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Hypersensitity, And Types of Hypersensitivity I, II, III, IV
2
Hypersensitivity
III and IV
Presenters:

Pervez Ali Mangnejo
Hypersensitivity
Hypersensitivity
 Hypersensitivity (Immunological reaction) refers to

undesirable immune reactions produced by the normal immune
system.

 Hypersensitivity reactions: When an immune response result

in exaggerated OR in appropriate reactions harmful to the host
the term hypersensitivity OR allergy used.

 Hypersensitivity reactions: four types; based on the

mechanisms involved and time taken for the reaction, a
particular clinical condition (disease) may involve more than
one type of reaction.
5
Classification of Hypersensitivity
 Type

I
 Type II
 Type III
 Type IV
___________________________________
Type I, II and III
Antibody Mediated
Type IV
Cell Mediated
6
Classification of Hypersensitivity

7
Type I (Immediate) Hypersensitivity


Commonly called allergy



Mediated by IgE antibodies produced by plasma cells in
response to stimulation of Th2 cells by an antigens.



The antigens that stimulate it are called allergens
(i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)



Exposure may be ingested, inhalation, injection or direct
contact.



Type I hypersensitivity reactions can be systemic (e.g.,
systemic anaphylaxis) or localized to a specific target
tissue or organ (e.g., allergic rhinitis, asthma).

8
Type II (Cytotoxic) Hypersensitivity



Cytotoxic



Type II hypersensitivity involves IgG or IgM antibody-mediated



IgM or IgG immunoglobulin react with cell-surface antigens to
activate the complements system and produce direct damage
of the sell surface.



Transfusion reactions and hemolytic disease of the newborn
are examples of type II hypersensitivity.

9
Hypersensitivity
Type III
Type III (ICM) Hypersensitivity
Type III (Immune Complex–Mediated) Hypersensitivity


Type III hypersensitivity is also known as immune complex
hypersensitivity.



The reaction may take 3 - 10 hours after exposure to the
antigen (as in Arhus reaction).



The reaction may be general (e.g., serum sickness) or may
involve individual organs including or other organs.



Antigens causing immune complex mediated injury are:
 Exogenous
 Endogenous

11
Type III (ICM) Hypersensitivity
Mechanism of Type III Hypersensitivity


Antigens combines with antibody within circulation and form
immune complex



Wherever in the body they deposited



They activate compliment system



Polymorphonuclear cells are attracted to the site



Result in inflammation and tissue injury

12
The mechanism of type III (immune-complex mediated) hypersensitivity-overview
Antigens combine with
antibodies to form
antigen-antibody complexes.
Antigen
Antibody (IgG)
Antigen-antibody complex

Phagocytes remove most
of the complexes, but
some lodge in the walls
of blood vessels.

There the complexes
activate complement.
Inactive complement
Active complement

Antigen-antibody complexes
and activated complement
attract and activate
neutrophils, which release
inflammatory chemicals.
Neutrophil
Inflammatory chemicals

Inflammatory chemicals
damage underlying
blood vessel wall.
Type III (ICM) Hypersensitivity
Hypersensitivity Type III Reactions

Local Reactions
 Arthus Reaction:
 Arthus Reaction:
It is named for Dr. Arthus.
It is named for Dr. Arthus.
Inflammation caused by the
Inflammation caused by the
deposition of immune
deposition of immune
complexes at a localized site.
complexes at a localized site.
Clinical Manifestation is ::
Clinical Manifestation is
Hypersensitivity Pneumonitis
Hypersensitivity Pneumonitis

Systemic Reactions
 Serum Sickness:
 Serum Sickness:
Systemic inflammatory response
Systemic inflammatory response
to deposited immune complexes at
to deposited immune complexes at
many areas of body.
many areas of body.
Few days to 2 weeks after
Few days to 2 weeks after
injection of foreign serum or drug itit
injection of foreign serum or drug
results in ::
results in
Fever, Urticaria, Artheralgia,
Fever, Urticaria, Artheralgia,
Eosinophila, Spleenomegally, and
Eosinophila, Spleenomegally, and
Lymph adenopathy
Lymph adenopathy
14
Immune Complex
Diseases
Type III (ICM) Hypersensitivity

