Transcript Hypersensitivity

AN OVERVIEW OF HYPERSENSITIVITY
REACTIONS
Type I.
Type II.
„immediate”
Type III.
Type IV.
„late”
Antibody mediated
T cell mediated
TYPES OF ANTIBODY MEDIATED
HYPERSENSITIVITY REACTIONS
FcRIα)
TYPE II HYPERSENSITIVITY
IgG type antibodies bound to
cell surface or tissue antigens
• cells expressing the antigen become sensitive to complement
mediated lysis or to opsonized phagocytosis
• frustrated phagocytosis  tissue damage
• the antibody inhibits or stimulates target cell function
no tissue damage (e.g. M. gravis – receptor-blocking antibodies)
MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS
NK
Mf
Killing of target
cell by effectormacrophage or
NK-cell
IgG
ADCC
IgG
C'
complement
activation
Killing of target
cell by complementmediated lysis
Receptor-specific
autoantibody
interferes with
signal transduction
FRUSTRATED PHAGOCYTOSIS MEDIATED BY
IgG TYPE ANTIBODIES
Binding
Opsonization Internalization
C3b
C3b
C3b
C3b
Enzyme
release
C3b
C3R
FcR
The tissue, which
can not be
phagocytosed, is
damaged
C3b
Absorbed antigen
Opsonized surface Binding Frustrated
(drug)
phagocytosis
Enzyme release
EXAMPLES - TYPE II HYPERSENSITIVITY
Newborn haemolytic anaemia
Transfusion reaction
Hyperacut allograft rejection
Drug-derived
• Haemolitic anaemia
• Thrombocytopenia
• Agranulocytosis
•
•
Penicillin-based antibiotics
Anti-arithmic quinidine
Goodpasture syndrome (kidney, basal membrane - collagen type IV)
Pemphigus vulgaris (mucosal bubbles)  against desmosomal antigens,
interruption of epidermal and mucosal connections, acantolysis
(desintegration into single cells)
Myasthaenia gravis (anti-acetyl-choline receptor antibodies)
Graves-Basedow-Flajani disease (anti-TSH-receptor antibodies)
DEVELOPMENT OF DRUG
SENSITIVITY I.
DEVELOPMENT OF DRUG SENSITIVITY II.
TYPE III HYPERSENSITIVITY
Antibodies binding to soluble antigens
forming small circulating immune complexes
which are deposited in various tissues
Depends on:
Size of immune complexes
Antigen-antibody ratio
Affinity of antibody
Isotype of antibody
THE PROCESS OF TISSUE DAMAGE CAUSED BY IMMUNE
COMPLEXES
Antigen
C'
Immune complex
Antibody
Complementa ctivation
(C3a , C5a )
PMN
Chemotaxis
C'
Endothelium Ba sophil
Ba sa l membra ne
gra nulocyte
Vessel wa ll
Thrombocytes
Deposition
Blood vessel
wall
permeability
Frustrated
phagocytosis
Vasoactive
a mines
Immune complexes activate the complement system,
neutrophils, basophils and thrombocytes
SYPMPTPOMES CAUSED BY TYPE III HYPERSENSITIVITY REACTIONS
DEPEND ON THE SITE OF IMMUNECOMPLEX DEPOSITION
ARTHUS-REACTION
• Localized Type III hypersensitivity
• Local vasculitis develops as a result of immune complex deposition
• Inhaled antigens (fungi, animal feces) may induce similar reaction in
the lung
• IgG type antibody
• ‘Farmers lung’ and ‘piegeon-breeder’s lung’
MANIFESTATION OF TYPE III HYPERSENSITIVITY IN
LUPUS ERYTHEMATOSUS
Facial, malar "butterfly" rash with characteristic
shape across the cheeks.
Discoid lupus erythematosus (DLE) involves
mainly the skin, it is relatively benign compared
to systemic lupus erythematosus (SLE). In either
case, sunlight exposure accentuates this
erythematous rash. A small number
(5 to 10%) of DLE patients go on to
develop SLE (usually the DLE patients
with a positive ANA).
Here is a more severe inflammatory skin
infiltrate in the upper dermis of a patient
with SLE in which the basal layer is
undergoing vacuolization and dissolution,
and there is purpura with RBC's in the
upper dermis (which are the reason for the
rash).
RENAL FAILURE IN IMMUNECOMPLEX DISEASES
Glomerulus of a healthy
individual. Relatively wide
spaces between capillary
loops.
One of the feared complications
of the systemic autoimmune
diseases is renal failure. This is
most likely to occur in SLE.
Here is a glomerulus in which
the capillary loops are markedly
pink and thickened such that
capillary lumens are hard to
see. This is lupus nephritis.
TYPE IV HYPERSENSITIVITY
REACTION
T CELL MEDIATED PROCESS
TYPE IV HYPERSENSITIVITY REACTION
DELAYED-TYPE (TYPE IV)
HYPERSENSITIVITY
DELAYED-TYPE (TYPE IV) HYPERSENSITIVITY
DELAYED-TYPE HYPERSENSITIVITY (DTH)
(e.g. tuberculin skin test)
TH1 from a previous
immunization (memory)
Tuberculin skin test
Introduction of Ag
Ag = antigen
Purified protein
derivate (PPD)
CHEMICAL MEDIATORS OF DTH
DTH as a result of a contact-sensitizing agent*
CONTACT DERMATITIS
*a contact-sensitizing agent is usually a small molecule that penetrates
the skin then binds to self-proteins, making them “look” foreign
Poison ivy
Anacardiaceae (family), Toxicodendron (genus)
Toxicodendron radicans or Rhus toxicodendron
CELIAC DISEASE
Delayed-type hypersensitivity is mediated by T cells