Lecture 6 Flashcards
What induces clonal deletion?
If B cells recognise self antigens
How many BCR are on each B cell surface?
1 - each b cells has a different BCR
How can B cells escape death?
By replacing the light chain with another one
When can RAG genes make a new light chain?
If the flight light chain is autoreactive
What are the 3 antibody functions?
Neutralisation, opsionisation and complement activation
What is Antibody neutralisation?
Antibody prevents bacterial adherence
What is antibody opsonisation?
Antibody promotes phagocytosis
What is antibody complement activation?
Antibody activates complement which enhances opsonisation and lyses some bacteria
What is found at the constant?
IgM and IgD
What is special about a BCR?
It only recognises one antigen
Where will the b cells look to find an antigen?
In the lymphatics and blood
What produces signal 1?
Binding of an antigen to a BCR
What activates intracellular kinases?
Cross linking BCR
What does kinases being activated lead to?
Transcription factors and gene expression
What types of motifs does the CD3 complex contain?
ITAM motifs
What do kinases phosphorylate?
Tyrosines
What makes signal 1 stronger?
Complement receptors
What is an example of a complement receptor?
CR2
What happens if the antigen that binds BCR is coated with C?
It can also bind CR2 on b cells and give an increased signal
What does signal 2 depend on?
Depends on the type of antigen that the B cell is recognising
Where does signal 2 come from in thymus independent antigens?
Antigen or cross linking of BCR
What are the two types of antigens that can move to trigger a B cell response?
Thymus independent and thymus dependent
What is a thymus independent antigen?
Can get a response to an antigen without the use of T cells, can get a B cell response in an antigen where you’ve taken the thymus out
What is thymus dependent?
Need T cells in order for a B cell response, do not get a B cell response in the absence of a thymus
Where does signal 2 come from in thymus dependent antigens?
Signal 2 is provided by CD4+ T cells
What is TI?
It is a complex protein which has different components and has a receptor on its antigen which the B cell recognises
What happens in TD?
The antigen binds to the b cells giving signal 1 but it also needs signal 2
How is signal 2 found in TD?
Through MHC class II, the B cell will take a peptide from the MHC class II onto its surface and this produces signal 2
How is signal 2 found on TI?
Delivered by the thymus independent antigen
What are the two types of TI-antigens?
TI-1 and TI-2
What do TI antigens do?
Induce antibodies in absence of T cells
What antibody is produced from TI antigens?
Only IgM
What happens in high concentrations to the antigens?
They act as polyclonal activators for B cells
What does polyclonal activators mean?
The antigens will activate many B cells irrespective of their different BCR
What are the two signals from in TI-1?
Signal 1 = BCR signal 2 = from TLR
What structure is TI-2?
A polysaccharide, has repeating structures so it can bind to lots of different BCRs on the surface
What are TI-2 important in?
Bacterial infections
What do TI-2 do to BCR molecules?
Cross link BCR on the same B cell surface
How long does it take for TI-2 antigens antibody responses to develop?
More than 5 years
What signals are seen in TI-2?
Only signal 1 or a strong signal 1
What are the antibody responses like in TD compared to TI?
They are much better
How is signal 2 carried out in a TD antigen?
Is from the T cell but need a CD40 ligand interaction to cytokines
What do cytokines secreted by the T cells do?
Drive class switching
What do IgM and IgD switch to?
IgG and IgA
How are epitopes joined?
Physically joined together by viral particles, protein and a sugar
What happens when converting a TI antigen to a TD antigen?
Makes a conjugate vaccine
What is an example of a conjugate vaccine?
Haemophilias influenza type b
What is the TI antigen in influenza type b vaccine?
Protective responses capsular polysaccharide
What is the TD in the influenza type b vaccine?
Protein tetanus toxoid
When can you get a conjugate vaccine?
5 years and older
What happens if the antigen is TD?
B cell presents peptides from Ag to CD4+Thelper cells
What do the CD4+Thelper cells form in the lymph node?
B/T cell conjugate
How do activation induced deaminase (AID) get induced?
By CD40 signal
What does AID induce?
Somatic hypertension in b cells
What hypermuates in the B cells?
The V,D,J segments
What are germinal centres?
Proliferating B cells
What do the b cells divide into in the germinal centres?
Centroblasts
What happens inside the centroblasts?
Hypermutation and class switching
What happens after centroblasts?
Turn into a non dividing state called a centrocytes
What is the process states of a B cell?
- B cell
- Centroblasts
- Centocytes
What is the dark zone?
Loads of proliferating cells
How is signal 3 delivered?
By antigen-presenting cells
What happens to B cells in a germinal centre? - 3 ways
Differentiate into plasma cells, form long lived memory cells or die within the lymphoid
What is somatic hypermuation?
Randomly mutate the DNA at the V,D,J regions
What are also present in the GC (germinal centre)?
Follicular dendritic cells and antigens
What do follicular dendritic cells do?
Display the antigens to the b cells
What do centrocytes do?
Compete with each other for an antigen
What are follicular T helper cells?
Help B cells
Where to Thelper cells Come from,?
CD4+Th
What is the role of CD40?
Projects centrocytes from apoptosis
What does CD40 a signal induce?
Class switching
What cytokine is needed for IgE class switching?
IL-4