Immune Complex Diseases:





Hypersensitivity Pneumonitis
Glomerulonephritis
Rheumatoid Arthritis
Systemic Lupus Erythematosus

16
Type III (ICM) Hypersensitivity
Hypersensitivity pneumonitis
 Inhalation of antigens into lungs stimulates antibody
production
 Subsequent inhalation of the same antigen results in
formation of immune complexes
 Activates complement

17
Type III (ICM) Hypersensitivity
Glomerulonephritis
 Immune complexes in the blood are deposited in
glomeruli
 Damage to the glomerular cells impedes blood
filtration
 Kidney failure and, ultimately, death result

18
Type III (ICM) Hypersensitivity
Rheumatoid arthritis
 Immune complexes deposited in the joint
 Results in release of inflammatory chemicals
 The joints begin to break down and become
distorted

 Trigger not well understood
 Treated with anti-inflammatory drugs

19
The crippling distortion of joints characteristic of rheumatoid arthritis
Type III (ICM) Hypersensitivity
Systemic lupus erythematosus
Autoantibodies against DNA result in immune
complex formation
Many other autoantibodies can also occur
 Against red blood cells, platelets, lymphocytes,
muscle cells

Trigger unknown
 Immunosuppressive drugs reduce autoantibody
formation
Glucocorticoids reduce inflammation
21
The characteristic facial rash of systemic lupus erythematosus
Hypersensitivity
Type IV
Type IV (Cell Mediated) Hypersensitivity
Type IV (Delayed or Cell-Mediated) Hypersensitivity


Delayed hypersensitivity is a function of T Lymphocytes, not
antibody.



It starts hours (or Days) after contact with the antigen and often
lasts for days.



It can be transferred by immunologically committed
(Sensitized) T cells, not by serum.



Principal pattern of immunologic response to variety of intra
cellular microbiologic agents
i.e.: Mycobacterium Tuberculosis
Viruses
Fungi
Parasites
24
Type IV (Cell Mediated) Hypersensitivity
Mechanism of Type IV Hypersensitivity


Activated T Lymphocytes



Release of cytokines and macrophage activation
T-cell mediated cytotoxicity

25
Type IV (Cell Mediated) Hypersensitivity

26
Clinically Important
Delayed Hypersensitivity Reactions
Type IV (Cell Mediated) Hypersensitivity
The tuberculin response


An injection of tuberculin beneath the skin causes
reaction in individual exposed to tuberculosis or
tuberculosis vaccine



Used to diagnose contact with antigens of
M. tuberculosis
 No response when individual not infected or
vaccinated
 Red, hard swelling develops in individuals
previously infected or immunized
28
A positive tuberculin test
Type IV (Cell Mediated) Hypersensitivity
Allergic contact dermatitis


Cell-mediated immune response



Results in an intensely irritating skin rash



Triggered by chemically modified skin proteins that
the body regards as foreign



Acellular, fluid-filled blisters develop in severe cases



Can be treated with glucocorticoids

30
Allergic contact dermatitis
Type IV (Cell Mediated) Hypersensitivity
Graft rejection


Rejection of tissues or organs that have been
transplanted



Grafts perceived as foreign by a recipient undergo
rejection



Immune response against foreign MHC on graft cells



Rejection depends on degree to which the graft is
foreign to the recipient
 Based on the type of graft
32
Types of grafts

Autograft

Isograft
Genetically identical
sibling or clone

Allograft
Genetically different
member of same species

Xenograft
Hypersensitivity Reactions Conclusion:

34
References:



Books:







