients not being treated with gluten free diet, there's production of.......
disease specific antibody compared to patients under gluten free diet -production of antibody against deaminated form of gluten peptide which is a good indicator of disease
45
how do you diagnose celiac disease?
through measuring the production of an antibody against transglutaminase or against deaminated gluten peptide wich mirrors the fact that TG2 has been activated
46
anti-glutaminase is the golden standard and this is confirmed by...
biopsy
47
true or false; there is a corrolation with the threshold of antibody titers associated with tissue damage in celiac
nah the more severe the disease is, the more you have antibodies but there is no strict correlation
48
what is plasmacytosis
another indication that humoral immunity might play a role is that there is a huge expansion of plasma cells in the mucosa
49
in celiac; between ... and ...% are specific for the TF2 meaning that the plasma cell recognizes the TG2
1 and 10%
50
true or false: 7% of plasma cells recognize gluten peptide
false 2%
51
b cell directed therapies for the treatment of celiac disease
--rituximab (anti-cd20) can be used in patients that have celiac disease along with an additional autoimmune disease
52
which type of cells that are required for the development of villous atrophy in a mouse model of celiac disease
b cells
53
development of humanized model of mice that was born and raised on a gluten-free disease; this can allow to.....
be able to assess if B cells play a role
54
development of humanized model of mice that was born and raised on a gluten-free disease; they used what type of mouse ?
used the mouse counterpart of the rituximab anti cd20 depleting antibody and treated the mouse with this over the course of the disease
55
mouse model for celiacts disease; when does the first tissue damage will occur after starting eating gluten
30 days
56
celiac disease; mouse model histology, what can u see
you can see an atrophy with the villi when the gluten is fed to the mice
57
when you ko B cells in mouse model for celiac disease
there is a significant reduction of the atrophy in the mice suggesting that b cells are involved
58
is there a tole for anti-tg2 and anti-gluten antibodies and/or immune complexes in tissue damage and systemic manifestations?
they don't believe that antibodies in the context of celiac are pathogenic but they have a role -a few studies show that they could impact the antigenesis, perturbation, intestinal permeability, attach to epithelial cells and promote leaky gut consensus
59
intestinal deposits of anti-tg2 IgA and immune complexes containing gliadin specific IgA and transglutaminase in patients with celiac disease. They showed that.....
IgA that atises in celiac could be involved in capturing gluten peptides and transporting across the epithelium and creates an amplification of the immune response
60
true or false: the repertoire of tg2-specific antibody secreting cells is not diverse and the tg2 specific antibodies have a lot of somatic mutations
false the repertoire of tg2-specific antibody secreting cells is highly diverse and the tg2 specific antibodies have limited of somatic mutations
61
some scientists observed that the repertoire of the tg2 specific antibody secreting cells is highly restricted with....
the predominant usage of vh5-51 -they also had very limited accumulation of somatic mutations
62
evidence for a B cell T cell crosstalk in celiac disease; the hapten carrier model
-explains why we have antibody response in celiac -complex between transglutaminase 2 and gluten peptide that will be internalized and processed leading to the production of the antibodies
63
the hapten carrier model; how was it proven
-in vitro with a coculture of T cells in mouse cell line that expressed human tcr and cd4 -only when putting the gluten complex with B cells expecting the right hla with the T cells recognizing the right peptide they could observe T cell expansion -indicated you need the complex between tg2 and gluten peptide to get this cross talk
64
ways B cells could participate as apcs and how can that be testes
-fluorescent microscopy ex vivo to see when these cells come together -cytokine production in vivo -make a b cell line without mhc that cannit present the antigen to the t cell
65
B cells are required in the case of celiacs for the acquisition of ...
cytotoxic properties by intraepithelial lymphocytes -main cell type impacted by the b cells are the cd8s in the epithelium -when b cells are removed, there is a decrease in intraepithelial lymphocytes and they express less of the nk receptor, perforin and gransyme

MIMM 314 (11 decks)

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