i hope it ll help you in better understanding about hypersensitivity reactions.

1. Classification of Immune
Injuries/ Hypersensitivity
Allergic Contact Dermatitis
Respiratory Allergies
Faraza Javed
Mphil Pharmacology

2. Hypersensitivity
Hypersensitivity refers to
undesirable reactions produced by the
normal immune system,
including allergies and autoimmunity
These reactions may be damaging,
uncomfortable, or occasionally fatal.

3. Classification
Type I – Immediate, Atopic,
Anaphylactic
Type II – Antibody Dependent
Type III – Immune Complex
Type IV – Cell Mediated / Delayed
Type Of Hypersensitivity

4. TYPE I. Immediate OR Anaphylactic
Hypersensitivity
 Type I hypersensitivity is also known as
immediate
or anaphylactic hypersensitivity.
 The reaction may involve skin (urticaria
and eczema), eyes (conjunctivitis),
nasopharynx (rhinorrhea, rhinitis),
bronchopulmonary tissues (asthma) and
gastrointestinal tract (gastroenteritis).

5. Mediated by IgE antibody to specific
antigens
The primary cellular component in this
hypersensitivity is the mast cell or
basophil.
The reaction is amplified and/or
modified by platelets, neutrophils and
eosinophils.
 Mast cells stimulated and release
histamine.

6. Most of the IgE in the body is bound
with high affinity receptors (Fc
epsilonRI), found on mast cells and
basophils.
The cells are activated by cross-linking
of Fc epsilonRI receptors via antigen
binding to the bound IgE molecules.

8. Such cross-linking leads to rapid
degranulation of the mast cells and the
release of primary inflammatory
mediators stored in the granules.
Mast cell activation via Fc epsilonRI also
leads to the production of two other
types of mediators. These secondary
mediators.

9. Molecules SOME SPACES Effects
Primary mediators
Histamine
Vascular permeability,
sm contraction
Serotonin
vascular permeability,
sm contraction
Secondary mediators
Leukotrienes
vascular permeability,
sm contraction
Prostaglandins
vasodilation, sm
contraction, platelet
activation
Bradykinin
vascular permeability,
sm contraction

11. Treatment
Drugs
Non-steroidal anti-inflammatories
Antihistamines
Steroids
Theophylline OR epinephrine -prolongs or
increases cAMP levels in mast cells which
inhibits degranulation
Cromolyn Sodium Prevents release of
mediators

12. Type II Hypersensitivity
The second class of damaging reactions
is caused by specific antibody binding to
cells or tissue antigens.
The antibodies are of the IgM or IgG
classes and cause cell destruction.
It involves binding of antibodies (IgG or
IgM) to cell surface antigen or
extracellular matrix molecules.
Antibody directed to cell surface
antigens can activate complement to
damage the cells.

13. Red Blood cell
with Ag on cell
membrane
IgG binds to Ag
on membrane
Membrane attack
complex of
compliment lysis red
cell (cell death)

14. The result may be complement
mediated lysis as occurs in
Haemolytic Anemia
ABO Transfusion Reactions.
Pencillin allergy also belong to this
class.

15. Type III (Immune-Complex Mediated)
Hypersensitivity
Due to the formation of antigen-antibody
complexes, also called immune-
complexes.
Type III hypersensitivity is mediated by
immune complexes essentially of IgG
antibodies.
When antibody combines with specific
antigen, immune complexes are formed.
Normally they are promptly removed by
reticulo-endothelial system.

16. Occasionally, they persist and deposit in
tissues resulting in disorders.
In persistent microbial or viral infections,
immune complexes may be deposited in
organs eg. Kidneys - resulting in
dysfunction, in joints – arthirits, in BV –
Vasculitis.
Wherever the immune complexes are
deposited, they cause inflammation and
tissue injury.

18. Type IV Hypersensitivity
This is the only class of hypersensitive
reactions to be triggered by antigen -
specific T lymphocyte cells (not
antibodies).
Cell mediated hypersensivity is induced
mainly in skin.
When skin again comes in contact with
those agents, the sensitized person
develops erythema, itching, eczema or
necrosis within 12 – 48 hours.

19.  The Langerhans cell in the epidermis
interacts with CD4 T cells to cause
contact sensitivity.
It occurs after sensitisation with simple
chemicals, (e.g nickel & formaldehyde),
plant materials (Ivy poison, Oak poison),
topically applied drugs (sulfonamides &
neomycin), some cosmetics and soaps.

21. (a) In the sensitization phase after initial
contact with antigen (e.g., peptides
derived from intracellular bacteria), TH
cells proliferate and differentiate into
TH1 cells. Cytokines secreted by these
T cells are indicated by the dark blue
balls.

23. (b) In the effector phase after subsequent
exposure of sensitized TH1 cells to
antigen, the TH1 cells secrete a variety
of cytokines and chemokines. These
factors attract and activate macrophages
and other nonspecific inflammatory cells.
Activated macrophages are more
effective in presenting antigen, thus
perpetuating the DTH response, and
function as the primary effector cells in
this reaction.

25. A prolonged DTH response can lead to
formation of a granuloma, a nodule-
like mass. Lytic enzymes released
from activated macrophages in a
granuloma can cause extensive tissue
damage.

26. Examples
Tuberculin response
Allergic contact dermatitis
Graft rejection
Corticosteroids and other immunosuppressive
agents are used in treatment.

