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Samenvatting Immunologie Research and Clinic
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Immunology Research and ClinicLecture 1 – Immunological interactions and B cell research
Innate immune response → aspecific
➔ Macrophages (mature monocytes) are phagocyting cells
o Monocytes circulate in blood
o Macrophages are in tissues and are long living
➔ Dendritic cells (DCs) are phagocyting cells in immature form in tissues, activate acquired immune system
➔ Neutrophils → short living and are being produced extra during infection, migrate via blood to infection
➔ Mast cells are secretory and long living in tissues, anti-parasitic and allergies, secretion of content of their
granules
➔ ILCs (innate lymphoid cells) and NK cells (natural killer cells, viruses)
Infection starts with inflammation
- Infection: phagocytosis by macrophages → cytokines and
chemokines → inflammation
- Inflammation: influx of plasma, neutrophils, and monocytes
→ increased inflammatory reaction → increased lymph
drainage to lymph nodes + activation antigen presenting
cells (APCs) → induction specific immune response → influx
of antibodies and T cells
Dendritic cell takes up antigen → activation
through binding of PAMPs (pathogen-associated
molecular patterns) to PRRs (pattern recognition
receptors) → DC differentiates and migrates to
lymph node → activation of B and T cells
CD8+ effector cell → activated, cytotoxic cell
CD4+ effector cell → activated, Thelper cell
TLR activation by PAMPs
induces innate and
adaptive responses → by
the intracellular signal of
the brought together
TLRs and then gene
transcription
Acquired T cell response → the fate of the T cell in the lymph node
depends on antigen recognition
What happens when a naive T cell does not recognize antigen? → T cell releases again from the
dendritic cell and sometimes migrate to a different lymph node
What happens when a naive T cell does recognize antigen? → clonal expansion
MHC I → endogenous/exogenous antigen. MHC II → exogenous antigen
Antigen presentation to T cells by MHC proteins → immunological synapse
, T cells scan immunological synapse for the peptide-MHC
complex which is recognized by their TCR
Immunological synapse contains different domains
➔ Required for priming and effector function of T cells
o Priming → activation recognition,
proliferation/differentiation in the lymph nodes
- Central SMAC → all TCRs bound to peptide-MHC complex
- Peripheral SMAC → co-factors bound to their ligands
TLR activation of APC gives rise to 4 signals for T cell responses
→ APC determines what kind of T cell it becomes
1. TCR/MHCpeptide complex
2. Co-stimulation
3. Cytokines
4. Induction homing
After recognition of PAMPs in the APC, there is upregulation of
co-stimulatory receptors and cytokine production
PAMPs determine what kind of cytokines there are produced
→ cytokines determine what kind of Thelper cell
➔ When DC are not well activated → naïve T cell becomes regulatory T cell (anti-inflammatory cytokines IL-10
and TGF-β)
Acquired B cell response → B cell
differentiation and B cell effector
function
B cell receptor (BCR) complex consists of mIg and mIg and Iga/Igb
- mIg (=membrane-bound immunoglobulin) recognizes specific antigen
- Iga/Igb initiate cell signaling upon crosslinking of mIg by specific antigen
, B cell activation, survival and proliferation requires two signals
T cell independent antibody response → only IgM
production
- BCR = signal 1
- TLR = signal 2 (rescue of apoptosis)
T-cell dependent antibody response → all Igs
What makes IgM different compared to other antibodies?
➔ Produced immediately, low affinity, penta/hexamer, does
not need T cell help or GC reaction
What is the use of the penta/hexameric structure of IgM?
➔ IgM does not need somatic hypermutation and affinity
maturation. Therefore, it has a low affinity. Multimeric
structure generates high avidity
T cell dependent B cells differentiate in the lymphoid organs →
- Signal 1 → BCR (B cells can phagocytose antigen and flag
themselves with MHC-peptide complex)
- Signal 2 → CD40 and MHC II
- Signal 3 → CD4 T cell cytokines
o Class switching to IgG/IgE, somatic hypermutation and affinity maturation
→ elimination of pathogens
B cell class switch is generated via a
controlled recombination process via
specific switch regions and regulated
by CD40 costimulation and Tfh
cytokines
Different
antibodies have different effector functions
Follicular Thelper cells → help in antibody production
- Tfhs are needed for GC-reaction and therefore
needed for long-lived humoral immunity
o B cell class switching
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