Type 1 2 3 and 4 hypersensitivity reactions Their mechanism of actions and advantages and disadvantages Introduction Categories Causes Diagnosis Signs and symptoms

1. Hypersensitivity
reactions
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WAQAS SIDDIQUE (06332013059)
M. NAZAF IQBAL (06332013055)
USAMA AFZAL (06332013024)
KHAIR MUHAMMAD (06332013050)
ZAHID ULLAH (06332013054)
MARYAM NAFEES (06332013023)
DANIYAL SAQIB (06332013064)
USWA MANSOOR (06332013042)
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3. PRESENTED TO
SIR FAKHAR UD DIN.
Table of
contents
Introduction and
Classification
Type 1 Hypersensitivity
Reactions
Type 2 Hypersensitivity
Reactions
Type 3 Hypersensitivity
Reactions
Type 4 Hypersensitivity
Reactions

4. Introduction
and
classification

5. •Hypersensitivity (also called hypersensitivity
reaction or intolerance) refers to undesirable
reactions produced by the normal immune
system, including allergies and
autoimmunity.
They are usually referred to as an over-
reaction of the immune system and these
reactions may be damaging and
uncomfortable.
• It may also be termed as Allergy.
WHAT
IS...?

6. •“Hypersensitivity” generally
represents the “dark side,” signifying
the undesirable aspects of an
immune reaction.
Whereas the term “immunity”
implies a desirable effect
WHAT
IS...?

7. 1
Immediate hypersensitivities refer to humoral immunity
(antigen/antibody reactions)
2
Delayed hypersensitivities refer to cell-mediated
immunity (cytotoxic T-lymphocytes, macrophages, and
cytokines).
Categories of adaptive
hypersensitivities:

8. 1 Autoimmunity: reactions against self antigens
2 Reactions against microbes.
3 Reactions against non-microbial environmental antigens.
4 Family history
General causes of
hypersensitivity:

9. Mechanism of a generalized
hypersensitivity reaction

10. #1. Type 1 hypersensitivity #2. Type 2 hypersensitivity
#3. Type III hypersensitivity, #4. Type 4 hypersensitivity
Classification

12. #1.In type 1 hypersensitivity
symptoms are skin rashes, tingling
around the mouth, diarrhea, etc
#2. In type 2 hypersensitivity
Redness and swelling are major
symptoms
#3. In type III hypersensitivity,
complex deposition in the tissues
can give rise to symptoms such as
fever, rashes, joint pain, lymph node
enlargement, and protein in the
urine
#4. In type 4 hypersensitivity
symptoms include redness and
hardness associated with pain
Symptoms of
hypersensitivity::

14. Diagnosis of hypersensitivities is a complex process
requiring several diagnostic tests in addition to a well-
documented patient history. Serum IgE levels can be
measured, but elevated IgE alone does not confirm allergic
disease
Diagnosis of
hypersensitivity:

15. •A prick puncture skin test (PPST) or an intradermal test
can be performed.
• PPST is carried out with the introduction of allergens in a
series of superficial skin pricks on the patient’s back or
arms.
Diagnosis of hypersensitivity:
continued......

16. •A prick puncture skin test (PPST) or an intradermal test
can be performed.
• PPST is carried out with the introduction of allergens in a
series of superficial skin pricks on the patient’s back or
arms.
Diagnosis of hypersensitivity:
continued......

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Diagnosis

18. • People can identify the specific allergens
which trigger the inflammatory
reaction and learn to avoid them.
• The most important preventive guideline
is avoiding the substance that is
responsible for hypersensitivity.
• Although hypersensitivity care can be
performed at home, consult with a dental
clinic if you have severe symptoms.
Prevention

19. • Hypersensitivity reactions are very
common. Fifteen percent of the world
population will be affected by a type of
allergic reaction during their lives.
• In the second half of this century,
allergic diseases have increased.
Hypersensitivity reactions represent
about one third of all adverse drug
reactions.
• Adverse drug reactions affect 10-20%
of hospitalized patients and more than
7% of the general population.
Epidemiology

21. Type I
Hypersensitivity:
•Definition:
When a individual is exposed to an
allergen, it can lead to a rapid immune
response that occurs almost immediately.
Such a response is called an allergy and is
classified as a type I hypersensitivity.

