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Hypersensitivity (超敏反应)
Qingqing Wang
Institute of Immunology
Zhejiang University School Of Medicine
[email protected]
Type II hypersensitivity
(cytotoxic type)
 Type II hypersensitivity reactions are
mediated by IgG and IgM antibody binding
to specific cells or tissues. The damage
caused is thus restricted to the specific cells
or tissues bearing the antigen.
 The antibodies damage cells and tissues by
activating complement, and by binding and
activating effector cells carrying FcR.
I. Pathogenic mechanisms
Ags on the surface of target cells
↓
body→IgG, IgM
↓
1. damage the target cell
1) activation of complement
2) opsonization: FcR, C3bR
3) ADCC: NK cells, M
2. target cell dysfunction
NK cell
opsonization
Effector
mechanisms of
Ab-mediated
diseases
Graves’
disease
In myasthenia gravis
the Abs against Ach
receptor inhibit
neuromuscular
transmission and cause
paralysis
II. Clinical disease
1. Transfusion reactions
A型血
输血
A型血输入B型血体内
B型血体内存在抗A抗体
A型血抗原
血细胞溶解
补体
抗原
抗体
反应
2. Hemolytic disease of the newborn
Mainly occurs when an Rh- mother gives
birth to an Rh+ infant.
Prevention: The administration of anti-Rh Ab
to an Rh- mother within 72 hours of
delivering an Rh+ infant will prevent
sensitization and problems with subsequent
pregnancies.
母体内的IgG与胎
儿体内的Rh抗原
结合，导致胎儿出
生后发生新生儿溶
血症。
3. Autoimmune hemolytic disease
Some drugs or viruses stimulate Ab
formation by changing the erythrocyte
surface components to form new epitopes.
The resulting Abs can cross react with
epitopes on unmodified RBCs.
Human antibody-mediated diseases
4. Drug-induced reaction to blood components
These diseases have been associated with
many different chemotherapeutics, such as
penicillin, the sulfonamides. These drugs
stimulate Ab formation by forming new epitopes
with serum proteins, which then adsorb
nonspecifically to the red blood cell surface so
that its new epitopes are expressed.
5. Graves’ disease
The patients produce antibodies to
thyrotropin (thyroid stimulating hormone,
TSH) receptor. The end
result
is
overproduction of thyroid hormone and
hyperthyroidism.
Type III hypersensitivity
(immune complex type)
Immune complexes (IC) deposit in
basement membranes of small
blood vessels in various organs.
I. Pathogenic mechanisms
Ag→body→IgG, IgM, IgA
↓
immune complexes (IC)
↓
soluble IC
↓
ICs are deposited from the circulation
into vascular basement membranes
①↓
② ↓FcR
activation of complement plat. and basophils
↓
C3a, C5a →mast cell → release of vasoactive amines
↓
basophils
③ Neutrophils
vasodilation
aggravate
↓
lysosomal
edema
enzymes→damage the tissue
IC are capable of triggering a variety
of inflammatory processes
 ICs interact with the complement system to
generate C3a and C5a. These complement
fragments stimulate the release of vasoactive
amines and are chemotactic factors for mast
cells and basophils, eosinophils and neutrophils.
 ICs interact directly with basophils and platelets
(via FcR) to induce the release of vasoactive
amines.
 Neutrophils exocytose their lysosomal enzymes
onto the site of IC deposition and damage the
underlying tissue.
Deposition of IC in tissues
 An increase in vascular permeability
In general, complement, mast cells, basophils and
platelets must all be considered as potential producers of
vasoactive amines.
 Local high blood pressure and turbulence
The blood pressure in the glomerular capillaries is
approximately four times that of most other capillaries.
II. Clinical diseases
1. Arthus reaction
An animal is immunized repeatedly until it has
appreciable levels of serum Ab (mainly IgG).
Following subcutaneous or intradermal
injection of the antigen a reaction develops at
the injection site, sometimes with marked
edema and hemorrhage.
