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HDM Final > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

1
Q

What is the primary function of mucosal immunity?

A

Provide defense at ALL mucosal surfaces: GI, respiratory, and urogenital

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2
Q

What are the 2 secondary functions of mucosal immunity?

A

Prevent Ags from entering into circulation

Prevent a systemic immune response to an inappropriate Ag exposure

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3
Q

What is the major difference between mucosal immunity and systemic immunity?

A

Mucosal immunity = tolerant

Systemic immunity = active

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4
Q

What effect does low dose oral administration of Ag have on GALT?

A

Induction of Th2 and TGF-beta secreting regulatory cells

Active suppression and immunologic hyporesponsiveness

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5
Q

What effect does high dose oral administration of Ag have on GALT?

A

Deletion or anergy of Th1 and Th2 cells

Clonal anergy and clonal depletion leading to immunologic hyporesponsiveness

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6
Q

___________ is a mechanism of mucosal immune regulation that minimizes direct contact between bacteria and epithelial surface

A

Stratification

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7
Q

What components of mucosal immunity participate in stratification, that is minimization of direct contact between bacteria and epithelial surfaces?

A

Mucins

Anti-bacterial proteins

IgA

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8
Q

______ is a mechanism of mucosal immune regulation that confines bacteria to intestinal sites and limiting systemic exposure

A

Compartmentalization

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9
Q

What components of mucosal immunity participate in compartmentalization, which confines bacteria to intestinal sites and limits systemic exposure?

A

Action of phagocytes in lamina propria

Homing of activated lymphocytes to mucosal surfaces

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10
Q

Immunity in mucosal tissues:

Cell types undergo _______ development

Cells respond differently to Ag in that B cells are skewed toward _____ production

Mucosa encounters very different antigens and uses different ______ signals

A

Alternative

IgA

Homing

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11
Q

T/F: there is regional preference in mucosal immunity (intestine to intestine, lung to lung, etc.)

A

True

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12
Q

_________ ________ is the process by which s-IgA/mucin provides a barrier to macromolecular absorption

A

Immune exclusion

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13
Q

During immune exclusion, which is the process by which sIgA/mucin provides a barrier to macromolecular absorption, binding of antigen at the mucosal surface by s-IgA leads to ________ of the Ag in the mucous layer, subjecting it to __________

A

Entrapment; degradation

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14
Q

IgA is _________ and __________, which is what allows it to trap Ag effectively in mucous layers

A

Hydrophilic; mucophilic

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15
Q

What aspect of innate mucosal immunity has mucus secreting barrier function and antibacterial?

A

Goblet cells

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16
Q

What aspect of innate mucosal immunity has barrier and antibacterial functions?

A

Epithelial cells

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17
Q

What aspect of innate mucosal immunity are the antibacterial secreting cells?

A

Paneth cells

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18
Q

What aspect of innate mucosal immunity participate in antigen sampling?

A

M cells

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19
Q

What 2 cell types participate in barrier function in mucosal immunity?

A

Enterocytes

Normal flora

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20
Q

What non-cellular aspects of mucosal immunity have barrier function?

A

Digestive activity - pepsin, papain, trypsin, chymotrypsin, pancreatic proteases, lactoferrin, lactoperoxidase, lysozyme

Mucin - protective barrier between a pathogen and the mucosal epithelium, reservoir for sIgA

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21
Q

Intestinal epithelial cells, or enterocytes, participate in absorption of nutrients via the _____ border.

They are joined by _______ ________ apically and basally which prevents the passage of macromolecules

A

Brush

Tight junctions

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22
Q

What type of antigen presentation is performed at intestinal epithelial cells?

A

Nonprofessional

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23
Q

Nonprofessional antigen presentation and inducible cell surface molecules result in selective activaiton of _____ and ______ T cells at intestinal epithelial cells

A

CD8; regulatory

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24
Q

There is constant translocation of ____ at intestinal epithelial cells, as well as inducible ______, which may result in cross-linking –> fluid and electrolyte secretion

A

sIgA

FceR

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25
Q

Where are the innate receptors for bacterial PAMPs expressed in mucosal immunity?