22. Allergens may be!
• Harmless substances
(molds, or pollen)
• Hazardous substances
(insect venom or
therapeutic drugs)
• Foods (peanuts or
shellfish)

23. Characteristics of Type-I
hypersensitivity
•It is also known as immediate or anaphylactic
hypersensitivity and is mediated by IgE.
•The reaction occurs on exposure to allergen second
time. The first exposure (sensitizing dose) results in
sensitization of host to allergen and subsequent
exposure (s) (shocking dose) will cause reaction
1
2

24. Characteristics of Type-I
hypersensitivity
••Anaphylactic shock occurs in sensitized animals within seconds
to minutes (15-30minutes after exposure to the allergen) after
exposure to the antigen, now called as an allergen. Sometimes
the reaction may have a delayed onset (10-12 hours).
••In type I hypersensitivity reactions, the
allergens are proteins with a molecular weight
ranging from 10 to 40 kD.
3
4

25. Examples:
(a) Allergens in plant pollen may trigger allergic reactions or hay fever in sensitive
individuals. (b) Skin rashes are often associated with allergic reactions. (c) Peanuts
can be eaten safely by most people but can provoke severe allergic reactions in
sensitive individuals.

26. Pathology of Type-I hypersensitivity
•The primary cellular component in Type-I is mast cell or basophil.
The reaction is amplified or modified by platelets, neutrophils and
eosinophils.
•The reaction may involve skin, eyes, nasopharynx,
bronchopulmonary tissues (asthma) and gastrointestinal tract.
•In most domestic species, the lungs are the primary target organs.
•In dogs, the major organ affected is liver, and signs are associated
with constriction of hepatic veins, resulting in hypertension.

27. IgE mediated diseases in
different species:
In humans include;
Asthma,
Hay fever (allergic),
Skin reactions (eczema)
or
Food allergies
The IgE mediated diseases
in animals include;
Asthma in cats.,
Food allergies and
Pulmonary infiltration in
dogs

28. Types of antigens
•Food: nuts, eggs, soy, wheat, shellfish, etc.
•Animal source: bee, wasp, cats, insects, rats, etc.
•Environmental factors: dust mites, latex, pollen, mold, etc.
•Atopic diseases: allergic asthma, allergic rhinitis,
conjunctivitis, dermatitis, etc.
•Medication-induced reactions: antibiotics

29. Mechanism
•On first exposure to an allergen in a individual, antigen-presenting cells
process and present allergen epitopes with major histocompatibility complex
(MHC) II to T helper cells.
•Allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE
molecules. Within minutes, this cross-linking of IgE activates the mast cells and
triggers degranulation. Preformed components that are release from granules
include histamine, serotonin, and bradykinin.
The activated mast cells also release newly formed lipid mediators and as well as
newly formed chemical mediators that collectively cause the signs and symptoms of
type I hypersensitivity reactions

31. Effects of Type-I
Hypersensitivity

32. The inflammatory agents released or
produced cause the following:
•Dilation of blood vessels, which causes local
redness at the site of allergen delivery.
•Stimulation of mucous secretion, which leads
to congestion of airways
•stimulation of nerve endings, which leads to
itching and pain in the skin.
•If dilation is widespread, this can contribute to
• Decreased vascular resistance, a drop in
blood pressure, and shock.
• Decreased blood volume and shock.

34. Type II Hypersensitivity
(Antibody-mediated cytotoxic hypersensitivity)
Definition:
Type II hypersensitivity reaction is a form of immune-mediated
reaction in which antibodies are directed against cellular or
extracellular matrix antigens. This antibody-mediated response
leads to cellular destruction, functional loss, or damage to tissues.

35. Characteristics
•Type II hypersensitivity are antibody mediated cytotoxic reactions
occurring when an antibody binds to antigens located on the surface
of cells (usually RBCs). The reaction time is minutes to hours.
•It is mediated primarily by antibodies of IgM or IgG class.
•The bound antibody can cause cell lysis by activating the classical
complement pathway, promoting phagocytosis.
•Many different antigens may trigger this cell destruction.
Antigens are normally endogenous, although exogenous chemicals
(haptens, or drugs) that can attach to cell membranes can also induce
type II reactions.

