2. NIMISHA KAIKKOLANTE
What is an allergy?
Allergies are caused by an abnormal response of the immune system and is
also referred to as atopy.
The immune system reacts to a usually harmless substance in the
environment known as Allergens
The substance can be pollen, mold, dust, animal dander, certain foods,
insect stings, etc.
3. NIMISHA KAIKKOLANTE
Hypersensitivity
and Allergy
Allergy: A hypersensitive response to an environmental
antigen. Often presents as hay fever, asthma, dermatitis or
anaphylaxis
Hypersensitivity: An exaggerated immune response
that may cause damage to the host. The trigger is often an
innocuous antigen
4. NIMISHA KAIKKOLANTE
Known as immediate or anaphylactic hypersensitivity, mediated by IgE
antibodies which trigger the mast cells and basophils to release
pharmacologically active agents
Eg: Allergic reactions
Type I Hypersensitivity
01
Known as cytotoxic hypersensitivity, IgM or IgG antibodies binds to antigen on
the surface of cells and activate complement cascade
Eg: ABO Transfusion reaction
Type II Hypersensitivity
02
Known as Immune complex hypersensitivity reaction. Complexes of antigen and
IgM or IgG antibodies accumulate in the circulation or in tissue and activate the
complement cascade. Granulocytes are attracted to the site of activation and
release lytic enzymes
Eg: Serum sickness
Type III Hypersensitivity
03
Known as cell mediated or delayed type hypersensitivity. Mediated by T cells,
which release cytokines upon activation to cause accumulation and activation of
macrophages
Eg: Tuberculin reaction
Type IV Hypersensitivity
04
Hypersensitivity
6. NIMISHA KAIKKOLANTE
Characteristics of Food Allergy
Resistant to proteolytic digestion,
heat and acidic conditions
Have multiple, linear IgE binding epitopes
Soluble
Acidic isoelectric points
o Almost all food allergens are proteins with high stability due to the presence of intra molecular disulphide bonds
Low molecular weight glycoproteins
7. NIMISHA KAIKKOLANTE
Stages of Allergic Reaction
It covers all the changes in immune system
during the penetration of an allergen into the
organism, formation of antibodies or sensitized
lymphocytes and their binding with the
repeatedly entering allergen
Immunological stage
Its sense is in formation of biological active
substances. The stimulus to their formation is the
binding of allergen to antibodies or sensitized
lymphocytes at the end of immunological stage
Pathochemical stage
It is described by pathogenic action of formed
mediators onto cells, organs and tissues of the
organism with a clinical display
Pathophysiological stage
01
03
02
8. NIMISHA KAIKKOLANTE
Sensitization to food antigens can take place in the GI tract, oral cavity, skin and occasionally in the respiratory tract
After ingestion, the vast majority of food proteins are broken down largely by gastric acid and digestive enzymes in the stomach and
intestine
Subsequently, the remaining intact food proteins and peptides are transported from the lumen to mucosa through gut epithelial cells
(ECs) (M cells that are localized above Peyer patches)
Antigens/allergens can occur when mucosal dendritic cells (DCs) extend dendrites into the gut lumen.
In the mucosa DCs internalize and process these proteins and peptides and move to T-cell areas of draining lymph nodes, where the
DCs can interact with naïve T cells and present antigen on MHC class II molecules.
The activation of different DC subsets and expression of costimulatory molecules are important in determining the subsequent
immune response
Eg:- The interaction between CD28, which is present on T cells, with CD80 and CD86, which are expressed on DCs, induces T-cell
activation, whereas interaction of CD80 and CD86 with cytotoxic T lymphocyte-associated protein 4 present on T cells downregulates T-
cell activation
9. NIMISHA KAIKKOLANTE
Sensitization phase
The first exposure is usually asymptomatic, but
the body will become sensitized
Challenge phase
Upon re-exposure to the same antigen, the
antigen binds to adjacent IgE molecules
bringing their receptors together, triggering a
signaling cascade that induces the release of
histamine and other inflammatory chemicals
These chemicals cause dilation and increased
permeability of blood vessels, mucus secretion,
stimulation of sensory nerves, smooth muscle
spasms and are responsible for allergic
symptoms, which can range from mild to severe
Mechanism
10. NIMISHA KAIKKOLANTE
Cross Reactivity
Cross-reactivity in allergic reactions occurs when the proteins in one substance
(typically pollen) are similar to the proteins found in another substance
(typically a food).
