Mucosal Immunity - Hudig Flashcards
(114 cards)
1
Q
in what mucosal organ does the response to pathogens start?
A
tonsils! they’re the first to see them
2
Q
t/f: food molecules are often recognized as antigens
A
false! that’s how we can eat
3
Q
What cells secrete mucus and mucins?
A
goblet cells
4
Q
what is the function of commensal bacteria?
A
provide protection from harmful bacteria
5
Q
t/f: commensal bacteria can be harmful if they become systemic
A
true
6
Q
how much bacteria is present in the small intestine?
A
10^7 / ml
7
Q
in what three IgA secreting areas are commensals not found?
A
eyes, breast, and lung
8
Q
What cell type secretes b-defensins?
A
enterocytes
9
Q
what cell type secretes a-defensins?
A
paneth cells
10
Q
Describe how mucins and defensins work to kill bacteria?
A
mucins bind the defensins to the mucus layer and keep them from washing out. Defensins insert into the bacterial PM, create pores, and kill the bacteria
11
Q
What cell “samples” the intestinal contents for bacteria and antigens?
A
M cells
12
Q
what cells are inside the pocket created underside (basally) the M cell?
A
DCs, T and B cells
13
Q
What is the predominant T cell type in the GI tract?
A
Tregs
14
Q
A healthy GI tract has few T(blanks) and neutrophils
A
few TH17s and neutrophils
15
Q
antigens that drain from intestinal villi and M cells can travel to which lymph nodes?
A
mesenteric
16
Q
Mucosal B cells secrete what two types of Ig that are transported to the gut lumen?
A
IgM and IgA
17
Q
Which Ig type is NOT found in the mucosa?
A
IgG`
18
Q
Why do B cells pump IgA and M into the gut lumen?`
A
- directly anti-viral and antibacterial
- Abs aggregate pathogens and block their transport across the mucus
- block pathogen adhesion to epithelium
19
Q
what percent of all lymphs are in the mucosa?
A
50%
20
Q
how many grams of IgA are secreted per day?
A
3-4g
21
Q
Intra-epithelial lymphoctyes are CD(blank)
A
CD8 T cells
22
Q
What two specialized functions do the IELs have?
A
- standard CD8 mediated killing of virally infected cells
2. expression of NK cell receptor proteins to be able to kill non-specifically based on the presence of stress proteins
23
Q
Describe the process of Ab formation from Ag presentation to an M cell
A
- M cell takes in Ag
- Ag presented to DC cell
- DC express Ag peptide via MHC II
- T cell activated from DC
- T cell travels to germinal center in Peyer’s patch and activates B cell
24
Q
What regulatory cell responds in the mucosal system to DC displayed ags?
A
Tregs
25
What determines how Th0 cells differentiate in the gut?
The cytokine environment created by the DC cells
26
If Th0 cells become Tfh, what type of Ig is secreted from B cells?
IgA
27
If Th2 is the dominant differentiation, what IL do they release and what Ig does this induce?
Th2 releases IL 4 to make B cells to make IgE
28
What two cytokines do Tregs produce to shut down all T and B cell responses to ag?
IL10
| TGF beta
29
t/f: Treg shut down of immune function is only seen in pathological conditions
false!! that's what it should be, we want the gut to let everything just pass on through!
30
what are induced Tregs?
T regs activated by M cell activated DC cells
31
what antigens will induced Tregs recognize?
food and bacteria
32
Besides DC cells, what other cell secretes TGF beta to suppress the gut immunity?
enterocytes
33
The DC cells in the mucosa have what special CD marker on them?
CD103
34
t/f: IELs stay only withing mucosal tissues
true; they never see the spleen!
35
How does mucosal homing work?
binding of integrins to addressins to get lymphs into mucosal tissue from the blood then chemokines to attract them to the specific area
36
Where do you find addressins?
on the membranes of blood vessels and epithelium/enterocytes.
37
What addresssin is on high endothelial venules
MADCAM1
38
what addressin is on enterocytes?
E-cadherin
39
Where are integrins found?
on the surface of T cells activated in peyer's patches or the mesenteric lymph nodes
40
Which integrin interacts with MADCAM1?
a4b7
41
Enterocytes/intestinal epithelia produce what chemokine to attract lymphs?
CCL25
42
What is the receptor on lymphs for CCL25?
CCR9
43
Which integrin binds to E-cadherin?
aEb7
44
What cell type expresses aEB7 and binds to E-cadherin?
IELs
45
everything except the IELs and the epithelial cells are found in what layer of the villus?
lamina propria
46
what Ig class do the granules of the mast cells contain in the LP of the villus?
IgE
47
Thzero cells acted on by TGF0-beta and IL6 will differentiate into what cell type?
Th17
48
Th1 cells are involved in (cytotoxicity/ADCC)
cell mediated cytotox
49
Th2 cells are involvedin (cell mediated/ADCC)
ADCC
50
Th17 cells recruit what cell type to the location?
neutrophils
51
Are Tregs CD4 or CD8?
CD4
52
what portion of the Ab structure is needed for the Ig to be transported into the gut lumen?
J chain
53
Which two Abs have a J chain that allow them to be transported into the gut lumen?
IgA and IgM
54
What is the molecule that binds to the J chain to allow Ig passage across the epithelial layer into the gut lumen?
plgR
55
When IgA is released into the gut lumen, it is still attached to...
the secretory component of plgR
56
IELs are CD4 or CD8?
CD8; they kill infected epithelial cells, that's why theyre intraepithelial!
57
In response to bacteria, memory Th17 cell secrete what cytokine?
IL17
58
What is the target of IL17?
FIBROBLASTS; they then release chemokines to attract neutrophils
59
which two chemokines do fibroblasts release to attract neutrophils?