27. Comparison of Different Types of hypersensitivity
characteris
tics
type-I
anaphylactic
type-II
(cytotoxic)
type-III
(immune
complex)
type-IV
(delayed type)
antibody IgE IgG, IgM IgG, IgM None
antigen exogenous cell surface soluble tissues & organs
response
time
15-30 minutes minutes-hours 3-8 hours 48-72 hours
histology
basophils and
eosinophil
antibody and
complement
complement and
neutrophils
monocytes and
lymphocytes
transferred
with
antibody antibody antibody T-cells
examples
allergic asthma,
hay fever
erythroblastosis
fetalis,
Goodpasture's
nephritis
SLE, farmer's lung
disease
tuberculin test,
poison ivy,
granuloma

28. Allergic Contact Dermatitis

29. Allergic Contact Dermatitis
 ACD accounts for approximately 20% of all
contact dermatitis
ACD is a type IV, delayed or
cell-mediated immune reaction
that is elicited when the skin
comes in contact with a chemical
to which an individual has been
previously sensitized
Synonyms include contact dermatitis and
contact eczema

30. Allergic contact
Dermatitis to
Leather shoes

31. Pathogenesis
ACD is a type IV hypersensitivity
response
Requires prior sensitization to the
chemical
Once sensitized a low concentration of
causative chemical elicits a response

32. Clinical Features of ACD
Acute blistering
Scaly plaques
Patchy and diffuse distributions may be
seen with body washes and shampoos

33. Treatment of ACD
Involves identification of causative
allergens
Clear the dermatitis with topical, or if
necessary systemic corticosteroids
Complete and prolonged clearing can
take up to 6 weeks or more, even when
allergens are being avoided

35. Nickel
Most common allergen
tested by the NACDG,
with 14% of patients
Reacting to it.
Commonly used in jewelry,
Buckles and other metal
containing objects.

36.  Individuals with
nickel allergy should
avoid custom jewelry
and can usually wear
stainless steel or gold.

37. Neomycin Sulphate
Most commonly used
topical antibiotic used
with other antibacterial
Agent e.g Bacitracina &
Polymixin, as well as
Corticosteriods.
Co-reactivity is commonly seen with
neomycin and bacitracin

38. Thimerosal
Thimerosal is used as a preservative.
Most sensitization may be due to its use
as a preservative in vaccines.
Other exposures include:
o Contact lens solution
o Otic and opthalmic solutions
o Antiseptics and
o Cosmetics

39. Systemic Contact Dermatitis
Systemic exposure to a chemical may
result in a diffuse dermatitis
Patient has had a prior contact allergy
and then becomes exposed through a
systemic route, such as injection, oral,
intravenous, or intranasal administration

40. One of most
common examples
is patient with
ethylenediamine
allergy and
Subsequent reaction
to aminophylline.

42. Respiratory Allergies
(Allergic Asthma)

43. Asthma
Asthma is a condition characterized by
reversible bronchospasm and chronic
inflammation of airway passages.

44. Individuals with asthma appear to
produce large amounts of the Antibody
IgE that attach to the mast cells present
in many tissues.
Exposure to a trigger such as pollen
will result in the allergen-binding mast
cell-bound IgE, which in turn causes the
release of inflammatory mediators such
as Histamine and Leukotrienes.

45. The response of a patient with asthma
to these triggers can be divided into
an ―early phase‖ and a ―late phase.‖

46. Early Phase of Asthma
The early phase of asthma is characterized by:
a. Marked constriction of bronchial airways
(bronchospasm)
b. Difficulty in breathing
c. Production of excess mucus.
The bronchospasm that occurs may be the
result of the increased release of certain
inflammatory mediators such as histamine,
prostaglandins and bradykinin that, in the early
stages of asthmatic response, promote
bronchoconstriction rather than inflammation.

47. Allergen
Antigen-
presenting
cell
Processed
allergen
Plasma Cells IgE antibodies

48. Early
Phase
Late
Phase
Allergen
IgE antibodies Inflammation
Complications
Cellular
Infiltration
Glands
NervesBlood
vessels
Sneezing
Itching
Rhinorrhea
Congestion
Mediator
release Eosinophils
Basophils
Monocytes
Lymphocytes
Mast
cell
Irreversible
Disease?
Priming
Hyper-
responsiveness
Late-phase
reaction

49. Late Phase of Asthma
 The late phase of asthma can occur several hours
after the initial onset of symptoms and manifests
mainly as an inflammatory response.
 The primary mediators of inflammation during the
asthmatic response are the white blood cells
Eosinophils that stimulate mast cell degranulation
and release substances that attract other white cells
to the area.
 Subsequent infiltration of the airway tissues with
white blood cells such as Neutrophils and
lymphocytes also contributes to the overall
inflammatory response of the late phase of asthma.

50. Some Potential Asthma Triggers..
Allergens — Pollen, pet dander, fungi,
dust mites
Perfumes
Pollutants
Cigarette smoke
Respiratory tract infections

51. Sign and Symptoms
Early Phase:
Shortness of breath
Cough
Chest tightness and pain
Wheezing
Cyanosis

52. Late Phase:
Mucosal odema
Severe bronchoconstriction
Epithelial damage

53. Staging of Severity
Type Day Attacks Night Attacks
Mild Intermittant < 2 times in a week < twice in a month
Mild Persistant > 2 times in a week > Twice in a month
Moderate
Persistant
> 3 times in a week
or Daily
> 4 times in a
month
Severe Persistant Continous or At
any time
Daily

54. Treatment
Type Quicker Relief Long Term
Mild Intermittant Short Acting B2
Agonist
Short Acting B2
Agonist
Mild Persistant Short Acting B2
Agonist
Low Dose Inhaled
Steroid OR
SR Theophylline OR
Leukotriene
Antagonist
Moderate
Persistant
Short Acting B2
Agonist
High Dose Inhaled
Steroid OR
Low Dose Inhaled
Steroid + Short
Acting B2 Agonist

55. Severe
Persistant
Short Acting B2
Agonist
High Dose
Inhaled Steroid +
Long Acting
Bronchodilators
OR
SR Theophylline
+ Oral
Prednisolone