For example, if you are allergic to birch tree pollen, you may also find that
eating apples causes a reaction for you. Certain tree nuts also demonstrate
cross-reactivity.
11. NIMISHA KAIKKOLANTE
Allergic
Symptoms
Mild symptoms
Watery eyes
Runny Nose
Sneezing
Mild rash
Severe reactions
Swelling
Hives
Difficulty in breathing due to bronchospasm
Digestive problems due to increased gastrointestinal motility
12. NIMISHA KAIKKOLANTE
Expression of Proteins
CD28 CCR6
CD80 and
CD86
CTLA-4
A protein expressed on T cells that
provides co-stimulatory signals
required for T-cell activation and
survival, cytokine production, and
TH2 development
Expressed on dendritic cells,
activated B cells, and monocytes
that work in tandem to provide a
co-stimulatory signal necessary for
T-cell activation and survival
Important for B-lineage maturation and
antigen-driven B-cell differentiation
and is thought to regulate the migration
and recruitment of dendritic and T cells
during inflammatory and immunologic
responses.
A receptor that functions as an
inhibitory signal that
downregulates immune responses
when bound to CD80 and CD86
(Sampson et al., 2017)
13. NIMISHA KAIKKOLANTE
Expression of Proteins
GM-CSF IL-1beta
Granzymes
A and B
IL-6
Functions as a white blood cell
growth factor and stimulates stem
cells to produce granulocytes
(neutrophils, eosinophils, and
basophils) and monocytes
Serine proteases that are released by
cytoplasmic granules within cytotoxic
T cells and natural killer (NK) cells.
They induce programmed cell death in
the target cell, thus eliminating
cancerous or infected cells
IL-1b is an important mediator of the
inflammatory response and is involved
in a variety of cellular activities,
including cell proliferation,
differentiation, and apoptosis
IL-6 is implicated in a wide variety of
inflammation-associated disease states,
has been associated with the maturation
of B cells, and has been shown to act as
an endogenous pyrogen capable of
inducing fever in patients with
autoimmune diseases or infections
14. NIMISHA KAIKKOLANTE
Expression of Proteins
IL-22 MHC
Class II
IL-35 Programmed
cell death 1
(PD-1)
It is unique in that it is produced
by immune cells, including TH cell
subsets and innate lymphocytes,
but acts only on non-hematopoietic
stromal cells, in particular
epithelial cells, keratinocytes, and
hepatocytes
An IL-12 family cytokine produced by
regulatory, but not effector, T and B
cells and plays a role in immune
suppression
A complex critical in initiating immune
responses, MHC class II is found on
antigen-presenting cells and presents
antigen derived from extracellular
proteins to T-cell receptors
A cell-surface receptor that plays an
important role in downregulating the
immune system and suppressing
inflammatory T-cell activation. PD-1 is an
immune checkpoint that serves the dual role
of promoting apoptosis in antigen-specific T
cells while simultaneously reducing
apoptosis in regulatory T cells
15. NIMISHA KAIKKOLANTE
Factors can influence tissue
responses and immune
response to food antigens
Food related factors
Epithelial barrier–damaging factors (alcohol, toxins,
unknown ingredients, detergents)
Allergen type and exposure dose
Type of adjuvants in the allergen and their dose,
microbial products, and contamination of
microorganisms
Route of exposure
Food matrix effects, such as aggregated or repetitive
proteins, lipids, and glycosylated sugars
Cooking temperature
Individual factors
Age and immune status
Microbiome
Barrier defects (filaggrin mutations)
Certain drugs (antacids)
Underlining disease (atopy, dermatitis, rhinitis, and
immune deficiency)