Lec 19 Mucosal Immunity Flashcards

1
Q

____ tissue is contiguous with epithelium of skin

A

mucosal

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2
Q

Mucosal sites

A
  • respiratory tract
  • gastrointestinal tract
  • urogenital tract
  • mammary gland
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3
Q

Mucosal sites are special in function because they must allow for ______ of material

A

exchange/absorption

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4
Q

What are anatomical features of mucosal immune system?

A
  • interactions between mucosal epithelia and lymphoid tissue
  • discrete compartments/organized structure of diffuse lymphoid tissue (Peyer’s patch/tonsils)
  • specialized antigen uptake mechanisms (M cells)
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5
Q

What are the effector mechanisms of mucosal immunity?

A
  • activated/memory T cells even in absence of infection
  • activated natural effector/regulatory T cells
  • Secretory IgA
  • distinctive microbiota
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6
Q

Describe the immunoregulatory environment of the mucosal immune system

A

active downregulation of immune responses (food and other nondangerous foreign antigens)
inhibitory macrophages and tolerance inducing DCs

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7
Q

adenoids, palatine tonsils, and lingual tonsils make up _________, the entry to the GI tract

A

Waldeyer’s ring

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8
Q

________ increase surface area and the interactions between lymphoid tissue and the lumen at mucosal immune sites

A

invaginations

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9
Q

GALT are comprised of _____ and ______

A

scattered lymphoid cells and organized lymphoid tissues

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10
Q

_______ is an example of an organized lymphoid tissue

A

Peyer’s patch

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11
Q

Peyer’s Patch has lymphatics draining to _____ lymph node

A

mesenteric

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12
Q

organized tissue sites are ______ sites, where _____ occurs

A

inductive;
antigen presentation to B and T cells

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13
Q

scattered lymphoid cells are nonorganized and are ____ sites

A

effector

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14
Q

scattered lymphoid cells can be _______ or ______

A

intraepithelial
lamina propria

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15
Q

lamina propria

A

subepithelial tissue in gut

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16
Q

scattered lymphoid cells are ____ cells from Peyer’s patch

A

effector (activated)

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17
Q

Peyer’s patch has _____ made up of M cells, two _____ areas, and B cell areas: a _____ and a ______

A

a dome;
T cell;
follicle;
germinal center

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18
Q

M cells

A

multifenestrated or microfold cells
- do not secrete mucus
- no glycocalyx
- interact directly with particple in gut lumen

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19
Q

M cells take up antigen by _____ and _____

A

endocytosis and phagocytosis

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20
Q

antigen is transported _____ M cells in _____ and released at the basal surface (transcytosis)

A

across;
vesicles

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21
Q

at basal surface of M cells, antigen is bound by ______

A

DC

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22
Q

In peyer’s patch, DC antigen presentation to T cells occurs _____, unlike in non-mucosal areas

A

locally

23
Q

Naive T cells with _____ and _____ enter Peyer’s patch through ______where they encounter antigen being presented by DC to become active

A

CCR7 and L-selectin;
high endothlial venules

24
Q

Activated T cells in Peyer’s Patch gain expression of _____ and _____ instead of CCR7 and L-selectin, homing to ________ after being drained to mesenteric lymph node, to thoracic duct, to blood

A

CCR9 and alpha4:beta 7 integrin;
lamina propria and small intestinal epithelium

25
Q

Activated gut epithelium expresses _______, binding alpha4:beta7 integrin and L-selectin on effector T cell

A

MAdCAM-1

26
Q

CCR9 interaction with ____ brings cells into lamina propria

A

CCL25

27
Q

Some lymphocytes will move into ____. They stop expressing alpha4beta7 and gain expression of _____, which binds with E-cadherin

A

IEL (epithelium);
alphaEbeta7

28
Q

Mechanisms of antigen capture in the lumen

A
  • nonspecific transport across lumen
  • FcRN dependent transport
  • apoptosis dependent transfer
  • Antigen capture by macrophages
  • Uptake via goblet cells
  • capture by intraepithelial DC
29
Q

