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NIMISHA KAIKKOLANTE
Mechanism of
Allergic
Reactions
Nimisha Kaikkolante
MSc Food Science and Technology
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.
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
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
NIMISHA KAIKKOLANTE
Types of Allergies
Food Allergy
Skin Allergy
Dust Allergy
Insect sting Allergy
Pet Allergy
Eye Allergy
Drug Allergy
Allergic Rhinitis
Latex Allergy
Mold Allergy
Cockroach Allergy
Food Allergies
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
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
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
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
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.
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
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)
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
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
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)
NIMISHA KAIKKOLANTE
Thank You

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Mechanism of Allergy-Nimisha Kaikkolante

  • 1. NIMISHA KAIKKOLANTE Mechanism of Allergic Reactions Nimisha Kaikkolante MSc Food Science and Technology
  • 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
  • 5. NIMISHA KAIKKOLANTE Types of Allergies Food Allergy Skin Allergy Dust Allergy Insect sting Allergy Pet Allergy Eye Allergy Drug Allergy Allergic Rhinitis Latex Allergy Mold Allergy Cockroach Allergy Food Allergies
  • 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)