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Mucosal Immunity Flashcards

1
Q

What are the physiological functions of mucosal tissues?

A

Gas exchange
Food adsorption
Sensory activites
Reproduction

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2
Q

Where are the mucosal tissues of the body?

A 
Lachrymal gland, salivary gland
Mammary gland 
Kidney
Urogenital tract
GI tract
Respiratory tract
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3
Q

What occurs in a lymph node?

A

Hub where immune response happens. Dendritic cells enter the lymph and look for T cells. T cells arrive via blood and are activated by MHC receptors

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4
Q

What are the anatomical features of the gut mucosal immune system?

A

Intimate relationship between mucosal epithelia and lymphoid tissue
Organised lymphoid structures unnique to mucosal sites
Specialised antigen uptake mechanisms

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5
Q

What are the effector mechanisms of the gut mucosal immune system?

A

Activated/memory T cell predmoniate

Naturel effector/regulatory T cells `which constantly damp down the immune respose to non-pathogenic antigens

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6
Q

What is the immunoregulatory environment of the gut mucosal immune system?

A

Active down regulation of immune response

Inhibitory macrohpages and tolerising denditiric cells

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7
Q

What is peyer’s patch?

A

A specialized lymph node that sits within the wall of the epithelium within the gut. Site of antigen sampling within the gut

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8
Q

What immunological function occurs within the lamina propria?

A

Where the effects happen, contains lymphoid cells (T cells, macrophages, B cells, dendritic cells, neurtophils and eosinophils)

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9
Q

What is an M cell?

A

M cells are specialized epithelial cells of the mucosa-associated lymphoid tissues. A characteristic of M cells is that they transport antigens from the lumen to cells of the immune system, thereby initiating an immune response or tolerance.

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10
Q

What is the course of activation of a T cell?

A

Partially activated in peyer’s patch but will leave and move to mesenteric lymph nodes and then will enter the systemic circulation and enter the lamina propria as an activated T cell

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11
Q

How are antigens transported through M cells?

A

Take up antigens via endocytosis and phagocytosis, the antigen is then transported across the M cell in a vesicle and released at the basal surface where it binds to a dentritic cell which activates T cells

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12
Q

What immune cells are contained within the lamina propria?

A 
Dendritic cells
Plasma cells
CD4 T cells 
Mast cells 
Macrophages 
IgA
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13
Q

What immune cells are contained within the epithelial layer?

A

CD8+ Cytotoxic T cells

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14
Q

How do T cells enter peyer’s patch?

A

From blood vessels, directed by the homing receptors CCR7 and L-selectin (bound to T cells)

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15
Q

What happens to T cells once they enter peyer’s patch?

A

Encounter antigens transported across M cells and become activated via dendritic cells.

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16
Q

What do the T cells do once they have been activated in peyer’s patch?

A

They drain via mesenteric lymph nodes to the thoracic duct and return to the gut via the blood stream. Activated T celle home to the lamina propria and intestinal epithelium of the small intestine

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17
Q

What is MAdCAM?

A

MADCAM is selectively expressed on mucosal endothelial cells, driving memory T-cell re-circulation through mucosal tissues. Addressins are the ligands to the homing receptors of lymphocytes.[6] The task of these ligands and their receptors is to determine which tissue the lymphocyte will enter next. They carry carbohydrates in order to be recognized by L-selectin.

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18
Q

What is L-selectin?

A

L-selectin acts as a “homing receptor” for lymphocytes to enter secondary lymphoid tissues via high endothelial venules. Ligands present on endothelial cells will bind to lymphocytes expressing L-selectin, slowing lymphocyte trafficking through the blood, and facilitating entry into a secondary lymphoid organ at that point

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19
Q

What is the makeup of immunoglobulins within the intestine?

A

IgA 80% (IgA2, dimeric)
IgM 15%
IgG 5%

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20
Q

What is the makeup of immunoglobulins within the systemic humoral immune response?

