Hypersensitivity reactions. Prof . Mohamed Osman Gad El Rab. College of Medicine & KKUH. Introduction: Immune reactions leading to pathological tissue damage. - Occur as :
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Prof . Mohamed Osman Gad El Rab.
College of Medicine & KKUH.
Immune reactions leading to pathological
- Occur as :
1.Secondary heightened (increased) immune
2.Secndary inappropriate (abnormal ) immune
are mediated by antibodies .
Is generated by cell-mediated immune responses.
Hypersensitivity reactions differ inthe rate at which they occur :
- can occur as isolated reactions,
- more than one reaction can occur
in the same patient.
e.g. : Type I and Type III.
*Immediate H/S ( can literally occur within minutes to hours ).
* Anaphylactic reactions .
* Allergic reactions.
- Cellular components:
Mast cells , basophiles & eosinophils.
- Antigens :
termed allergens ( antigens with low
molecular weight & highly soluble.
* Evolved as a defense against parasitic infections.
* However , many reactions in some
predisposed individuals are directed towards harmless molecules (allergens) and these are said to be :
- genetic factors .
- environmental factors.
depend on exposure to allergens of
diverse nature ( pollens , foods , drugs
fungal spores , bee - sting venoms ,
house dust mites and animal dander.
- Sensitization phase .
Allergen enter tissues , induce an
immune response . B – cells transform
to plasma cells & produce IgE.
- IgE bind to receptors on Mast cells and
basophiles ( FcЄRI - high affinity receptors).
individuals become :
“ Sensitized . “
Challenge phase .
-Subsequent encounter with same allergen cross – link IgE on Mast cells .
-This generate an intracellular signal that prompts the Mast cells to:
Development of Allergy Requires
Sensitization , Re - exposure & Degranulation
Naive Mast Cell
Sensitized Mast Cell
Degranulated Mast Cell
1. primary mediators.
2. secondary mediators.
Some effects of mediators :
- Histamine ( increase vascular permeab.).
(constriction of vasc. smooth muscle).
- Heparin ( counters coagulation ).
-IL – 5 (eosinophils).
-IL – 8 (neutrophils).
- IL – 4. ( IgE)
Prostaglandins :vasodilatation, contraction of
pulmonary smooth muscle
Leukotrienes :increased vascular permeab.
contraction of smooth muscle.
Platelet-activating factor: platelet aggregation,
contraction of smooth muscle .
are clinical signs of Type I reactions.
* Vasodilatation and increased capillary
* Vasoconstriction ( arteries and arterioles )
* Increased mucus secretion.
and bronchial tissues result in :
- Allergic rhinitis.
- Allergic asthma.
(life - threatening).
are non - IgE mediated.
may result from contrast media or
1. Skin prick test (SPT).
2. Intradermal test.
3. Specific IgE measurement (RAST).
4. Challenge test ( Nasal , Bronchial).
4. Elimination / Provocation test (Food allergy).
- Antigens ( Bound to cell membranes
or extra cellular matrix).
- Self - antigens.
- Exogenous antigens. (microbial )
- Complement activation (Invariable).
- Activate complement.
- Complement generate
chemotactic agents (C5a).
- Attract neutrophils and other
A. Complement receptors -(immune -adherence).
B. Antibody receptors - (Opsonic -adherence).
- They secrete their enzymes to the
- They cause direct damage.
- Membrane attack complex
- Direct lytic damage on target
1, Incompatible blood transfusion (ABO).
-massive intravascular hemolysis of RBC.
-Immediate reactions-IgM mediated.
-Delayed reactions-(2-6 days ),IgG mediated.
2. Hemolytic disease of the new -born (HDN).
3. Drug reactions (Drugs bind to R.B.C , W.B.C , platelets).
- Lead to:-
- Hemolytic anemia.
4. Autoimmune diseases (Self-antigens).
5. Graft rejection (Hyper - acute).
- Preformed antibodies in the recipient .
- Detection of antibodies and antigens by immunofluorecence. (Biopsy).
- IgG or IgM.
- Soluble antigens.
- Immune – Complex formation.
- Complement activation.
- Depend on the nature and conc. of
antigens and antibodies.
- As long as they are not :-
- Extremely large.
they are readily cleared.
1. The mononuclear- Phagocyte system.
- Macrophages and dendritic cells
degrade particles and debris.
2. Erythrocytes bind complexes via FcR1
receptors and release them in the liver.
1. Complexes accumulate and deposit in
blood vessels and tissues.
2. They activate complement.
Therefore : induce immune - complex
Complexes deposit in blood vessels and tissues and result in vasculitis , arthritis …et
1. Complexes with antibody excess ,
are termed Arthus – type reactions (localized ).
2. Complexes with antigen excess ,
are termed serum – sickness reactions (systemic).
1. Glomeruli .
- high blood flow .
- filtration of the blood.
- complement receptors .
Lead to glomerulonephritis .
2. Blood vessel walls .
- complexes deposit on walls of veins and arteries .
3. Synovial membrane of joints .
- immune- complexes.
deposition can damage bone and
4. Skin .
- a common site for deposition of immune
complexes manifest as rashes .
1. Autoimmune disease ,(self – antigens ).
2. Chronic infections ,(microbial antigens)
3. Cancer , (tumor antigens).
4. Drug reactions , (chemical haptens ).
- cell-mediated (CD 4 T-cells).
- activated macrophages .
- delayed- onset (2 – 4 days).
- secondary abnormal cellular
- granuloma formation .
1. Basophil H/S ( Jones-mote reaction ).
2. Contact sensitivity ( chemical antigens )
3. Tuberculin reactions ( mantoux test )
4. Granuloma formation .
This lead to intense inflammation that
cause permanent damage .
1. Chronic infections :
- leprosy .
- fungal infections .
2. Contact dermatitis.
1. Delayed skin test .
2. Patch test.
3. Lymphocyte transformation test.
( detection of activation markers by flow cytometry ).
A drop of the allergen is placed on the forearm & pricked through by a lancet.
The reaction is read after 15 minutes.
The symptoms included severe bouts of sneezing, itching in the nose, eyes ,ears & throat. .
After a short time he had watery
nasal discharge & congestion (nasal block).
Examination of a nasal smear showed high level of granulocytes .
The patient was given a drug to control the
symptoms but the tablets were not effective & he was given a topical steroid (nasal spray)
2.What is the type of granulocytes detected in the nasal smear ?
3.Explain the underlying immunopathology of all the symptoms & signs mentioned in this condition ?
4.What type of drug was given to control the symptoms ?
5. What is the mechanism by which cortisone help in control of symptoms in this condition ?