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MSc Allergy
The role of our immune system
• Protect us from infection
BUT
• Do not damage self
– Autoimmune disease
• Recognising what is a pathogen or not
– Bacteria vs food
– Allergy!
• Difficult job!
MSc Allergy
What you need to cause an allergic reaction
• Allergen (what you are allergic to)
– Food, pollen, drug
• IgE antibody specific for above
• Mediator cells
– Mast cells or basophils
MSc Allergy
The process
Histamine
Mast Cell
MSc Allergy
Food allergy in children
• Foods are an important component of childhood allergy
• Common causes: cow's milk protein, eggs, peanut, soy, tree nuts, fish, and wheat.
• Clinical manifestations
– Urticaria/angioedema, anaphylaxis, atopic dermatitis, respiratory symptoms, or a gastrointestinal (GI) disorder.
• GI allergic manifestations
– Immunoglobulin E (IgE) mediated (immediate GI hypersensitivity and oral allergy syndrome)
– "mixed" GI allergy syndromes (involving some IgE components and some non-IgE or T-cell-mediated components) include eosinophilic esophagitis and eosinophilic gastroenteritis.
– Non-IgE-mediated or T-cell-mediated allergic GI disorders include dietary protein enteropathy, protein-induced enterocolitis, and proctitis
MSc Allergy
Antibodies
• How do we make IgE?
• IgE antibodies are key to the development of an allergic reaction
– We make different types of antibody IgG, IgM, IgA and IgE
– Randomly created (shuffling a pack of cards)
– Most do not work or cause damage to self and are removed
– Those that are functional and are safe survive
• We have the potential to produce antibodies to most pathogens out there!
• Sometimes it goes wrong
– Autoimmune disease (IgG)
– Allergy (IgE)
MSc Allergy
Antibodies
MSc Allergy
Where do antibodies come from
• Lymphocytes are a subgroup of white cells
– B cells, T cells
• We make millions of different B and T cells
– B cells make antibody with the help of T cells
– Individually recognise a slightly different shape
– Shape is “non self”
– If they recognise “self” they usually die
– When a B cell sees/recognises non self it changes into an antibody factory (plasma cells)
A plasma cell
MSc Allergy
More on IgE
– Important in our immune response to parasites
– The same mast cell and basophil chemicals released via IgE can help kill parasites
– In modern society the role of IgE is overtaken by allergy
– Allergy and IgE
– You are not born with allergies, they develop– IgE; very low levels at birth (cord blood)
– We can measure IgE specific for allergens, pollen, food, drugs etc.
– Specific IgE (RAST)– Blood test for allergy– Allergen specific IgE difficult to detect at birth
MSc Allergy
How and why allergies develop
• Knowing how IgE antibodies are made can help to understand why people develop allergies?
– Explain what goes wrong
– Why are allergies increasing
MSc Allergy
How does your immune system make IgE?• IgE is made by B cells (type of white cell)
• External factors influence the “decision” for a B cell to
– Make an antibody to a non pathogen e.g. pollen or food
– Make IgE , not IgG, IgA or IgM
• Important external factors:
– T cells: Important accessory cells in generating IgE
– Chemicals (cytokines) produced by the T cells
MSc Allergy
How are T cells important?
• Need T cell help (helper T cells)
– Helper cells add level of control
– Important in helping B cells make antibody
• Types of Helper T cells (TH)
– TH1 important in immune response to viruses and bacteria
– Cytokines Interferon Gamma– TH2 important in generating IgE
– Cytokines IL-4, IL-13,
• Too much TH2 influence =allergy
T cell (TC) influences the type of antibody the B cell (BC) makes by direct contact and chemicals (cytokines) they produce
MSc Allergy
Other types of cells
• Regulatory T cells
– Prevent immune system from recognising “self” prevent autoimmunity and allergy
• Antigen presenting cells
– Important in TH cell function
– Present small fragments of pathogens e.g. bacteria or viruses to T cells to activate them
– Also present allergens to TH cells=allergy
T Cell in close contact with larger antigen presenting cell. This is essential for the T cell to function
MSc Allergy
• Now the basic immunology has been covered:
• Allergy in the developing infant
– A few points
– Why our immune system goes wrong and allergies develop
– Genetics– Environmental factors– Hygiene hypothesis– Mother’s influence
MSc Allergy
Role of allergy in the developing infant
• A few points:
– You can develop allergy at any age
– Your immune system has to have “seen” the agent you are allergic to at some point previously
– Allergies can resolve e.g. egg and milk
– Modification of immune response (regulatory T cells, IgG4 antibodies?)
MSc Allergy
Why our immune system goes wrong and allergies develop
• Genetics
– Allergic predisposition does run in families
– But no clear inheritance pattern recessive , dominant X-linked
• HLA:
– Some autoimmune disorders have a strong genetic link e.g. HLA B27 and ankylosing spondylitis
– No such HLA association with allergy
• Allergy most likely polygenetic multiple factors genetic and environmental
MSc Allergy
Environmental factors
• Hygiene hypothesis: Why is childhood allergy increasing?
• Environment is too clean
• Most responses to viruses and bacteria are TH1, generating IgG,
• If infants immune system is shielded from pathogens is there and increased propensity for TH2 to dominate?
• Will the immune system to make IgE inappropriately?
MSc Allergy
Hygiene hypothesis evidence:
• Individuals who were exposed to a farming environment in childhood are less likely to develop allergies
– Mainly livestock farming and exposure to pathogens
– TH1 biased immune response
– Raised number of regulatory T cells in cord blood (protect against TH2 pro allergic responses)
MSc Allergy
Alterations to DNA
• DNA methylation
• Biochemical modification of DNA affecting cellular function
– DNA methylation has been described in immune cells, particularly
– Regulatory T cells
– Helper T cells (TH1 and TH2)
• Role of environmental factors influencing immune function at a genetic level
MSc Allergy
Studies on DNA methylation
• Farmers (hygiene hypothesis)
– Different DNA methylation patterns in children exposed to farming environment
– Particularly influencing IL-13 and IL-4 (TH2 cytokines)
• Mothers influence
– Mothers living in farming environment have different placental immune cell DNA methylation (CD14)
– Vitamin B12 and folic acid levels influence DNA methylation
– Role of mothers diet?
MSc Allergy
Diet and nutrition
• Maternal diet
– Reduced tobacco exposure and increased intake of oily fish during pregnancy and early childhood may be effective in reducing the incidence of asthma at 2 years of age
– Maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze
– Antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child's risk of atopic diseases
MSc Allergy
Childhood nutrition:
• Vitamin D supplements
– Vitamin D deficiency is common!
– Role of nutrition and lack of sun exposure
– Immune modulator (influences B and T cell function)
– Vitamin D deficiency common in allergy
– Asthma– Urticaria– Rhinitis
– Should we supplement vitamin D?
• Allergen avoidance in high risk groups: Carina
MSc Allergy
Summary
• Key components of an allergic response
– IgE, mast cells/basophils, mediators (histamine)
• What is IgE and how it’s made
• Clinical features of allergic reactions
• Possible explanations for why individuals develop allergies
• Many questions still not many answers!
MSc Allergy
Any questions?
