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GI 3 > Mucosal immunity > Flashcards

Mucosal immunity Flashcards

1
Q

Challenges to GI tract

A

• Tolerance to food antigens • Tolerance to microbiota BUT responsive to pathogens • Enormous surface area

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2
Q

Anatomical immune features in GI

A

• Tonsils • Peyer’s patches • Lamina Propria Follicles

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3
Q

special GI immune fuctions

A
  • Epithelial cells: mucus secretion
  • M cells: luminal sampling
  • Paneth cells: defensins
  • Secretory IgA, IgM: neutralization
  • DC subsets: luminal
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4
Q

Describe a Peyers Patch

A

B and T cells located close to surface and connected to Mesenteric lymph node

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5
Q

Describe M cell function

A

located btw epi cells in GI, surrounded by bacteria, uptake bacteria and gives to DC cell to present

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6
Q

DC are key for devo TOLERANCE:

what vitamin is a Key player? How

A

Vit A:

vitA–> hyrolyzed to reitnoic acid

retinoic acid + TGF-b adn TSLP create tolerogenic DC cell to make tolerogenic T cells

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7
Q

what markers are important on T cell to be tolerogenic

A

MadCAM and CCL25 and CCR9

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8
Q

“gut-homing” traffic signals

– Immune Cells:

A

alpha4beta 7 integrin and CCR9

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9
Q

gut homing traffic signasl

– Endothelium:

A

mucosal addressin MadCAM

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10
Q

gut homing signal

Epithelium: mucosal trafficking signal

A

CCL25

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11
Q

Mucosal Dendritic Cells produce retinoic acid (RA) from dietary Vitamin A through expression of _____

• Intestinal epithelial cells also express ______ –> elevated retinoic acid in gut tissues

A

retinal dehydrogenases.

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12
Q

• T-dependent Class switch

– DCs in Peyer’s patch present Ag and activate naïve T cells to Th1 cells

–_____ on Th1 cells and ____ from DCs activates naive B cells

A

CD40L (onTh1)

TGF-b (from CD)

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13
Q
A
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14
Q

• T-independent class swtiching in gut

: – TLRs on DC stimulate release of

A

TGFb ,and Retinoic Acid

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15
Q

RECOGNITION by T Cells (MHC II)

• T cell Receptor =

A

– 1 st signal recognize peptide antigen

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16
Q

• Co-stimulatory Molecule for T cells

– 2 nd signal recognize costimulatory receptor (CD28) expressed on

A

APC

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17
Q

• B cell Receptor

– 1 st signal is by

A

membrane bound IgM

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18
Q

• Costimulation of B cells

– 2 nd signal

A

• A) complement receptor • B) Toll-like receptor

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19
Q

IgA secreting plasma cells in

A

lamina propria

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20
Q

Process of IgA secreation to lumen

A

IgA plasma cell with J chain in the Lamina propria–> makes dimeric IgA–>

binds to receptor and enters mucosal epi cell–> cleaved once reaches lumen to:

Secreated IgA

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21
Q

specialized to deliver gut antigens / bacteria directly to immune cells in Peyer’s patch

A

M cells

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22
Q

B cells skewed to produce

A

secretory IgA

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23
Q

• T cells skewed to

A

Th17 and regulatory T cells

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24
Q

Elevated levels of ____in mucosa Cumulatively help develop tolerogenic immune responses