36. Examples
•Autoimmune haemolytic anaemia
• Pernicious anemia
• Immune thrombocytopenia
• Transfusion reactions
• Graves' disease
• Myasthenia gravis
• Hemolytic disease of the newborn

37. Pathalogy
Mediated by antibiodies directed towards antigens present on cell surfaces or
the extracellular matrix (type IIA).
• The most common cells involved are blood cells. The outcome may be:
ØHemolytic anemia if RBCs are involved,
ØLeukopenia involving WBCs,
ØThrombocytopenia involving platelets.
• Under some circumstances, a cytotoxic attack on vascular epithelial cells will
cause vasculitis with local vascular leakage.
• The lesion contains antibody, complement and neutrophils

38. IgM or IgG are made against self antigens either as a result of failure of immune
tolerance or cross-reactive antibodies can develop during infections, which may
bind to normal tissue antigens and trigger antibody-mediated cytotoxicity.
• Subsequent binding of these antibodies to the surface of host cells leads to:
Ø phagocytes sticking to host cells by way of IgG and discharge its lysosomes.
ØActivation of the classical complement pathway causing membrane attack
complex *MAC* induced lysis.
•Antibody-dependent cellular cytotoxicity (ADCC) mediated destruction of the
host cells whereby natural killer (NK) cells attach to the Fc portion of the antibodies
Mechanism

39. Are there any
questions?

40. Hemolytic Disease
of the Newborn!

41. During the 1st pregnancy small amounts of fetal blood pass
through the placenta but not enough to induce a responses.
During delivery larger amounts of fetal blood cross the
placenta causing an activation of B-cells that are Rh specific
thus leading to memory B-cells (anti-Rh antibodies)
The IgM antibody clears the Rh+ cells from the mother.
In subsequent pregnancies with an Rh+ fetus, the Rh+ RBC
cross the placenta activating the memory B-cells.
These in turn cross the placenta and damage the fetal RBC
because they are seen as “foreign”.

42. This type of reaction can be prevented by administering antibodies
against the Rh antigen within 25-48 hours after the 1st delivery.
Rhogam-is the antibody that is injected
it will bind to the fetal RBC that enter the mother’s circulation and facilitate
the clearance of them before Bcell activation
In subsequent pregnancies the mother is unlikely to produce IgG anti-Rh
antibodies
If the mother doesn’t receive this injection there are other ways to treat
this, depending ontheseverity Drug-Induced Hemolytic Anemia.

43. This is where certain antibiotics can absorb
nonspecifically to the proteins on RBC membranes.
Examples: penicillin, streptomycin.
• Sometimes antibodies form inducing complement-
mediated lysis and thus results in progressive
anemia.
• When drug is withdrawn the hemolytic anemia
disappears
Drug-Induced Hemolytic Anemia

45. Type 3 hypersensitivity
In type III hypersensitivity soluble immune complexes
(aggregations of antigens and IgG and IgM antibodies)
form in the blood and are deposited in various tissues
(typically the skin, kidney and Joints)

46. Continued
This may trigger an immune response according to the
classical pathway of complement activation. The reaction
takes hours to days to develop

47. Step 1
Large quantities of soluble antigen antibody complexes form in the blood and are not
completely removed by macrophages.
Step 2
These antigen-antibody complexes lodge in the capillaries between the endothelial cells
and the basement membrane.
Step 3
These antigen-antibody complexes activate the classical complement pathway leading to
vasodilatation.
Step 4
• The complement proteins and antigen antibody complexes attract leukocytes to the area.
Step 5
• The leukocytes discharge their killing agents and promote massive inflammation.
• This can lead to tissue death and hemorrhage.
M e c h a n i s m

48. EXAMPLES
I m m u n e c o m p l e x g l o m e r u l o n e p h r i t i s
• R h e u m a t o i d a r t h r i t i s
• S e r u m s i c k n e s s
• S u b a c u t e b a c t e r i a l e n d o c a r d i t i s
• S y m p t o m s o f m a l a r i a
• S y s t e m i c l u p u s e r y t h e m a t o s u s
• A r t h u s r e a c t i o n

49. Arthus reaction:
A hypersensitivity reaction that occurs several hours to days
following the intradermal injection of a vaccine into an animal and is
marked by the formation of Ag-Ab complexes accompanied by
localized inflammation, pain, redness, and sometimes tissue
destruction