A

IgG 80%
IgM 15%
IgA 5%

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21
Q

Where do plasma cells make IgA in the gut?

A

Within the lamina propria

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22
Q

What happens once IgA is made in the gut?

A

Binds to poly-Ig receptor on the basal membrane of the epithelial cells and is transported into the lumen on the gut. This coats the mucosa of the gut with IgA giving it protection

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23
Q

What is the function of IgA on the gut lumen?

A

Secreted IgA on the gut surface can bind and neutralize pathogens and toxins . It is also able to bind to and neutralise antigens in internalized endosomes. It can also export toxins and pathogens from the lamina propria whilse being secreted

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24
Q

What is an intaepithelial lymphocyte?

A

T CD8+ cells that are highly activated (don’t need cytokines)
They have a restricted antigen receptor repertoire
Express intergrin anchors to keep them in the epithelium

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25
Q

What will the IEL cells do if the cell is infected?

A 
Virus infects mucosal epithelium
Infected cell displays viral peptide to CD8+ cells via MHC class 1 receptors. The activated IEL cells kill infected epithelial cells by perofrin/granzyme and fas-dependent pathways
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26
Q

What is oral tolerance?

A

Default response to oral administration of protein state of specific peripheral unnresponseiveness

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27
Q

What do commesnal organisms do in immunity?

A

When bacteria bid to Toll-like receptors it activates the IKK pathway. This pathway phosphorlaytes a protein called IKB allowing it to detach from the transcription factor NFKB which will then move to the nucleus to activate gene transcription. Commensal bacteria can activate a protein called PPAR-gamma wchich removes NFKB from the nucleus preventing it from activating gene transpcription or they can prevent the phosphorylation of IKB

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28
Q

What do commensal bacteria do to dentritic cells?

A

In the presence of commensal bacteria, production of protiens that activate dendtiric cells are inhibited preventing dendritic cell maturation

29
Q

What is the effect of an immature dendritic cell in the mesenteric lymph node?

A

They give weak co-stimulatory signals and innduce CD4 T cells to differentiate into TH3 or T-regulatory cells via IL-10

30
Q

What is the effect of a mature dendritic cell in the mesenteric lymph node?

A

Express strong co-stimulatory ligands and innduce CD4 T cells to differentiate into effector TH1 and TH2 cells via IL-12

31
Q

What is the mucosal response to infection?

A

Activation through ligation of PRRs activate the NFkB pathway that initates gene transcription of inflammatory genes and therefore the production of cytokinnes, chemokinnes and defensins. These inflammatory markers activate neutrophils, macrophages and dendritic cells

32
Q

What does IL-13 do?

A

Induces epithelial cell repair and increases mucus production. This allows increased cell turnover and movement helps to shed the parasite. Mucus prevents adherence and accelerates the loss of the parasite

33
Q

What are TH2 cell effector funnctions?

A

Production of IL-13 and IL-5. Drive B cells to produce IgE. Drive mast cell recruitment via IL-3, IL-9

34
Q

What is the effect of IL-5 production?

A

Recruits and activates eosinophils.

Esoinophils produce MBP which kills parasites,

35
Q

What is the effect of B cells producing IgE?

A

IgE arms mast cells and can mediate ADCC

36
Q

What is the effect of increased mast cell recruitment?

A

Mast cells produce mediators such as histamine, TNF-alpha and MMCP. They also recruit inflammatory cells and remodel the mucosa

37
Q

What are the TH1 cell effector functions?

A

Activate macrophages

Activate B cells to produce IgG

38
Q

What is the effect of macrophage activation?

A

Products of activated macriphages cause tissue damage and tissue remodeling

39
Q

What is the effect of the production of IgG?

A

They do not bind to mast cells and therefore cannot clear parasites

40
Q

What is preferred in a helminth infection - TH2 or TH1?

A

TH2

41
Q

What part do dendritic cells play in the transfer of an infection?

