The document discusses hypersensitivity reactions, outlining the definition, classification, and mechanisms involved, particularly focusing on immediate (Type I) and delayed (Type IV) reactions. It details various types of hypersensitivity, including anaphylaxis, and provides examples of associated diseases and testing methods. Additionally, treatment options and factors influencing hypersensitivity responses are described.

1. HYPERSENSITIVITY REACTION
DR. MANISH TIWARI
TUTOR MICROBIOLOGY SMC
UNNAO

2. PNEUMONIC

3.  Hypersensitivity:-it is a condition in which an exaggerated or
augmented immune response after contact of the antigen that is
harmful to the host.
 Allergy:- it is refers to all immune process harmful to the host,
such as hypersensitivity and autoimmunity .Its some time
called atopy
 Sensitizing dose:- the initial contact which is sensitizes the
immune system, leading to priming of appropriate B or T
lymphocyte.

4.  Shocking dose:- subsequent contact with the allergen causes
manifestation of hypersensitivity.
 Based on the time required for sensitized host it develop
clinical reaction on re- exposure to the antigen.
 Hypersensitivity reactions have been classified traditionally
into “IMMEDIATE” and DELAYED
 Immediate and delayed reactions are subdivided into several
distinct clinical types:

5. 1. IMMEDIATE HYPERSENSITIVITY (B CELL OR ANTIBODY
MEDIATED)
1. Anaphylaxis
2. Atopy
3. Antibody mediated cell damage
4. Arthus phenomenon
5. Serum sickness.

6. 2. DELAYED HYPERSENSITIVITY (T CELL
MEDIATED)
1. Infection(Tuberculin)
2. Contact dermatitis
3. Basophilic hypersensitivity

7. WHAT IS DIFFERENT FEATURE OF IMMEDIATE AND
DELAYED HYPERSENSITIVITY.

8. CLASSIFICATION
 Coombs & Gell classified into four type based on the different
mechanism of pathogenesis
Type 1 hypersensitivity: it is IgE mediated , which causes mast cell
degranulation after contact with soluble antigen.
Type 2 hypersensitivity reaction: it is IgG or rarely IgM mediated,
which causes complement activation or antibody dependent
cellular cytotoxicity (ADCC) in response to cell surface bound
antigen.

9.  Type 3 hypersensitivity reaction: it is immune complex
mediated, which are formed due to interaction between soluble
antigen and antibody (usually IgG) .
 Delayed hypersensitivity reaction: it occurs after few days
contact of antigen , as a result of abnormal cell mediated
immune response. Its also called type 4 hypersensitivity.
 It is mediated by specific subset of T helper cells called
delayed.

10.  Type 5 stimulatory hypersensitivity: this is
modification of type 2 reaction, where instead
of binding to cell surface components, the
antibodies recognize and bind to the cell
surface receptors.

11. TYPE OF HYPERSENSITIVITY REACTION &
FEATURES.

13. TYPE 1.(IGE MEDIATED )
 Type 1 reaction also called as immediate hypersensitivity
reaction
 It is induced by certain types of antigen ,referred to as allergens
 The allergen induces a humoral antibody response
 IgE binds with high affinity to Fc receptors on the surface of tissue
mast and basophils
 Such IgE- coated mast cells and basophils are sensitized.

14.  A later exposure to the same allergen
cross- links the membrane- bound IgE on
sensitized mast cells and basophils,
causing degranulation of these cells
 The pharmacologically active
mediators released from the granules
act on the surrounding tissues

15. MECHANISM OF TYPE 1
HYPERSENSITIVITY

16. WHAT IS ANAPHYLAXIS & ITS FEATURE.
 It is classical immediate hypersensensitivity reaction.
Features
1. It induce by antigen & hapten at interval of 2-3 weeks
between sensitizing dose & shocking dose.
2. Once sensitized, the person remains for long periods.
3. Shocking dose is most effective when injected IV.
4. Shocking dose mostly related to sensitizing antigen.
5. The clinical feature is same with any antigen but vary
between species.

