Transcript Hypersensitivity

Fachpraktikum
Immunreaktionen der Haut
Unterlagen zum Selbstudium vor dem
Praktikum oder als Repetitorium
Prof Dr. Beda M. Stadler
Institut für Immunologie
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Das wissen Sie!
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Working Definition
HYPERSENSITIVITY
adverse clinical reaction to the antigen or,
“when the immune system does something
bad to the host, i.e. tissue damage”
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Coombs and Gell’s Classification of Hypersensitivity
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Type I Hypersensitivity
• Known as:
– Immediate
hypersensitivity
– Anaphylaxis
– IgE-associated
immune
responses
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Type-I Hypersensitivity: Animation I
Production of IgE in Response to an Allergen
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Type-I Hypersensitivity: Animation II
Allergen Interaction with IgE on the Surface of Mast
Cells triggers the Release of Inflammatory Mediators
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Sensitization
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Triggering Phase
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Mast cells and Basophils
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IgE-mediated Activation
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Biochemical Pathways of IgE-FcRI Activation of Mast Cells
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Complement: Classical Pathway
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Anaphylactic-type Degranulation of a Mast Cell
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Products of Human Mast Cells
Granule proteins
MBP, ECP, EPO
Epithelial damage / loss
Muscarinic M2 dysfunction/ AHR
LTC4, PAF
Mucus hypersecretion,
Airway narrowing
Attract/activate
pro-inflammatory cells
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Cytokines
IL-3, IL-4, IL-5, GM-CSF,
IL-6, IL-12, TGF-b
Attract/activate eosinophils
Airway remodelling, IgE,
Th2 polarisation
Chemokines
Eotaxin, RANTES
Attract/activate eosinophils
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Skin Prick Test
In this test a small needle is used to
gently prick the skin through a drop of
fluid containing a known allergen. It is
usually done on the forearm, although
with young children it may be done on
the back so they don't have to see what
is happening.
A negative reaction means that you do
not have an allergy to that particular
allergen.
Your clinical symptoms should correlate
with the allergens to which you test
positive, only then can an allergy be
confidently diagnosed.
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Die Normale Haut
…in einem sensibilisierten Individuum
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Sofort-Reaktion (Minuten)
1.
2.
3.
4.
5.
6.
7.
8.
9.
Allergen überwindet Barrieren
Rezeptorgebundenes IgE wird
kreuzvernetzt
Mediatoren verusachen arterielle
Dilatation
Erhöhung der venösen
Permeabilität
Blutstau
Erythem entsteht, Extravasation
von Plasma
Schwellung (Quaddel); Histamin
wirkt auf sensorische Nerven
Neuropeptide stimulieren
arterielle Dilatation
Es kommt zur peripheren Rötung
(flare)
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Die Spätreaktion
1.
2.
3.
Mastzellen und
Th2 Zellen produzieren
Zytokine,
wodurch weitere
Entzündungszellen aus
der Peripherie angelockt
werden. Dadurch
entsteht eine nochmalige
Schwellung und Rötung.
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Immediate and Delayed Phases of Type I Hypersensitivity
Immediate
Delayed
Hier ein guter Link mit Beispielen
http://www.fpnotebook.com/ENT48.htm
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Vasculature
Skin
Upper
respiratory
Lower
respiratory
GI Tract
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Products of Human Eosinophils
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Inflammation during Bronchial
Asthma
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Higher magnification of Bronchial Asthma
Infiltration of eosinophils (bright red cytoplasmic granules).
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Intervention for Type I Hypersensitivity
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Intervention for Type I Hypersensitivity
Animation: Treatment with monoclonal anti-IgE antibody
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Type II Hypersensitivity
• Directed at Cell-surface or
Matrix Antigen
• Mediated by IgG
• Immune Processes involved:
– Classical Complement Pathway
– Phagocytosis via FcR and
Complement receptor
– ADCC via NK cells or
eosinophils
• Many autoimmune diseases
result from type II
hypersensitivity generated by
autoantibodies
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Type II Hypersensitivity
Antibody-Complement Dependent Mediated Lysis
Animation: IgG or IgM reacts with epitopes on the host cell membrane and
activates the classical complement pathway. Membrane attack complex (MAC)
then causes lysis of the cell.
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Type II Hypersensitivity
Antibody-Complement Dependent Mediated Lysis
Example: Autoimmune Hemolytic Anemia
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Complement Cascade
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Type II Hypersensitivity
Antibody Dependent Cell Mediated Cytotoxicity
Animation: Antibodies react with epitopes on the host cell membrane and
NK cells bind to the Fc of the antibodies. The NK cells then lyse the cell with
pore-forming perforins and cytotoxic granzymes
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Type II Hypersensitivity
Antibody-Mediated Cell Disfunction
Example: Myasthenia Gravis
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Type III Hypersensitivity
• “Immune complex
disease”
• Soluble Ag/IgG or IgM
– high titers of each required
• Immune processes
involved:
– classical complement
pathway
– phagocytic cells
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Type-III Hypersensitivity: Immune Complex
Animation: Large quantities of soluble antigen-antibody complexes form in the blood and are
not completely removed by macrophages. These antigen-antibody complexes lodge in the
capillaries between the endothelial cells and the basement membrane. The antigen-antibody
complexes activate the classical complement pathway and complement proteins and antigenantibody complexes attract leukocytes to the area. The leukocytes then discharge their killing
agents and promote massive inflammation. This leads to tissue death and hemorrhage
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Arthus Reaction
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Serum sickness
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Sites of Complex Deposition
Site
Outcome
glomeruli
glomerulonephritis
blood vessel wall
arteritis
synovial membrane
arthritis
skin
rash
Note: Ab responsible for immune complexes may be
generate at a site distant from the point of deposition.
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Predisposing Conditions
• Repeated antigenic exposure
• Chronic infection
• Autoimmunity
• Cancer
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Acute Vascular Rejection
Following Cardiac Transplant
Note: Immune complex deposition in the vessels.
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Examples of Type IV Hypersensitivity
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TH1-mediated Type IV Hypersensitivity
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TH1 Influence of Immune Response
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Positive Tuberculin Reaction
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Pathways of Cytotoxicity utilized by CTL’s
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Contact Dermatitis
Maybe due to either TH1 or CTL mediated hypersensitivity
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Patch test
This test is used to diagnose
delayed allergic reactions
such as Contact Dermatitis. It
involves taping traces of
various known contact
allergens on the skin and
keeping them there for 48
hours. It can test for allergy to
Rubber, Nickel, Lanolin, dyes,
cosmetics, solvents,
preservatives, and
medication.
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THE END!
• To understand various forms of
hypersensitivity  Coombs and Gell is
helpful, but…
• remember that many response reflect
input for more than one type!
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