Transcript HYPERSENSITIVITY - Dr. Raj Kumar Sharma

HYPERSENSITIVITY
BY
Dr Mahesh Mathur,MD, DCP (UK)
PRE TEST
1.
WHICH OF THE FOLLOWING CELLS ARE INVOLVED IN DELAYED
TYPE HYPERSENSITIVITY
A. LYMPHOCYTES
B. EOSINOPHILS
C. NEUTROPHILS
D.MONOCYTESED
2. NOT AN EXAMPLE OF DELAY TYPE HYPERSENSITIVITY
A.TISSUUE GRAFT REJECTION
B.TUBERCULAR GRANULOMA
C. ARTHUS RECATION
D. CONTACT DERMATITIS
3. WHICH OF THE FOLLOWING STATEMENT IS NOT CORRECT
A . BLOOD TRANSFUSION REACTION – TYPE II REACTION
B. ALLOGRAFT REJECTION – TYPE IV REACTION
C. SERUM SICKNESS – TYPE II REACTION
4. A GIRL DEVELOPED REDNESS & SWELLING OF EAR LOBULES AFTER
WEARING SOME EARINGS THS IS A EXAMPLE OF WHICH TYPE OF
HYPERSENSITIVITY
A.CELL MEDIATED
B..IMMUNE COMPLEX
C.CYTOTOXIC
D.IMMEDIATE TYPE
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5. IN POS STREPTOCOCCAL GLOMERULONEPHRITIS
THE TYPE OF HYPERSENSITIVITY INCLUDES
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A. TYPE IV
B. TYPE III
C. TYPE II
D. TYPE I
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6. WHICH OF THE FOLLOWING IS THE TYPE I
REACTION
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A. SICK TEST
B. MOUNTOUX TEST
C. CASONI’S TEST
D. PATCH TEST
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7. WHICH OF THE FOLLOWING IS AN EXAMPLE OF
IMMEDIATE HYPERSENSITIVITY
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A. LEPROMINE TEST
B. SERUM SICKNESS
C. TUBERCULINE TEST
D. CASONI’S TEST
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8. WHICH Ig IS RESPONSIBLE FOR TYPE I REACTION
A. IgM
B. IgA
C. IgG
D. IgE
9. WHICH IS NOT A TYPE III REACTION
A.TUBERCULOSIS
B. RHUMATOID ARTHRITIS
C. SLE
D. ARTHUS REACTION
10. ALL ARE TRUE ABOUT TYPE III REACTION EXCEPT
A. SERUM SICKNESS
B. ARTHUS REACTION
C. ANAPHYLAXIS
D. LUPUS NEPHRITIS
The
term hypersensitivity
describe immune responses
which are damaging rather
than helpful to the host.
 Nearly
40 years ago Gell and Coombs
proposed a classification scheme which
defined 4 types of hypersensitivity
reactions.
 The first 3 are mediated by antibody, the
fourth by T cells.
TYPE
1
DESCRIPTIVE
NAME
IgE-mediated
hypersensitivity
2
3
4
Antibodymediated
cytotoxic
hypersensitivity
Immunecomplex
mediated
hypersensitivity
cell-mediated
hypersensitivity
INITIATION
TIME
MECHANSMS
EXAMPLES
2-30
MINS
Ag induces cross-linking
of IgE bound to mast cells
with release of vasoactive
mediators
Systemic
anaphylaxis, Local
anaphylaxis, Hay
fever, Asthma,
Eczema
5-8
HOURS
Ab directed against cellsurface antigens mediates
cell destruction via ADCC or
complement
Blood transfusion
reactions, Haemolytic
disease of the
newborn, Autoimmune
Haemolytic anaemia
2-8
HOURS
Ag-Ab complexes deposited at
various sites induces mast cell
degranulation via FcgammaRIII,
PMN degranulation damages
tissue
Arthus reaction
(Localised); Systemic
reactions
disseminated rash,
arthritis,
glomerulonephritis
Memory TH1 cells release
cytokines that recruit and
activate macrophages
Contact dermatitis,
Tubercular lesions
24-72
HOURS
The Rapid ('Immediate') allergic
reaction Type I
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The symptoms produced by exposure of a
sensitised person to antigen depend upon the
site of contact.