17. TYPE OF ANAPHYLAXIS
1.Cutaneous anaphylaxis:- a very small shocking dose of
antigen intradermally causes local wheal & flare
response(local anaphylaxis). it is used for testing of the
hypersensitivity reaction & identify the allergen that is
responsible of atopic disease.
2. Passive cutaneous:- this test is developed by ovary(1952) It is
extremely sensitive in vivo method for detection of antibodies.

18. A small volume of antibodies is injected intradermally into a normal
animal. If the antigen along with a dye such as Evans blue, is
injected intravenously 4-24 hrs. after blueing at the site of
intradermal injection due to vasodilation & increased capillary
permeability( wheal and flare reaction) It is used to detection of
human IgG antibody.
3. Anaphylaxis in vitro:- isolated tissue from sensitized guinea pigs,
uterus muscle strips held in water bath of ringer’s solution will
contract vigorously on addition of specific antigen to the bath. This
is called Schultz- Dale phenomenon.

22. ATOPY
 The term atopy ( literally out of place or strangeness)
 It was introduced by COCA (1923).
 It is refer to naturally occurring familiar hypersensitivity
reaction of human beings, typed by hay fever and asthma.
 The antigen commonly in atopy such as inhalants( pollen,
house dust) or ingestants ( eggs , milk).
 It induce IgE antibodies, formally known as reagin antibodies.

23. P-K REACTION
 Serum, suspected to contain IgE antibody, is drown from
allergic patients.
 This serum injected intradermally into a non allergic person.
 After 24-48 hrs. suspected antigen injected at the same site.
 Then wheal and flare reaction are developed at the site.
 This is the 1st to demonstrate that antibodies in the serum are
responsible for the allergy and it is transferable from one
person to other.

24. FACTORS INFLUENCING TYPE 1
HYPERSENSITIVITY
 Genetic makeup:- mostly genetic factors are play important role in
mounting an immune response against an allergen. There are several
gene loci identified which encode protein that is involved in the
immune response a towards allergen.
 Allergen dose:- it is observed that repeated small doses of allergen
that induce a persistent IgE response in mice.
 T H1 vs TH2 Response:- the balance between TH1 & TH2 response
determine the response of an individual towards an antigen.
 TH1 Produce cytokine interferon y that is inhibitory where as TH2
induce cytokine IL3,IL4 and IL5 promotes IgE mediated allergic
response.

25. DETECTION OF TYPE I
HYPERSENSITIVITY
1. Radioallergosorbent test (RAST)-
Quantify Nano gram amounts of
serum IgE specific for a particular
allergen
2. Radioimmunosorbent test (RIST)-
Quantify Nano gram amounts of
total serum IgE. highly sensitive
technique.
3. Skin prick test:-small amount of
suspected potential allergen are
introduced at the different skin site
by intradermal.

26. TREATMENT
1. Antihistamine :- block H1 receptors on the target cells.
2. Epinephrine :- stimulate Camp in the mast cells; thereby
prevents mast cells degranulation.
3. Cortisone :- block of conversion of histidine to histamine
and stimulate Camp in the mast cells
4. Theophylline :- prolongs high Camp levels in the mast cells.
5. Cromolyn sodium:- block calcium influx into mast cells.

28. ANTIBODY – MEDIATED CYTOTOXIC HYPERSENSITIVITY
 Type II hypersensitivity reaction
involve antibody- mediated
destruction of cells
 This type is best exemplified by blood –
transfusion reactions, in which host
antibodies react with foreign antigens on the
incompatible transfused blood cells and
mediate destruction of these cells
 Results when IgG or IgM bind to cell
surface Ag’s
 Activating Complement
 Binding Fc receptors on Tccells
promoting ADCC
 Both processes result in lysis of the Ab-
coated cell

29. CLINICAL EXAMPLES OF TYPE II
RESPONSES INCLUDE:
– Certain autoimmune diseases where Ab’s produced vs
membrane Ag’s
1. Grave’s Disease – Ab’s produced vs thyroid hormone receptor
2. Myasthenia Gravis – Ab’s produced vs acetylcholine receptors
3. Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane
Ag’s
– Hemolytic Disease of the Newborn
– Hyper acute graft rejection
• Blood Transfusion
• Graft rejection