IgA is produced by plasma cells at ____

A

base of crypt in small intestine

30
Q

FcR of IgA binds to ____ on basolateral face of _______ cells

A

pIgR;
epithelial

31
Q

bound complex of IgA (____) and secretory component is taken up by _____ and transcytosed to the _____ face of epithelial cells

A

(dimer);
endocytosis;
apical

32
Q

IgA dimer and secretory component is released into the _____

A

lumen

33
Q

IgA can neutralize pathogens and toxins in the ______ and in ______

A

lumen;
endosomes

34
Q

IgA can transport toxins/pathogens from the ____ into the _____

A

lamina propria into the lumen

35
Q

Antigen bound to secretory IgA can bind via carbohydrate residues on Fc portion of IgA to _______ on M cells in _____ and be transported to DC. Complex can bind to ______ on DC to induce IL-10 production

A

Dectin-1;
Peyer’s Patch
DC-SIGN+

36
Q

IgA is involved in pathogen/toxin ______, ______, and ______

A

neutralization, export to lumen, and capture by DC

37
Q

_______ are ____ lymphocytes that lie within the epithelial lining of the gut

A

Intraepithelial lymphocytes (IELs);
CD8+

38
Q

IELs have two major types:

A

type a (alpha:beta TCR, CD8 alpha:beta heterodimer)
type b (CD8 alpha:alpha homodimer

39
Q

IELs kill infected epithelial cells by release of _______/________ and ______ dependent pathways

A

perfornin/granzyme;
Fas

40
Q

Epithelial cells express ____ and _____ after infection due to stress

A

MIC-A and MIC-B

41
Q

MIC molecules on _______ release ____, which activate type b IELs which engage MIC via _____

A

stressed epithelial cells;
IL-15;
NKG2D

42
Q

type b IELs kill stressed cells via _____/____ pathway through ________ recognition of MIC A/B

A

perfornin/granzyme;
NKG2D

43
Q

Salmonellae can penetrate gut epithelium in 3 ways:
1. enter and kill _____, and go onto infect macrophages and epithelial cells
2. invading _______ surface of epithelial cells
3. entering ________ cells that are sampling gut luminal contents

A

M cells;
luminal;
phagocytic

44
Q

Salmonella enterica target ____ on epithelial cells (______) and activate them via NFkappaB pathway. This causes inflammatory signals to initiate

A

TLR 5 (flagellin)

45
Q

What is immune response to S. enterica?

A

chemokines and cytokines (IL-18, CXCL8, IL-1beta) produced by macrophages recruit neutrophils from blood vessels and activate them. DCs get antigen from macrophages and present in mesenteric lymph node to lymohcytes

46
Q

If immune defenses fail for S. enterica, what can occur?

A

salmonellae can enter bloodstream and cause systemic infection

47
Q

Shigellae penetrate gut epithelium through _____ and then invade _____ surface of epithelial cells and spread to other cells

A

M cells;
basal

48
Q

Shigella cell wall peptides bind and oligomerize ____ which activates _____ pathway in epithelial cells

A

NOD1;
NFkappaB

49
Q

Epithelial cells activated by NFkappaB secretes _____ which recruits neutrophils

A

CXCL8

50
Q

Shigella causes inflammation which can result in _____

A

dysentery (bloody diarrhea)

51
Q

Describe concept of oral tolerance

A

mice fed ovalbumin are tolerant to later being injected with it plus adjuvant due to anergy in T cells. The normal response in the gut without inflammation is tolerance. T cells presented with peptide in absence of costimulation are rendered nonresponsive to subsequent stimulation

52
Q

Antigens for ________ are taken up in Peyer’s Patch and lymphoid follicles by resting DC and stimulate T cells to be ______

A

commensal organisms;
toleragenic (not cytotoxic)

53
Q

DC drive generation of _______ plasma cells to block ______ in lumen to stabilize mucosal/epithelial barrier

A

IgA switched;
commensals

54
Q

How does HIV exploit immune responses in the gut to drive infection?

A

HIV uses CD4+ and CCR5+ receptors to infect cells, so T cells in the gut (Peyer’s patch, resting lymph nodes) need to be activated and homed to effector sites (intestinal lamina propria and activated lymph nodes). Effector sites of GI tract show largest depletion of T cells during acute HIV infection -> they kill memory and effector T cells so you die from co-infection