Review of Medical Microbiology and Immunology
(Warren Levinson)
Pathophysiology (Carol Mattson Porth)
Basic Pathology

(Robins)

Internet:





www. pathmicro.med.sc.edu
www. en.wikipedia.org
www. inkling.com
www. medical-dictionary.thefreedictionary.com
35
Questions

36
37

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Hypersensitity, And Types of Hypersensitivity I, II, III, IV

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  • 5. Hypersensitivity  Hypersensitivity (Immunological reaction) refers to undesirable immune reactions produced by the normal immune system.  Hypersensitivity reactions: When an immune response result in exaggerated OR in appropriate reactions harmful to the host the term hypersensitivity OR allergy used.  Hypersensitivity reactions: four types; based on the mechanisms involved and time taken for the reaction, a particular clinical condition (disease) may involve more than one type of reaction. 5
  • 6. Classification of Hypersensitivity  Type I  Type II  Type III  Type IV ___________________________________ Type I, II and III Antibody Mediated Type IV Cell Mediated 6
  • 8. Type I (Immediate) Hypersensitivity  Commonly called allergy  Mediated by IgE antibodies produced by plasma cells in response to stimulation of Th2 cells by an antigens.  The antigens that stimulate it are called allergens (i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)  Exposure may be ingested, inhalation, injection or direct contact.  Type I hypersensitivity reactions can be systemic (e.g., systemic anaphylaxis) or localized to a specific target tissue or organ (e.g., allergic rhinitis, asthma). 8
  • 9. Type II (Cytotoxic) Hypersensitivity  Cytotoxic  Type II hypersensitivity involves IgG or IgM antibody-mediated  IgM or IgG immunoglobulin react with cell-surface antigens to activate the complements system and produce direct damage of the sell surface.  Transfusion reactions and hemolytic disease of the newborn are examples of type II hypersensitivity. 9
  • 11. Type III (ICM) Hypersensitivity Type III (Immune Complex–Mediated) Hypersensitivity  Type III hypersensitivity is also known as immune complex hypersensitivity.  The reaction may take 3 - 10 hours after exposure to the antigen (as in Arhus reaction).  The reaction may be general (e.g., serum sickness) or may involve individual organs including or other organs.  Antigens causing immune complex mediated injury are:  Exogenous  Endogenous 11
  • 12. Type III (ICM) Hypersensitivity Mechanism of Type III Hypersensitivity  Antigens combines with antibody within circulation and form immune complex  Wherever in the body they deposited  They activate compliment system  Polymorphonuclear cells are attracted to the site  Result in inflammation and tissue injury 12
  • 13. The mechanism of type III (immune-complex mediated) hypersensitivity-overview Antigens combine with antibodies to form antigen-antibody complexes. Antigen Antibody (IgG) Antigen-antibody complex Phagocytes remove most of the complexes, but some lodge in the walls of blood vessels. There the complexes activate complement. Inactive complement Active complement Antigen-antibody complexes and activated complement attract and activate neutrophils, which release inflammatory chemicals. Neutrophil Inflammatory chemicals Inflammatory chemicals damage underlying blood vessel wall.
  • 14. Type III (ICM) Hypersensitivity Hypersensitivity Type III Reactions Local Reactions  Arthus Reaction:  Arthus Reaction: It is named for Dr. Arthus. It is named for Dr. Arthus. Inflammation caused by the Inflammation caused by the deposition of immune deposition of immune complexes at a localized site. complexes at a localized site. Clinical Manifestation is :: Clinical Manifestation is Hypersensitivity Pneumonitis Hypersensitivity Pneumonitis Systemic Reactions  Serum Sickness:  Serum Sickness: Systemic inflammatory response Systemic inflammatory response to deposited immune complexes at to deposited immune complexes at many areas of body. many areas of body. Few days to 2 weeks after Few days to 2 weeks after injection of foreign serum or drug itit injection of foreign serum or drug results in :: results in Fever, Urticaria, Artheralgia, Fever, Urticaria, Artheralgia, Eosinophila, Spleenomegally, and Eosinophila, Spleenomegally, and Lymph adenopathy Lymph adenopathy 14
