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Host Defense > Lecture 13: Mucosal Immunity > Flashcards

Lecture 13: Mucosal Immunity Flashcards

1
Q

True or false: 70-80% of all IgG producing cells in the body are physically located within the tissues of the mucosal immune system

A

TRUE

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2
Q

What kind of cells initiate a mucosal immune response?

A

inductive cells

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3
Q

What kind of cells enact the mucosal immune response?

A

effector cells

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4
Q

What are the 7 components of the mucosal immune system? (MALT)

A

1) GALT (gut)
2) BALT (bronchial)
3) NALT (nasal)
4) Genitourinary
5) Lacrimal
6) Salivary
7) Mammary

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5
Q

Give 2 reasons for why mucosal immunity is so important

A

1) pathogens enter our bodies via mucosal surfaces

2) mucosal surfaces cover a huge part of our bodies

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6
Q

What are the leading 2 causes of death from mucosal infections?

A

1) acute respiratory infections

2) diarrheal disease

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7
Q

What kind of cells predominate in the absence of infection?

A

activated/memory T cells and Tregs

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8
Q

What immunoglobulin dominates in mucosa?

A

IgA

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9
Q

What are the 2 distinct compartments that make up the mucosal immune system?

A

1) epithelium

2) lamina propria

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10
Q

What cell type stretches from the lamina propria to the surface of the gut (thru the epithelium) to sense bacteria?

A

dendritic cells

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11
Q

What are the 2 patterns of lymphoid cell arrangement in the gut?

A

1) Scattered (inductive)

2) Effector (organized like Peyer’s patch)

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12
Q

What kind of cells take up antigen from the gut?

A

M cells (microfold - the lumenal face is much different looking)

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13
Q

How does the M cell process antigen?

A

it doesn’t really, it endocytoses it then transports it across the M cell in vesicles before releasing it at the basal surface

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14
Q

Once pathogen has been funneled from the lumen to the lamina propria via the M cell, what happens?

A

DCs bind the antigen and activate T cells

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15
Q

Where do the T lymphocytes that encounter the DC in the lamina propria of the gut come from?

A

Peyer’s patch

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16
Q

Once activated, where do the T cells go?

A

leave the mucosal site and travel to the mesenteric lymph then the lymph

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17
Q

Expression of what on activated T cells helps them to home to the lamina propria of the gut?

A

a4b2 and CCR9

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18
Q

Where do lympocytes exit the lymph and enter circulation?

A

thoracic duct

19
Q

What are 4 methods of antigen uptake in the mucosa?

A

1) M cells across the epithelium
2) Fc receptor transport
3) apoptosis dependent transfer
4) antigen capture

20
Q

True or false: lymphocytes activated in mucosa can home to other mucosal sites?

A

True

(which is why administering antigen at one mucossal site results in specific antibody production at distant mucosal sites)

21
Q

Why is there more IgA in the gut than other isoforms?

A

because B cells in the mucosa are selectively induced to produce dimeric IgA rather than other isotypes

22
Q

What class of T cells specifically is important in MALT?

A

CTLs (cytotoxic T cells)

23
Q

Does mucosal immunity result in systemic immunity?

A

YES (serum antibodies can be detected indicating that a mucosal encounter with antigen generates subsets the T and B cells that home to mucosal sites as well as spleen and regional nodes)

24
Q

Does systemic immunity result in mucosal immunity?

A

NO, only the reverse is true

25
Q

What are the 4 unique features of mucosal immunity?

A

1) Ag at one mucosal site and lead to Ab at a distant mucosal site
2) B cells in MALT selectively produce dimeric IgA
3) CTLs are important
4) Mucosal immunity results in systemic immunity

26
Q

What are intraepithelial lymphocytes?

A

lie within the epithelial lining of the gut

Unclear function: think they readily kill infected epithelial cells

27
Q

What CD is present on IELs?

A

CD8

28
Q

What kind of infections can CD8+ IEL cells take care of?

A

viral infections (infect mucosal epithelium cell so that cell displays viral peptide to CD8 IEL via MHC class I)

29
Q

How do IEL cells kill infected epithelium cells?

A

perforin/granzyme/Fas-dependent pathway

30
Q

What is the first line of mucosal defense?

A

epithelial cells (provide innate defense against most pathogens)

-endocytosed bacteria are recognized by TLRs in intracellular vesicles

31
Q

What happens if the epithelium fails/doesn’t provide that first layer of defense and the pathogen slips into the lamina propria?

ex: salmonella typhimurium

A

1) bacteria enters, kills M cells, infects macrophages and epithelial cells
2) invade luminal surface of ep cells
3) enter DCs that sample the gut

32
Q

How does bacterial dysentery (Shigella flexneri) infect the host?

A

1) penetrates gut via M cells
2) spread to other epithelial cells
3) LPS on Shigella binds and oligomerizes NOD1 to activate NF-kB
4) activated epithelium secretes CXCLB, recruiting neutrophils

TRIGGERS NFkB and INFLAMMATION

33
Q

How does IgA protect from infection?

A

prevents access to epithelium

no clinical symptoms in IgA deficient patients

34
Q

What is the structure of secretory IgA?

A

DIMERIC (attached by J chain)

35
Q

How is IgA transported to the gut lumen from the lamina propria?

(the synthetic secreted dimer version)

A

binds to poly-Ig receptor on the basolateral membrane then is endocytosed and moved to lumen and secreted

36
Q

What is present in breast milk that provides passive immunity?

A

secreted IgA

37
Q

What are the advantages of oral/mucosal immunization?

A

1) ease of administration

2) generate mucosal and systemic immunity

38
Q

What are the disadvantages of oral immunization?

A

1) short lived response
2) difficult to elicit robust immune response (because of tolerance (gut is super tolerant to food and commensal bacteria, etc)

39
Q

Does systemic vaccination provide mucosal immunity?

A

NO but mucosal vaccination provides both mucosal and systemic

40
Q

What determines whether the response will be tolerance or immunity?

A

how the antigen interacts with DCs (activated express different corecptors)

41
Q

What kind of bacteria have colonized the gut and what does it do?

A

commensal - they protect the epithelium from pathogens

42
Q

What happens when C. diff gains a foothold in the gut?

A

produces toxins that cause mucosal injury and neutrophils/RBCs leak into gut between injured epithelial cells

43
Q

True or false: most pathogens enter body via mucosa

A

True

Host Defense (21 decks)

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