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GI lectures > Immunology 1 > Flashcards

Immunology 1 Flashcards

1
Q

why do mucosal surfaces require high level of immunity?

A

they are the primary source of entry of infections
perform critical functions
vulnerable due to fragility and permeability

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2
Q

what are the possible consequences of dysregulated mucosal immunity?

A

primary immunodeficiency
allergy
coeliac disease
inflammatory bowel disease

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3
Q

what are the 4 functions of mucosal tissue?

A

gas exchange
food absorption
sensory activities
reproduction

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4
Q

what 2 types of movement can occur through epithelium?

A

paracellular (between cells through tight junctions)
transcellular (through cell)
Both are passive, but selective

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5
Q

there is a system of mucosal immunity throughout the body, what are the implications of this?

A

if there is an invasion in a single mucosal site, you can get an immune response in many sites

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6
Q

secondary lymphoid tissue covers most mucosal sites to monitor pathogen entry, true or false?

A

true

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7
Q

what happens in the lymph nodes during an immune response?

A

dendritic cells enter lymph node via afferent lymphatic vessel into the paracortical area
T cells enter lymoh node in the blood
If antigen presented by dendritic cell and specific T cell match, T cells become activated and leave to return to site of infection

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8
Q

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

A

organised lymphoid structures unique to mucosal sites

specialised antigen uptake mechanisms

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9
Q

describe the effector mechanisms of the gut mucosal immune system

A

predominantly activated and memory T cells

natural effector/regulatory T cells also work in the background to dampen down immune response

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10
Q

what is the immunoregulatory environment and what is its importance?

A

active down regulation of immune response via inhibitory macrophages and tolerizing dendritic cells
prevents inflammatory response to non-harmful substances (hypersensitivity)
prevents chronic inflammation - ie Chrons

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11
Q

what is a peyers patch?

A

small mass of lymphoid tissue in lamina propria of organized gut tissue
where gut contents (potential antigens) are sampled

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12
Q

where are immune cells found in the lining of the gut?

A

in the lamina propria

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13
Q

describe the covering of peyers patches

A

“Dome” of follicle associated epithelium interspaced by M cells (microvilli cells)

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14
Q

what happens inside peyers patches?

A

antigens can pass through M cells to be sampled by dendritic cells below.
Dendritic cells present antigen to T cells (enter peyers patch from blood vessels, directed by CCR7 and L selectin)
If its a match the T cells move to lymph node (via mesenteric lymphatics) for full activation then come back to the gut in the blood expressing CCR9 and alpha4;Beta7

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15
Q

what do peyers patches look like histologically?

A

dense purple as they are packed with unactivated lymphocytes

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16
Q

apart from antigens passing through M cells, how else can antigens be sampled?

A

dendritic cells can extend a process through the endothelial layer and grab antigens from gut lumen

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17
Q

what immune cells exist in the lamina propria?

A 
CD4 T cell
Dendritic cell
Macrophages
Mast cell
IgA
Plasma cell
CD8 T cell
18
Q

what immune cells exist in the epithelial layer?

A

Dendritic cells

CD8 T cells

19
Q

how are activated T cells directed back towards the lamina propria?

A

via the action of MAdCAM-1
CCR9 on T cell binds to MAdCAM-1 on blood vessel epithelium
Gut epithelial cells chemokines specific for the T cells

20
Q

if mucosal lymphocytes are activated in one site, why to they migrate back to several areas?

A

MAdCAM-1 is expressed in many areas

21
Q

by what methods is passive immunity achieved?

A 
placenta
breast milk (IgA)
22
Q

In what ways are gut antibodies different to circulatory antibodies?

A

IgA = most abundant (80%)
IgG = least abundant (5%)
IgA = dimeric, joined by J chain
Mostly IgA1

23
Q

How does dimeric IgA work?

A 
Secreted in lamina propria
Binds to poly Ig receptor on endothelial cell
Endocytosed into epithelial cell
Transcytosed across cell to apical face 
Released directly into lumen of gut
24
Q

through which 3 methods can dimeric IgA get rid of antigens?

A

1) IgA coating the gut lining can bind and neutralize pathogens and toxins
2) IgA can bind and neutralize antigens inside the endosome while passing through the cell
3) IgA can bind to pathogens and toxins in the lamina propria and pass through the cell binded to them
The IgA-antibody complexes are then swept away with the mucus lining the gut

25
Q

why can an IgA deficiency be asymptomatic?