  • 16. Type III (ICM) Hypersensitivity Immune Complex Diseases:     Hypersensitivity Pneumonitis Glomerulonephritis Rheumatoid Arthritis Systemic Lupus Erythematosus 16
  • 17. Type III (ICM) Hypersensitivity Hypersensitivity pneumonitis  Inhalation of antigens into lungs stimulates antibody production  Subsequent inhalation of the same antigen results in formation of immune complexes  Activates complement 17
  • 18. Type III (ICM) Hypersensitivity Glomerulonephritis  Immune complexes in the blood are deposited in glomeruli  Damage to the glomerular cells impedes blood filtration  Kidney failure and, ultimately, death result 18
  • 19. Type III (ICM) Hypersensitivity Rheumatoid arthritis  Immune complexes deposited in the joint  Results in release of inflammatory chemicals  The joints begin to break down and become distorted  Trigger not well understood  Treated with anti-inflammatory drugs 19
  • 20. The crippling distortion of joints characteristic of rheumatoid arthritis
  • 21. Type III (ICM) Hypersensitivity Systemic lupus erythematosus Autoantibodies against DNA result in immune complex formation Many other autoantibodies can also occur  Against red blood cells, platelets, lymphocytes, muscle cells Trigger unknown  Immunosuppressive drugs reduce autoantibody formation Glucocorticoids reduce inflammation 21
  • 22. The characteristic facial rash of systemic lupus erythematosus
  • 24. Type IV (Cell Mediated) Hypersensitivity Type IV (Delayed or Cell-Mediated) Hypersensitivity  Delayed hypersensitivity is a function of T Lymphocytes, not antibody.  It starts hours (or Days) after contact with the antigen and often lasts for days.  It can be transferred by immunologically committed (Sensitized) T cells, not by serum.  Principal pattern of immunologic response to variety of intra cellular microbiologic agents i.e.: Mycobacterium Tuberculosis Viruses Fungi Parasites 24
  • 25. Type IV (Cell Mediated) Hypersensitivity Mechanism of Type IV Hypersensitivity  Activated T Lymphocytes   Release of cytokines and macrophage activation T-cell mediated cytotoxicity 25
  • 26. Type IV (Cell Mediated) Hypersensitivity 26
  • 28. Type IV (Cell Mediated) Hypersensitivity The tuberculin response  An injection of tuberculin beneath the skin causes reaction in individual exposed to tuberculosis or tuberculosis vaccine  Used to diagnose contact with antigens of M. tuberculosis  No response when individual not infected or vaccinated  Red, hard swelling develops in individuals previously infected or immunized 28
  • 30. Type IV (Cell Mediated) Hypersensitivity Allergic contact dermatitis  Cell-mediated immune response  Results in an intensely irritating skin rash  Triggered by chemically modified skin proteins that the body regards as foreign  Acellular, fluid-filled blisters develop in severe cases  Can be treated with glucocorticoids 30
  • 32. Type IV (Cell Mediated) Hypersensitivity Graft rejection  Rejection of tissues or organs that have been transplanted  Grafts perceived as foreign by a recipient undergo rejection  Immune response against foreign MHC on graft cells  Rejection depends on degree to which the graft is foreign to the recipient  Based on the type of graft 32
  • 33. Types of grafts Autograft Isograft Genetically identical sibling or clone Allograft Genetically different member of same species Xenograft
  • 35. References:  Books:     Review of Medical Microbiology and Immunology (Warren Levinson) Pathophysiology (Carol Mattson Porth) Basic Pathology (Robins) Internet:     www. pathmicro.med.sc.edu www. en.wikipedia.org www. inkling.com www. medical-dictionary.thefreedictionary.com 35
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