Immunopathology Unit
Department of Pathology
College of Medicine &
Medical City
King Saud University
Reference
Kuby Immunology 8th Edition
Chapter 15
Objectives
• To know that hypersensitivity reactions are over and excessive
immune responses that can be harmful to body in four different
ways
• To be familiar with inflammatory processes in Type I
hypersensitivity reaction that mediates allergic inflammation
• To recognize that Type II hypersensitivity deals with immune
responses against antigens that are integral part of cell membrane
and are usually associated with autoimmune disorders
• To know that Type III hypersensitivity reactions are mediated by
immune complexes and cause vasculitis
• To describe Type IV hypersensitivity is a purely cell mediated
immune response associated with chronic inflammation
What is hypersensitivity?
• Protective immunity: desirable reaction
• Hypersensitivity: undesirable reaction
• Undesirable responses can be mediated by
– Antibody binding to antigens (Types I-III)
– Cell mediated reaction to chemicals or proteins
(Type IV)
Gel and Coombs Classification
Type I: IgE Ab Type IV: Cell
Mediated
Immunity
Type II: IgG Type III:
Ab to tissue IgG
antigens Immune
Complexes
Type I: Immediate Hypersensitivity
Most people will not react to these allergens
but some individuals “atopic” respond by
producing large amounts of IgE in response
to those otherwise harmless substances
Non-allergic individuals respond to these
allergens by producing IgG antibodies
Type I Hypersensitivity
• Also termed as:
Immediate Hypersensitivity
Allergic reactions
Anaphylactic reactions are severe and
rapidly progressing systemic forms which
can be quickly life threatening
(Occurs within minutes to hours)
Features
- Antibody type: IgE
- Cellular components:
Mast cells, basophiles & eosinophils
- Antigens:
Also known as allergens
(antigens with low molecular weight &
highly soluble)
Allergens
Some of the allergens involved in type I
hypersensitivity are: pollens, dust mite
allergens, animal dander, nuts, shellfish,
various drugs etc
Type I reactions occur in two phases
• Phase I :
- Sensitization phase
- Sensitization phase .
First contact
Type
Allergen Ienter with
Reaction allergens
occur
tissues in 2 phases:
, induce an
immune response . B – cells transform
to plasma cells & produce IgE.
- - IgE bind to receptors
Challenge phaseon Mast cells and
basophiles ( F c ЄRI - high affinity receptors).
Subsequent contact
individuals becomewith
: allergens
“ Sensitized . “
Type I Hypersensitivity (Immediate)
Sensitization
Challenge
Primary and Secondary Mediators
October 8, 2019 Med 1 12
Allergy is a systemic disorder
Nose
Pharynx
Allergic rhinitis
Lungs
Esophagus Asthma
Food allergy
Stomach
Skin
Eczema
Urticaria
Allergic dermatitis
Allergy: Rhinitis, Eczema & Conjunctivitis
Normal nose
* Injected allergens:
Hymenoptera (bees, wasps, ants) sting venom
enters the blood stream
Systemic inflammation
Anaphylactic shock
(life - threatening)
Anaphylactoid reactions:-
Are non - IgE mediated
may result from contrast media or
local anesthetics
Diagnosis of Allergy
Skin Prick test
1. Skin prick test (SPT)
2. Specific IgE measurement
(RAST)
3. Elimination / Provocation test
(Food allergy)
Type II Hypersensitivity Reactions
• Features:-
- IgG (or IgM)
- Antigens: bound to
cell membranes
(Self antigens)
- Exogenous antigens
(microbial)
- Complement
activation
(Invariable)
Clinical examples:
Glomerulonephritis
(anti-glomerular
basement membrane)
Mis-matched blood
transfusion
Diagnosis
- Detection of antibodies and antigens by
Immunofluoresence in tissue biopsy specimens
e.g. kidney, skin etc.
Type III: Immune complex
hypersensitivity
When an antigen reacts with an antibody the
product they form is called an immune complex
which is capable of inducing an inflammatory
response
Immune complexes are deposited in tissues like
kidneys (nephritis), joints (arthritis) or blood
vessels (vasculitis)
Type III Hypersensitivity
(immune–complex mediated)
• Features
Antibody (IgG/ or IgM) + Antigen (soluble)
- Immune – Complex formation
- Complement activation
- Attraction of inflammatory cells
Type III Reactions
Type III Hypers. Reactions
Clinical examples:
Glomerulonephritis: Rheumatoid arthritis, SLE
Diagnosis of Type III Hypers.
Reactions
Demonstration of specific immune
complexes in the blood or tissues by:
Immunofluoresence
Type IV hypersensitivity reactions
(Delayed Hypersensitivity)
• Features
• Cell mediated immune response
– Antigen dependent T cell (CD4 generally
and CD8 occasionally) activation via MHC
Class I or II
• Activated macrophages
• Delayed onset (2-4 days)
• Abnormal cellular response
– (Granuloma formation)
Mediators released by TDTH cells
Development of
DTH Response
Sensitization
phase:
1-2 week period
Effector phase:
24-72 hours
Effector cells
(activated macs)
act non-specifically
Pathophysiology of Contact dermatitis.
Type IV clinical examples:
Contact dermatitis
TB granuloma
(persistent antigen)
Diagnosis (Type IV)
1. Delayed skin test (Mantoux test)
2. Patch test (Contact dermatitis)
3. Lymphocyte transformation test
Skin Patch Test
Take Home Message
• 1. Type I (IgE), II (IgG) and III (IgG)
hypersensitivity reactions are mediated by
antibodies whereas Type IV hypersensitivity
reaction is a cell mediated immune response.
• 2. Hypersensitivity reactions are undesirable,
excessive, and aberrant immune responses
associated with disorders such as allergy,
autoimmunity and chronic inflammation.