CXCL2
| CXCL8
60
What affect could mAbs to IL17 receptors have?
useful in dz like RA where you want to limit neutrophil migration but overall disastrous to immune health in the gut
61
t/f: celiac dz is different than wheat intolerance or wheat allergies
true; No auto-ab’s in wheat intolerance… No enteropathy to villi
62
in the cases that are NOT classic Celiac, what are the two common findings?
malabsorption and
| anemia
63
what are the classical Sx of Celiac?
diarrhea
abd pain
failure to thrive
DAMAGED VILLI in small intestine
64
What are the non-classical Sx of celiac?
delayed puberty
reduced growth
anemia
DAMAGED VILLI in small intestine
65
What are the pathological changes to the villi in Celiac?
1. villi are shortened
2. cryptic hyperplasia
3. >25 IELs per 100 enterocytes
4. Clinical Sx MUST occur at time of biopsy
66
What type of anemia presents in celiac and why?
megaloblastic; failure to uptake B12-intrinsic factor complex
67
what is the shortfall of using IgA auto-antibodies to tTG-2 to test for celiac?
person must have been exposed to gluten within the last two weeks
68
What test for celiac has 100% specificity with a high negative predictive value?
serum IgA auto-Abs to EMA (endomysium antigens)
69
Besides tTG-2 and EMA, what one other thing can patients develop IgA auto-Abs against in celiac?
IgA to de-amidated gliadin (gluten)
70
What are the two most common HLA allelles in celiac?
90% DQ2
5% DQ8
last 5% positive for one alpha DQ2/8 and one beta DQ2/8 chain
71
what is the caveat when doing a biopsy to determine celiac?
pts must have had gluten in the last two weeks for the biopsy to be positive
72
how many sites are sampled in a celiac biopsy?
4
73
How long does it take for symptoms to resolve once gluten has been removed from the diet?
months to years :(
74
what is the half life of IgA in the serum?
6 days
75
What is the characteristic malabsorption pattern seen in the mucosal folds of pt with celiac?
scalloping
76
Describe the changes to the villi in celiac
villous atrophy and complete loss of villi
77
How much gluten is needed to sustain/trigger the disease?
MICROGRAMS!!
78
tTG2 modifies gluten to gliadin to fit into MHCII DQ2 and DQ8 which is then presented to what cell?
CD4 T cells
79
T/F: the formation of autoantibodies are central in the formation of pathology in celiac
FALSE; no role! dz is caused by gluten directly stimulating T cells that damage small intestine architecture!
80
how many IELs are seen per 100 enterocytes in celiac?
>25
81
Over activated IELs produced by activated anti-gliadin CD4 TH(blank) IELs kill enterocytes
TH1
82
what extra set of receptors do CD8 IELs have in celiac?
NK cell receptors; they then kill enterocytes that are releasing stress signals
83
what are the 2 T cell mucosal integrins and the one MALT chemokine receptor that are targets for mAb therapy in celiac?
t cell integrins: a4b7 and aEb7
| chemokine: CCR9
84
Refractory celiac disease may be due to (blank) spreading
epitope spreading
85
(Crohns/UC) affects only the colon
UC
86
(Crohns/UC) affects the ileum and the colon
Crohns
87
(Crohns/UC) is associated with defensins
Crohns
88
(Crohns/UC) is associated with mucins/mucus
UC
89
(Crohns/UC) more often presents with abd pain and perianal disease
Crohns
90
(Crohns/UC) tends to have GI bleeding
UC
91
Cobblestoning of mucosa, and aphthous or linear ulcers are seen on endoscopy of...
Crohns
92
Diffuse continuous involvement of the mucosa is seen on endoscopy of..
UC
93
Fistulae, asymmetry, and ileal movement are seen on radiographs of...
Crohns
94
Which dz shows mucosal discontinuity, transmural involvement, and granulomas?
Crohns
95
Crypt abscesses and granulomas are only present in..
Crohns
96
Loss of haustra and the formation of pseudopolyps are seen in (Crohns/UC)
UC
97
Cobblestoning and fat wrapping are seen in...
(Crohns/UC)
98
t/f: there is no HLA association in Crohns
true
99
What is the monozygotic twin concordance in Crohns?
50%
100
In Crohns, there is a genetic association with the variant of (blank) intracellular receptors and genes for autophagy
NOD2
101
ileal Crohns is due to a lack of (a/b) defensins produced by Paneth cells
a-defensins
102
colonic Crohns is due to a lack of b-defensins produced by the (blank) cells
enterocytes
103
In Crohns, CD4 T cells differentiate into what two types predominately?
Th1 and Th17
104
In what percent of cases of Crohns do we see granulomatous lesions
35%
105
Studies indicate Tregs are (low/high) in Crohns
low; Tregs are used to dampen the immune response in the gut!
106
What Ab drug can induce remission in crohns?
Rifaximin
107
Anti-(blank cytokine) biologicals such as mAbs or decoy recepotors can reduce symptoms in Crohns
anti-TNFalpha
108
Describe the overall process of T cell differentiation in Crohns
1. Low levels of defensins
2. More live bacterial ags presented in the lamina propria
3. Activated APCs release profinflammatory cytokines
4. Cytokines induces Th1 and Th17 and suppress Tregs
109
What cytokine is released from mac's and APCs to induce TH1?
IL12
110
what cytokine is released from mac's and APCs to induce Th17?
IL6
TGFb
IL1b
IL23
111
How deep does the damage extend in UC?
to mucosa and submucosa only
112
Which MUC transporters are low in UC?
secretory MUC2
| transmembreane MUC3/4
113
t/f: paneth cells and defensins are normal in UC
true
114
Future therapies for UC include agonist ab to the (blank cyotkine) receptor made by Th2 cells which upregulates MUC5AC production
IL13