A

IgM is also polymeric so can take over the role of IgA (but not as well)

26
Q

what lymphocytes lie in between epithelial cells?

A

mainly CD8 T cells

27
Q

what anchors CD8 T cells in the epithelium and what do they do there?

A

alpha E; Beta 7 anchors them
Highly activated cytotoxic killing cells
directly kill pathogens that invade the epithelium via perforin/grazyme or fas dependant pathways

28
Q

describe the intraepithelial lymphocyte (IEL) response to epithelial stress (eg as a result of infection, damage, toxins etc)

A

stressed epithelial cell expresses MIC-A and MIC-B
NKGD on IEL and CD8 alpha:alpha homodimers bind to MIC-A and B and activate IEL
Activated IEL directly target and kill affected epithelial cell via perforin/granzyme pathway

29
Q

how can an infection or epithelial stress lead to malabsorption?

A

stem cells constantly producing new cells from the bottom
Virus or stress etc causes cells at the top to die
Action of stem cells making new cells cant keep up with how many are dying at the top so microvilli are lost and the epithelium becomes flat, reducing surface area resulting in malabsorption

30
Q

what is oral tolerance and give an example

A

Body distinguishes between harmful and innocuous antigens so doesn’t respond to an antigen that isn’t actually harmful
Eg. gluten is a strong antigen but the body doesn’t usually respond to it as its harmful

31
Q

Why are T cell and IgE mediated responses controlled more than IgG mediated responses?

A

It is the T cell and IgE responses that cause damage to the tissue

32
Q

what 3 mechanisms may be responsible regulating for mucosal hypersensitivity?

A

commensal gut organisms (PPAR gamma)
Anergy or deletion of antigen specific T cells (no co stimulation)
Generation of regulatory T cells (CD4+ TGF b producing Th3 cells)
- weak costimulation
- Both Immunosuppressive and induces switching of B cells to IgA production

33
Q

what is the pathway involving TLR, IKK, IKb and NFkR?

A

pathogen recognition by TLR triggers cascade that activates IKK
IKK phosphorylates IkB triggering it to degrade
This translocates NFkR to the nucleus where it activates gene transcription

34
Q

How can gut commensal bacteria block gene transcription?

A

2 pathways

1) activates PPAR gamma which removes NFkB from the nucleus
2) block degredation of phosphorylates IkBpreventing NFkB translocation to the nucleus

35
Q

describe dendritic cell and T cell maturation in the absence of pathogenic microorganisms

A

in the presence of commensal gut bacteria, PGE2, TGF-B, and TSLP inhibits dendritic cell maturation
Immature dendritic cells in the lymph nodes give wek co-stimulatory signals inducing CD4 T cells to differentiate into regulatory T cells (Th3 or T-reg cells)

36
Q

describe dendritic cell and T cell maturation in the presence of pathogenic microorganisms

A

invasive microorganisms invade the epithelium to activate dendritic cells
Activated dendritic cells in the lymph nodes express strong co-stimulatory ligands and induce CD4 T cells to differentiate into effector Th1 and Th2 cells
This process occurs all the time in chrons

37
Q

name 5 diseases where mucosal immunity comes into play

A 
infectious disease
Coeliac disease
Chrons disease
IBD
Allergy
38
Q

What are the steps involved in regulation of mucosal immune response?

A

Ligation of PRRs in epithelial cells
Activates NFkB pathway
Gene transcription and production of cytokines, chemokines and defensins
Activation of underlying immune response

39
Q

What are the 4 functions of Th2 cells in response to a parasitic infection?

A

Produce IL-13 (induces endothelial repair and mucus production)
Produce IL-5 (recruits and activates eosinophils)
Drive B cells to produce IgE
Produce IL-3 and IL-9 (drives mast cell recruitment

40
Q

what are the 2 functions of Th1 cells in response to a parasitic infection?

A

Activate macrophages

Activate B cells to produce IgG2a

41
Q

Everyone produces both a Th2 and Th1 response in equal measures, true or false

A

False

Type of response is on a spectrum, someone could produce only Th2, only Th1 or a bit of both (determined by genetics)

42
Q

Which type of response causes damage to the host tissue, Th2 or Th2?

A

Th1

GI lectures (75 decks)

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