B cells Flashcards
What are the stages of immune response to infection?
- Innate immunity - involves neutrophils, macrophages & dendritic cells.
- Antigen presentation to T-cells by APCs (bridge)
- T-cells help B-cells
- B-cells make antibodies.
- Antibodies remove pathogen.
What are the cells of the adaptive immune response?
B lymphocytes
T lymphocytes
Types of adaptive immunity?
Humoral- due to B lympochytes
Cellular- due to T lymphocytes
Where are B cells produced and mature?
Produced- bone marrow out of Haematopoietic Stem Cells
Mature- bone marrow-undergo VDJ recombination. Go to spleen to mature further
What do B cells mature into?
- Memory cells - long lasting cells that remember the antigen structure & results in the rapid production of that specific antibody- produced at end of adaptive primary immune response
- Plasma cells - produce antibodies
What is gene arrangement?
- B cells use rearrangement of hundreds of gene segments to provide diversity*of receptors.
- The variable region of the BCR heavy chain is made up of V, D, & J segments
- The variable region of the BCR light chain is made up of V & J segments.
- Genetic rearrangement of all possible combinations of V-J-D & V-J provides for millions of unique antigen-binding sites for the B-cell receptor & for the antibodies secreted after activation.
What is an epitope?
The part of an antigen molecule that an antibody attaches itself too.
Explain clonal expansion?
- B cells express antigen-specific receptors before antigens are ever encountered in the body.
- The B cells undergo clonal expansion
- During each cellular division, random mutations occur that gradually increase the binding affinity for B cell-produced antibodies to antigens
Describe B cell maturation
- Mature in the bone marrow
- They gain antigen receptor molecules, called B cell receptors (BCRs)- created through VDJ recombination.
- The receptors contain antibodies- enables specific antigen recognition.
- Positive selection occurs for B-cells w/ normal functional receptors.
- B cells that recognise self antigens are killed by apoptosis before they can mature - this reduces the risk of autoimmunity - negative selection
- Once B cells mature in the bone marrow, they travel to the spleen or their final stages of maturation.
- They become naive mature B cells
What is the structure of a BCR & what do they do
- On B cells, receptors contain antibodies, which are responsible for antigen binding.
- An antibody is specific for one particular antigen- will not bind to anything else.
- Upon antigen binding to a B cell receptor, a signal is sent into the B cell to turn on an immune response.
How do BCRs interact w/ antigens?
BCRs do not require antigen presentation w/ MHC; they can interact w/ free antigens or w/ epitopes displayed on the surface of intact pathogens
TCRs only recognise protein antigens, whereas BCRs can recognise epitopes associated with different molecular classes (e.g. proteins, polysaccharides, lipopolysaccharides).
Describe T-cell independent activation of B-cells
Activation:
1. Occurs when BCRs interact w/ T-independent antigens (e.g., polysaccharide, lipopolysaccharide) i.e. any antigen that’s not protein.
2. T-independent antigens haverepetitive epitope units w/in their structure- repetition allows for thecross-linkageof multiple BCRs, providing the first signal for activation.
3. Because T cells are not involved, the second signal comes from other sources, e.g. interactions oftoll-like receptorsw/PAMPor interactions w/factors from thecomplement system
Differentiation:
1. Once a B cell is activated, it undergoesclonal expansion & daughter cells differentiate into plasma cells
2. After differentiation, surface BCRs disappear & plasma cell secretes IgM molecules that have the same antigen specificity as the BCRs
Describe T Cell dependant activation of B Cells & what happens next to produce the immune response?
Activation:
1. Interaction between the BCRs*on B cell & free antigen/antigen on pathogen stimulate internalisation of the antigen.
2. Once inside the B cell, protein antigen is processed & presented w/ MHC II.
3. The presented antigen is then recognised by helper T cells specific to the same antigen.
4. The TCR of the helper T cell recognises the foreign antigen, & the T cell’s CD4 molecule interacts w/ MHC II on the B cell- called linked recognition
5. Once activated by linked recognition,TH2 cells produce & secretecytokines(ILs) that activate the B cell.
Differentiation:
1. TH2 cytokines stimulate B cell proliferation & differentiation into memory & plasma B cells- Plasma cells secrete IgM
2. After initial secretion of IgM, cytokines secreted by TH2 cells stimulate the plasma cells to switch from IgM production to production of IgG, IgA, or IgE
3. Class switching occurs by genetic rearrangement of gene segments encoding the constant region of the antibody, which determines an antibody’s class. The variable region is not changed, so the new class of antibody retains specificity
4. Immune response is much stronger & memory is developed
What are the types of B cell response?
Primary response:
- Measured by detectable specific antibody in serum
- a response to a completely new antigen.
- Lag period (10 weeks) - no antibody can be detected in serum- time required for all of the steps of cell activation (binding, antigen presentation, helper T cell activation, clonal proliferation).
- end of lag period- characterised by rise of IgM levels
- IgG may reach a comparable concentration after approx 11 days
- Antibody levels are often low again by approx 3 weeks
- During the primary response, some of the cloned B cells are differentiated into memory B cells programmed to respond to subsequent exposures.
Secondary response:
- initiated by memory B cells
- The majority of the antibody is IgG.
- The secondary response:
- develops quicker (3 days)
- produces a higher peak
- longer plateau of response
- produces antibodies w/ higher affinity for the specific antigen.
- amplified response
- sends multiple lymphocytes & antibodies specific to that pathogen only
- system is adaptable- immunological memory of pathogen remains in body for ever
What is humeral response of adaptive immunity (B cell activation)?
Involves B-lymphocytes- produced in bone marrow, found in lymph nodes
During innate immune response- macrophages engulf & destroy pathogens- it keep antigens & display them on their membrane
- B-lymphocytes contain b-cell receptors that bind to macrophage-bound antigens
- T-cells help differentiate b-lymphocytes- produces plasma cells & memory cells
- plasma cells produce antibodies specific to that antigen
- memory cells keep copy of antigen in case of reinfection
-antibodies- bind to specific antigens- leads to agglutination
