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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
How are peyer's patches and isolated lymphoid follicles connected to lymphatics?
Mesenteric lymph node (largest lymph nodes in the body)
26
Why is the immune response og GALT different to that in spleen and lymph nodes?
Microenvironment of GALT has its own lymphoid cells and hormones
27
M cells structure
Massive pockets filled with B and T cells and dendritic cells
28
How do M cells directly take up antigen?
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
In the intestine where are effector lymphocytes mainly found?
Epithelium | Lamina propia
30
What does the epithelium of intestine mainly consist of?
Lymphocytes - especially CD8
31
What does the lamina propia mainly consist of ?
CD4 and CD8 T cells | and some macrophages, plasma cells, dendritic cells and sometimes eosinophils and mast cells
32
What is the circulation of lymphocytes in the mucosal immune system controlled by?
Adhesion molecules | Chemokines
33
Circulation of lymphocytes in mucosal immune system
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
What must happen before activated lymphocytes differentiate into effector cells?
Leave via lymphatics into bloodstream then back into lamina propia
35
What do activated B cells do in the peyer's patch once they have recirculated and reentered lamina propia?
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
What antibody class is associated with mucosal immune system?
IgA (produced by plasma cells)
37
What do IgA do?
Prevent bacteria adhering to host cell | Neutralise toxins made by pathogen
38
What do broad-spectrum drugs do regarding commensal micro-organisms?
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
What do commensal bacteria do?
Stimulate IgA production | Inhibit inflammation
40
Immune response to commensal bacteria
T cells can respond to commensal bacteria | But T cells= regulated to prevent this
41
What is caused when regulatory mechanism of preventing immune response to commensal bacteria?
Inflammatory bowel disease e.g Crohn's | Systemic immune response against flagellin of commensal bacteria
42
What prevents immune response to commensal bacteria?
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
What are germinal centres?
Lots of lymphoid follicles found in secondary lymphoid follicle
44
What do germinal centres consist of?
B cells, macrophages, follicular dendritic cells
45
What happens in germinal centres?
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
What happens in the dark zone of the germinal centre? (near left)
Naive B cell undergoes clonal expansion | Somatic hypermutation- in V region of BCR gene- nucleotides are added/delete
47
What happens in the light zone of germinal centre?
``` 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
What is somatic hypermutation?
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
What happens when somatic hypermutation causes a bad mutation in B cell?
Decreased affinity of antibody for antigen Can recognise self -proteins Causes apoptosis of B cell (by dendritic follicular cell)
50
Favourable mutations made by somatic hypermutation leads to?
Increased affinity of antibody for antigen | Selection of B cells with highest affinity- these cells are given survival signals
51
What happens after somatic hypermutation is done?
``` 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
mesenteric lymph node?
Contains naive T and B cells(IgM) | Connected to areas of GI tract
53
What is the lamina propia?
Connective tissue | Contains activated immune cells (CD4 and CD8 T cells and plasma cells- activated B cells)
54
How do naive lymphocytes (T and B) enter peyer's patches?
via High endothelial venules
55
Where are naive B and T cells found in peyer's patches?
Naive T cell= outside follicle | Naive B cell= within follicle
56
What happens if there are no antigens or dendritic APCs present in peyer's patches?
Lymphocytes recirculate through bloodstream or go to spleen
57
In mucosal immunity what must happen to naive B cells?
Naive B cells igM is converted to igA | IgA is major in mucosal immunity
58
What happens once dendritic APC has activated T and B cells?
T and B cells leave peyer's patches and travel through body then end up in lamina propria
59
in mucosal immunity once B cells are class switched to igA how are the actually activated?
``` 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
Route of antigen in lymph node?
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
Tonsils function
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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