30. TYPE II HYPERSENSITIVITY
 Produced by mismatched blood types
 Destroys foreign RBC by
complement-mediated lysis
triggered by IgG
 Produces fever, intravascular clots,
lower back pain, Hgb in urine
 Free Hgb produced has 2 fates:
passes to the kidneys –
hemoglobinuria
 Breaks down to bilirubin. Can be
toxic

31. 1.HEMOLYTIC DISEASE OF THE NEWBORN
• Occurs via maternal IgG Ab’s crossing
the placenta
• In severe cases causes
erythroblastosis fetalis
– Most commonly develops in Rh-
mother with Rh+ fetus
– Exposure to Rh+
fetal RBC’s
stimulates prod of
memory/plasma
– Activation of memory cells in
subsequent
pregnancy
IgG Ab’s which can cross the
placenta
– mild-severe hemolytic anemia
ensues along with bilirubin which
affects the brain/CNS

32. 2.DRUG-INDUCED HEMOLYTIC ANEMIA
 Drugs such as aspirin and antibiotics can bind to the surfaces of
RBC’s
 These interactions act similar to hapten- carrier conj.
 Such complexes can trigger Ab-mediated cell lysis by
complement activation

33. 3.GOODPASTURE’ SYNDROME
 In this syndrome autoantibody of IgG are produced against
basement membrane of the lungs & kidneys.
 These autoantibody bind to tissue of the lungs & kidney and
activate the complement.
 Increased the production of C5a, a component of the
complement.
 The C5a causes attraction of the leukocytes , that produced
enzyme protease that act on the lung & kidney tissue and
causing damage of the tissue.

34. 4.RHEUMATIC FEVER
 In this condition, antibodies are produced against group A
streptococci that cross react with cardiac tissue and activate the
complement , that is turn causes damage of cardiac tissues.

36.  This is the immune complex hypersensitivity reaction.
 This reaction is mediated by antigen- antibody immune
complex, which induce an inflammatory reaction in tissues.
 In this condition the plasma concentration of complement are
loss due to massive complement activation and fixation by the
antigen –antibody complexes.

37. MECHANISM
 Antigens combine with the antibody
within circulation and form immune
complex.
 Whenever in the body they diposeted,
(a)on blood vessel walls, (b) synovial
membrane of the joints (c) basement
membrane of the kidney, and (d)
choroid plexus of the brain.
 They activate the complement system
and PMN cells are attracted to the site.
 Resulting in inflamation and tissue
injury.

38. MANIFESTATION OF TYPE 3
REACTION

39. 1.ARHUS REACTIONS
 It is inflammatory reaction caused by
deposition of immune complexes at the
localized site.
 This reaction is named after Dr. arthus who 1st
described this reaction.
 This reaction is edematous in the early stages,
but later can become hemorrhagic.
 The lag time between antigen challenge and the
reaction is usually 6 hrs.
 Tissue damage is caused by deposition of
antigen- antibody immune complexs and
complement.
 The activation of complement that cause
vascular occlusion & necrossis.

40. 2. SERUM SICKNESS
 Systemic inflammatory reaction
caused by deposition of immune
complexes at the many site of the
body.
 Manifests after a single injection of
high concentration of foreign serum
such as diphtheria antitoxin.
 Appears a few days to 2 weeks after
injection of foreign serum or certain
drugs, like penicillin.
 It is also considered as an immediate
hypersensitivity reaction, because
symptoms appears immediately after
formation of immune complex.

41. IMMUNE COMPLEX DISEASE
1. Autoimmune disease:
 Systemic lupus erytheromatosus (SLE)
 Rheumatoid arthitis.
2. Drugs reaction:
 Allergies to penicillin and sulfonamides.
3. Infectious disease:
 Poststreptococcal glomerulonephritis,
 Meningitis,
 Hepatitis,
 Infectious mononucleosis,
 Malaria & Trypanosomiasis.

