Fachpraktikum Immunreaktionen der Haut

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FachpraktikumImmunreaktionen 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 DefinitionHYPERSENSITIVITY

• 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 Gells 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
Cytokines IL-3, IL-4, IL-5, GM-CSF, IL-6, IL-12,
TGF-b
Granule proteinsMBP, ECP, EPO
Epithelial damage / loss Muscarinic M2
dysfunction/ AHR
Attract/activate eosinophils Airway remodelling,
IgE, Th2 polarisation
LTC4, PAF
Chemokines Eotaxin, RANTES
Mucus hypersecretion, Airway narrowing Attract/act
ivate pro-inflammatory cells
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. Allergen überwindet Barrieren
2. Rezeptorgebundenes IgE wird kreuzvernetzt
3. Mediatoren verusachen arterielle Dilatation
4. Erhöhung der venösen Permeabilität
5. Blutstau
6. Erythem entsteht, Extravasation von Plasma
7. Schwellung (Quaddel) Histamin wirkt auf
   sensorische Nerven
8. Neuropeptide stimulieren arterielle Dilatation
9. Es kommt zur peripheren Rötung (flare)

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Die Spätreaktion

1. Mastzellen und
2. Th2 Zellen produzieren Zytokine,
3. 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.fpno
tebook.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 HypersensitivityAntibody-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 HypersensitivityAntibody-Complement
Dependent Mediated Lysis
Example Autoimmune Hemolytic Anemia
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Complement Cascade
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Type II HypersensitivityAntibody 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 HypersensitivityAntibody-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 antigen-antibody
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 RejectionFollowing 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 CTLs
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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!