Download Allergy

The immunology of allergy
and allergic predisposition
Efrem Eren
[email protected]
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!
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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
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The process
Mast Cell
Histamine
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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 Tcell-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
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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)
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Antibodies
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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)
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A plasma cell
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
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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
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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
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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
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T cell (TC) influences the type
of antibody the B cell (BC)
makes by direct contact and
chemicals (cytokines) they
produce
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
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T Cell in close contact with
larger antigen presenting cell.
This is essential for the T cell
to function
• 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
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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?)
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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
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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?
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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)
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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
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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?
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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
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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
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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!
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Any questions?
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