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mucosal immunity Flashcards

1
Q

where in the body does mucosal immunity affect?

A

mucosal tissues (epithelial barrier)
- intestinal
- respiritory
- reproductive
- urinary tracts
-

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2
Q

what is the need for mucosal immunity?

A

it protects the body from surfaces continuously exposed to microbes and constantly stimulated

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3
Q

what does microbiota mean?

A

its a community of commensal bacteria that live in harmony at the mucosal surfaces

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4
Q

what does microbiome mean?

A

its the collective activites and genetic potential of microbes

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5
Q

why do we need to know the mechanisms of mucosal immunity?

A
  • Most pathogens enter via mucosal route
    o Is it better to immunise via the mucosal route
  • You need to understand the mechanisms so that you can devise strategies against inflammatory bowel disease, asthma and COPD
  • Could you have oral tolerance to prevent autoimmue diseases
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6
Q

what does homeostasis refer to?

A

it refers to the healthy balance between microbes and the vertebrate immune system at the epithelial barrier

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7
Q

what is homeostasis maintained by?

A

mechanisms that inhibit inflammation, whilst promoting tolerance

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8
Q

what is physiological inflammation?

A

its also called helpful inflammation and requires immune cell activity and doesn’t involve damage to the epithelial layers

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9
Q

what do epithelial cells do for protection to infections?

A

they provide a physical barrier to infection but theyre also active participants in our immune system

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10
Q

what does pathologic or harmful inflammation follow?

A

it follows an infection that breaches epithelial cell barriers

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11
Q

what are epithelial cells?

A

epithelial cells are considered to be part of the innate immune system and play an active role in defence

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12
Q

what are the key points of mucosal immunity?

A
  • Mucosal immunity is incredibly important as most pathogens enter via the mucosal route
  • Epithelial cells play an integral part of mucosal immunity and not just as a barrier
  • Microbiota/microbiome has gained significant interest regarding it’s role in immunity, however much has still to be deciphered.
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13
Q

what is oral tolerance?

A

its a unique phenomenon that prevents us from developing an immune response to the food that we eat

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14
Q

what is the surface area of the GI tract?

A

400m2

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15
Q

what are the mechanical nono-specific immune responses?

A

epithelial barrier
peristalsis -weep and sweep means that fluid is secreted accross the barrier into gut and moves infections out
diarrhoea

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16
Q

what are the humoral non-specific immune responses?

A

o Gastric acid (pH 1)
o Lysozyme
o Peroxidase
o Mucin
o Calprotectin
o Anti-microbial peptides
o Defensins (α and β)
o Trefoil proteins

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17
Q

what is mucosal associated lymphoid tissue (MALT)?

A

its a unique lymphoid micro-environment and allows lymphocytes direct access to microbial antigens
its found in the gut, lungs and urogenital
there are also other types

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18
Q

what are the types of MALT?

A

Bronchus associated lymphoid tissue (BALT)
Gut-associated lymphoid tissue (GALT)

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19
Q

what is the best characterised of all the MALTs?

A

GALT gastrointestinal associated lymphoid tissue

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20
Q

what are some different types of cell types involved in the GALT?

A

payers patch
mesenteric lymph nodes
intra-epithelial lymphocytes

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21
Q

what is the role of payers patches (in the small intestine) in the GALT?

A

they share many features of that of traditional lymph nodes

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22
Q

what is the role of mesenteric lymph nodes in the GALT?

A

they drain into the intestine and it alerts and activates naive lymphocytes

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23
Q

what are the innate immune cells of the mucosal immune system?

A

dendritic cells
mast cells
innate lymphocyte cells

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24
Q

what are the adaptive immune cells of the mucosal immune system?