Nicolas Arthus 1862-1945
Arthus’s reaction
（1903）
经抗原反复免疫之后,注射抗原的皮下出现局部红肿、出血
和坏死等剧烈炎症反应。
基底膜
1
2
内皮细胞
抗原
抗体
复合物
免疫复合物沉淀
中性粒细胞
补体
C3a
C5a
血小板
血小板凝聚
C5a
肥大细胞
微血栓形成
血管活性胺
血管壁
趋化
2. Serum sickness
Serum sickness is a complication of
serum therapy, in which massive doses
of anti-serum are given in conditions
such as snake bite.
Serum sickness（血清病）
Clemens Pirquet 1874-1929
3. Postinfectious glomerulonephritis
常见于A族溶血性链球菌感染后2-3周。抗体与链球菌可溶性
抗原形成复和物，沉积于肾小球基底膜处
Human immune complex disease
4. Rheumatoid arthritis
 Rheumatoid factor (RF): an immunoglobulin
(mainly IgM but also IgG and IgA) with antibody
specificity for the Fc portion of IgG.
 The joint synovial fluid contains IC consisting of RFIgG-complement.
 Many patients with rheumatoid arthritis also have
antinuclear antibodies.
5. Systemic lupus erythematosus (SLE)
 antinuclear antibodies
 hypergammaglobulinemia
RA，SLE
自身抗体与可溶性自身抗原形成免疫复和物，
沉积于皮下、关节和肾小球基底膜等处。
SLE
Type IV hypersensitivity
(Delayed type hypersensitivity)
 Delayed type hypersensitivity is initiated
by sensitized T cells reacting with specific
antigens. The reactions are manifest as
inflammation at the site of antigen
exposure, which usually peaks 24-72
hours after exposure.
 This reaction is independent of antibody
and complement.
I. Pathogenic mechanisms
Ag-MHC
Antigen→APC→T cells
co-stimulating factors
↓
sensitized T cell
↓
effector and memory cells
↓
↓
CD4+T cell (Th1 type) CD8+T cell (CTL)
↓
release of cytokines
↓
inducing the inflammatory
response
(primarily M and T cells)
↓
killing target cells
by the release of
perforin and granzymes
or by the FasL-Fas pathway
Mechanisms of T cell-mediated tissue injury

II. Clinical diseases
1. Infectious DTH
In the infective process, intracellular
parasitical bacteria (Mycobacterium
tuberculosis, Mycobacterium leprae,
Brucella), viruses and fungi cause T cellmediated immune responses, which are
referred to as infectious delayed type
hypersensitivity.
结核菌素试验
Tuberculin-type hypersensitivity
The tuberculin skin test (OT) reaction principally involves M
tuberculin→body→T cells are activated
↓
IFN-→M→TNF, IL-1
↓
endothelial cells in dermal blood vessels
↓express
CAM: E-selectin, ICAM-1, VCAM-1
↓
recruiting monocytes and T cells
(Monocytes constitute 80-90% of
the total cellular infiltrate)
Tuberculin-like delayed type hypersensitivity
reaction are used practically in two ways.
1) To confirm past infection with M. tuberculosis,
but not necessarily active disease.
2) To be a general measure of cell-mediated
immunity.
2. Contact dermatitis
 Langerhans cells and keratinocytes acting as
APCs have key roles in contact hypersensitivity.
 Keratinocytes produce a range of cytokines.
 A contact hypersensitivity reaction has two
stages: sensitization and elicitation.
Sensitization produces a population of memory T
cells and elicitation involves recruitment of CD4+
lymphocytes and macrophages.
接触羽毛
接触橡胶
 Many important sensitizing allergens are
organic chemicals, and some are metals
such as nickel, chromate. It is assumed
that they function as haptens.
 When allergen again penetrates the skin,
these memory cells rapidly evolve into
effectors that mediate a delayed-type
hypersensitivity reaction at the site of
penetration.
T cell-mediated diseases
Comparison of 4 types of hypersensitivity
Thanks for your attention!
 Thank you very much for your support and
cooperation in my teaching
 If you have any question and suggestion,
please feel free to contact me:
[email protected]