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2021Advanced molecular
Immunology and Cell
Biology
SUMMARY LECTURE
JANNIEK MORS
,Advanced Molecular Immunology and Cell Biology 2021-2022 Period 1
Janniek Mors
Advanced Molecular Immunology and Cell Biology
Introduction into immunology ................................................................................................................ 2
Dendritic cells in tailored adaptive immunity ......................................................................................... 4
T cell priming in the Covid-19 era.......................................................................................................... 11
(auto)antibodies in inflammation and infection ................................................................................... 18
Immunometabolism .............................................................................................................................. 24
Immune responses to glycolipids and polysaccharides ........................................................................ 29
Primary immune deficiency: inborn errors of immunity....................................................................... 34
Lymphoid organ development .............................................................................................................. 40
Neuro-immunology ............................................................................................................................... 44
,Advanced Molecular Immunology and Cell Biology 2021-2022 Period 1
Janniek Mors
Introduction into immunology
In secundaire lymphoide organen interacteren innate met adaptive. T cell komen van de thymus naar
bloedstroom. Komen aan bij de lymphenodes→binnen via high endothelial venules. Komen hier dendritische
cellen tegen die antigen presenteren→maturatie en selectie. (ook humorale reactie van Bcel→plasmacel +
antibodies)
When immature DC recognizes antigen via TLRs they become activated and differentiated. They produce much
more lysosomal protein and eventually upregulated MHCII. They change shape (handiger voor transport). They
are mature and can not present antigen.
- Immature DCs are very good at phagocytosis
Complement factors are present in serum, lymph and extracellular fluids. Synthesized by the liver. Binds
pathogens, causing them to undergo phagocytosis.
- 3 complement activation pathways→ C3 → C3a and C3b
- C3b: opsonization. C3a: recruite inflammatory cells
- C5-C9: MAC
T cell and B cell receptors
- T cell receptoren associeren zich met CD3 molecules om zich heen in het membraan. CD3 hebben
intracellulair onderdeel dit nodig is voor celsignalling
T cell receptor after selection never changes
- B cell receptors are membrane bound antibody worden constant klein beetje aangepast zodat ze sterker
kunnen binden met hun antigen →somatic hypermutation in germinal centers (affinity maturation)
B cell hebben Igbeta en Igalpha nodig voor intracellular signaling
B cell receptors are altered to recognize antigen better
B cells need the hinge region flexibility in B cell receptors for recognition of whole proteins
Required for rearrangement of immunoglobulin genes:
- RAC enzymes (recombinases (Recombination-activating genes)) dmv recombinatie zorgt voor diversity
- Only lymphocytes express RAG enzymes
T cell selection in thymus
- First positive selection→als ze MHC herkennen (1 of 2) en dan wordt het een CD4 of CD8 ( de ander wordt
downgeregaleerd)
- Negative selection→has to bind to MHC en en peptide maar als ze te strak blinden is hij wss autoreactive.
Intermediate binding is important.
- Costimulation is hier helemaal niet bij betrokken
T cell kan alleen gepresenteerde antigen peptides herkennen in MHC
- MHC class 1→laadt peptides vanuit cytosol door ER en golgi
- MHC class 2→laadt peptides vanuit phagosome→lysosome
In de lymphe nodes als de T cellen worden geactiveerd door dendritische cellen die antigen aan ze presenteren
geeft de dendritische cel cytokines af die de t cel vertellen welke soort t cel ze moeten worden→ dendritische
cel komt van plaats van infectie en weet wat de oorzaak is ( info via Tol like receptor)en welke cellen nodig zijn
om het te bestrijden
Singal 3: Cytokines → subset specification
Effectors: Th1, Th17, Th2, Tfh, Treg
TFH→zorgt ervoor dat een B cell antibodies gaat produceren. En dat doet de Tfh cel alleen bij B cellen waarvan
ze de gepresenteerde antigen herkennen
Co simulation is alleen nodig voor het activeren van naive T cells, when they are effector T cells they only need
MHC and peptide
, Advanced Molecular Immunology and Cell Biology 2021-2022 Period 1
Janniek Mors
Two waves of plasma cell formation at 2 different sites
- First antibody (IgM) is made in medulla
- Then the focus of the response shifts → germinal centers are created → in germinal center: affinity
maturation and isotype switching
- Different isotypes have different Fc tails → different function because bind different Fc receptors
Beneficial role for gut microbiota
- Synthesize essential metabolites
- Help metabolism of fibers and make molecules that are essential
- Inactivate toxic substances
- Limit the space for pathogenic micro-organisms
- Establishment of the gut-associated lymphoid tissue
Systemic and mucosal immune defense differs
- Mucosal associated lymphoid tissue: tolerogenic immune response by DC
Epithelial cells contribute to mucosal defense
M-cells can take up and transport antigens
- Take up bacteria from the gut lumen and deliver them and their antigens to DCs and lymphocytes in
the Peyer’s patch
- Causes production of bacteria-specific effector T cells, plasma cells. Making bacteria specific secretory
antibodies
DCs can extent processes across the epithelium to sample content of the lumen.
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