50. •Injection of an antigen:
C a n l e a d t o a n a c u t e A r t h u s r e a c t i o n w i t h i n 4 - 8
h o u r s
• L o c a l i z e d t i s s u e a n d v a s c u l a r d a m a g e r e s u l t s
f r o m a c c u m u l a t i o n o f f l u i d ( e d e m a ) a n d R B C
( e r y t h e m a )
• S e v e r i t y c a n v a r y f r o m m i l d s w e l l i n g t o r e d n e s s
t o t i s s u e n e c r o s i s
I n s e c t b i t e :
• M a y f i r s t h a v e a r a p i d t y p e I r e a c t i o n
• S o m e 4 - 8 h o u r s l a t e r , a t y p i c a l A r t h u s r e a c t i o n
d e v e l o p s

52. Serum sickness
• It is a disease caused by the
injection of large doses of a
protein antigen into the blood and
characterized by the deposition of
antigen-antibody complexes in
blood vessel walls, especially in
the kidneys and joints

54. Systemic lupus erythmatosus
The disease is characterized by the presence
of autoantibodies, which form immune
complexes with autoantigens and are
deposited within the kidney glomeruli
• The resulting type III hypersensitivity is
responsible for the glomerulonephritis
(Inflammation of blood capillary vessels in the
glomeruli)

56. Type 4 hypersensitivity is often called as
delayed type as the reaction takes two to
three days to develop.
Unlike other types, it is not antibody mediated
but rather a type of cell mediated response.
Type 4 Hypersensitivity reactions

57. •In the fourth type or type 4, the reaction are caused by T lymphocytes,
or T cells, and so type IV is also sometimes known as T-cell-mediated
hypersensitivity.
T cells are called T cells because they mature in the thymus.
The two types of T cells that cause damage to tissues in type
IV hypersensitivity are CD8+ T cells also known as killer T cells
or cytotoxic T cells, as well as CD4+ T cells also known as
helper T cells

58. Characteristics
• The reaction takes more than 12 hours to develop. Typically the maximal reaction
time occurs between 48 to 72 hours
• It is mediated by cells that cause an inflammatory reaction to either exogenous or
autoantigens.
• The major cells involved are T lymphocytes and monocytes/macrophages.
• This reaction to exogenous antigens involves T cells and also antigen-presenting
cells (APC), all produce cytokines that stimulate a local inflammatory response in a
sensitized individual.
• DHR cannot be transferred from an animal to another by means of antibodies or
serum. However, it can be transferred by T cells, particularly CD4 Th1 cells.

60. • CD8 cytotoxic T cells and CD4 helper T cells recognize antigen in
a complex with either type I or II MHC antigens •
• The antigen-presenting cells in this case are macrophages and
they release interleukin 1, which further stimulates the proliferation
of CD4 cells.
• These cells release IL-2 and IFN-λ, which together regulate the
immune reaction; other lymphokines involved in delayed
hypersensitivity reaction include monocyte chemotactic factor, TNF
α etc.

61. • •Cytokines produced by keratinocytes, APC, and T cells recruit
antigen-nonspecific T cells and macrophages to participate in a
local inflammatory reaction.
• Activated CD8 cells destroy target cells on contact, while activated
macrophages produce hydrolytic enzymes and, transform into
multinucleated giant cells

65. Types
There are three subtypes of Type IV hypersensitivity:
Contact dermatitis, tuberculin-type hypersensitivity, and granulomatous-type
hypersensitivity.

66. Types

67. Importance
The AIDS virus illustrates the vitally important role of the DTH
response in protecting against various intracellular pathogens.
• The disease cause severe depletion of CD4+ T cells, which
results in a loss of the DTH response.
• AIDS patients develop life-threatening infections from intracellular
pathogens that normally would not occur in individuals with intact
DTH responses.

68. Disadvantages
•The initial response of the DTH is nonspecific and often results in
significant damage to healthy tissue. • In some cases, a DTH
response can cause such extensive tissue damage that the
response itself is pathogenic. • Example: Mycobacterium
tuberculosis – an accumulation of activated macrophages whose
lysosomal enzymes destroy healthy lung tissue. • In this case,
tissue damage far outweighs any beneficial effects.