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HYPERSENSITIVITY
& IT’S CLASSIFICATION
Dr Akshay Shetty
Associate Professor
SSRAMCH Inchal
Contents
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 2
Objectives
Definition of
Hypersensitivity
Classification of
Hypersensitivity
Hypersensitivity
with examples
Summary References
Objectives
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 3
By the end of the presentation the students must be able to---
• Define hypersensitivity
• Classify hypersensitivity
• Discuss hypersensitivity with examples
1
Hypersensitivity reactions (HR) are immune
responses that are exaggerated or
inappropriate against an antigen or allergen.
Our immune system plays a crucial
role in protecting our body against pathogens,
but sometimes there is an exaggerated
response. This exaggerated response is
triggered by the interaction of the immune
system with an antigen (allergen) and is
referred to as hypersensitivity
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 4
• Type I: reaction mediated by IgE antibodies
• Type II: cytotoxic reaction mediated by IgG or
IgM antibodies
• Type III: reaction mediated by immune
complexes
• These reactions are known as immediate
hypersensitivity reactions (IHR) because they
occur within 24 hours. Antibodies including
IgE, IgM, and IgG mediate them
• Type IV : delayed reaction mediated by cellular
response
Coombs and
Gell classified
hypersensitivity
reactions into
four forms.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 5
Type I or Anaphylactic Response
The anaphylactic response is mediated by IgE antibodies that are produced by
the immune system in response to environmental proteins (allergens) such as
pollens, animal danders, or dust mites.
These antibodies (IgE) bind to mast cells and basophils, which contain
histamine granules that are released in the reaction and cause inflammation.
Type I hypersensitivity reactions can be seen in bronchial asthma, allergic
rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, and anaphylactic
shock
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 6
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 7
Anaphylaxis
Anaphylaxis is a medical emergency as it can lead to acute, life-threatening
respiratory failure.
It is an IgE-mediated process.
It is the most severe form of an allergic reaction, where mast cells suddenly
release a large amount of histamine and later on leukotrienes.
In severe cases intense bronchospasm, laryngeal edema, cyanosis,
hypotension, and shock are present
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 8
Allergic Bronchial Asthma
Allergic bronchial asthma is an atopic disease, characterized by bronchospasm.
It may also be a chronic inflammatory disease.
In its etiology, environmental factors along with a genetic background play an
important role.
The diagnosis is dependent on history and examination.
In allergic bronchial asthma, IgE is elevated, and sputum eosinophilia is common.
Epidemiologically, a positive skin prick test or specific IgE are risk factors for
asthma.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 9
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 10
Allergic Rhinitis
• Allergic rhinitis is another atopic disease
where histamine and leukotrienes are
responsible for rhinorrhoea, sneezing, and
nasal obstruction. Allergens are similar to
those found in bronchial asthma. Nasal polyps
may be seen in chronic rhinitis.
Allergic Conjunctivitis
• Allergic conjunctivitis presents with rhinitis
and is IgE-mediated. Itching and eye problems
including watering, redness, and swelling
always occur.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 11
Food Allergy
• Clinicians must differentiate food allergy
(IgE-mediated) from food intolerance that
can be a cause for a variety of aetiologies
including malabsorption and celiac disease.
• It is more frequent in children as seen in
cow's milk allergy.
• Food allergy symptoms mostly affect the
respiratory tract, the skin, and the gut.
• Skin prick tests are helpful to test for food
allergens that can trigger severe reactions,
e.g., peanuts, eggs, fish, and milk.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 12
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 13
Atopic Eczema
Atopic eczema is an IgE-mediated
disease that affects the skin and
has an immunopathogenic very
similar to that of allergic asthma
and allergic rhinitis, which are
present in more than half of
these patients.
Radioallergosorbent (RAST) may
reveal the specificity of the IgE
antibody involved but has little
help in management.
Drug Allergy
• Drugs may cause allergic reactions by
any mechanism of hypersensitivity.
• For example, penicillin may cause
anaphylaxis, which is IgE-mediated but
most responses are trivial. Penicillin
cross-reacts with other semisynthetic
penicillins including monobactams and
carbapenems and may also cross-react
with other antibiotics such as
cephalosporins
HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty)
06/04/2024 15
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 16
Type II or Cytotoxic-Mediated Response
IgG and IgM mediate cytotoxic-mediated responses against cell surface and
extracellular matrix proteins.
The immunoglobulins involved in this type of reaction damage cells by
activating the complement system or by phagocytosis.
Type II hypersensitivity reactions can be seen in immune thrombocytopenia,
autoimmune hemolytic anemia, and autoimmune neutropenia
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 17
Immune Thrombocytopenia (ITP)
ITP is an autoimmune disorder that occurs at any age. Phagocytes destroy
sensitized platelets in the peripheral blood.
