Hypersensitivity Type I
atopic/allergic individuals;
IgE: produced after contact with low levels of innocuous environmental
allergens
IgE――――mast cells ―――――→release mast cell mediators(autocoids,
bind via Fc RI
cytokines)
IgE produced is due to a genetic predisposition to make TH2/Il-4 type immune
response to allergen
This response can be considered an unfortunate side effects of its activity
hypersensitivity: adaptive immune response occurs in an - exaggerated - form
- inappropriate -
――→ inflammator reaction
cause tissue damage
-antibody-mediated: type I, II, III
-mediated mainly by T cell - :type IV
macrophages-
type I(immediate)
:innocuous environmental antigens 에 IgE가 response 할 때
→IgE-sentsitized mast cell
→release pharmacological mediators(fig. 22.3)
type II(antibody-dependent cytotoxic hypersensitivity)
:antobody――――self antigen
bind
foreign antigen
→phagocytosis
killer cell activity
complement-mediated lysis
type III
i)immune complex가 large quantities 형성
ii) reticuloendothelial system에 의해 clear되지 않음
→serum-sickness type reaction
type IV(delayed type hypersensitivity)
:most serious
:antigens ― trapped in ― macrophage ―――→ cannot cleared
T cell stimulated
↓
elavorate cytokines
↓
inflammatory response
■Immunoglobulin E
APCs 의 antigen-presenting/ TH2 cell 과의 cooperation
→B cell stimulate
→IgE production
→IgE response is a local event occurring at the site of the allergen's entry into
the body
↓
locally produced
↓
enter circulation
↓
binds to specific receptors on both circulating basophils and tissue-fixed mast cells
: IgE half life
- free form: only a few days
- mast cell binding form: many months
:
irradiated
IgE response , prolonged
thymectomized thymocytes/spleen cells from ascaris-primed cell
IgE production suppress
(∵transferred cell population 의 suppressor T cell때문)
: TH cell 에서 나오는 cytokine 이 IgE production regulate(fig. 22.5)
――→ cytokines produced by TH2 cells
(IL-3,4,5,9.13) is encoded in a *gene cluster on chromosome 5 in humans and
chromosome 13 in mice
■Genetics of the allergic response in mice
:allergic parents―→ allergic child
∴ genetic mechanism
regulate - total IgE levels
- allergen-specigic response
-general hyperresponsiveness
IgE levels
IL-4/another genes, regulates total(but not specific) IgE levels
genes controlling the allergen-specific response are linked to HLA
■mast cells
morphological differences
-CTMC(Connective Tissue Mast Cells): blood vessel
-MMC( Mucosal Mast Cells):highest concentration mucosa of the midgut
and in the lung
<differences between mast-cell populations-I>
<differences between mast-cell populations-II>
mast cell proteases
: tryptase, /chymase asthma 의 hallmark
fibroblast growth factor
bronchial mucosal surface is the first site of contact for inhalled allergen
locally applied corticosteroids also suppress the increase in nasal mast-cell
numbers
∴corticosteroids inhibit cytokine production by TH cells
IgE 에 binding 하는 다른 cell
allergen
IgE cross-linking to mast cell
other molecules
aggregation of the Fc receptor
influx of calcium ions into the cell
degranulation
i) exocytosis of granule contents with the release
of preformed mediators(ex: histamine)
ii) induction of synthesis of newly formed
mediators(fig 22.14 22.20)
■Cutaneous Reactions
-skin prick test
-skin patch test
■Bronchial Reactions
■Factors involved in the development of allergy
-genetic disposition 외에도 allergy developing factor는 많다
<T-cell deficiency, environmental pollutants>
T-cell deficiency is associated with atopy
:reduced T-cell response in vitro correlate with reduced cell-mediated immunity which
may be reflected in vivo as depressed delayed hypersensitivity
environmental pollutants act to increase antigen-specific IgE
↓
increase mucosal permeability
enhance allergen entry
■Hyposensitization
:hyposensitization therapy ; injection of increasing doses of allergen
→increase in serum levels of allergen-specific IgG and suppressor T-cell activity
Hypersensitivity-Type II
i) caused by (IgG/IgM) against (cell suface/extracellular matrix antigens)
ii) transfection reactions to erythrocytes
iii) antibody cells/ tissues
damage by activating complement
iv) haemolytic disease (maternal antibodys destroy the fetal
erythrocytes
v) antibody-basement membrane
intercellular adhesion molecules
receptor
tissue damage
:damage is restricted to the specific cells or tissues bearing the ahtigens
■Mechanisms of Damage
: antibody directed against cell surface or tissue antigens interacts with complement
and a variety of effector cells to bring about damage to the target cells
: antibody attach surface of cell/tissue.
――→ bind and active complement component c1
――→ i) C3a, C5a ; attract macrophages and polymorphs to the site
; stimulate mast cells and basophils
→ produce molecule(attract and activate other effector cells)
ii) deposition of C3b, C3bi, C3d
iii) classical component pathway and lytic pathway
→ production of the C5b-9 membrane attack complex
: complement fragment/IgG
→ opsonins으로 작용
→ phagocyte 가 take up
(by ; lysosomal activity를 높임
→reactive oxygen intermediates production)
→ hypersensitivity type II
※NEUTROPHIL ACTIVATION
■Reactions against Blood cells and Platelets
<1> transfusion reaction occur when a recipient has antibodies that react against
donor erythrocytes
: blood group system consists of a gene locus that specifies an antigen on
the surface of blood cells
∴ transfusion of allogenic(nonself) erythrocytes into an individual who
already has antibodies against them may produce erythrocyte destruction
and symptoms of a transfusion reaction
∴ the aim of cross-matching is to ensure that the blood of a recipient
does not contain antibodies that will be able to react with and destroy
transfused erythrocytes
ABO system antibody → IgM (대다수 )
→ cause agglutination
complement activation
intravascular haemolysis
other blood group → induce IgG
→ less agglutination
take up by phagocytes
→ circulatory shock 유발
<2> haemolytic disease of the newborn is due to maternal IgG antibodies which react
against the child's erythrocytes in utero
<3> autoimmune haemolytic anaemias arise spontaneously as autoimmune disease or
may be induced as reaction to drugs
:patients prodece antibodies to their own erythrocytes
-warm-
reactive autoantibodies
-cold-reactive autoantibodies
-antibodies provoked by allergic reaction to drugs
■Reactions against Tissue Antigens
:antigen are extracellular, and may be expressed on structural proteins or on the
surface of cells
-Goodpasture's syndrome
-Pemphigus
-Myasthenia gravis