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Immunology > Mucosal Immune System > Flashcards

Mucosal Immune System Flashcards

1
Q

What is the only physical barrier against invasion of MO in mucosal surfaces?

A

Thin layer of mucosal epithelium

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2
Q

Innate defences of mucosal tissues?

A 
Anti-micorbial peptides (defensins)
Antimicrobial peptides- lysosomes
Cilia
Goblet cells- mucus 
Tight Epithelia junctions
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3
Q

What body surfaces are lined by mucus-secreting epithelium that is protected by the mucosal immune system?

A
  1. Gastrointestinal tract
  2. Respiratory tract
  3. Urogenital tract
    Vast majority of infectious agents invade body thrpugh these routes
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4
Q

What diseases are associated with pathogen entering mucosal surfaces?

A 
Diarrheal diseases
Acute respiratory infections
Tuberculosis 
HIV/AIDS
Measles 
Whooping cough
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5
Q

Commensal micro-organsims/microbiota

A

Most found in colon of large intestine
Live in symbiosis with host
Do no harm
Beneficial to host

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6
Q

Inflammatory bowel disease (crohn’s), celiac disease

A

Happen when there is an immune response against commensal bacteria

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7
Q

Where are commensal micro-organisms found?

A 
Colon
Mouth
Skin
Oesophagus
Stomach
Vagina
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8
Q

Mucosal immune system

A

Largest part of body’s immune tissues
Produces most of immunoglobulins
Contains 3/4 of all lymphocytes

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9
Q

Anatomical features of mucosal immune system

A 
Mucosal epithelia
Lymphoid tissue
Peyer's patches
Lymphoid follicles
Tonsils
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10
Q

Effector mechanisms of mucosal immune system

A

Activated/memory T cells
T regulatory cells
IgA
microbiota

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11
Q

Immunoregulatory environment of mucosal immune system

A

Inhibitory macrophages

Tolerance inducing dendritic cells

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12
Q

Where are lymphocytes, macrophages, dendritic cells and other immune cells found?

A

Throughout mucosal tissues
Surface epithelium of mucosa
Lamina propia

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13
Q

What are the secondary lymphoid tissues in the gut?

A

Group of organs called GALT

with draining mesenteric lymph nodes

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14
Q

What happens at secondary lymphoid organs?

A

immune response is initiated

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15
Q

What does GALT include?

A

Peyer’s patches in submucosa of small intestine= large collection of lymphoid tissue
Isolated lymphoid follicles throughout intestine
Appendix
Palatine and lingual tonsils and adenoids

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16
Q

What are palatine, adenoid and lingual tonsils?

A

Large aggregates of lymphoid tissue
Covered by a layer of squamous epithelium
Form a ring= Waldeyer’s ring at back of mouth- entrance of gut and airways

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17
Q

Why do tonsils become enlarged in childhood?

A

Recurrent infections

In the past- had to be removed by surgery

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18
Q

What happens in people with tonsils and adenoids removed?

A

Reduced IgA response

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19
Q

Where are the peyer’s patches, isolated lymphoid follicles and lymphoid tissue of the appendix located?

A

Intestinal wall (GALT)

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20
Q

What happens in the peyer’s patches?

A

Initiation of immune response in gut

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21
Q

Structure of peyer’s patches

A

Dome like aggregates of lymphoid cells

Project into intestinal lumen

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22
Q

What are found in peyer’s patches?

A

Richer in B cells then lymph nodes and spleen
Large number of B cell follicles
With germinal centres
Small areas of T cells
Subepithelial dome= layer between epithelium and follicles- rich in dendritic, T, B cells

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23
Q

What is the surface epithelium of peyer’s patches?

A

Follicle associated epithelium

Single layer of columnar epithelial cells

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24
Q

What cells are found in the follicle associated epithelium of peyer’s patches?

A

M cells (microfold)

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25
Q

How are peyer’s patches and isolated lymphoid follicles connected to lymphatics?

A

Mesenteric lymph node (largest lymph nodes in the body)

26
Q

Why is the immune response og GALT different to that in spleen and lymph nodes?

A

Microenvironment of GALT has its own lymphoid cells and hormones

27
Q

M cells structure

A

Massive pockets filled with B and T cells and dendritic cells

28
Q

How do M cells directly take up antigen?

A
  1. M cell takes up antigen by endocytosis/phagocytosis
  2. Antigen transported across M cells in vesicles and released at basal surface
  3. Antigen presented by dendritic cell
  4. Dendritic cell activates T cells
  5. Dendritic cell moves to T cell area of peyer’s patches and meet naive antigen specific T cells= activated T helper cell
  6. They activate B cells- induce class switching to IgA (when T helper cell releases cytokines IL-4/IL-10/IFN-Gamma)
29
Q

In the intestine where are effector lymphocytes mainly found?

A

Epithelium

Lamina propia

30
Q

What does the epithelium of intestine mainly consist of?

A

Lymphocytes - especially CD8

31
Q

What does the lamina propia mainly consist of ?

A

CD4 and CD8 T cells

and some macrophages, plasma cells, dendritic cells and sometimes eosinophils and mast cells

32
Q

What is the circulation of lymphocytes in the mucosal immune system controlled by?

A

Adhesion molecules

Chemokines

33
Q

Circulation of lymphocytes in mucosal immune system

A

Naive lymphocytes enter peyer’s patches and mesenteric lymph nodes through high endothelial venules
If lymphocyte encounters antigen in GALT= it is activated
Activated lymphocyte enters lymphatics via mesenteric LN
end up in thoracic duct
circulate in bloodstream
re-enter lamina propia
Lymphocytes differentiate into effector cells

34
Q

What must happen before activated lymphocytes differentiate into effector cells?