A

naive T cells
Th cells
B cells
plasma cells

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25
what are the intestinal epithelial cells involved in the mucosal immune system?
absorptive epithelial cells goblet cells paneth cells endocrine cells tuft cells M cells stem cells transit amplifying cells
26
what is the GALT made up of?
The gut-associated lymphoid tissue (GALT) consists of isolated or aggregated lymphoid follicles forming Peyer's patches
27
what is the role of goblet cells in the intestine?
they secrete a thin layer of mucus
28
what does FAE stand for?
it stands for follicular associated epithelium and it overlays the peyers patch
29
what are enterocytes?
theyre absorptive epithelial cells which are the main cell type for absorbing digested food
30
what are paneth cells?
they secrete anti-microbial peptides and cytokines and secrete trefoil proyeins and defensins
31
what are tuft cells?
theyre rare chemosensory cells that secrete IL-25 and help to control the immune system
32
what are stem cells (epithelial layer)?
theyre responsible for producing/ replacing all epithelial cells
33
what are M cells (and what does the M stand for)?
microfold cells which are responsible for antigen handling in the gut
34
what system are mucosal surfaces protected by?
the mucosal immune system (MALT) which contains a number of unique features and cells
35
what system protects the GI tract?
the GALT (gut-associated lymphoid tissue)
36
what is the major type of antibody actively secreted in the gut lumen?
IgA
37
what is the role of IgA in the gut lumen?
it prevents attachment of bacteria, toxins, viruses and the absorption of foreign substances it also has a secretory component to prevent degradation by enzymes or pathohens and its good at preventing the attachment of pathogens to epithelial cells
38
what antibodies are the first responders during infection?
IgM and IgG
39
why are IgA secreting plasma cells critically important in the laminia propria?
its central to maintain a healthy distance between the intestine and the commensal luminal microbes its also the first line of defence and transports antigen form the lumen to the laminia propria for evalultion - it also defends against pathogenic microbes and toxins
40
where does the IgA in the gut come from?
it mostly comes from plasma cells in isolated lymphoid folicles (ILF) which are found within the folicle assiciated epithelium which i strategically placed under M cells
41
what are intraepithelial lymphocytes?
(IELs) are important to intestinal immunity and insert themselves between epithelial cells, they're resident cells in the epithelium but they can also be recruited and they participate in homeostasis
42
what are gamma-sigma T cells? and what overall percentage of lymphocytes in the body are they?
theyre T cells in the intestine which make up about 20% of intraepithelial cells in humans, but only 5% in other lymphoid tissues altogether in the body, they make up about 15% of T cells in humans as 70% of T cells are found in the gut
43
what is the role of gamma-sigma T cells?
theyre the first line of defence in the gut, act as regulatory cells to maintain homeostasis and act as a bridge between the innate and adaptive responses
44
what may gamma-sigma T cells be activated by?
alarm sigals such as heat shock proteins as theyre of an invarient nature
45
what type of cells may have an important role in recognition of lipid antigens in the gut?
gamma-sigma T cells
46
why are gamma-sigma T cells peculiar?
they dont seem to require antigen processing and MHC presentiation of peptide epitopes
47
whats the difference in development between gamma-sigma T cells and alpha-beta T cells?
alpha beta T cells are tightly regulated within the thymus whereas gamma-sigma T cells can develop extra-thymically in the liver and the gut
48
what type of T cells express RAG-1?
gamma-sigma T cells
49
what does the RAG-1 gene do?
it recognises the DNA substrate
50
what type of TCR repitore is polyclonal in newborns?
gamma-sigma TCR repertoire
51
what type of T cells are made first, alpha-beta or gamma-sigma?
gamma sigma and theyre important in mucosal defense early in life before alpha beta T cell + IgA responses develop
52
what is the function of gamma-sigma intraepithelial lymphocytes?
theyre role os surveillance of intestinal epithelial layer against microbial invasion, cytotoxic activity against microbial pathogens via lysis of infected epithelial cells, providing B cell help (in the form of producing cytokines) production of cytokines and chemokines - support epithelial cell growth and maintain epithelial barrier integrity - immuno-regulatory
53
what cytokines and chemokines are produced by gamma-sigma T cells?
e.g. IL-1, IL-2, IL-4, IL-5, IL-10, IFN-g, TNF-a, TGF-β, lymphotactin
54
how do gamma-sigma T cells support epithelial cell growth and maintain epithelial barrier integrity?
they produce growth factors and remove damaged or transformed epithelial cells
55
what are peyers patches made up of?
Specialised follicle-associated epithelium (FAE) Overlying a sub epithelial dome (SED) Overlying multiple B cell follicles that contain germinal centres (GC), Within GC – Inter-follicular regions (IFR) contain T cells, high endothelial venules (HEV) and efferent lymphatics All lymphoid migration occurs from the blood across HEV as there are no afferent lymphatics
56
what are M cells?
theyre the primarysite of antigen handling in the git and theyre specialised epithelial cells
57
what makes M cells different to other epithelial cells?
- poorly developed brush borders (so they dont absorb nutrients) - no microvilli - thin glycoalyx - absence of hydrolytic enzymes - express MHC II on basolateral surface - theyre ruch in pinocytotic vesicles (to engulf antigens)
58
what happens to antigen in the gut?
they go through preprocessing via gastric acid, gastric enzymes and pancreatic proteases then the antigen is absorbed but it doesnt cause a response. preprocessing happens in the stomach to breakdown proteins into peptides then the antigen is absorbed accross the luminal surface by epithelial cells
59
what do you need for an immune response in the mucosal immune system?
antigen presenting cells, they can be macrophages or dendritic cells, process and present the antigen via MHC as peptides to T cells. this leads to upregulation of co-stimulatory molecules and cytokines are released
60
how does antigen sampling in the gut via the dendritic cell route happen?
dendritic cells have long finger like projections called dendrites and they push through the epithelial barrier to grab the antigens, they then process antigen and enter the lymphatics and eventually present it to the t cell
61
how does antigen sampling via the epithelial cell route happen?
epithelial cells can absorb antigen accross brush border and can express MHCII they then enter the HEV (high endothelial venules) to present the antigen to the T cell or pass it to macrophages
62
how does antigen sampling via M cells work?
this is the most important route regarding the immune response they express receptors which allow them to convey specific classes of microbes to the lamina propria they express recepotrs for antibody that allow them to carry IgA-antigen complexes from the lumen to the lamina propria
63
how do all lymphocytes know to return to the gut?
theyve got tissue-selective trafficing so they always try to go back to the place where they were generated/ activated
64
how do naive lymphocytes migrate from the blood into the intestine?
they leave the blood through high endothelial venules in Peyer's patches
65
where does initial exposure to antigen in mucosal inductive sites happen?
at peyer's patches
66

immunology BM323 (3 decks)

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