B Cells- Adaptive Immunity

Question 1

What is the main function of B cells?

Answer 1

To produce antibodies

Question 2

whats a fancy word for anibodies?

Answer 2

immunoglobulins

Question 3

Describe the origins of B cells / development

Answer 3

1) Pro-B cell - has selected the B cell lineage instead of the T cell lineage (does not have a B cell receptor (BCR))
2) pre-B cell - in bone marrow begins to acquire a BCR using gene rearrangement
3) B cells undergo negative selection to eliminate self-reactive B cells
4) B cell development culminates in the generation of naiive B cells
5) naiive B cells circulate in the spleen, lymph, and blood waiting for antigen

*Naiive B cells have not yet met an antigen*

Question 4

Are B cell general or specific?

Answer 4

B cells have unique b cell receptors (BCRs) that recognize one specific antigen (protein, lipid, or polysaccharide)

*T cells only recognize peptides*

Question 5

Are B cell induced antibodies identical or just similar to the b cell receptor ?

Answer 5

They are identical to the BCR - they also have the same binding affinity consequently

Question 6

Explain the diversity of B cell receptors

Answer 6

each B cell receptor is unique due to BCR gene rearrangement - where the variable region is mixed up randomly and *hopefully* one of these random mixes matches an antigen perfectly.

This gene rearrangment is called VDJ recombination or somatic recombination

Question 7

By what process do B cell receptor genes rearrange?

Answer 7

They rearrange via VDJ exon recombination/somatic recombination

Where the genes are mixed up or deleted to make a new type of receptor - remember that they are always paired with a Constant region that makes the whole thing a functional heavy chain

Question 8

Describe the process of Negative selection in B cell development

Answer 8

BCR gene rearrangement is totally random- therefore you have to make sure that none of these receptors unintentionally recognize self.

Negative selection tests for BCR recognition of self and removes these before they enter circulaiton -

*occurs in bone marrow*

Question 10

When B cells leave the bone marrow, do they have a funcitoning BCR?

Answer 10

Yes! they are naiive B cells - which are fully functional, they just haven’t met an antigen yet so they aren’t mature

Question 11

Where do B cells come across antigens?

Answer 11

in circulation or in a lymph node

they can recognize soluble antigen or antigen bound to cells/pathogen

*remember B cells can recognize any substance such as peptides, proteins, lipids, DNA, carbohydrates*

Question 12

What is the First signal required for B cell activation?

Answer 12

Signal 1= antigen binding to BCR-

• triggers phagocytosis of antigen
• B cells excellent phagocytes and APCs
• peptides now presented on MHC class 2-
• up regulation of CD40 co-stimulator receptor -this is a checkpoint, if the CD40 also recognizes it as an antigen then it’s a go ahead
• Get upregulation of cytokine receptors

*full activation of the B cell requires T helper cells *

Question 13

Describe the second step of B cell activation

Answer 13

• T helper cell specific for antigen on MHC binds to it
• T cell help through upregulation costimulatory molecules (CD40L)
• production of cytokines by T cell drive B cell activation, proliferation and differentiation

Question 14

What happens after the B cell is activated?

Answer 14

• IgM type are the first antibodies secreted - but if the antibody isn’t particularly effected, it switches to IgG
• if the antibody does not bind tightly enough, The B cell goes back through to mature and become a more effective antigen recognizer -
• Memory B cells travel back to bone marrow and continously produce those antibodies at low levels specific to the antigen

Question 15

are antibodies carbohydrates, lipids or proteins?

Answer 15

• The are proteins produced by the B cells which are identical to the BCR

Question 16

What to antibodies recognise?

Answer 16

they recognize ‘epitopes’ on the surface of bacteria/viruses/other pathogens

these epitopes can be any biological molecule- protein, peptide, lipid, DNA/RNA sugars

Question 17

Describe the important structural features of the antibody

Answer 17

1) antigen binding site- recognizes antigen and bights incredibly tightly - once of the tightest interactions in all biology - very specific
2) complement binding site - site where C1q protein binds to start the classical complement cascade
3) Fc portion - reocgnized by macrophages, mast cells, basophils - they all have Fc receptors that recognize this portion of the antibody and bind to it

Question 18

What are the antibody effector functions

Answer 18

• neutralization of microbes and toxins
• opsonization and phagocytosis of microbes
• antibody -dependent cellular cytotoxicity
• With complement activation - phagocytosis of microbes opsonized with complement fragments
• With complement activation- inflammation
• With complement activation- lysis of microbes

Question 19

explain how antibodies perform

‘neutralisation’

Answer 19

• antibodies neutralize microbes and toxins by binding to them and preventing them from entering cells, binding to cell receptors, or infecting adjacent cells
• this only requires the antigen-binding regions of antibodies

Question 20

what is ‘opsonisation?’

