Mucosal Immunity-Hudig Flashcards
1
Q
In celiacs, you get a loss of (blank)
A
duodenal villi
2
Q
What is GALT?
A
tonsils, stomach, small intestine and colon
3
Q
What is waldeyers ring?
A
the tonsils, and adenoids form a ring of lymphoid tissue around the entrance of the gut and airway
4
Q
Where do responses to pathogens and antigens start?
A
germinal follicles with T and B cells
5
Q
what are the absorptive cells of the intestine?
A
enterocytes
6
Q
Food peptides and lipid micelles are absorbed from the GI lumen and are carried via (blank) to the liver. Food molecules are rarely recognized as foreign antigens.
A
hepatic portal vein
7
Q
(blank) secrete mucus into the lumen.
A
Goblet cells
8
Q
WHere do we have the most commensal bacteria?
What do they do?
A
colon > small intestine
Provide protection from harmful bacteria
9
Q
Commensal bacteria has pathogenic potential if bacteria becomes (blank)
A
systematic
10
Q
Commensals are not found where in the body?
A
eyes, breast, lungs
11
Q
What 2 things control bacteria?
A
mucus and defensins
12
Q
(blank) cells secrete mucus to bind defensins
(blank) secrete beta-defensins
(blank) secrete alpha-defensins
(blank) kill bacteria
A
goblet cells
enterocytes
Paneth cells
Defensins
13
Q
Alpha definins are also called (blank)
A
cryptidins
14
Q
(blank) are any of the granular epithelial cells with large acidophilic nuclei occurring at the base of the crypts of Lieberkühn in the small intestine and appendix.
A
paneth
15
Q
Which has more goble tcells, the colon or small intestine?
A
colon
16
Q
Defensins are (anionic/cationic) Mucus is (anionic/cationic)
A
anionic
cationic
17
Q
(blank) bind to mucus, are retained and concentrated to kill bacteria. THey protect the underlying cells from bacteria
A
Defensins
18
Q
Alpha and beta definisins are (bank) molecules and insert into bacterial membanes to form (blank) and kill bacteria. THis has major potential for recominant therapy
A
amphipathic
pores
19
Q
For (blank) immunity, both mucus and defensins are critical
A
innate`
20
Q
Less than (blank) millimeters of mucus binds defensins, and bacteria, promotes bacterial killing, and is protective barrier
A
1
21
Q
What is the adaptive mucosal immunity of healthy people in response to oral pathogens?
A
- antigens detected by M cells
- Dendritic cells and T and B cells in the M cell area get activated (peyers patches)
- Make a lot of T-regs
- memory cells are made
- cytotoxic T ells kill stuff
- Mucosal B cells secrete IgM and IgA-> kill pathogen
22
Q
(blank)% of all lymphocytes are in the mucosa. (blank) of IgA are secreted per day
A
50%
3-4 grams
23
Q
What are the organized lymphoid tissues of the gut?
A
Peyers patches (m cells are found here)
24
Q
What are the 4 cell types of the gut epithelium?
A
- entercoytes
- IELS (intra-epithelial lymphocytes)
- neuroendocrine cells
- goblet cells
25
(bank) cells are located above Peyer's patches to transport antigens
M cells
26
Peyers patches are covered by an epithelial layer containing specialized cells called (blank) which have characteristic membrane ruffle.
M cells
27
M cells are highly specialized for antigen transport and are named for their (blank)
microfolds
28
Can M cells take up large antigens?
yes, whole proteins and bacteria
29
M cells provide an inner pocket for the presentation of transported antigens. (blank) cells digest proteins and microbes to present antigens. What regulatory cells respond in mucosal system to DC antigen?
T cells
30
What four cells divide in response to antigens?
TH1, TH2, TH17, T regs
31
DCs determine how (Blank) cells differentiate into subsets.
TH0
32
If THzero cells go to T follicular helpers, you get (blank) from B cells
IgA
33
If TH2 dominant, high IL-4 may generate (blank) from B cells
IgE
34
(blank) normally produced in high numbers, secrete IL-10 and TGF beta to shut down all T and B responses to antigen
T reg
35
(Blank) in the healthy mucosa directs CD4 T cells into induced, antigen specific T regs.
TGF beta
36
The unifected mucosal environment is rich in (blank). What resleased this?
TGF beta
Entercoytes
CD103 Pos DCs
37
T cell specific for self antigen recognized in thymus becomes a (blank) regulatory T cell.
Natural regulatory T cell
38
T cell specific for self or commensal microbiota antigen recognized in presence of TGF-beta becomes a (blank)
induced regulatory T cell (T reg)
39
What molecules are selectively expressed in GI?
Chemokines
addressin
adhesion molecules
40
(blank) is when you have mucosal selective trafficing i.e selective up regulation of certain receptors and integrins.
Lymphocyte homing
41
What are the chemokines and adhesion molecules utilized in lymphocyte homing?
