Types of hypersensitivity diseases

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Types of hypersensitivity diseases

• ?????? ?? ???? ??? ????????? ?????? ?????? ?? ??
  ???? ??? ????? ?? ????
• ???)?????? ???? ??? ????? ? ??????? ???
  ?????????? ?? ???? ?? ???? ?? ????
• ?)????? ? ?????? ???? ??

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Types of hypersensitivity diseases

• ???????????? ???? ???? IgE ????? ?? ???
• ???????????? ??? II ?????? ???? ??????? ????? ???
  ?? IgE ????? ?? ??? ?? ?? ????? ???? ????
  ???????? ?? ?????? ????? ???? ?? ???
• ??? III ?????? ?????? ???? ?????? ????????? ?????
  ?? ???? ??
• ??? IV ?????? ?????? ?? ??? ?????? ??????
  ??????? T ??????????? ????? ?? ???

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Hypersensitivity type I
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Disease caused by Immune responses

• Activation of Th2 cells and production of IgE
• Allergen Activation of Th2 B
  cell activation IgE binding of IgE
  to Fc receptor reexposure to Allergen
• release of mediators pathologic
  reactions

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• ?????? ?? ????????? ?????? ?????? ???? ??? ?????
  ???? ?? ???? ????? ??? ??????? ????? ?? ???? ??
  IgE ? ??????? Th2 ? eosinophils ?? ?? ??? ?????
• ?????? ?????? ??? I ??? ?? ??? ????? ??? ??
  ?????? ?? ????? ???? ?? ??? ???? ?? ??
  ????(Immediate) ?? ???????? ?????? ??? ?????
  ????? ??????? ?????? (Late phase reaction)??? ??
  ?????? ?? ?? ?????????? ?????????????? ??????????
  ???????? Th2 ? ??????????? ????????? ?? ????

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• ????? ?????? ?? ???? ?? ???????? ????? ?? ??????
  ?? ????? ????? ?????? ????? IgE ????? ?? ????.??
  ??? ??? ?? ???? Th2 ??? ? ????? ? ??? ???? ??
  ???????? ???? ?? ???? ?? ????? ????.??? ???? ????
  ?? ??? ??????? ???? ? ????????? ?????? ????.

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• ??????? ? ?? ???? ?????? ?? ????? ??? ??????
  ?????? ???? ?? ???? ?? ???? ?????? ??????? ? ??
  ???? ??????? ???? ?? ????????? ????? ?? ?????
  ?????? ???? ???? ?? ???? ???? ?? ?????.???? ?????
  ?? ???? ???????????? ????? ?? ?????? ? ???????
  ????? ?? ??????? ?????????? ??? ????????????
  ????? ????? ??????? ??? ??? ????? ??? ???.
• ???? ?? ???????? ??????? ??????? ?? ???) ?? ????
  ?????? ???? ? ????? ????? ?? ???? ???? ???? ??
  ????? ?)?????? ???????? ?????? ????? ???? ??
  ????? ??? ????
• ?????? ?? ???????? ??????? ?? ???? ?? ?????
  ??????? ??? ???? ?? ????? ?????? ??? ??????? ??
  ?? ????????????? ?????????????? ? ??????? ???? ??
  ?????? ???

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Activation of Th2 cells

• ??????? ???????? ?? ??? ???? ???? ???? ?? ????? ?
  ?? ???? ??? ???? ????? ? ?? ?? ??? ???? ??
  ??????? Th ???? ?? ????.??? ?????? ??? ?? Th2 ?
  TfH ????? ?? ?????.IL-4 ???? ??? ?? ???? ?
  ????????? ???? ????? ??????? Th2 ?Thymic stromal
  lymphopoietin(TSLP) ?? ???? ??????? ??? ????? ??
  ???? ? ?????? ????? ???? ?? ???? ?? ??? ???????
  ?????????? ????? ?? ??????? ???????? ???? ?? ????
  ????? ??????? Th2 ?????? ?? ???.??????? Th2 ??
  ???? IL-4 ? IL-13 ?CD40L ???? ????? ???????? ????
  ???? ?? IgE ?? ????