Answer 20

marking a pathogen for ingestion and destruction

Question 21

what region of the antibody is necessary for opsonisation?

Answer 21

requires the Fc region of the antibody - and the antigen binding site

Question 22

Describe the process of opsonisation

Answer 22

1. microbe bound by the antibody
2. phagocytic cell has FcR receptor that binds to the Fc region on the antibody attached to the microbe
3. the Fc receptor signals activate the phagocytes
4. phagocytosis of microbe occurs
5. microbe is killed within the phagocyte

Question 23

Describe the process of complement activation using the antibody

Answer 23

*requires the antigen binding site and complement recognition site*

1. antibody binds to pathogen surface
2. complement binding site exposed
3. C1q binds (complement factor)
4. Get activation of proteolytic complement cascade and cell death

Question 24

What is adenosine deaminase deficiency?

Answer 24

deficiency in the adenosine deaminase enzyme

buildup of dATP blocks transcription

B and T cells are particularly affected as they are mitotically active and they require regeneration in huge numbers

Question 25

What is X linked agamma globulemia?

Answer 25

it is a mutation in a protein called Bruton’s tyrosine kinase- where you cannot generate mature B cells

• symptoms start at 9 months to 2 years of age - suffer from recurrent infections
• treat with intravenous immunoglobulin (IVIG) - collection of donor plasma

Question 26

What are the 5 classes of antibodies?

Answer 26

• IgG
• IgM
• IgA
• IgE
• IgD

Question 27

what is different about the classes of antibodies (immunoglobulins)?

Answer 27

They all have different Fc regions - but of course their antigen binding site is varialbe as always

Question 28

Which antibody/immunoglobulin class recognizes allergens?

Answer 28

IgE

Question 29

What are class switching signals?

Answer 29

They are cytokines produced by T helper cells which tell the antibody to keep the antigen presenting part, but switch up the class of antibody (switch the Fc region)

Question 30

What actually changes when the antibody switches ‘classes’?

Answer 30

The Fc portion of the antibody changes

it does this by keeping the genetic VDJ rearangement (responsible for antigen specific site)- but it actually changes the ‘constant’ region- switching it for another constant region

so it picks the constant region that will give it the function it requires

Question 31

What is the first antibody to be made by naive B cells when it is stimulated by antigen?

Answer 31

IgM is the first antibody to be made by naive B cells

Question 32

What is the predominant effector function of the IgM antibody?

Answer 32

complement activity

and clumping of microorganisms for eventual elimination from the body

Question 34

What functions can IgG carry out?

Answer 34

all the functions of the antibodies

• neutralising
• opsonisation

complement activation

agglutination

Question 35

what immunoglobulin cross the placenta?

Answer 35

•Only IgG crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG.

Question 36

What is the most common immunoglobulin in the blood?

Answer 36

IgG

Question 37

What does IgE do?

Answer 37

IgE plays a role in parasitic helminth disease - eosinophils have Fc receptors for IgE and binding of eosinophils to igE coated helminths - resuling in killing of the parasite

IgE also plays a role in allergies - once produced, IgE binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen - binding of the allergen to the IgE bound to mast cells trigger their activation and release of histamines = allergic reaction

Question 38

Where are IgA secreted from?

Answer 38

They are secreted across mucosal epithelium to defend against infection - very importnat for mucosal immunology -

Question 39

What is IgA used mainly for?

Answer 39

it is the major class of Ig in secretions - tears, saliva, colostrum, mucus etc. - mainly functions to neutralise or aggregate

Question 40

What is the most rare type of Ig?

Answer 40

IgD

role is unclear - but recently shown to bind mast cells and basophils and drive the production of anti-microbial peptides

Question 41

What is selective IgA deficiency?

Answer 41

it is the most common immunodeficincy - many are asymptomatic so don’t know how many have it

symptoms= recurring viral and bacterial respiratory infections starting early in life - Chrons, or ulcerative colitis

This is due to a failure of B cells to differentiate into IgA producing plasma cells