Clinically, it manifests as thrombocytopenia with shortened platelet survival
and increased marrow megakaryocytes.
Sudden onset of petechiae and bleeding from the gums, nose, bowel, and
urinary tract occurs.
Bleeding can accompany infections, drug reactions, malignancy, and other
autoimmune disorders such as thyroid disease and SLE
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 18
Autoimmune Hemolytic anemia (AIHA)
There are two types of immune hemolytic anemia:
• IgG-mediated (warm AIHA)
• IgM-mediated (cold AIHA).
The warm type may be idiopathic autoimmune or secondary to other diseases
such as malignancy affecting the lymphoid tissues.
The cold type may be idiopathic or secondary to infections such as Epstein-Barr
virus.
The primary clinical sign of the two is jaundice.
The laboratory diagnosis is made by a positive Coombs test, which identifies
immunoglobulins and C3 on red blood cells
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 19
Autoimmune Neutropenia
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 20
Autoimmune neutropenia may be present with bacterial and fungal infections, or
it may occur alone or with autoimmune diseases (systemic lupus erythematosus,
rheumatoid arthritis, autoimmune hepatitis), infections and lymphoma.
Bone marrow examination is needed if neutropenia is severe.
For associated autoimmune disorders, an autoimmune antibody panel is
necessary (ANA, ENA, and dsDNA)
Hemolytic Disease of the Fetus and the Newborn
(erythroblastosis fetalis)
The maternal immune system suffers an initial sensitization to
the fetal Rh+ red blood cells during birth when the placenta tears
away.
The first child escapes the disease but the mother, now
sensitized, will be capable of causing a hemolytic reaction against
a second Rh+ fetus, which develops anemia and jaundice once
the maternal IgG crosses the placenta
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 21
Myasthenia Gravis
• Myasthenia gravis is an autoimmune
disorder caused by antibodies to post-
synaptic acetylcholine receptors that
interfere with neuromuscular
transmission.
• It is characterized by extreme
muscular fatigue, double vision,
bilateral ptosis, deconjugate eye
movements, difficulty swallowing, and
weakness in the upper arms
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 22
Type III or Immunocomplex Reactions
These are also mediated by IgM and IgG antibodies that react with soluble
antigens forming antigen-antibody complexes.
The complement system becomes activated and releases chemotactic agents
that attract neutrophils and cause inflammation and tissue damage as seen in
vasculitis and glomerulonephritis.
Type III hypersensitivity reactions can classically be seen in serum sickness and
Arthus reaction.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 23
Serum Sickness
• Serum sickness can be induced with
massive injections of a foreign antigen.
• Circulating immune complexes infiltrate
the blood vessel walls and tissues,
causing an increased vascular
permeability and leading to
inflammatory processes such as
vasculitis and arthritis.
• It was a complication of anti-serum
prepared in animals to which some
individuals produced antibodies to the
foreign protein.
• It was also experienced in the treatment
with antibiotics such as penicillin.
HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty)
06/04/2024 24
Arthus Reaction
• Arthus reaction is a local reaction seen
when a small quantity of antigens is
injected into the skin repeatedly until
detectable levels of antibodies (IgG) are
present.
• If the same antigen is inoculated,
immune complexes develop at the
mentioned local site and in the
endothelium of small vessels.
• This reaction is characterized by the
presence of marked edema and
hemorrhage, depending on the
administered dose of the foreign
antigen
HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty)
06/04/2024 25
Type IV hypersensitivity
A Type IV hypersensitivity reaction is mediated by T cells that provoke
an inflammatory reaction against exogenous or endogenous antigens.
In certain situations, other cells, such as monocytes, eosinophils, and
neutrophils, can be involved.
After antigen exposure, an initial local immune and inflammatory
response occurs that attracts leukocytes..
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 26
Cont…
The antigen engulfed by the macrophages and monocytes is
presented to T cells, which then becomes sensitized and activated.
These cells then release cytokines and chemokines, which can cause
tissue damage and may result in illnesses.
Examples of illnesses resulting from type IV hypersensitivity
reactions include contact dermatitis and drug hypersensitivity
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 27
https://www.youtube.com/watch?v=jXTW4F-8jd4
HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty)
06/04/2024 28
Summary
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 29
1.Define hypersensitivity
Classify hypersensitivity
Discuss hypersensitivity with examples
References
1. Khaled Marwa, Noah P. Kondamudi Type IV Hypersensitivity Reaction
https://www.ncbi.nlm.nih.gov/books/NBK562228/
2. Angel A. Justiz Vaillant,Rishik Vashisht, Patrick M. Zito, Immediate
Hypersensitivity Reactions
https://www.ncbi.nlm.nih.gov/books/NBK513315/#:~:text=Hypersensi
tivity%20reactions%20are%20exaggerated%20or,to%20the%20antigen
%20or%20allergen.