43.  Cell mediated hypersensitivity
 This reaction is called delayed type(48-72hrs) hypersensitivity
reaction, because response is delayed.
 It starts hours to days after contact with antigen.
 It is characterized by nonspecific inflammatory cells in
particular macrophages.
 This reaction due to activation of specially sensitized T
lymphocytes.
 It is 1st described by Robert Koch in tuberculosis as a localized
reaction.

44. MECHANISM
 This type of reactions occurs through two
phases:-
1. Sensitization phases.
2. Effectors phase

45. 1.SENSITIZATION PHASE
 This is starting phase of 1-2 weeks,
which after exposure of antigen.
 Here antigenic presenting cells (APCs)
process and present the antigenic
peptide along with MHC II to helper T
cells. TH cells are differentiated to from
TDTH cells.
 Most T- delayed type hypersensitivity
cells are derived from TH cells; but
occasionally other T cells, such as
CD8+ T cells & CD4+ TH 17 can also act as
TDTH cells.

46. 2.EFFECTORS PHASE
 Here subsequent contact with the
antigen.
 Secrete variety of cytokine which
attract and recruit various
inflammatory cells( macrophage,
dendritics )at the site of DTH
reaction.

47. CYTOKINE SECRETED FROM TDTH CELLS
1. Interferon –γ
2. Interleukin-
3. MCAF (monocyte chemotactic and activating factors)
4. TNF-B ( tissue necrosis factor)
5. MIF-( migration inhibitory factor)
6. interleukin 3
7. GM- CSF ( granulocyte- monocyte colony stimulating factor.

48. TYPE OF DTH REACTIONS

49. 1.CONTACT DERMATITIS
 This reactions are developed after
sensitization with certain substance.
 Theses include drugs such as
sulfonamides & neomycin; plant
product such as poison ivy & poison
oak; chemical, such as formaldehyde
& nickel; cosmetics, soaps & other
substances.
 This reactions are produced, when
these substances enter into the skin &
combine with body protein.

50. 2.TUBERCULIN TEST

51. 3.CUTANEOUS BASOPHILIC
HYPERSENSITIVITY
 It is local reaction related to tuberculin response
that is produced by intradermal injection of some
protein antigen.
 This is not delayed type hypersensitivity as it can
be passively transferred by serum.

52. MCQ
1. Which of the following statement is true about DTH reaction?
a) It derived from TH 1 cells
b) It derived from TH 2 cells
c) Both
d) Non of these
2. Which type of hypersensitivity reaction is responsible for hyper
acute graft rejection?
a) Type 1
b) Type 2
c) Type 3
d) Type 5

53. 3. Type iv hypersensitivity reaction are responsible for:
a) Hay fever
b) SLE
c) Type 1 DM
d) Erythroblastosis fetalis
4. Type I hypersensitivity reaction are NOT responsible
for:
a) Food allergies
b) Drugs allergies
c) Hay fever
d) Multiple sclerosis

54. 5. Which of the following statement is false about bradykinin?
a) Muscle contraction
b) Increased vascular permeability
c) Both
d) Bronchial mucus secretion.
6. Delayed type of hypersensitivity is seen in:
a) Pénicillin allergies
b) Contact dermatitis
c) Arthus reaction
d) Anaphylaxis

55. 7. Immediate type of hypersensitivity reactions are mediated by:
a) T-cells
b) β-cells
c) Mast cells
d) Macrophages
8. Immediate type hypersensitivity reactions are
a) Type-I
b) Type-II
c) Type-III
d) All a, b and c

56. 9. Immunoglobulin is associated with delayed hypersensitivity reaction
a) IgE
b) IgA
c) Non of these
d) IgM
10. The rejection of an organ transplant such as a kidney transplant, is an
example of _____ Hypersensitivity.
a) Immediate
b) Delayed
c) Allergy
d) None of these

57. SHORT NOTE:
1. Anaphylactic reactions and its mechanism.
2. Discuss IgE mediated hypersensitivity reactions.
3. Tabulate difference between immediate and delayed
hypersensitivity reactions.
4. Type-II / Cytotoxic hypersensitivity.
5. Chemical mediators of anaphylaxis.