Adaptive Immunity - B cells Flashcards
Where do B cells mature?
In the bone marrow
Where are B cells found?
Circulate in the blood and the lymph and are found in large numbers in lymphoid organs
How do B cells recognise antigens?
Through B cell receptors which are the actual antibodies against the antigen they respond to (IgM or IgD)
What does ‘diversity’ in BCR mean?
They have the potential to respond to numerous antigens
Once activated what do B cells change into?
Plasma cells which churn out lots of antibodies against that specific antigen
What are the 3 main molecules that are involved in recognition of foreign antigen by adaptive immune system?
- T cell receptor
- B cell receptor (Immunoglobins)
- Major histocompatibility complex
What allows the development of a repertoire of receptors with specificity for wide ranges of antigens?
Multiple genes encoding
What 2 chains are immunoglobins made up of?
A heavy chain and a light chain
What 2 regions are present in immunoglobins?
A constant region and a variable region
What shape is an immunoglobin?
Y-shaped
What region in immunoglobins is the region that changes between antibodies?
The variable region
What does the springy section of immunoglobins allow them to do?
lets it bind with other molecules and cells
How many different classes of immunoglobins are there?
5
What are the main antibody functions?
- Neutralisation - antibody can bind to and stop from working
- Opsonisation - main function - Stick to surface of microbe
- Complement activation
What are the main components of opsonization?
- Opsonized phagocytosis (IgG)
- ADCC (NK cell-mediated killing) (IgG)
- Mast cell degranulation (IgE)
What is each development stage of B cell development defined by?
Rearrangements of the immunoglobin heavy and light chain genes
How do B cell receptors generate diversity?
- Heavy chain involves rearrangement of Variable, Diversity and Joining genes
- Light chain rearrangement of Variable and Joining genes
- Binding site for antigen is in the variable region so cell can choose any combination of these genes to produce unique antibody binding sites
During B cell development what are the B cell receptors?
- Immature B cell receptor is mainly IgM (mainly produce IgM not only on surface to act as receptor - they also release IgM)
- IgM can be classed as early receptor but main receptor is IgD
- Mature B cell express both IgM and IgD on surface
What is negative selection in B cell development?
- Like the TCR there is great diversity in the B cell receptor repertoire
- Need to ensure that there is no reactivity against self antigens
- Therefore in bone marrow as B cells are developing they undergo negative selection
What is meant by mature B cells being antigen naïve?
Have not yet been exposed to a foreign antigen
How can B cell activation occur in regards to T cells?
In a T cell dependent or independent manner
Whether B cells are activated by T cells or not depends on the type of antigen. What are these antigens called?
- Antigens which require T cell help are called thymus dependent antigens
- Antigens that don’t require T cell help are called thymus-independent
Where does B cell activation mainly occur?
In lymphoid organs such as lymph nodes
Apart from lymphoid organs where can B cell activation occur?
Can get naïve B cells in periphery so some peripheral activation (particularly thymus-independent)
What does the activation of naïve B cells result in?
The rise of plasma cells
- Plasma cells are antibody factories
What is the process of thymus dependent B cell activation?
- Interaction between T cell and BCR also requires co-receptor binding (CD40 and CD40L) to stabilise the interaction
- Cytokine signals released from T helper cell induce proliferation
- Generates a pool of plasma cells which produce antibody
- Also generated memory B cells
- Plasma cells initially produce IgM before undergoing ‘class switching’
What is meant by the term ‘class switching’ in thymus dependent B cell activation?
- Initially the plasma cells produce IgM which is quite effective, but not as effective as IgG
- Eventually will stop producing IgM and will switch to IgG
- IgM produce is specific for unique antigen and when switches to IgG is still specific for unique antigen - antigen binding site remains the same
What does ‘affinity’ mean?
Strength of binding of single antibody to antigen
What does ‘avidity’ mean?
Ability of antibodies to form complexes (antibody-antibody binding)
How does antibody affinity and avidity increase towards antigen on secondary exposures?
- IgM response is weak. Cells therefore class switch to IgG (or IgA/IgE)
- Occurs by gene rearrangement but antigen binding site remains the same
- Repeated exposure to antigen causes affinity maturation. The antibody has increasing affinity for the antigen which produces a stronger response
What is the process of thymus independent B cell activation?
- Certain antigens such as bacterial LPS can activate B cells directly
- Cells differentiate into plasma cell and produce IgM however antibody response is weaker than TD B cell activation
- TI B cell activation does not lead to the generation of memory B cells (no long term immunity)
In lymphoid organs cross talk between B and T cells leads to generation of both arms of the adaptive immune response. What are the ‘two arms’ of the adaptive immune response?
- Humoral Immunity
- Cellular immunity
- Peak of activity of immune response is when the body has B and T cells both working optimally
What is the primary and secondary immune response?
- Primary exposure to antigens leads to the development of memory - this is the primary immune response and takes time to develop
- In the primary immune response IgM acts early but as B cells undergo class switching an IgG response follows
- Due to the generation of memory T and B cells this means that upon a second exposure we have a pool of cells waiting to respond immediately so the response is immediate
- In addition, we have cells that are primed to produce a more effective IgG (rather than IgM) response immediately
- This is the basic principle of vaccination
What is immunological tolerance?
- A state of immune unresponsiveness to a particular antigen or set of antigens
- Immunological tolerance is an active response to a particular epitope and is just as specific as an immune response
Which cells can be made tolerant?
Both B and T cells - more important to tolerise T cells as B cells cannot make antibodies to most antigens without the help of T cells
What are the 2 main types of tolerance depending on anatomical location?
- Central - occurs while developing immune cells are still present in the primary lymphoid organs (the thymus and the bone marrow), prior to export into the periphery
- Peripheral - occurs out with thymus and bone marrow
Where does central tolerance T cells occur?
Occurs in the thymus
What is the process of central tolerance T cells?
- T cells have to bind to MHC molecules (but not too strongly). Those that bind with correct MHC binding survive (positive selection)
- T cells must not bind to self-antigens. Those that do are eliminated (negative selection)
- This process leads to elimination of over 90% of T cells
- The rest emigrate to peripheral tissues and secondary lymphoid organs
- However, not all self reactive T cells are eliminated
Explain the process of peripheral tolerance T cells?
- Not all self reactive T cells are eliminated centrally
- However, peripheral tolerance prevents their action
- T cell activation is a 3 signal process
- Signal 1 but no signal 2 results in anergy. APC upregulates CD80/86 in response to TLR stimulation
- Signal 1 and 2 but no 3 (cytokine survival signal) results in deletion by apoptosis
- Treg’s can also directly block activity by binding to the antigen (both self and foreign)
Where does central tolerance B cells occur?
In the bone marrow
Explain the process of central tolerance B cells?
- B cell central tolerance involves negative selection only
- Therefore B cells which bind strongly to self antigen are eliminated
Where does peripheral tolerance in B cells occur?
In secondary lymphoid organs
Explain the process of peripheral tolerance in B cells?
- Self reactive B cells still require help from self reactive T cells
- Since most self reactive T cells are eliminated, self reactive B cells do not receive T cell help and therefore become anergic
- Having B and T cells that both respond to a specific self antigen is slim
What des breach of tolerance to ‘self-antigens’ mean?
Autoimmune diseases occur where our body does attack self antigens
- A breach of tolerance mans there has been a breakdown in the process somewhere