A

Retinoic Acid

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25
: a molecule that induces an immune response : a molecule that binds to (is recognized) by antibody (B cells) or T cells ' : a molecule that induces immune unresponsiveness to subsequent doses of the molecule
* Immunogen: a molecule that induces an immune response * Antigen: a molecule that binds to (is recognized) by antibody (B cells) or T cells ' * Tolerogen: a molecule that induces immune unresponsiveness to subsequent doses of the molecule
26
SPECIFIC unresponsiveness to an individuals SELF antigens
Immunologic Tolerance = • Both T cells and B cells can immunologically tolerate antigenic molecules
27
What causes increased immunogenicity to shit
large size intermediate dose subQ\>intraperitoneal\>IV if its bacteria if has effective MHC interaction
28
the state of local and systemic immune unresponsiveness that is induced by oral administration of innocuous antigen such as food protein
Oral tolerance=
29
state of local and systemic unresponsiveness induced by the commensal microbiota
Mucosal tolerance:
30
s – Food allergy – Celiac disease – Inflammatory bowel diseases all examples of
mucosally induced tolerance helps prevent intestinal disorders
31
Mucosal Tolerance • Humoral neutralizing\_\_\_ is the most prevalent form of **adaptive immunity** in the gut
IgA
32
In mucosal tolerance:\_\_\_\_\_\_response is the most predominant **cell mediated immune** response
Th17
33
In mucosa, Non-responsiveness to food and microbiota is mediated by
regulatory T cells
34
Mucosla gut tolerance • Gut dendritic cells take up antigens from the gut (food or microbiota) travel to MLN and present Ag to naïve T cells.: These cells produce \_\_\_\_and \_\_\_\_\_--\> drives differentiation of CD4+ naïve T cells to become regulatory T cells (FoxP3+)
retinoic acid and TGFb
35
• These cells produce retinoic acid and TGFb --\> drives differentiation of CD4+ naïve T cells to become
regulatory T cells (FoxP3+)
36
Autoimmunity is when what three things overlap
Genetic susceptibility + uncontrolled immune response + Envitornomental trigger
37
• The principle factors in the development of autoimmune disease are: – Inheritance of susceptibility genes which may contribute to failure of self-tolerance. which are: – Environmental triggers which may activate self-reactive or tolerized (suppressed) lymphocytes – Over-activation of immune system to typically innocuous antigens (hyper-sensitivity)
HLA genes • Non-HLA genes
38
Autoimmunity: • Currently estimated that 1-2% of individuals suffer from autoimmune disease. – However, many diseases with uncontrolled immune response may be classified as “autoimmune” disorders without formal evidence that the response is
SPECIFIC for SELF-ANTIGEN.
39
In autoimmune diseases the antibodies and T cells lose tolerance and during their response to the antigen the immune response damages tissue
(hypersensitivity)
40
excessive or aberrant immune responses following challenge with antigen.
Hypersensitivity:
41
•Hypersenstivity Caused by: – 1. dysregulated or uncontrolled response to ______ resulting in tissue damage and injury. – 2. failure of self-tolerance followed by immune responses directed against\_\_\_\_\_\_ (Autoimmunity)
foreign antigens “self” antigens
42
Mech of Immediate Hypersensitivity: type I
IgE Mast cells and eosinophils vasoactive amines, cytokines
43
Cell mediated type IV hypersenstivity mechanism
T cells CD4: macrophage activation, inflammation
44
HLA genes: many autoimmune diseases have been linked to mutations in the genes encoding the MHC. – Mutations in HLA genes are
NOT causal
45
Two key non HLA genes causing autoimmunity
• Non-HLA genes: – Nod2 – ATG16
46
Mutations in MHC may contribute to autoimmune disease through:
– Inefficient in displaying self-antigens – Poorly stimulate regulatory T cells
47
How to treate autoimmune diseases
• Systemic immune suppression: – Danger: opportunistic infections * Non-systemic immune suppression therapies: – Antibodies to TNF (Infliximab) and Soluble TNFR (Etanrecept) have been shown to be effective in reducing inflammation in IBD. * Plasmapheresis or competitive FcR inhibition
48
• Loss of oral tolerance to wheat (gluten) – Increased levels of de-amidated gliadin peptide
Celiacs
49
Celiacs: • Autoimmune disorder: – Associated with _____ and \_\_\_\_\_ – Presence of antibodies to tissue transglutaminase (diagnostic), endomysium, gliadin peptide
HLA-DQ2 & HLA-DQ8
50
Celiacs is what type of hypersensitivity
Type IV hypersensitivity – Th1 T cells and inflammatory response damage tissues
51
How does Celiacs occur?
ingest gluten--\> to deanimated gliaden VIA tTG Class II DQ2 or DQ8 picks up deanimated gliadin presents to CD4 cells--\> Th1 Th1 releases--\> INF-g causes activation of plasma cells make IgG and IgA
52
Celiacs is hypersensitivy with what three antibodies made
anti-gliadin anti-tTG anti-ednomysoium
53
Pathogenesis of IBD mutation is what two genes?
• Loss of tolerance to microbiota – Mutations in Nod pattern recognition receptor gene – Mutations in autophagy (cellular homeostasis) genes
54
IBD are autoimmune disorders associated with what two HLAs?
• Autoimmune disorder(s) – Associated with HLA-DR and HLA-B27
55
UC anc crohs are what type of hypersenstivty
Cell mediate Type IV
56
Th1 is ___ disease Th2 is \_\_\_\_\_diseaes both lead to imflammatory damage
Th1= crohns Th2= UC
57
Crohns T cell release IL-12 to induce:
Th1 to make IL6 and TNF
58
In UC, Th2 cells are indcued by\_\_\_\_\_
IL-5 and IL-13--\> Th2 Th2 releases Il-6 and TFN
59
* NO loss of tolerance, NOT autoimmunity * Type I hypersensitivity – Sensitized to food antigen – Immediate response
Food allergy
60
• Eosinophilic esophagitis • Food Protein Induced Enterocolitis Syndrome – More rare – Cell-mediated immunity
examples of food allergy
61
Pathogenesis of food allergy
food seen by DC presents to CD4 in Peyers--\> Th2 (this is helped out by mast cell) releasing Il-4 Th2 will release IL-4 to cause naive B cell devo B cell releases IgE IgE releaese serotoine and protesases = diarrhea

GI 3 (15 decks)

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