Guest lectures
Joost van Neerven
The two faced story of milk and allergy
• Basic immunology
- Diet and allergy
o Role of normal diet (person, pregnant women) in developing allergies
o Dietary management of food allergy preventing you get the food allergy or by
actively treating the allergy
o Early introduction of food: studies showed that early introduction of food into diet of
young children can help to prevent the development of food allergy training
immune system
- Tolerance and immunity: a double edged sword
o Perfect immune system perfect balance responds when should respond and
does not respond when should not respond
▪ Low immune response good for 1 spectrum of immune related conditions
but bad for other group of conditions
▪ Strong activation of immune system no infection excessive reactions
inflammatory diseases or allergy
- Kinetics of innate and adaptive immune responses
o Innate immunity: cells that have first interaction with pathogen that comes a long
quick response
o Adaptive immunity: B and T cells can produce allergy IgE
▪ Most of memory in adaptive immunity
▪ T cell will tell B cell what to do
153
,- Immunoglobulin anatomy
o Constant region: antibody binds to pathogen/allergen only binding = no effect to
immune system
o Constant regions bind to receptor specific for IgE/IgG effector functions IgE
allergic responses
o V region contains part that is very specific for three dimensional structure
▪ Specificity of antibody is in this region
- Crystal structure of Bet v 1 / BV16 (Fab) Complex
o Bet v 1 (protein) complexed by fragment of
antibody specific for this allergen
o Size relation between antibody and allergen is such
that you can only have few epitopes on allergen
that can at same time be recognized by antibody
otherwise antibody would be in the way
▪ Size of allergen is limiting for enabling
multiple antibodies to bind
o You need binding of IgE to crosslink and to get
degranulation of basophils/mast cells
- Antigen processing
o Antigen presenting cells (dendritic cells) take up proteins from environment
proteins become present in endosomal pathway small peptides loaded on MHCII
complex antigen presenting cell to T cell
o Peptide can bind to MHCII talk to immune system
o Antibody does not bind to small peptides
154
,- MHC-restricted recognition of peptide by TCR
o T cell receptor very similar to antibodies but recognition is different
- Environmental and microbiological stimuli determine the differentiation of T cells
o Depending on environment and type of stimuli that are given dendritic cell can
become Th cells
▪ Th2 cells play role in allergy producing cytokines IgE
▪ Th1 = severe infections
▪ Th1 and Th 2 are opposite of each other
155
, - Th cell differentiation in human T-cells
• Prevalence of and mechanisms in allergy
- Decreased infectious pressure is associated with an increase in chronic inflammatory
disorders:
o West: decrease in severe infectious diseases + increase in inflammatory diseases
▪ How can this be explained? hygiene hypothesis
▪ Less Th1 more Th2 more development of allergies
▪ Problem: regulation of immune system
➢ Immune system not educated for quick response and stop again
repeated immune defence inflammatory disease
- Allergy prevalence has increased
dramatically: the allergy & asthma
epidemic
o Especially in western world
asthma increased
dramatically
156
Joost van Neerven
The two faced story of milk and allergy
• Basic immunology
- Diet and allergy
o Role of normal diet (person, pregnant women) in developing allergies
o Dietary management of food allergy preventing you get the food allergy or by
actively treating the allergy
o Early introduction of food: studies showed that early introduction of food into diet of
young children can help to prevent the development of food allergy training
immune system
- Tolerance and immunity: a double edged sword
o Perfect immune system perfect balance responds when should respond and
does not respond when should not respond
▪ Low immune response good for 1 spectrum of immune related conditions
but bad for other group of conditions
▪ Strong activation of immune system no infection excessive reactions
inflammatory diseases or allergy
- Kinetics of innate and adaptive immune responses
o Innate immunity: cells that have first interaction with pathogen that comes a long
quick response
o Adaptive immunity: B and T cells can produce allergy IgE
▪ Most of memory in adaptive immunity
▪ T cell will tell B cell what to do
153
,- Immunoglobulin anatomy
o Constant region: antibody binds to pathogen/allergen only binding = no effect to
immune system
o Constant regions bind to receptor specific for IgE/IgG effector functions IgE
allergic responses
o V region contains part that is very specific for three dimensional structure
▪ Specificity of antibody is in this region
- Crystal structure of Bet v 1 / BV16 (Fab) Complex
o Bet v 1 (protein) complexed by fragment of
antibody specific for this allergen
o Size relation between antibody and allergen is such
that you can only have few epitopes on allergen
that can at same time be recognized by antibody
otherwise antibody would be in the way
▪ Size of allergen is limiting for enabling
multiple antibodies to bind
o You need binding of IgE to crosslink and to get
degranulation of basophils/mast cells
- Antigen processing
o Antigen presenting cells (dendritic cells) take up proteins from environment
proteins become present in endosomal pathway small peptides loaded on MHCII
complex antigen presenting cell to T cell
o Peptide can bind to MHCII talk to immune system
o Antibody does not bind to small peptides
154
,- MHC-restricted recognition of peptide by TCR
o T cell receptor very similar to antibodies but recognition is different
- Environmental and microbiological stimuli determine the differentiation of T cells
o Depending on environment and type of stimuli that are given dendritic cell can
become Th cells
▪ Th2 cells play role in allergy producing cytokines IgE
▪ Th1 = severe infections
▪ Th1 and Th 2 are opposite of each other
155
, - Th cell differentiation in human T-cells
• Prevalence of and mechanisms in allergy
- Decreased infectious pressure is associated with an increase in chronic inflammatory
disorders:
o West: decrease in severe infectious diseases + increase in inflammatory diseases
▪ How can this be explained? hygiene hypothesis
▪ Less Th1 more Th2 more development of allergies
▪ Problem: regulation of immune system
➢ Immune system not educated for quick response and stop again
repeated immune defence inflammatory disease
- Allergy prevalence has increased
dramatically: the allergy & asthma
epidemic
o Especially in western world
asthma increased
dramatically
156
