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Summary - Advanced molecular immunology and cell biology (AM_470656) (Vrije Universiteit Amsterdam)
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Summary - Advanced molecular immunology and cell biology (AM_470656) (Vrije Universiteit Amsterdam)
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Advanced ImmunologyDendritic cells in tailored adaptive immunity
The immune system consists of multiple components together regulating health and disease
Lymphatic system, Skin, Innate immune cells, Adaptive Immune cells
Three main phases are initiated upon first infection with a pathogen
Anatomic barrier Innate immunity (recognition by nonspecific and broadly specific factors,
eating by macrophages, 0-4 h) Early induced innate response (recognition of PAMPs, activation
of effector cells and inflammation, 4-96 h) Adaptive immune response (transport to lymphoid
organs, B and T cells, >96 h)
The complement system consists of preformed factors which respond immediately upon infection
Is not tested on exam
C3a: increased vascular permeability, leukocyte recruitment
C3b: Enhanced phagocytosis, bacterial lysis
Macrophages and dendritic cells (DC) are phagocytes of the innate immune system with different
functions
Macrophages don’t migrate and mostly phagocytose and cause inflammation
DCs can migrate from the site of infection to the lymph nodes and present the antigen to adaptive
immune cells.
They have specific receptors for recognition of self versus non-self via associated molecular
patterns (pathogen, damaged, self).
They can bind pathogen through direct and indirect (binding the complement or antibodies)
binding and cause phagocytosis and intracellular signaling (cytokine production).
Dendritic cells (DC) are the bridge between innate and adaptive immunity via activation and
skewing of naïve T cells
3 Signals make a naïve T cell proliferate
1. T cell/DC binding of the antigen on MHC and the receptor on T cells
MHC I = CD8+ cytotoxic T cells
MHC II = CD4+ helper T cells
2. Co-stimulation that induces proliferation (activation or inhibition signal)
CD80/86 (B7.1/B7.2)- CD28
Essential for proliferation and survival
3. Cytokines that determine the proliferation of the naïve T cell
,Only mature DC can activate naïve T cells for induction of adaptive immunity upon recognition of
pathogens
DC maturation
Phagocytosis Antigen processing and presentation (MHC expression) Co-stimulatory
molecules Migration Inflammatory cytokines
Pathogen binding via specific receptors enables DC to shape adaptive immune responses
Fc receptors can activate or inhibit immune cells by binding of immune complexes
Immune cells have either activation FcR or inhibitory FcR
C-type lectin receptors (CLR) are a diverse family of receptors important for antigen uptake,
presentation and signaling
CLRs have a carbohydrate recognition domain (CRD), are calcium dependent and mostly found on
the cell surface for detecting (pathogen) specific carbohydrate structures.
Antigen internalization (Taking antigen inside the cell)
Antigen presentation
Adhesion
Signaling within the cell
Toll-like receptors (TLR) are important signaling receptors leading to specific cytokine secretion
TLR can be extra- and intracellular, they phagocytose and signal to produce cytokines and/or IFN I.
DCs have different types of TLR which can lead to different responses of the DC.
Toll-like receptors (TLR) recognize different pathogens via specified PAMPs
Depending on the pathogen and ligand, multiple pattern recognition receptors (PRR) are stimulated
leading to tailored immunity
, A combination of intracellular signaling cascades drives antigen handling and cytokine responses
Cytokine responses:
Inflammatory or priming cytokines (IL4, IL6, IL12, TNFa, TGFB)
Transcription via NFkB
Different microbial infections
Type I interferons (IFN) (IFNa, IFNB)
Transcription via IRF3/7
Viral infection
IL1 family (IL1a, ILB, IL18)
Upon inflammasome activation
Cytosolic infection
TLR signal via MyD88 or TRIF for activation of transcription factors and cytokine secretion upon
infection
TLR detects extracellular infection via PAMPs
Signal through MYD88 results in the activation of transcription factor NFkB and in pro-
inflammatory cytokine production and T cell differentiation
Signal through TRIF results in the activation of transcription factor IRF3 and in anti-viral immunity
Cytokine production by mature dendritic cells defines T helper cell responses during priming
Endosomal TLR and RLR induce the interferon response during viral infection
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