Hayfever (allergic rhinitis),
eczema,
Asthma and urticaria all result from type I
hypersensitivity.
It is caused upon contact with antigen against
which the host has pre-existing IgE antibody.
IgE
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IgE is present in very low levels in serum in most people
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50ng (ie 5 × 108gm) per ml.
It does not pass the placenta, although it is synthesized by the fetus.
It does not fix complement,
Its' half life in serum is only 2-3 days but much of the IgE in the body
is bound to high affinity receptors (Fc epsilonRI),
in the bound state the half-life is ~3 weeks.
The high affinity Fc epsilonRI receptors are found on mast cells and
basophils.
Amounts in serum do not always reflect the degree of allergic
sensitivity, because IgE antibody may sensitize tissues in the
absence of a detectable excess free in the serum
The affinity of IgE for skin being so great that the site remained
sensitized for 4 weeks or longer
Only a few molecules appear to be necessary for sensitization
the radioallergosorbent test (RAST)
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Incidence and genetic susceptibility
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20-30% of the population exhibit type I hypersensitivity
or atopic allergy to common environmental substances.
There is a genetic component to atopic allergy such that
if both parents exhibit this susceptibility more than 2
if neither parent has manifest allergies - less than half
likely to when compared to the population as a whole.
Some individuals have multiple and severe allergies,
typically both hayfever and eczema-these individuals
are termed atopic and frequently have raised total serum
IgE levels (10 -100 × normal).
There is a correlation between total [IgE] and atopy.
Mechanism Of Mast cell activation
THE MAST CELL & MEDIATORS
 Mast
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cell mediators & Properties
Molecule
Primary mediators
Histamine
Serotonin
ECF-A
NCF-A
proteases
effects
Vascular permeability, sm contraction
vascular permeability, sm contraction
eosinophil chaemotaxis
neutrophil chaemotaxis
mucus secretion, connective tissue
degradation
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Secondary mediators
Leukotrienes
Prostaglandins
Bradykinin
Cytokines numerous
vascular permeability, sm contraction
vasodilation, sm contraction, platelet activation
vascular permeability, sm contraction
effects inc. activation of vascular
endothelium, eosinophil recruitment and
activation
Systemic anaphylaxis
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Uncommon, but may follow
 insect bites or stings, skin tests,
 Administration of therapeutic sera or drugs,
 muscle relaxants, anaesthetics, radiological contrast
Media,
 Manifested by respiratory distress due to bronchospasm
or oedema of the mucosa of the larynx and bronchi,
cutaneous changes varying from erythema to angiooedema and urticaria, intestinal spasm accompanied by
vomiting or diarrhoea, and shock.
 Only one or a combination of these signs may be
present, and the results vary from transient discomfort to
rapid death.
ANGIOEDEMA
ANGIOEDEMA
Type II Hypersensitivity
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Caused by specific antibody binding to cells or tissue
antigens.
 The antibodies are of the IgM or IgG classes
 cell destruction by Fc dependent mechanisms either
directly or by recruiting complement via the classical
pathway.
 the target cells are foreign to the host Except where the
reaction is autoimmune.
 Usually seen in blood transfusion recipients ,
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The classic ABO incompatibility reaction with IgM antibodies causing
complement lysis of erythrocytes.
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Rhesus disease (or haemolytic disease of the newborn)
The IgG antibodies cause destruction of foetal RBC by
antibody dependent cellular cytotoxicity (ADCC) are
passively acquired by the host via the placenta.