A

In the cytoplasm and basolateral membrane, NOT on luminal surfaces

DCs in lamina propria also express low levels of TLRs

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26
Q

The functional response in mucosal immunity is biased towards an ________________ response

A

Anti-inflammatory

[this limits inflammation in GI tract]

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27
Q

The first susceptibility gene identified for Crohn’s disease was a _______ family member, a receptor for the muramyl dipeptide structural unit of bacterial peptidoglycan

A

NOD (NOD2)

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28
Q

IgA transport requires ________ ________, which cycles from basal to apical membrane regardless of whether IgA is present or not

A

Secretory component

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29
Q

What ensures that SC is not a limiting factor during an immune response?

A

It is constitutively made by epithelial cells and cycles regardless of whether IgA is present or not

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30
Q

What binds to IgA heavy chains and facilitates its transport?

A

J-chain

31
Q

What happens to SC when s-IgA is released from its vesicle into the lumen?

A

SC is cleaved and is degraded (it is not recycled, only used once)

32
Q

________ cells are Peyer’s patch dome cells that are modified at both apical and basolateral surfaces

A

Microfold (M) cells

33
Q

What is the purpose of Microfold (M) cells?

A

Found at dome of peyer’s patch; promote uptake and transport of luminal contents - “sampling” mechanism

34
Q

T/F: Microfold (M) cells transfer processed Ags only, because they must fit through the cell itself

A

False! Microfold cells transfer whole Ags only, NO processing takes place

35
Q

What CD marker is found on the specialized intestinal DCs in the GALT?

A

CD103+

[these are regulatory DCs]

36
Q

Where are CD103 DCs found?

A

In GALT: under basolateral membrane of IECs and M cells so that they can extend dendrites directly to sample

37
Q

What do CD103+ intestinal DCs produce in terms of mediators and cytokines?

Where do they travel to present to T cells?

A

Produce retinoic acid (RA) and produce primarily anti-inflammatory cytokines: TGF-beta, IL-10, and IL-2

Travel to mesenteric LNs to present to T cells

38
Q

What are the two primary functions of mucosal humoral immunity and IgA?

A

Neutralization

Enhancement of innate immune factors

39
Q

What is the primary function of mucosal cell-mediated immunity?

A

Suppression!

There is a high percentage of Treg cells, regulatory CD103+ DCs, and TGF-beta, IL-10, and IL-2

40
Q

What type of B cell is abundant in GALT?

A

B-1 cells

Mostly IgA expressing plasma cells or IgA surface expressing cells

[IgG and IgM plasma cells are found infrequently]

41
Q

GALT is considered a reservoir for __________ antibodies

A

Natural

[during times of inflammation, these cells can increase IgG and IgM expressing cell populations, which are not usually as common]

42
Q

What is the physiologic role of serum IgA?

A

Unknown/unclear

43
Q

Serum IgA in humans is mostly __________

In terms of its physiological role (which is unclear), mucosal Ag that gets into circulation will not induce a systemic _________ response

A

Monomeric

Inflammatory

44
Q

What form of IgA functions as a neutralizing Ab, serum or secretory?

A

Secretory

45
Q

Does secretory IgA fix complement?

A

NO

Thus it will not induce an inflammatory response. It prevents colonization without inflammation

46
Q

What GI movement allows for clearance of IgA-Ag immune complexes without inducing inflammation?

A

Peristalsis

47
Q

Most intraepithelial lymphocytes are ______ cells

A

CD8+ T cells

48
Q

The majority of intraepithelial lymphocytes (IELs) are CD8+ T cells. What other cells are present?

A

CD4+ gamma/delta T cells

Large population of Tregs (produce large amounts of anti-inflammatory cytokines)

49
Q

Where do gamma/delta T cells typically “live”

A

In epithelial/mucosal compartments (make up 10-40% of the T cell pop)

50
Q

Gamma/delta T cells can be differentiated from alpha/beta T cells in that:

They recognize _____ Ags

They can be directly activated by ______ and ________

They do not seem to be ______-restricted

A

Lipid

PAMPs; DAMPs

HLA

51
Q

Th17 cells in the gut are protective against _________ and __________

They are influenced by ______ cells

A

Extracellular bacteria; fungi

Dendritic

52
Q

________ cells’ inflammatory activity in the gut is balanced by Tregs and anti-inflammatory cytokines

A

Th17

53
Q

What cytokine is needed for induction of tolerance in the mucosa?

