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HDM Final > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

(73 cards)

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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
Where are the innate receptors for bacterial PAMPs expressed in mucosal immunity?
In the cytoplasm and basolateral membrane, NOT on luminal surfaces DCs in lamina propria also express low levels of TLRs
26
The functional response in mucosal immunity is biased towards an ________________ response
Anti-inflammatory [this limits inflammation in GI tract]
27
The first susceptibility gene identified for Crohn's disease was a _______ family member, a receptor for the muramyl dipeptide structural unit of bacterial peptidoglycan
NOD (NOD2)
28
IgA transport requires ________ ________, which cycles from basal to apical membrane regardless of whether IgA is present or not
Secretory component
29
What ensures that SC is not a limiting factor during an immune response?
It is constitutively made by epithelial cells and cycles regardless of whether IgA is present or not
30
What binds to IgA heavy chains and facilitates its transport?
J-chain
31
What happens to SC when s-IgA is released from its vesicle into the lumen?
SC is cleaved and is degraded (it is not recycled, only used once)
32
________ cells are Peyer's patch dome cells that are modified at both apical and basolateral surfaces
Microfold (M) cells
33
What is the purpose of Microfold (M) cells?
Found at dome of peyer's patch; promote uptake and transport of luminal contents - "sampling" mechanism
34
T/F: Microfold (M) cells transfer processed Ags only, because they must fit through the cell itself
False! Microfold cells transfer whole Ags only, NO processing takes place
35
What CD marker is found on the specialized intestinal DCs in the GALT?
CD103+ [these are regulatory DCs]
36
Where are CD103 DCs found?
In GALT: under basolateral membrane of IECs and M cells so that they can extend dendrites directly to sample
37
What do CD103+ intestinal DCs produce in terms of mediators and cytokines? Where do they travel to present to T cells?
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
What are the two primary functions of mucosal humoral immunity and IgA?
Neutralization Enhancement of innate immune factors
39
What is the primary function of mucosal cell-mediated immunity?
Suppression! There is a high percentage of Treg cells, regulatory CD103+ DCs, and TGF-beta, IL-10, and IL-2
40
What type of B cell is abundant in GALT?
B-1 cells Mostly IgA expressing plasma cells or IgA surface expressing cells [IgG and IgM plasma cells are found infrequently]
41
GALT is considered a reservoir for __________ antibodies
Natural [during times of inflammation, these cells can increase IgG and IgM expressing cell populations, which are not usually as common]
42
What is the physiologic role of serum IgA?
Unknown/unclear
43
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
Monomeric Inflammatory
44
What form of IgA functions as a neutralizing Ab, serum or secretory?
Secretory
45
Does secretory IgA fix complement?
NO Thus it will not induce an inflammatory response. It prevents colonization without inflammation
46
What GI movement allows for clearance of IgA-Ag immune complexes without inducing inflammation?
Peristalsis
47
Most intraepithelial lymphocytes are ______ cells
CD8+ T cells
48
The majority of intraepithelial lymphocytes (IELs) are CD8+ T cells. What other cells are present?
CD4+ gamma/delta T cells Large population of Tregs (produce large amounts of anti-inflammatory cytokines)
49
Where do gamma/delta T cells typically "live"
In epithelial/mucosal compartments (make up 10-40% of the T cell pop)
50
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
Lipid PAMPs; DAMPs HLA
51
Th17 cells in the gut are protective against _________ and __________ They are influenced by ______ cells
Extracellular bacteria; fungi Dendritic
52
________ cells' inflammatory activity in the gut is balanced by Tregs and anti-inflammatory cytokines
Th17
53
What cytokine is needed for induction of tolerance in the mucosa?
TGF-beta Retinoic acid produced by DCs in the gut
54
What are some host factors associated with oral tolerance?
Digestion, physical barriers, GALT, immune cells, immune regulation
55
What are some environmental factors associated with oral tolerance?
Breastfeeding Time of introduction of solid food Intestinal flora
56
What are some management factors associated with oral tolerance?
AIT | Probiotics
57
What are some immune regulation mechanisms associated with oral tolerance?
``` Tregs Effector T's DCs TLRs IL-10 TGF-beta IgA IgG4 ```
58
What is the most common primary antibody deficiency?
Selective Ig-A deficiency [genetic, most are never diagnosed, usually found incidentally or by recurrent sinus infections]
59
Why are most selective Ig-A deficiencies never diagnosed?
IgM also has a J chain and is able to cross the mucosa
60
What are the 3 categories of diseases related to inappropriate mucosal immune responses?
1. Inflammatory bowel disease (crohns and UC) 2. Food allergies 3. Celiac disease
61
How would you differentiate between the two types of inflammatory bowel diseases: Crohn's disease and Ulcerative Colitis
Crohn's: affects entire thickness of bowel wall Ulcerative colitis: restricted to colonic mucosa
62
In what part of the intestine does Crohn's disease most frequently affect?
Terminal ileum
63
What are the 2 dysregulated aspects of the innate immune system in IBD?
Defective defensin expression Inadequate negative immune regulation to commensal organisms
64
What are the 2 abnormal aspects of cell-mediated immunity in IBD?
Overactive Th17 response Granulomatous inflammation by IFN-y producing Th1 cells
65
IBD may result from defective _________ T cell function, due to FOXP3 and IL-2 or IL-2R deficiencies
Regulatory
66
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
Autophagy
67
Conditions of malnutrition and starvation result in: Mucosal ________ Increase in intestinal __________ Decrease in cytokines ____ and _____ Change in the ___:____ ratio (1:1) Decrease in antibody ______
Atrophy Permeability IL-4; IL-10 CD4+:CD8+ sIgA
68
In conditions of malnutrition and starvation, what are the two methods of restoring nutrition?
TPN: Total parenteral nutrition EN: enteral nutrition
69
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?
Sepsis, multi-organ failure, hypermetabolism
70
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?
TPN
71
What are the three general types of food allergies in terms of immunological classification?
IgE mediated Non-IgE mediated (Th2 mediated) Mixed (both IgE and Th2)
72
Which type of food allergy is most common in young children and results in acute or chronic cutaneous symptoms or anaphylaxis?
IgE mediated (food-specific IgE is made)
73
What type of food allergy results in chronic skin and/or GI symptoms as well as eosinophilic disorders?
Non-IgE mediated (Th2 mediated)

HDM Final (12 decks)

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