Advanced molecular immunology
Inhoud
Week 1 ..................................................................................................................... 2
Lecture Introduction to immunology ........................................................................ 2
Lecture Dendritic cells in tailored adaptive immunity ............................................. 12
Week 2 ................................................................................................................... 30
Lecture T cell priming ........................................................................................... 30
Week 3 ................................................................................................................... 46
Lecture The spatial tumor microenvironment in cancer .......................................... 46
Week 4 ................................................................................................................... 59
Lecture Antibodies in health and disease ............................................................... 59
Week 5 ................................................................................................................... 77
Lecture Immune responses to glycolipids and polysaccharides .............................. 77
Week 6 ................................................................................................................... 97
Lecture Neuro-immunology (MS) ........................................................................... 97
Week 7 ................................................................................................................. 117
Lecture lymph node development ....................................................................... 117
Lecture immunometabolism............................................................................... 127
1
,Week 1
Lecture Introduction to immunology
Cells of the immune system and activation of innate & adaptive immune system
Adaptive cells
• B-cell → plasma cells
• T cell → effector T cell
Innate cells
• Macrophages – come from monocytes
• DCs – come from monocytes
• Neutrophils
• Eosinophils
• Basophils
• Mast cells
• NK cells → come from NK/T cell precursor
Innate immunity
• Fast (hours)
• Fixed
• Limited number of specificities
• Constant during response
• Initiation at site of infection
Adaptive immunity
• Slow (days to weeks)
• Variable
• Numerous high selective specificities
• Improves during response
• Has memory
• Initiation in lymph node
2
,Innate and adaptive both cause destruction of pathogens
Innate cells can distinguish ‘self’ and ‘non self’
Macrophage receptors recognize the cell surface carbohydrates of bacterial cells, but not
those of human cells
NK cell receptors recognize changes at the surface of human cells that are caused by viral
infection. They can detect absence or alteration of MHCI, similar to CD8+ T cells but those
recognize specific peptides presented on MHCI.
Innate response to pathogens:
• Macrophage receptors recognize pathogen → MO is bound by phagocytic receptors
on the macrophages surface (phagocytosis)
o Toll like receptors for signaling (triggers cytokine release)
• Degradation and innate cell activation
o Binding of bacteria to phagocytic receptors on macrophages induces their
engulfment and degradation
o Binding of bacterial components to signaling receptors on macrophages
induces their synthesis if inflammatory cytokines.
Adaptive immunity starts in the secondary lymphoid organs (lymph nodes, spleen, MALT)
Structure where the naïve lymphocytes leave the bloodstream and enter the lymph: High
Endothelial Venules (HEV), they express L-selectin.
DC maturation
1. Immature DCs: take up antigen (good at phagocytosis, but not at presenting
antigens)
2. Activation
3. Antigen processing
4. Mature DCs: present antigen (good at presenting antigen, but not at phagocytosis)
3
, An adaptive immune response starts when the DCs meet the T cells. It is important that
there are two signals when and antigen is presented to the T cell. The two signals are:
1. MHCI or MHCII
2. Co-stimulation
3. Later there will also be a third signal (cytokines)
Co-stimulation
T cells need both antigen (via MHC) and a danger signal (via CD80/CD86) to activate. TLRs
on DCs detect danger and trigger the expression if CD80/CD86 (B7) to enable proper T cell
activation. The CD80/CD86 from the DC binds to CD28 on the T cell. TLR signaling in the D
triggers the upregulation of CD80/CD86 in the DC. If the T cell does not get the second
signal than there is anergy or tolerance.
Complement
The complement helps innate cells to take up bacteria. Antibodies recognize and cover the
bacteria, so that macrophages can evolve even more receptors and recognize the bacteria
better, so that it can phagocyte them. This is via Fc receptors (for the immunoglobulins).
Cover the pathogen in antibodies to make phagocytosis easier (opsonization) →
phagocytosis occurs readily when bacteria are covered in antibodies (so when
opsonization has taken place) → complement further stimulates phagocytosis.
Complement factors
• Factors present in serum, lymph, and extracellular fluids
• Synthesized by the liver
• Bind pathogens, causing them to undergo phagocytosis
• Without these factors many bacteria would not be phagocytosed
Complement proteins are made by the liver (the liver gets signaled to make more when
there is an infection) and circulate in body fluids. They bind to pathogens, tagging them for
destruction and making it easier for immune cells like macrophages to phagocytose them.