Mechanism of type II Reaction
MECHANISM OF TYPE III REACTION
TYPE II HYPERSENSITIVITY
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Autoimmune hemolytic anemia
 Goodpasture's syndrome
 Erythroblastosis Fetalis
 Pemphigus
 Pernicious anemia (if autoimmune)
 Immune thrombocytopenia
 Transfusion reactions
 Hashimoto's thyroiditis
 Graves' disease
 Myasthenia gravis
 Rheumatic fever
 Hemolytic disease of the newborn
Pemphigus vulgaris
Immunofluracence of Skin
Type III Hypersensitivity
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Mediated by immune complexes essentially of
IgG antibodies with soluble antigens.
 Only preformed complexes can bind to the low
affinity FcgammaRIII.
 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) where they
may trigger an immune response according to
the classical pathway of complement activation
MECHANISM OF IMMUNE COMPLEX
FORMATION
TYPE III REACTION
Type III Hypersensitivity
 Immune
complex glomerulonephritis
 Rheumatoid arthritis
 Serum sickness
 Subacute bacterial endocarditis
 Symptoms of malaria
 Systemic lupus erythematosus
 Arthus reaction
 Farmer's Lung (Arthus-type reaction
Type IV Hypersensitivity
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This is the only class of hypersensitive reactions to be
triggered by antigen-specific T cells.
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CD8+ cytotoxic T cells and CD4+ helper T cells recognise antigen in
a complex with either type 1 or 2 major histocompatibility complex.
The antigen-presenting cells in this case are macrophages which
secrete IL-12, which stimulates the proliferation of further CD4+ T
cells.
CD4+ T cells secrete IL-2 and interferon gamma, further inducing
the release of other Type 1 cytokines, thus mediating the immune
response.
Activated CD8+ T cells destroy target cells on contact while
activated macrophages produce hydrolytic enzymes and, on
presentation with certain intracellular pathogens, transform into
multinucleated giant cells.
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MECHANISM OF IV REACTION
MECHANISM OF IV REACTION
Type IV Hypersensitivity
 Contact
dermatitis
 Temporal arteritis
 Symptoms of leprosy
 Symptoms of tuberculosis
 Transplant rejection
 Coeliac disease
TUBERCULOID LEPROSY
SKIAGRAM OF TUBERCULOSIS PATIENT
Contact Dermatitis Hairdye
Post test
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13 A 35 year old man comes to see you. He is keen to have his
thyroid function tested because his younger sister has just
been diagnosed with hypothyroidism. His mother also suffered
from this at an early age. You agree to do some blood tests. But
within a few minutes of taking his blood he becomes acutely
breathless with marked facial and tongue oedema. He tells you
that he ate a prawn mayonnaise sandwich three hours earlier.
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Shellfish allergy
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Egg allergy
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Vasovagal reaction
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Latex allergy
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The patient returns one year later. He was at a dinner party for his
thirty-sixth birthday. After the dessert he felt tingling and tightness in
his throat. He remembers the pudding was a fruit salad containing
mostly banana and kiwi fruit.
What is the likely diagnosis?
a Cross reactive allergy
B Lactose intolerance
c Food intolerance
d Latex contamination of food
e Pesticide allergy
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15 What dose of adrenaline would you give the patient?
0.5 ml intramuscular adrenaline 1:1000
 0.5 ml subcutaneous adrenaline 1:1000
 0.5 ml intravenous adrenaline 1:1000
 0.5 ml intravenous adrenaline 1:10 000
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He attends after yet another anaphylactic reaction. He
treated himself with adrenaline and oral antihistamine,
and after lying down for an hour he felt better. He asks
you what the best site to inject his adrenaline is.
 Where should you advise him to give his injection?
 A The shoulder
 b The buttock
 c The upper arm
 d The thigh
 e The abdomen
 When, if ever, should he use the second autoinjector?
 After one minute if he does not improve
 After five minutes if he does not improve
 After 20 minutes if he does not improve
 Never after a previous dose
THANK
YOU