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 30
THANK YOU
06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 31

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Hypersensitivity and its classification .pptx

  • 1. HYPERSENSITIVITY & IT’S CLASSIFICATION Dr Akshay Shetty Associate Professor SSRAMCH Inchal
  • 2. Contents 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 2 Objectives Definition of Hypersensitivity Classification of Hypersensitivity Hypersensitivity with examples Summary References
  • 3. Objectives 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 3 By the end of the presentation the students must be able to--- • Define hypersensitivity • Classify hypersensitivity • Discuss hypersensitivity with examples 1
  • 4. Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Our immune system plays a crucial role in protecting our body against pathogens, but sometimes there is an exaggerated response. This exaggerated response is triggered by the interaction of the immune system with an antigen (allergen) and is referred to as hypersensitivity 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 4
  • 5. • Type I: reaction mediated by IgE antibodies • Type II: cytotoxic reaction mediated by IgG or IgM antibodies • Type III: reaction mediated by immune complexes • These reactions are known as immediate hypersensitivity reactions (IHR) because they occur within 24 hours. Antibodies including IgE, IgM, and IgG mediate them • Type IV : delayed reaction mediated by cellular response Coombs and Gell classified hypersensitivity reactions into four forms. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 5
  • 6. Type I or Anaphylactic Response The anaphylactic response is mediated by IgE antibodies that are produced by the immune system in response to environmental proteins (allergens) such as pollens, animal danders, or dust mites. These antibodies (IgE) bind to mast cells and basophils, which contain histamine granules that are released in the reaction and cause inflammation. Type I hypersensitivity reactions can be seen in bronchial asthma, allergic rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, and anaphylactic shock 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 6
  • 7. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 7
  • 8. Anaphylaxis Anaphylaxis is a medical emergency as it can lead to acute, life-threatening respiratory failure. It is an IgE-mediated process. It is the most severe form of an allergic reaction, where mast cells suddenly release a large amount of histamine and later on leukotrienes. In severe cases intense bronchospasm, laryngeal edema, cyanosis, hypotension, and shock are present 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 8
  • 9. Allergic Bronchial Asthma Allergic bronchial asthma is an atopic disease, characterized by bronchospasm. It may also be a chronic inflammatory disease. In its etiology, environmental factors along with a genetic background play an important role. The diagnosis is dependent on history and examination. In allergic bronchial asthma, IgE is elevated, and sputum eosinophilia is common. Epidemiologically, a positive skin prick test or specific IgE are risk factors for asthma. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 9
  • 10. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 10
  • 11. Allergic Rhinitis • Allergic rhinitis is another atopic disease where histamine and leukotrienes are responsible for rhinorrhoea, sneezing, and nasal obstruction. Allergens are similar to those found in bronchial asthma. Nasal polyps may be seen in chronic rhinitis. Allergic Conjunctivitis • Allergic conjunctivitis presents with rhinitis and is IgE-mediated. Itching and eye problems including watering, redness, and swelling always occur. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 11
  • 12. Food Allergy • Clinicians must differentiate food allergy (IgE-mediated) from food intolerance that can be a cause for a variety of aetiologies including malabsorption and celiac disease. • It is more frequent in children as seen in cow's milk allergy. • Food allergy symptoms mostly affect the respiratory tract, the skin, and the gut. • Skin prick tests are helpful to test for food allergens that can trigger severe reactions, e.g., peanuts, eggs, fish, and milk. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 12
  • 13. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 13
  • 14. Atopic Eczema Atopic eczema is an IgE-mediated disease that affects the skin and has an immunopathogenic very similar to that of allergic asthma and allergic rhinitis, which are present in more than half of these patients. Radioallergosorbent (RAST) may reveal the specificity of the IgE antibody involved but has little help in management.