A

Leave via lymphatics into bloodstream then back into lamina propia

35
Q

What do activated B cells do in the peyer’s patch once they have recirculated and reentered lamina propia?

A

In secondary lymphoid follicle-germinal centre
Class switch= IgA producing plasma cells
Plasma cells and effector T cells rarely found in peyer’s patches

36
Q

What antibody class is associated with mucosal immune system?

A

IgA (produced by plasma cells)

37
Q

What do IgA do?

A

Prevent bacteria adhering to host cell

Neutralise toxins made by pathogen

38
Q

What do broad-spectrum drugs do regarding commensal micro-organisms?

A

Antibiotics kill large numbers of commensal MOs
Creates niche- commensal can’t compete with entering pathogens
e.g Clostridium difficile grows in an antibiotic treated gut
causes bloody diarrhea

39
Q

What do commensal bacteria do?

A

Stimulate IgA production

Inhibit inflammation

40
Q

Immune response to commensal bacteria

A

T cells can respond to commensal bacteria

But T cells= regulated to prevent this

41
Q

What is caused when regulatory mechanism of preventing immune response to commensal bacteria?

A

Inflammatory bowel disease e.g Crohn’s

Systemic immune response against flagellin of commensal bacteria

42
Q

What prevents immune response to commensal bacteria?

A

They lack virulence factors
So they are taken up by phagocytic cells and rapidly killed
Endotoxin made by commensal bacteria is sensitive to neutralisation

43
Q

What are germinal centres?

A

Lots of lymphoid follicles found in secondary lymphoid follicle

44
Q

What do germinal centres consist of?

A

B cells, macrophages, follicular dendritic cells

45
Q

What happens in germinal centres?

A

B cell proliferation
Proliferating B cells found in centre
Inactive B cells are pushed towards edge= mantle zone
B cells surrounded by their associated T helper cells
Somatic hypermutation

46
Q

What happens in the dark zone of the germinal centre? (near left)

A

Naive B cell undergoes clonal expansion

Somatic hypermutation- in V region of BCR gene- nucleotides are added/delete

47
Q

What happens in the light zone of germinal centre?

A 
Clonal expansion- B cell differentiates into plasma and memory cells,differentiation, class switching- induced by cytokines: IL-4, IL-10,IFN-Gamma
BCR are checked by follicular dendritic cells
B cells with non-functional BCR or crap BCR are killed by apoptosis a=by follicular dendritic cells
48
Q

What is somatic hypermutation?

A

Induces point mutations in variable region of DNA of BCR
at a very high rate
Mutant BCRs= selected for survival and move to light zone

49
Q

What happens when somatic hypermutation causes a bad mutation in B cell?

A

Decreased affinity of antibody for antigen
Can recognise self -proteins
Causes apoptosis of B cell (by dendritic follicular cell)

50
Q

Favourable mutations made by somatic hypermutation leads to?

A

Increased affinity of antibody for antigen

Selection of B cells with highest affinity- these cells are given survival signals

51
Q

What happens after somatic hypermutation is done?

A 
High affinity B cells selected to move to light zone
Receive second survival signal by T helper cell
Causes B cells to differentiate into plasma/memory cells 
Inducing class switching= different isotypes made- induced by IL-4, IL-10, IFN-gamma
52
Q

mesenteric lymph node?

A

Contains naive T and B cells(IgM)

Connected to areas of GI tract

53
Q

What is the lamina propia?

A

Connective tissue

Contains activated immune cells (CD4 and CD8 T cells and plasma cells- activated B cells)

54
Q

How do naive lymphocytes (T and B) enter peyer’s patches?

A

via High endothelial venules

55
Q

Where are naive B and T cells found in peyer’s patches?

A

Naive T cell= outside follicle

Naive B cell= within follicle

56
Q

What happens if there are no antigens or dendritic APCs present in peyer’s patches?

A

Lymphocytes recirculate through bloodstream or go to spleen

57
Q

In mucosal immunity what must happen to naive B cells?

A

Naive B cells igM is converted to igA

IgA is major in mucosal immunity

58
Q

What happens once dendritic APC has activated T and B cells?

A

T and B cells leave peyer’s patches and travel through body then end up in lamina propria

59
Q

in mucosal immunity once B cells are class switched to igA how are the actually activated?

A 
IgA B cells are activated when in tissues by T helper 2 cells that make IL-4
IL-4= allows class switching of B cell
60
Q

Route of antigen in lymph node?

A
  1. Antigen and APC from tissue fluid travel into lymph node in lymphatic fluid
  2. In paracortex of lymph node dendritic cell presents antigen= MHC II APC
  3. Dendritic cells and B cells activate T helper cell
  4. B cells are activated by T helper cell or by antigen directly
  5. Activated B and T helper cells form foci with many proliferating B cells
  6. A few B cells and T helper cells migrate to primary follicle of cortex and interact with follicular dendritic cells
  7. Causes a production of a secondary lymphoid follicle with a germinal centre causing B cells to differentiate and proliferate into plasma cells= creating antibodies
61
Q

Tonsils function

A

Adenoids, palatine, lingual
- Tonsils= macrophages, neutrophils, granulocytes and mast cells
- Discrete follicles and germinal centres= B cells
- Germinal centres and discrete follicles= surrounded by T cells
- Tonsils= meshwork of connective tissue= traps pathogen
- Contain primary and secondary lymphoid follicles= but NON-CAPSULATED (luminal surface covered in squamous epithelium)
Protect against pathogen entering nose/mouth (nasal and oral epithelia)

Immunology (7 decks)

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