Samenvatting
Summary Chapter 9
- Vak
- Immunology
- Instelling
- Vrije Universiteit Amsterdam (VU)
This is a summary of chapter 9. With all of my summaries for this course I passed it with an 7,7
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Voorbeeld van de inhoud
Immunology Chapter 9 – Immunity mediated by B cells andantibodies
CD4+ T cell dependent/ independent B cell responses
B-cell responses are subdivided:
1. Thymus dependent responses (TD):
a. Dependent on CD4+ T cells
b. Most frequent B cell response
c. High affinity and isotype switched antibodies
The antigen via the afferent lymphatics --> subcapsular sinus (SCS) -->
Macrophages pick up antigens
Follicular dendritic cells pick up antigens --> they keep intact antigen
on their surface by which B cells can be activated. Complement
receptors on FDC bind to complement coated antigen.
Naïve B cells search for antigen displayed by FDC in B-
cell area --> antigen-activated B cells move to the
boundary region
Naïve T cells search for antigen presented by dendritic
cells in T-cell area --> antigen-activated T cells
proliferate and differentiate
The activated B and T-cells move to the border of
the B and T-cell areas --> they interact. When T-
cells are specific for peptide-antigen that was
recognized by the B-cell interact with the same
B-cell (see cognate interaction!) --> B and T-cell
pairs move to the medulla and here the first
plasma cells (produce antibodies, IgM – low
affinity) are produced
Some of the B and T-cell pairs move back to the B-cell follicle -->
proliferate here now it is called a secondary follicle or germinal center --
> germinal center reaction --> plasma cells (effector B-cells) (produce
antibodies, not IgM see isotype switching) and memory B cells are
generated
The germinal center reaction is dependent on follicular helper T cells -->
T helper cell delivers extra signals via CD40 ligand and cytokines -->
this causes the expression of the enzyme activation-induced cytidine
deaminase (AID) --> AID causes: These 2 processes occur in secondary
lymphoid organs in the germinal center only after recognition of antigen
1. Isotype switching: changes the IgM isotype into IgG,
IgA or IgE isotype.
In naïve B cells IgM and IgD are produced.
AID mutates switch regions and induces
recombination. The Cm and Cd gene sequences are
spliced out. Other isotype constant regions are
transcribed.
, Cytokines influence the isotype switch. These cytokines are produced by
helper T cells:
• Lot of IL-4 – IgE is induced
• Lot of IFN-gamma – IgG2a is induced
2. Somatic hypermutation: additional variation by random point mutations in
variable domains. It results in affinity maturation
FDC has complement receptors on surface and bind to complement coated
pathogens and keep them on the cell surface
• BCR has higher affinity for antigen: --> BCR can bind to
antigen --> phagocytose the antigen --> present it to the
helper T cell --> helper T cell delivers extra signal via
CD40 ligand and cytokines --> B-cell differentiate into
plasma cells
• Change in specificity for antigen – this could lead to
danger that you generate self-reactive antibodies. This
has to be prevented by selection. FDCs are important
in this selection
• BCR has lower affinity for antigen: --> BCR cannot bind
to antigen --> B-cells will die by apoptosis
Cognate interaction: antigen specific recognition
When B cells bind their antigen they will phagocytose it --> the
antigens are degraded and peptide fragments are formed --> peptide
fragments bind to MHCII and the MHCII migrate to the surface of B-
cell --> T-cell recognize the peptide-antigen
Primary antibody vs secondary antibody
• Primary antibody response starts with low affinity IgM molecules
followed by high affinity IgG molecules
• Secondary antibody response starts with high affinity IgG molecules
2. Thymus independent responses (TI):
a. Independent on CD4+ T cells
b. This is not the normal B cell response
c. Low affinity and have an IgM isotype
2 types of TI:
1. TI1: occurs when there is simultaneous triggering of Toll-like receptor with
BCR
a. TLR4: which is binding LPS
b. TLR9: which is binding DNA
Only IgM is produced. No isotype switching and no somatic hypermutation
2. TI2: occurs when there is strong cross-linking of BCR by high density
antigens (e.g. repetitive carbohydrates)
Only IgM is produced. No isotype switching and no somatic hypermutation
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