  • 15. Drug Allergy • Drugs may cause allergic reactions by any mechanism of hypersensitivity. • For example, penicillin may cause anaphylaxis, which is IgE-mediated but most responses are trivial. Penicillin cross-reacts with other semisynthetic penicillins including monobactams and carbapenems and may also cross-react with other antibiotics such as cephalosporins HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 06/04/2024 15
  • 16. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 16
  • 17. Type II or Cytotoxic-Mediated Response IgG and IgM mediate cytotoxic-mediated responses against cell surface and extracellular matrix proteins. The immunoglobulins involved in this type of reaction damage cells by activating the complement system or by phagocytosis. Type II hypersensitivity reactions can be seen in immune thrombocytopenia, autoimmune hemolytic anemia, and autoimmune neutropenia 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 17
  • 18. Immune Thrombocytopenia (ITP) ITP is an autoimmune disorder that occurs at any age. Phagocytes destroy sensitized platelets in the peripheral blood. Clinically, it manifests as thrombocytopenia with shortened platelet survival and increased marrow megakaryocytes. Sudden onset of petechiae and bleeding from the gums, nose, bowel, and urinary tract occurs. Bleeding can accompany infections, drug reactions, malignancy, and other autoimmune disorders such as thyroid disease and SLE 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 18
  • 19. Autoimmune Hemolytic anemia (AIHA) There are two types of immune hemolytic anemia: • IgG-mediated (warm AIHA) • IgM-mediated (cold AIHA). The warm type may be idiopathic autoimmune or secondary to other diseases such as malignancy affecting the lymphoid tissues. The cold type may be idiopathic or secondary to infections such as Epstein-Barr virus. The primary clinical sign of the two is jaundice. The laboratory diagnosis is made by a positive Coombs test, which identifies immunoglobulins and C3 on red blood cells 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 19
  • 20. Autoimmune Neutropenia 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 20 Autoimmune neutropenia may be present with bacterial and fungal infections, or it may occur alone or with autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis), infections and lymphoma. Bone marrow examination is needed if neutropenia is severe. For associated autoimmune disorders, an autoimmune antibody panel is necessary (ANA, ENA, and dsDNA)
  • 21. Hemolytic Disease of the Fetus and the Newborn (erythroblastosis fetalis) The maternal immune system suffers an initial sensitization to the fetal Rh+ red blood cells during birth when the placenta tears away. The first child escapes the disease but the mother, now sensitized, will be capable of causing a hemolytic reaction against a second Rh+ fetus, which develops anemia and jaundice once the maternal IgG crosses the placenta 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 21
  • 22. Myasthenia Gravis • Myasthenia gravis is an autoimmune disorder caused by antibodies to post- synaptic acetylcholine receptors that interfere with neuromuscular transmission. • It is characterized by extreme muscular fatigue, double vision, bilateral ptosis, deconjugate eye movements, difficulty swallowing, and weakness in the upper arms 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 22
  • 23. Type III or Immunocomplex Reactions These are also mediated by IgM and IgG antibodies that react with soluble antigens forming antigen-antibody complexes. The complement system becomes activated and releases chemotactic agents that attract neutrophils and cause inflammation and tissue damage as seen in vasculitis and glomerulonephritis. Type III hypersensitivity reactions can classically be seen in serum sickness and Arthus reaction. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 23
  • 24. Serum Sickness • Serum sickness can be induced with massive injections of a foreign antigen. • Circulating immune complexes infiltrate the blood vessel walls and tissues, causing an increased vascular permeability and leading to inflammatory processes such as vasculitis and arthritis. • It was a complication of anti-serum prepared in animals to which some individuals produced antibodies to the foreign protein. • It was also experienced in the treatment with antibiotics such as penicillin. HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 06/04/2024 24
  • 25. Arthus Reaction • Arthus reaction is a local reaction seen when a small quantity of antigens is injected into the skin repeatedly until detectable levels of antibodies (IgG) are present. • If the same antigen is inoculated, immune complexes develop at the mentioned local site and in the endothelium of small vessels. • This reaction is characterized by the presence of marked edema and hemorrhage, depending on the administered dose of the foreign antigen HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 06/04/2024 25
  • 26. Type IV hypersensitivity A Type IV hypersensitivity reaction is mediated by T cells that provoke an inflammatory reaction against exogenous or endogenous antigens. In certain situations, other cells, such as monocytes, eosinophils, and neutrophils, can be involved. After antigen exposure, an initial local immune and inflammatory response occurs that attracts leukocytes.. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 26
  • 27. Cont… The antigen engulfed by the macrophages and monocytes is presented to T cells, which then becomes sensitized and activated. These cells then release cytokines and chemokines, which can cause tissue damage and may result in illnesses. Examples of illnesses resulting from type IV hypersensitivity reactions include contact dermatitis and drug hypersensitivity 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 27
  • 28. https://www.youtube.com/watch?v=jXTW4F-8jd4 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 06/04/2024 28
  • 29. Summary 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 29 1.Define hypersensitivity Classify hypersensitivity Discuss hypersensitivity with examples
  • 30. References 1. Khaled Marwa, Noah P. Kondamudi Type IV Hypersensitivity Reaction https://www.ncbi.nlm.nih.gov/books/NBK562228/ 2. Angel A. Justiz Vaillant,Rishik Vashisht, Patrick M. Zito, Immediate Hypersensitivity Reactions https://www.ncbi.nlm.nih.gov/books/NBK513315/#:~:text=Hypersensi tivity%20reactions%20are%20exaggerated%20or,to%20the%20antigen %20or%20allergen. 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 30
  • 31. THANK YOU 06/04/2024 HYPERSENSITIVITY & IT’S CLASSIFICATION (Dr Akshay Shetty) 31