CCL25
MADCAM
E-cadherin
42
Memory (Blank) are CTLs ready to kill and elminate viruses.
CD8 IELs
43
When a virus infects mucosal epithelial cells-> infected cells display viral peptide to (blank) via MHC class (blank). Activated IEL kills infected epithelial cell by (blank) and (blank) pathways
CD8 IEL
perforin/granzyme
Fas-dependent pathways
44
DC-derived cytokines direct (blank) differentiation
CD4 T cell
45
What T cell will be produced if a DC releases TGF-beta?
| What will these cells secrete?
T reg cells
-TGF-beta, IL-10
The immune system suppressors
46
What T cell will be produced if a DC releases IL-6?
| What will these cells secrete?
Tfh cells
| IL-21, ICOS
47
What T cell will be produced if a DC releases TGF-Beta and IL-6
What will these cells secrete?
Th17 cells
IL-6, IL-17
48
What T cell will be produced if a DC releases IL-12 and IFN-gamma?
What will these cells secrete?
TH1 cells
IL-2, IFN-gamma
49
What T cell will be produced if a DC releases IL-4?
| What will these cells secrete?
TH2 cells
| IL-4 and IL-5
50
(blank) is abundant in a healthy mucosa and favors T reg generation. Bacterial and viral products affects DCs to produce different cytokines
TGF beta
51
DC-derived (blank) drives Th1s to favor (blank) proliferation and arming.
IL-12
| CTL
52
"homed" plasma cells secrete (blank and blank) that is transported into GI lumen
IgM and IgA
53
The secreted IgA (from homed plasma cells) will bind to receptors on (blank) face of epithelial cell and will be endocytes --> then you will get (blank) to the apical face of epithelial cell takes place and the (blank) dimer is released into the lumen
basolateral
transcytosis
IgA
54
(blank and blank) are the only antibodies able to get into the lumen (no IgG)
IgA and IgM function by binding antigens in the lumen of the GI and prevent them from reaching to the epithelial cell layer and prevent adhesion.
IgA and IgM
55
IgM also has (blank) chain and is transported. Some IgM and (blank) may go into blood
J
| IgA
56
(blank) cells and (blank) cells are in the epithelium waiting for a viral infection so they can attack
CD8 IEL killers
| IgE loaded mast cells
57
(blank) cells are ready in case of bacterial infection
Memory Th17 (+ fibroblasts and neutrophils)
58
(blank) cells prevent responses to food antigens
memory T regs
59
(blank) cells call in neutrophils
Ag-Activated Th17 cells
60
Fibroblasts secrete what 3 things?
CXCL2 and CXCL8
| Chemokines
61
Certain drugs or monoclonal antibodies will bind IL-17 receptors and inhibit (blank) and thus inhibit (blank)
fibroblast activation
| neutrophil recruitment.
62
What are the effector mechanisms of the mucosal immune system?
- activated/memory T cells predominate even in the absence of infection
- multiple activated "natural" effector/regulatory T cells present
- Secretory IgA antibodies
- Presence of distinctive microbiota
63
What is the immunoregulatory environment of the mucosal immune system?
- active downreg of immune responses (e.g. to food and other innocuous antigens) predominates
- inhibitory macrophages and tolerance-inducing dendritic cells
64
What are the 3 diseases mediated by mucosal immunity?
- celiac disease
- chrons disease
- ulcerative colitis
65
celiac disase affects 1-2% of the population and occurs everywhere. What is the mortality rate? WHat causes this?
10-30%
| immune mediated
66
Who does celiac disease most commonly occur in?
children
| 50% cases are classic and other just have malabsorption and anemia
67
When do you typically diagnose celiac's disease?
4 yrs
68
Is celiac's treatable?
What are the classic symptoms?
What are the nonclassical symptoms?
yes! gluten free diet
- diarrhea
- abdominal pain
- failure to thrive
- damaged villi in small intestine
- delayed puberty, reduced growth
- anemia
- other symptoms
- damaged villi in small intestine
69
```
In celiacs disease, the villi are (blank). You have cryptic (blank).
Greater than (blank) IELs per 100 enterocytes.
```
shortened
hyperplasia
25
(clinical symptoms must occur at time of biopsy for pathology to be detectable)
70
What is the classic pathology of celiac disease?
- chronic diarrhea
- weight loss
- abdominal distention
- malabsorption of nutrient (stunting of children)
- malabsorption of iron
- failure to absorb vit B12 intrinsic factor complexes (megablastic anemia)
71
What is the test for celiac's disease?
When will this test work?
Whats the exception to this test?
-Serum IgA auto-antibodies to tissue transglutaminase 2
(97% specific, 94% sensitive)
- Person must have been recently exposed to gluten (last 2 wks) for positive test
- 3% of patients genetically lack all IgA
72
What are all the ways you can diagnose celiac's?