A

The innfected dendritic cells shuttle viruses from the site of expsoure to the regional lymph nodes where they concentrate virus particles and innfect CD4+ T cells

42
Q

What will selective IgA deficiency present as?

A

Sinopulmonary bacterial infections. Not too bad as IgM can take over immunity in the absence of IgA.

43
Q

What will CVID present as?

A

Presents in nadulthood with recurrent sinopulmonary and GI bacterial innfections

44
Q

What is CVID?

A

The failure to differentiate into Ig secreting cells and therefore low levels of IgG, IgA, IgM ad IgE

45
Q

What is XLA?

A

X linked (only affects males) and is the absence of B cells

46
Q

What will XLA present as?

A

Sinopulmonary and GI infections in baby boys ages 7-9 months. If untreated it can lead toa devastatinng systemic manifestation of chronic enterovirus

47
Q

What is CGD?

A

Chronic Granulamatous disesae

48
Q

How does CGD present?

A

Children with staph. aureus, inflammatory granulomaspneumona, liver abscess, perianal abscess and skin abscess

49
Q

What is the treatment of CGD?

A

Bone marrow transplant

50
Q

What is SCID?

A

Profound defect of T and B cell immunity

51
Q

What will SCID present with?

A

Oral candidiasis, chronic diarrhoea, intertitial pneumonitis, CMV, rotavirus and EBV

52
Q

What is type 1 hypersensitvity?

A

IgE secreted by plasma cells binds to a high-affinity Fc receptor on mast cells. Activated mast cells provide contact and secreted signals to B cells to stimulate IgE production
When the activated mast cell meets the allergen it will degranulate

53
Q

What is coeliac disease?

A

A genetically linked, auto immune disorder that causes daage to the small instestine leading to malnurition

54
Q

What genes are thought to make people more succeptible to coeliac disease?

A

HLADQ2 and HLADQ8 genes

55
Q

What does IL-15 do?

A

It innduces the proliferation and activation of IEL cells

56
Q

What does gluten break down to in the body?

A

Gliadin peptides

57
Q

What occurs when the gliadin peptides enter the cell in coeliacs?

A

APC (dendritic or macrophage) presents gliadin peptide to CD4 T cell via MHC class 2 receptor. This will acitvate the CD4 cell which in turn activates plasma cells, TH1 cells, CD8 cells and NK cells

58
Q

What is the effect of activated plasma cells?

A

Produce anti-gliadinn, anti-endomysial and anti-tissue transglutaminase antibodies

59
Q

What breaks down gliadin peptides to the antigen that allows it to be taken up by the APC cells?

A

Tissue transglutaminase

60
Q

What is the effect of the activation of TH1, CD8 and NK cells?

A

Release of pro-inflammatory cytokinnes (INF gamma, IL-4 annd TNF allpha) causinng enterocyte damage

61
Q

How is coeliac disease diagnonsed?

A

Positive IgA anti-tissue transgultaminase autoantibodies blood test
Biopsy

62
Q

What is Crohn’s disease?

A

Focal and discontinous innflammation with depp and erodinng fissures with or without granulomas

63
Q

What mediates crohn’s disease?

A

TH1 CH4+ T cells, gamma interferon, IL-12 and TNF alpha

64
Q

What is the function of interferon gamma?

A

Cytokine critical for innate and adaptive immunity against viral, some bacterial and protozoal innfections. Activates macrophages and innduces class 2 MHC molceule expression

65
Q

What is the function of IL-12?

A

Produced by activated antigen-presenting cells and promotes the development of TH1 responses and is a powerful innducer of IFN-gamma production by T and NK cells

66
Q

What is the function of TNF alpha?

A

It is an endogenous pyrogen and so can induce fever, apoptotic cell death, cahexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL-1 and IL-6 producing cells

67
Q

Where can UC be found?

A

Starts in rectum and moves proximally to the colon

68
Q

What causes UC?

A

Distortion of the crypts with infiltration of monocytes/neutrophils and plasma cells causing inflammation and ulceration

GI (42 decks)

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