Transcript 8_Hypersensitivity

HYPERSENSITIVITY REACTIONS
Innocous materials can cause
hypersensitivity in certain individuals
unwanted inflammation
damaged cells and tissues
Non-proper reaction of the immune system to foreign substances
Mainly harmless substances – after second or multiple times
The effector mechanisms and tissue destruction in hypersensitivity reactions
are identical to those seen in autoimmune diseases.
ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS
HYPERSENSITIVITY REACTIONS
TYPE I
ALLERGY
TYPE II
TYPE III
Soluble antigen
Cell surface or matrix
antigen
Soluble antigen
IgE
Mast cell
Hay fever
Asthma
Systemic anaphylaxis
1-2 min
IgG – immune complex
FcγR+ cells
NK, macrophage
Certain drug allergies
(penicillin)
4-8 h
IgG – immune complex
FcγR+ cells
Complement
Serum sickness
Arthus reaction
2-8 h
Type II hypersensitivity
IgG type antibodies bound to the cell surface or to tissue
antigens
• cells expressing the antigen become sensitive to complement mediated
lysis or to opsonized phagocytosis
• frustrated phagocytosiss  tissue demage
• the antibody inhibits or stimulates target cell function
– no tissue damage (e.g. M. gravis – receptor blocker antibodies)
MECHANISMS OF TYPE II HYPERSENSITIVITY
REACTIONS
Hemolytic anemia of newborns
Erythroblastosis fetalis
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
Drug induced
Hemolytic anemia
Trombocytopenia
Penicillin-based antibiotics
Anti-arythmic drug quinidin
Myastenia gravis
Penicillin-induced hypersensitivity
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
Absorbed antigen
(drug)
C3b
Opsonized surface Binding Frustrated Enzyme release
phagocytosis
TYPE III HYPERSENSITIVITY
Antibodies binding to soluble antigens
Small circulating immune complexes
Depends on:
Size of immune complexes
Antigen-antibody ratio
Affinity of antibody
Isotype of antibody
Size of immune complexes formed during immune responses
The pathology is determined by the site of
immune complex deposition
Arthus reaction
hard swelling,
erythema
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, bazophil granulocytes and thrombocytes
Serum sickness
• Mechanisms of tissue demage is independent on the site of
deposition
• Steps of tissue demage
– Formation immune complexes in the blood
– Deposition depends on the size, composition and cytophylic properties of the
antibody (IgM, IgG, IgA)
– FcγRIII has a pivotal role
– Permeability of endothelium
– Tissue demage
• Increased permeability of blood vessels
• Reqruitment of neutrophils – enzymes, chemoattractans, dilatators, prostaglandins
• fibrosis
• Consequences of tissue demage depends on the site of deposition
– Acute serum disease – 7 – 10 days
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Polyclonal antibodies against snake venom produced in horses
Immune suppresszive anti-lymphocyte globulin
Bacterial trombolytic streptokinase – treatment of miocardial infarction
Subacute bacterial endocarditis – pathogens are not eliminated
Chronic viral hepatitis
Serum therapy against diphtheria
Edwin Klebs
1834-1913
Emil von Behring
1854-1917
Corynebacterium diphtheriae
Klebs-Löffler bacillus (1883)
Nobel prize 1901
Tom (1894, London)
Skin symptoms of serum sickness
Serum sickness
TYPE IV HYPERSENSITIVITY REACTION
T CELL MEDIATED PROCESS
Type IV hypersensitivity reaction
Chemokines, cytokines,
cytotoxins
Tuberculin skin test
Ag = antigen
Mycobacterium
protein (PPD)
Introduction of Ag
Delayed-type hypersensitivity
(DTH) (e.g., tuberculin skin test)
TH1 from a previous
immunization (memory)
Contact Dermatitis
*a contact-sensitizing agent is usually a small molecule that penetrates the skin
then binds to self-proteins, making them “look” foreign
Delayed-type hypersensitivity is mediated by T cells