A

TGF-beta

Retinoic acid produced by DCs in the gut

54
Q

What are some host factors associated with oral tolerance?

A

Digestion, physical barriers, GALT, immune cells, immune regulation

55
Q

What are some environmental factors associated with oral tolerance?

A

Breastfeeding
Time of introduction of solid food
Intestinal flora

56
Q

What are some management factors associated with oral tolerance?

A

AIT

Probiotics

57
Q

What are some immune regulation mechanisms associated with oral tolerance?

A 
Tregs
Effector T's
DCs
TLRs
IL-10
TGF-beta
IgA
IgG4
58
Q

What is the most common primary antibody deficiency?

A

Selective Ig-A deficiency

[genetic, most are never diagnosed, usually found incidentally or by recurrent sinus infections]

59
Q

Why are most selective Ig-A deficiencies never diagnosed?

A

IgM also has a J chain and is able to cross the mucosa

60
Q

What are the 3 categories of diseases related to inappropriate mucosal immune responses?

A
  1. Inflammatory bowel disease (crohns and UC)
  2. Food allergies
  3. Celiac disease
61
Q

How would you differentiate between the two types of inflammatory bowel diseases: Crohn’s disease and Ulcerative Colitis

A

Crohn’s: affects entire thickness of bowel wall

Ulcerative colitis: restricted to colonic mucosa

62
Q

In what part of the intestine does Crohn’s disease most frequently affect?

A

Terminal ileum

63
Q

What are the 2 dysregulated aspects of the innate immune system in IBD?

A

Defective defensin expression

Inadequate negative immune regulation to commensal organisms

64
Q

What are the 2 abnormal aspects of cell-mediated immunity in IBD?

A

Overactive Th17 response

Granulomatous inflammation by IFN-y producing Th1 cells

65
Q

IBD may result from defective _________ T cell function, due to FOXP3 and IL-2 or IL-2R deficiencies

A

Regulatory

66
Q

Aside from dysregulated innate immune responses, abnormal cell-mediated immunity, and defective regulatory T cell function, another immunologic abnormality in IBD may be defective __________, which is an intracellular degradation system that usually delivers cytoplasmic constituents to the lysosome

A

Autophagy

67
Q

Conditions of malnutrition and starvation result in:

Mucosal ________

Increase in intestinal __________

Decrease in cytokines ____ and _____

Change in the ___:____ ratio (1:1)

Decrease in antibody ______

A

Atrophy

Permeability

IL-4; IL-10

CD4+:CD8+

sIgA

68
Q

In conditions of malnutrition and starvation, what are the two methods of restoring nutrition?

A

TPN: Total parenteral nutrition

EN: enteral nutrition

69
Q

TPN vs. EN has trauma and surgical implications due to shock cytokines TNF, IL-1, and IL-6, as well as ACTH and cortisol risks.

What are the potential biological complications?

A

Sepsis, multi-organ failure, hypermetabolism

70
Q

TPN vs. EN has trauma and surgical implications due to shock cytokines TNF, IL-1, and IL-6, as well as ACTH and cortisol risks.

Which nutrition restoration method causes significant changes in the lymphocyte population and carries a high rate of sepsis?

A

TPN

71
Q

What are the three general types of food allergies in terms of immunological classification?

A

IgE mediated

Non-IgE mediated (Th2 mediated)

Mixed (both IgE and Th2)

72
Q

Which type of food allergy is most common in young children and results in acute or chronic cutaneous symptoms or anaphylaxis?

A

IgE mediated (food-specific IgE is made)

73
Q

What type of food allergy results in chronic skin and/or GI symptoms as well as eosinophilic disorders?

A

Non-IgE mediated (Th2 mediated)

HDM Final (12 decks)

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