- Serum IgA tissue transglutaminas 2
- Serum IgA auto-antibodies to EMA (endomysium antigens)
- Serum IgA antibody to de-amidated gliadin (gluten peptide)
- HLA DQ2 or DQ8 allele
- Biopsy positive results essential
73
If you do an endoscopy of a small intestine of a person with celiacs, what will you see?
scalloping and villous atrophy
74
What is the therapy for celiac disease?
-gluten-free diet (no wheat, barley or rye)
75
What is gluten?
alcohol soluble protein of wheat
76
What are 3 essential cell types necessary to generate a CD8 T cell cytotoxic response?
Antigen-> CD4 T helper cell-> B cells-> CTLs
77
Gluten is digested to (blank) and is enzymatically modified by tissue transglutaminase 2 (tTG2) glutamic acid and gets a (blank) charge.
gliadin
| negative
78
The negatively charged Glu fits only into (blank) and (Blank). Now APCs can present antigen
MHC II DQ2 and DQ8
79
90% of patients with (blank) are positive for celiacs
| 5% of patients with (blank) are positive for celiacs
DQ2
| DQ8
80
When gluten is broken down to negatively charged Glu, it gets presented by MHC II on APCs and then activate (blank) and they will proliferate
CD4 T helper cells
81
What is endomesium?
lines outside of individual muscle fibers
82
What is the B cell response in celiacs?
- Abs to gliadin
- Abs to tTG2
- Abs to EMA
83
Pathologists find >(blank) IELs per 100 enterocytes
| in celiac disease
25
84
what is the current celiacs hypothesis?
| Why do the villi shrinK?
over activated IELs produced by activated anti-gliadin CD4 TH1s, IELs become numerous and activated IELs kill enterocytes.
-As enterocytes die, the villi shrink and become dysfunctional
85
In celiac disease, CD8 IELs also have (blank) receptors
NK
86
Ordinary CD8 CTL engages antigen in (blank)
MHC 1
87
CD4 gets hella up regulated due to gliadin antigen-> IEL’s induced to express (blank) receptors -> enterocytes present (blank and blank) stress receptors-> IEL’s (NK cell/ CD8 cells) kill stressed enterocytes
NK
| MIC A and MIC B
88
What are potential therapies for celiac disease?
mAbs to block either of 2 T cell mucosal integrins or a MALT chemokine receptor
89
refractory celiacs disease is thought to maybe be due to (blank0
epitope spreading
90
What part of the bowel is affected by Chrons disease?
| What is it associated with?
ileum and colon
| defects of defensins
91
What part of the bowel is affected by Ulcerative Colitis?
| What is it associated with?
Colon
| defects of mucus
92
Chron's disease may have lower (blank) recruitment than warranted for protection
neutrophil
93
Clinically, (blank) tends to present more frequently with abdominal pain and perianal disease, whereas (blank) is more often characterized by gastrointestinal bleeding.
Crohn's disease
| ulcerative colitis
94
(blank) mucosa and aphthous or linear ulcers characterize the endoscopic appearance of Crohn’s disease. Ulcerative colitis presents with (blank) involvement of the mucosa.
Cobblestoning
| diffuse continuous
95
Radiographic studies of patients with Crohn’s disease characteristically show (blank x 3). In contrast, radiographic studies of patients with ulcerative colitis show continuous disease without fistulizing or ileal disease.
fistulae, asymmetry, and ileal involvement
96
Pathologically, Crohn's disease features mucosal discontinuity, (blank), and (blank), whereas ulcerative colitis does not.
Crypt abscesses and granulomas are present only in (blank)
transmural involvement
granulomas
Crohn's disease
97
Which disease has fat wrapping and thickened walls?
Chrons disease
98
Which disease has ulceration and pseudopolyps, continually?
Ulcerative colitis
99
In chrons you have low (Blank)
| In UC you have low (blank)
defensins
| mucins
100
What is this:
Thickening, obstruction and fissures thorughout GI, small intestine involvement
Are there transmural lesions?
chrons disease
Yes!
101
Is there an association with HLA with Chrons disease?
Is there concordance in monozygotic twins?
Genetic associations?
```
NO
50%
Gene:
-intracellular NOD2 sensors
-Autophagy gene variants
```
102
There is an implication of lack of defensins in Chrons. (blank) in the ileum and (blank) in the colon
alpha-defensins (paneth cells)
| beta-defensins (enterocytes)
103
How do you treat Chron's disease?
Rifaximin
Anti-TNF alpha biologicals
Increase T regs
104
What is the pathogenesis of Chron's disease?
Not enough defensins, so more bacterial antigens-> bigger lymphocyte response -> sad colon
105
Ulcerative colitis is limited to the (Blank) and damage extends only to (Blank) and (blank)
colon
| mucosa and submucosa and no deeper
106
What is the major issue with UC?
```
low mucus
(normal paneth cell defensins)
```
107
What are the future immunotherapies for UC?
IL-13 stimulation to increase mucus secretion
