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Alimentary System > GI mucosal immunology > Flashcards

GI mucosal immunology Flashcards

1
Q

What does the upper GI tract consist of?

A

Oesophagus

Stomach

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2
Q

What does the lower GI tract consist of?

A

Small intestine

Large intestine

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3
Q

In basic terms, what are the 2 kinds of bacteria found in the GI tract?

A

Commensal bacteria

Pathogenic bacteria

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4
Q

What are some examples of challenges of antigen processing in the GI tract

A

Develop self-tolerance

Develop exogenous tolerance

Develop an effective immune response

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5
Q

What is self-tolerance?

A

Non-responsiveness of the immune system to self-antigens

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6
Q

What is exogenous tolerance?

A

Non-responsiveness of the immune systemto newly encountered environmental antigens that are harmless

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7
Q

What are examples of different facets to normal antigen processing in the GI tract?

A

Epithelial layer

Mucus layer

Innate immune response

Antigen presenting cells

Tolerance versus activated of adaptive immune response (T cell)

Soluble mediators of immunity

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8
Q

How does the epithelial layer provide protection?

A

Specialised tight junctions that regulate permeability

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9
Q

How does the mucus layer provide protection?

A

Physical barrier keeping microbes from host cells

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10
Q

What are examples of antigen presenting cels?

A

Dendritic cells

Macrophages

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11
Q

What are examples of soluble mediators of immunity?

A

Chemokines and cytokines

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12
Q

What are the 2 different parts of the immune system?

A

Innate immune system

Adaptive immune system

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13
Q

What kind of immune cells are innate?

A

Granulocyte (neutrophil, eosinophil, basophil)

Mast cell

Monocyte

Dendritic cell

Macrophage

Natural killer cell

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14
Q

What kind of immune cells are adaptive?

A

CD4+ T cell (memory)

CD8+ T cell (memory)

B cell (memory), which become plasma cells that produce antibodies

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15
Q

Where do all cells of the immune system originate from?

A

Haematopoitic stem cell which comes from bone marrow

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16
Q

What are the 2 things that a haematopoietic stem cell can differentiate into?

A

Myeloid progenitor cell

Lymphoid progenitor cell

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17
Q

What does myeloid progenitor cell differentiate into?

A

RBC

Platelet

All cells of innate immune system (except natural killer cells)

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18
Q

What do lymphoid progenitor cells differentiate into?

A

All adaptive immune system cells

Natural killer cells

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19
Q

Which immune system causes inflammation?

A

Innate immune system

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20
Q

What is a key determinant of T cell differentiation?

A

The cytokine milieu

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21
Q

How do cytokines vary in terms of inflammation?

A

Some are pro-inflammatory and some are anti-inflammatory

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22
Q

What is a T cell called before it has differentiated into its subtype?

A

Naive T cell

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23
Q

What are peyer’s patches?

A

Small masses of lymphatic tissue found throughout the ileum region of the small intestine

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24
Q

What do peyer’s patches allow?

A

Sufficient sampling of particulate antigens and delivery to antigen presenting cells

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25
Q

What is a macrophage?

A

Type of phagocyte which is responsible for detecting, engulfing and destroying pathogens and apoptotic cells

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26
Q

What is the first line of defence system in the gut?

A

macrophages

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27
Q

What are functions of macrophages?

A

Sampling of particulate antigens

Phagocytic (ingests harmful pathogens or dying/dead cells)

Secrete cytokines (such as IL-10 required for the survival of FoxP3 and Treg cells)

Antigen presenting cells to modulate adaptive immune response

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28
Q

Where are dendritic cells found in the GI tract?

A

Lamina propria and peyer’s patches

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29
Q

Why are dendritic cells important for mucosal immune responses?

A

Efficient sampling of antigen

Different dendritic cell subsets give rise to distinct T cell responses (such as tolerance vs immunity)

Different subsets distinguished by cell markers)

Present antigen to naive T cell

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30
Q

What to dendritic cells do after they have sampled gut bacteria and gut antigens?

A

Migrate to major lymph nodes

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31
Q

What do dendritic cells undergo maturation into?

A

Potent antigen presenting cells (APC)

32
Q

What 3 signals determine T cell response from an antigen presenting cell?

A

MHC/peptide-TCR

CD80-CD28

Cytokine

33
Q

Which of MHC/peptide-TCR is on the antigen presenting cell and naive T cell?

A

MHC on antigen presenting cell

Peptide-TCR on naive T cell

34
Q

Which of CD80/CD28 is on antigen presenting cell and naive T cell?

A

CD80 on antigen presenting cell

CD28 on naive T cell

35
Q

What is the innate immune system based on?

A

Recognition of pathogens associated molecular patterns (PAMPS/MAMPS)

36
Q

What T cell is required for clearance of intracellular pathogens?

A

Th1

37
Q

What T cell is required for maintaining the immune homeostasis and tolerance?

A

Treg

38
Q

What are 2 examples of what happens when the normal immune homeostasis goes wrong?

