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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
Q

: 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

A
  • 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
Q

SPECIFIC unresponsiveness to an individuals SELF antigens

A

Immunologic Tolerance =

• Both T cells and B cells can immunologically tolerate antigenic molecules

27
Q

What causes increased immunogenicity to shit

A

large size

intermediate dose

subQ>intraperitoneal>IV

if its bacteria

if has effective MHC interaction

28
Q

the state of local and systemic immune unresponsiveness that is induced by oral administration of innocuous antigen such as food protein

A

Oral tolerance=

29
Q

state of local and systemic unresponsiveness induced by the commensal microbiota

A

Mucosal tolerance:

30
Q

s – Food allergy – Celiac disease – Inflammatory bowel diseases

all examples of

A

mucosally induced tolerance helps prevent intestinal disorders

31
Q

Mucosal Tolerance

• Humoral neutralizing___ is the most prevalent form of adaptive immunity in the gut

A

IgA

32
Q

In mucosal tolerance:______response is the most predominant cell mediated immune response

A

Th17

33
Q

In mucosa, Non-responsiveness to food and microbiota is mediated by

A

regulatory T cells

34
Q

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+)

A

retinoic acid and TGFb

35
Q

• These cells produce retinoic acid and TGFb –> drives differentiation of CD4+ naïve T cells to become

A

regulatory T cells (FoxP3+)

36
Q

Autoimmunity is when what three things overlap

A

Genetic susceptibility + uncontrolled immune response + Envitornomental trigger

37
Q

• 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)

A

HLA genes • Non-HLA genes

38
Q

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

A

SPECIFIC for SELF-ANTIGEN.

39
Q

In autoimmune diseases the antibodies and T cells lose tolerance and during their response to the antigen the immune response damages tissue

A

(hypersensitivity)

40
Q

excessive or aberrant immune responses following challenge with antigen.

A

Hypersensitivity:

41
Q

•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)

A

foreign antigens

“self” antigens

42
Q

Mech of Immediate Hypersensitivity: type I

A

IgE

Mast cells and eosinophils vasoactive amines, cytokines

43
Q

Cell mediated type IV hypersenstivity mechanism

A

T cells

CD4: macrophage activation, inflammation

44
Q

HLA genes: many autoimmune diseases have been linked to mutations in the genes encoding the MHC. – Mutations in HLA genes are

A

NOT causal

45
Q

Two key non HLA genes causing autoimmunity

A

• Non-HLA genes: – Nod2 – ATG16

46
Q

Mutations in MHC may contribute to autoimmune disease through:

A

– Inefficient in displaying self-antigens

– Poorly stimulate regulatory T cells

47
Q

How to treate autoimmune diseases

A

• 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
Q

• Loss of oral tolerance to wheat (gluten) – Increased levels of de-amidated gliadin peptide

A

Celiacs

49
Q

Celiacs:

• Autoimmune disorder: – Associated with _____ and _____

– Presence of antibodies to tissue transglutaminase (diagnostic), endomysium, gliadin peptide

A

HLA-DQ2 & HLA-DQ8

50
Q

Celiacs is what type of hypersensitivity

A

Type IV hypersensitivity – Th1 T cells and inflammatory response damage tissues

51
Q

How does Celiacs occur?

A

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
Q

Celiacs is hypersensitivy with what three antibodies made

A

anti-gliadin

anti-tTG

anti-ednomysoium

53
Q

Pathogenesis of IBD

mutation is what two genes?

A

• Loss of tolerance to microbiota

– Mutations in Nod pattern recognition receptor gene

– Mutations in autophagy (cellular homeostasis) genes

54
Q

IBD are autoimmune disorders associated with what two HLAs?

A

• Autoimmune disorder(s) – Associated with HLA-DR and HLA-B27

55
Q

UC anc crohs are what type of hypersenstivty

A

Cell mediate Type IV

56
Q

Th1 is ___ disease

Th2 is _____diseaes

both lead to imflammatory damage

A

Th1= crohns

Th2= UC

57
Q

Crohns

T cell release IL-12 to induce:

A

Th1 to make IL6 and TNF

58
Q

In UC, Th2 cells are indcued by_____

A

IL-5 and IL-13–> Th2

Th2 releases Il-6 and TFN

59
Q
  • NO loss of tolerance, NOT autoimmunity
  • Type I hypersensitivity – Sensitized to food antigen – Immediate response
A

Food allergy

60
Q

• Eosinophilic esophagitis • Food Protein Induced Enterocolitis Syndrome – More rare – Cell-mediated immunity

A

examples of food allergy

61
Q

Pathogenesis of food allergy

A

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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