B cells and mucosal immunity

what is a B cell:

• what can they produce

• how do they recognise pathogens

• how do they recognise pathogens and what do they do to the cell

• what do they interact with when in LNs

• Release antibodies which help clear pathogens 

• Recognise pathogens through TLRs  

• Can recognise antigens through their B cell receptor and internalise it through phagocytosis 

• Presents phagocytosed antigen on MHCII to allow it to interact with T cells 

In the LN, B cells encounter antigens which have drained from tissues when recirculating  

who activates B cells

how do they do this

what then happens to the B cell once activated (brief)

T cells have been activated and they recognise the antigen presented by the B cell 

2. T helper cell releases cytokines 

3. B cell matures into a plasma cell and starts to produce specific antibodies  

what are the pairs of molecules between B/T helper cells (3)

B7.1/B7.2 + CD28

B CELL RECEPTOR + T CELL RECEPTOR/CD4

CD40 + CD40L

what are the four different parts of an antibody

• 2 regions described

• 2 chains

Variable region: recognises the pathogen (different peptide sequence) 

Constant regions: recognised by other Fc receptors on other immune cells to bind to their surface  

Heavy chain+light chain 

what are the five different classes of antibodies IgX

IgD - receptor on B cells for antibodies

IgG - induced by Th1/2, circulates in blood for long term immunity

IgA - secreted across mucosal epithelial cells as a dimer

IgM - forms a pentamer to present many binding sites

IgE - made in response to large pathogens

how do T follicular helper cells come about

what is their main function

• After activation by dendritic cell, some T helper cells upregulate Bcl-6 and become follicular helper cells  

• they activate B cells

what happens to B cells when activated (2)

• they make an early response by producing IgM which isnt specific but still an antibody

• they move to the germinal centre to undergo class switching

what are the two main halves of a germinal centre T,B

• what are the two parts of the bottom half DZ, LZ

T cell zone paracortex

B cell zone

• dark zone

• light zone

what happens in the germinal centre

• B/T cell interaction

• what happens to B cells, where

• what do B cells interact with now, where

• what do B cells turn into (3 options)

• what removes debris TBM

1. B cell moves away from the T cell zone border and starts to proliferate  

2. They start to undergo somatic hypermutation 

3. B cells interact with antigen presented on folitic dendritic cell and continue to interact with T folitic helper receptors receiving CD40L-CD40 signals (costimulating) to survive and continue proliferating 

4. If they recognise the antigen with high affinity, B cells mature into plasma cells and leave the germinal centre  

5. Some B cells will become memory B cells 

6. If B cell has low affinity for the antigen, it undergoes apoptosis and is removed by TINGIBLEBODY MACROPHAGE 

on what part of the antibody does the antibody does somatic hypermutation take place, what happens

what is a B cell receptor the same as

Many mutations occur in the VARIABLE region of the B cell receptor/ IgD

which antibody classes are responsible for:

• complement activation 2

• opsonisation, NK cell recognition 1

• neutralisation 3

• eosinophil activation and mast cell 1

explain binding for each and how pathogen is destroyed

IgM, IgG- complement activation

• bind to pathogen and complement, recognised by phagocyte

IgG - opsonisation, NK cell recognition

• antibody binds to both phagocyte/ NK cell and pathogen

IgG, IgA, IgM - neutralisation

• antibodies bind to bacterial toxins/virus and stop them reaching the CSR

IgE - activates eosinophils and mast cells

• it binds to parasite surface and is recognised by FceR1 on eosinophil

• eosinophils release granules to degrade parasite

• bind to FceR1 on mast cells and to pathogen

• mast cells degranulates by releasing histamines

what can B cells also be activated by

DCs

how can B cells be activated by DCs, two coutcomes for antibody class

• where are the two antigen binding sites

• what is relayed

• what is produced as a result

1. Antigen binds to B cell receptors 

2. Recognition by TLR sends a second signal  

3. Activated B cell produces IgM effective for neutralisation and complement initiation 

 

1. Antigen binds to B cell receptors and TLRs  

2. Activated dendritic cells and macrophages can produce BAFF (B cell activating factor) 

3. Activated B cell starts to produce class switched IgG or IgA 

 

what are the two main functions of enterocytes in the GIT

absorption (disaccharidases break down disaccharides) and secretion (paracellular/between+transcellular/through)

what defences do we have in the mouth

FSLB

• Flow of liquids 

• Saliva 

• Lysozome 

• Bacterial flora 

what defences do we have in the oesophagus

FP

• Flow of liquids 

• Peristalsis 

what defence do we have in the stomach

A

Acidic pH

what defences do we have in the small intestine

FPMBLEBA

-flow of gut contents 

- peristalsis 

- mucous,

- bile

- lymphoid tissue 

- epithelium shedding 

- bacteria 

-antibodies IgA

what defences do we have in the large intestine

PMEB

-peristalsis, mucous 

- epithelium shedding, commensal bacteria 

 

how can we get ill if we have defences, what can cause this

• stomach

• s intestine

• l intestine

Stomach: 

• They survive in low pH 

• Reduced stomach acidity – surgery, drugs 

S. intestine: 

• Impaired motility – surgery 

• Blockage of bile flow – gall stones 

• Suppressed immune system 

• damaged epithelium – disease, trauma 

• Altered commensal bacteria - drugs 

L. intestine 

• Altered commensal bacteria – drugs 

• Damaged epithelial lining – disease, trauma 

lymphoid tissue in the GIT, where is it, name

Gut associated lymphoid tissues (GALT), ileum

what can DCs do in peyers patches

• what IL can they produce, in resp to what

• how can they get antigens

• what can their dendrites do

• what are they resp for for the gut lumen

1. In resting conditions, DCs (dendritic cells) in peyers patches produce IL-10 in response to antigen uptake ---> T reg activation and antibody production 

2. Antibodies on Fc receptors can transcytose antigens to the DCs in lamina propria 

 3. Apoptotic cells infected with bacteria are phagocytosed by DCs  dendrites

4. DCs can also send processes between epithelial cells to sample the gut lumen 

what are microbiota

• non pathogenic bacteria and present only in outer layer 

• Constantly proliferating and being passed out of the gut  

describe the two mucous layers

Outer mucous layer: 

• Non sterile degrading mucous 

• Microbes utilise mucin carbohydrates  

Inner mucous layer: 

• Relatively sterile  

• Rich in antimicrobial peptides 

what is the main thing the gut avoids

• how is this achieved/by secreting what

• what do paneth cells do

• what removes damaged/infected cells

The mucosal sites are in a constant balance of inflammation to clear a pathogen but not too excessive that it causes damage of loss of function 

High levels of IgA towards commensal bacteria secreted in healthy gut 

Paneth cells produce defensins (Th17 release IL22/IL17 to induce procuction)

Intraepithelial leukocytes 

• Mainly CD8+ (cytotoxic T cells) 

• They survey and remove infected and damaged cells