4
Inhoud
Week 1 ..................................................................................................................... 2
Lecture Introduction to immunology ........................................................................ 2
Lecture Dendritic cells in tailored adaptive immunity ............................................. 12
Week 2 ................................................................................................................... 30
Lecture T cell priming ........................................................................................... 30
Week 3 ................................................................................................................... 46
Lecture The spatial tumor microenvironment in cancer .......................................... 46
Week 4 ................................................................................................................... 59
Lecture Antibodies in health and disease ............................................................... 59
Week 5 ................................................................................................................... 77
Lecture Immune responses to glycolipids and polysaccharides .............................. 77
Week 6 ................................................................................................................... 97
Lecture Neuro-immunology (MS) ........................................................................... 97
Week 7 ................................................................................................................. 117
Lecture lymph node development ....................................................................... 117
Lecture immunometabolism............................................................................... 127
1
,Week 1
Lecture Introduction to immunology
Cells of the immune system and activation of innate & adaptive immune system
Adaptive cells
• B-cell → plasma cells
• T cell → effector T cell
Innate cells
• Macrophages – come from monocytes
• DCs – come from monocytes
• Neutrophils
• Eosinophils
• Basophils
• Mast cells
• NK cells → come from NK/T cell precursor
Innate immunity
• Fast (hours)
• Fixed
• Limited number of specificities
• Constant during response
• Initiation at site of infection
Adaptive immunity
• Slow (days to weeks)
• Variable
• Numerous high selective specificities
• Improves during response
• Has memory
• Initiation in lymph node
2
,Innate and adaptive both cause destruction of pathogens
Innate cells can distinguish ‘self’ and ‘non self’
Macrophage receptors recognize the cell surface carbohydrates of bacterial cells, but not
those of human cells
NK cell receptors recognize changes at the surface of human cells that are caused by viral
infection. They can detect absence or alteration of MHCI, similar to CD8+ T cells but those
recognize specific peptides presented on MHCI.
Innate response to pathogens:
• Macrophage receptors recognize pathogen → MO is bound by phagocytic receptors
on the macrophages surface (phagocytosis)
o Toll like receptors for signaling (triggers cytokine release)
• Degradation and innate cell activation
o Binding of bacteria to phagocytic receptors on macrophages induces their
engulfment and degradation
o Binding of bacterial components to signaling receptors on macrophages
induces their synthesis if inflammatory cytokines.
Adaptive immunity starts in the secondary lymphoid organs (lymph nodes, spleen, MALT)
Structure where the naïve lymphocytes leave the bloodstream and enter the lymph: High
Endothelial Venules (HEV), they express L-selectin.
DC maturation
1. Immature DCs: take up antigen (good at phagocytosis, but not at presenting
antigens)
2. Activation
3. Antigen processing
4. Mature DCs: present antigen (good at presenting antigen, but not at phagocytosis)
3
, An adaptive immune response starts when the DCs meet the T cells. It is important that
there are two signals when and antigen is presented to the T cell. The two signals are:
1. MHCI or MHCII
2. Co-stimulation
3. Later there will also be a third signal (cytokines)
Co-stimulation
T cells need both antigen (via MHC) and a danger signal (via CD80/CD86) to activate. TLRs
on DCs detect danger and trigger the expression if CD80/CD86 (B7) to enable proper T cell
activation. The CD80/CD86 from the DC binds to CD28 on the T cell. TLR signaling in the D
triggers the upregulation of CD80/CD86 in the DC. If the T cell does not get the second
signal than there is anergy or tolerance.
Complement
The complement helps innate cells to take up bacteria. Antibodies recognize and cover the
bacteria, so that macrophages can evolve even more receptors and recognize the bacteria
better, so that it can phagocyte them. This is via Fc receptors (for the immunoglobulins).
Cover the pathogen in antibodies to make phagocytosis easier (opsonization) →
phagocytosis occurs readily when bacteria are covered in antibodies (so when
opsonization has taken place) → complement further stimulates phagocytosis.
Complement factors
• Factors present in serum, lymph, and extracellular fluids
• Synthesized by the liver
• Bind pathogens, causing them to undergo phagocytosis
• Without these factors many bacteria would not be phagocytosed
Complement proteins are made by the liver (the liver gets signaled to make more when
there is an infection) and circulate in body fluids. They bind to pathogens, tagging them for
destruction and making it easier for immune cells like macrophages to phagocytose them.
4