A

Inflammatory bowel disease (IBD)

Coeliac disease

39
Q

What is inflammatory bowel disease?

A

Chronic, relapsing, remitting inflammation of the GI tract

40
Q

What are the 2 main examples of IBD?

A

Crohn’s disease

Ulcerative colitis

41
Q

What is the difference between Crohn’s disease and ulcerative colitis?

A

Differ in type and location of inflammation

42
Q

examples of T helper cells

A

Th1, Th2, Th17

43
Q

examples of T regulatory cells

A

Th3, Tr1, Treg

44
Q

what is the innate immune system?

A

A universal and evoluntionarily conserved system of host defence Induced upon infection with microbes (eg.Intracellular pathogens)
Based on recognition of pathogen associated molecular patterns (PAMPS/MAMPS) Main players include Macrophages, monocytes, neutrophils and Dendritic cells General inflammatory response displayed by all cells

Plays a fundamental role in the induction and regulation of the adaptive immune response

45
Q

Adaptive Immune system?

A

Induced upon infection by specialized pathogens

Based on recognition of specific antigens presented by professional antigen presenting cells (eg. Dendritic cells)

Carried out by effector cells mainly, T and B cells.

46
Q

what do gut dendritic cells exist as?

A

several defined phenotypes which have distinguishable cell markers and functions

47
Q

what do DC subsets and macrophage have an important role in?

A

driving T cell differentiation eg. Th1 or Tregs

48
Q

what are required for are required for clearance of intracellular pathogens?

A

Th1 cells

49
Q

what are required for maintaining immune homeostasis and tolerance

A

Tregs (Tregs, Tr1, Th3)

50
Q

what cells contribute to mucosal tolerance.

A

B cells through differentiation in plasma cells and IgA

51
Q

What is inflammatory bowel disease?

A

Chronic, relapsing, remitting inflammation of the GI tract

52
Q

What are the 2 main examples of IBD?

A

Crohn’s disease

Ulcerative colitis

53
Q

What is the difference between Crohn’s disease and ulcerative colitis?

A

Differ in type and location of inflammation

54
Q

What does the pathogenesis of IBD involve?

A

Genome

Microbiome

Environment

Other unknown factors

55
Q

What is the innate immune systems involvement in IBD?

A

Dysfunctional innate receptor handling of bacteria

Breakdown of immune tolerance

ILCs

56
Q

What is the adaptive immune systems involvement in IBD?

A

Traditionally Th1 versus Th2 paradigm, many other lymphocyte populations are important (such as Th17, regulatory T cells, B cells)

57
Q

What are different treatment strategies for IBD?

A

Target lymphocytes directly

Target single cytokines

Target migration of immune cells to GI mucosa

Target multiple cytokines

Target cytokine intracellular signalling pathways

Modulation of microbiota

58
Q

What does anti-TNF biologics involve?

A

Inhibition of a single cytokine

59
Q

What is used to target migration of immune cells to GI mucosa?

A

Vedolizumab

60
Q

What are integrins?

A

Transmembrane proteins used to lymphocyte trafficking and cell adhesion

61
Q

What drug is used for multi-cytokine blockage?

A

Ustekinumab

62
Q

What does multi-cytokine blockage (Ustekinumab) target?

A

Towards p40 subunit of IL-12 and IL-23

63
Q

What does IL-12 control?

A

Proinflammatory Th1 cytotoxic T cell response

64
Q

What does IL-23 control?

A

Pro-inflammatory Th17 axis

65
Q

What drug is used for multi-cytokine blockage through inhibition of intracellular signalling?

A

Tofacitnib

66
Q

How does multi-cytokine blockage through inhibition of intracellular signalling with Tofacitnib work?

A

Pan JAK inhibitor (JAK1 and JAK3)

67
Q

What interleukins are inhibited by Tofacitnib?

A

IL2

IL6

IL7

IL9

IL12

IL15

IL21

IL23

IFN

68
Q

What do initial studies suggest about faecal transmission (FMT) and IBD?

A

Is likely effective in ulcerative colitis

69
Q

What is coeliac disease?

A

Common digestive condition where the small intestine becomes inflamed and unable to absorb nutrients

70
Q

What does coeliac disease cause intolerance to?

A

Dietary gluten in wheat and similar proteins

71
Q

What are symptoms of coeliac disease?

A

Malabsorption causing failure to thrive as a child

Iron deficiency anaemia

Fatigue

GI symptoms such as loose stool, abdominal pain or asymptomatic

72
Q

What causes genetic susceptibility to coeliac disease?

A

HLA-DQ2/8 on antigen presenting cell

73
Q

What does HLA stand for?

A

Human leukocyte antigen

74
Q

What does human leukocyte antigen (HLA) allow?

A

Immune cells to identify self and non-self antigens

75
Q

What are consequences of coeliac disease for the gut?

A

Loss of villi (loss of absorptive capacity)

Increase in intra-epithelial lymphocytes

Alimentary System (44 decks)

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