L6 - Generation of antibody Flashcards
Plasma cell structure
Large nucleus - transcription of antibodies
Extensive rER - Involved in antibody production
Large Golgi body - large secretion
Why are plasma cell nuclei lighter than most other nuclei?
Lots of euchromatin (unwound DNA), making the nucleus lighter
B cells: where do they develop, what do they do there, and what cells allow this to happen?
Bone marrow
Re-arrange their immunoglobulin genes
Stromal cells
B cell immunoglobin gene rearranging: what is the process and why is it useful?
- B cells express their re-arranged immunoglobulin molecule on the membrane surface as IgM class - if any of these interact very strongly with self-antigens in the bone marrow they are eliminated
- These cells now mature (and additionally begin to express their re-arranged immunoglobulin molecule as an IgD class)
- Allows production of only useful B cells
Mature B cells: what do they do and when do they produce antibodies?
Leave bone marrow and move around the body to populate secondary lymphoid organs and re-circulate through the bloodstream
When they encounter their specific antigen in lymph nodes they proliferate and eventually differentiate into plasma cells and long-lived memory B cells
(NB the B cells that leave the bone marrow cannot secrete antibody)
B cells: how do they move through lymph nodes?
IF INACTIVE:
* Enter through the bloodstream
* Travel to the cortex
* Exit through efferent lymphatic vessel
IF ACTIVE:
* Enter through the bloodstream
* Travel to the cortex (may be activated here)
* Travel towards the border of the paracortex where T-cells can stimulate activation even more
* Enter medullary cords and then form primary foci and either migrate to the primary follicle (forming a germinal centre) or starts to leave the LN (?????)
* Exit through efferent lymphatic vessel
B cell activation: how many signals are required, what is the process, and are there any special cases?
Require 2 signals:
* Signal 1 - recognition by the antigen-specific membrane immunoglobulin (Ig) molecule
* Signal 2 - most often from an interacting CD4+ T cell – this is T cell-dependent stimulation
In some cases – some antigens (e.g bacterial polysaccharides) can deliver strong enough antigens to stimulate B cells without T cells – this is T cell-independent stimulation
In these cases, the antibody is not usually as strong or efficient
Marginal zone: what is it, what does it allow to happen, and what is this process required?
The area of lymph nodes where special macrophages collect antigens draining into a lymph node or spleen
These macrophages allow conformational antigens to be recognised by any antigen-specific B cell migrating through the cortex region of the lymph node
More than one B cell receptor (Ig) on the surface of the cell needs to be stimulated – or cross-linked
MHC class II molecules: what are they, what do they do, and what are they produced by?
Major histocompatibility complex (MHC) molecules
Present processed antigens
APCs: macrophages, dendritic, and B cells
What benefit do B cells have in producing MHC class II molecules?
Allows binding with CD4+ T-cells to further activate B cells
What signals are required for B cell differentiation and clonal expansion?
- Co-stimulatory molecules (eg CD154 (CD40L) on the T cell and CD40 on the B cell)
- Cytokines from the T follicular helper cell
FDCs: what are they, where are they found, and what do they do?
Follicular dendritic cells
Lymph nodes cortex - primary follicles
Form a network throughout the primary follicle specially designed to hold antigen/antibody complexes on their surfaces in little nodules- iccosomes - holding antigens like this to provide them for stimulated B cells
Germinal centres: what parts to them are there?
Mantle zone - surround it
Dark zone - contains centroblasts
Basal dark zone - contains centrocytes (and lots of FDCs)
Apical light zone - contain plasma and memory cells
Centroblasts: what are they and what do they make?
Proliferating B cells that down-regulate their Ig membrane receptors and undergo affinity maturation
Centrocytes producing high-affinity antibodies
Centroblasts: what is the process behind affinity maturation?
As the centroblasts divide they undergo hypermutation of their H and L chains of their particular Ig molecule – causing random changes in the structure of the hypervariable regions of the antibody molecules
The net result of this is that some cells can now produce antibodies of a slightly higher affinity for the original antigen or a slightly lower affinity
Centrocytes: what are they, what do they do, how is affinity maturation done, how effective is it, and what is the final journey of centrocytes?
The name given to centroblasts that have stopped dividing and have begun expressing their surface Ig
They move over the FDCs expressing antigen - if they bind antigen with high enough affinity they will receive a survival signal – if not they die
As the immune response progresses, antigen levels will fall and the centrocytes compete for lesser amounts of antigen – only those of higher affinity will be selected
Very effective and can result in an increase in affinity of 10,000 to 100,000
Surviving centrocytes meet up with activated T-cells again and differentiate into plasma cells that secrete large amounts of high-affinity antibody or turn into memory B cells
Class switching: when can it occur, what is it, and what is it controlled by?
During the centroblast/centrocyte stage
The B cell can change its heavy chain constant region from µ (IgM) to γ (IgG) or α (IgA) or ε (IgE) whilst keeping the same heavy chain variable and light chain (the antigen binding parts)
Class switching is controlled by CD4 T helper cells and cytokines - ie without CD40/CD40L only make IgM
* Different cytokines induce the production of different antibody classes e.g. IL-4 induces IgE
Cytokine impact on antibody production
Cytokines also influence how much antibody is made
What antibody classes does IL-4 affect?
- IgM - inhibits
- IgE - inhibits
- IgA - none
- IgG1 - induced
- IgG2a - inhibit
- IgG2b - none
- IgG3 - induced
What antibody classes does IL-5 affect?
- IgM - none
- IgE - none
- IgA - augments production
- IgG1 - none
- IgG2 - none
- IgG2a - none
- IgG2b - none
- IgG3 - none
What antibody classes does IFN-γ affect?
- IgM - inhibit
- IgE - inhibit
- IgA - none
- IgG1 - inhibit
- IgG2a - induced
- IgG2b - none
- IgG3 - induced
What antibody classes does TGF-β affect?
- IgM - inhibit
- IgE - none
- IgA - induced
- IgG1 - none
- IgG2a - none
- IgG2b - induced
- IgG3 - inhibit
What class does IL-21 + IL-4 induce?
IgG1
What class does IL-21 induce?
IgG3
What class does IL-13 induce?
IgG3
What class does IL10, IL21 + TGFb induce?
IgA
What class do IL4 and IL13 induce?
IgE
What is the typical plasma cell rate of antibody production?
> 2000 Ab per second
What converts a B-cell into a memory cell?
The binding of CD154 on the T-cell to CD40 on the B cell
These can then leave the lymph node and go into the circulation