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• ??????? Th2 ???? ???? ??? ?? ????????
  ???????????? ???? ??? ???? ?? ????.IL-5 ??????
  ?????? ??? ?????? ???? ???? ???? ???????????? ??
  ????.IL-13 ?? ????? ??????? ??? ????? ???? ??
  ?????? ????? ???? ???? ????? ????? ?? ???. ??????
  ??????? Th2 ?? ?????? ??? ?????? ??? ???? ?????.

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Mast cells

• ??? ?????? ?? ??? ??????? ?????? ?? ????? ?????
  ?????? ???? ???? ??? ?? ???? ? ?? ?? ???? ????
  ???? ?? ?? ???? ?? ??? ??? ???? ????? ????? ??
  ?????? ???? ???? ? ????? ???? ??? ????? ? ??? ??
  ???? ??? ????????.
• ?? ????? ?????? ?????? ???? ?? ????.????? ????
  ??? ???????????? ????????? ???? ?? ???? ????
  ?????.???????? ???? ??????????????? ????? ??? ??
  ?????? ???? ????? ?? ????.

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Eosinophil and Basophil

• ??? ?????? ????? ?????? ??? high affinity ????
  IgE ???? FC?R ?? ?????
• ?????????? ?????????? ?? ???? ????? ?? ? ????
  ?????????? ????????????

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Mast cells

• ???? ????? ???? ??? ?????????? ?????? ?? ???? ??
  ????
• ???? ?? ?????? ???????? ???? ? ?????? ???????
  ??????? ???? ????? ?????? ?? ???? ???? ????
  ?????.
• ?? ??????? ? ???? ????? ???? ?????? ????? ?????
  ????? ???? ?????? ????????? ?? ??? ????? ?????
  ???????? ???? ????????? ?????? ????? ??
  ?????????? ???? ????? IL-3 ????? ?? ?????
• ?? ????? ??? ????? ????? ????????????
  ?????????????? ???? ?? ?????????? .
• ???? ????? ???? ?????? ?? ??? ? ???? ???? ????
  ??? ??? ??????? ?????????????? ?????? ? ?????
  ????? ???????? ?? ?????.
• ?? ????? ? ?? ????????? ???? ????? ??? ?????? ??
  ????? ?? ???? ???? ???? ???? ?? ???? ??
  ????????????????????????? ??????????? ????

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Fc?R

• ????? ??????? ???? ? ??????? ? ???????????? ?
  ????????? ???? ??? ???????? ????????? ???????
  Fc?RI???? ????
• ??????? ??? ?????? ?? ??? ??????? ???? ?
  ????????? ???? IgE ????? ???? ???
• ??? ?????? ?? ?? ?????? ? ??? ?????? ? ?????????
  ? ????? ??? ?? ??? Fc ???? ???? IgE ?? ???? ????
  ?? ??? ? ???? ?????? ?? ?? ?????? ?????? ???
  ?????.
• Fc?RI ??? ???????????? ? ????? ???? ???? ????
  ?????? ??? ?????
• ???? ??? ?????? ?? ??? ??????? ???? ? ???????
  ???? IgE ???? ?? ???

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???? ??? ???? ????

• ???? ??? ???? ???? ???? ?? ?? ??? ???? ????????
  ?? ????.
• ???) ???? ??????? ????? ? ?? ??? ????? ???(?????
  ???????)
• ?)???? ? ???? ?????????? ??????
• ?) ???? ? ???? ???????? ??

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Lipid mediators

• ???? ?????????? ?????? ?????? ???? ??? ?????????
  A2 ???????? ????? ?? ???
• ???????? ??? ?? ???? ??? ???? ????? ????????????
  ????? ?? ???????? ???? ? ?????????? ???? ???? ??
  ???
• ?????????? ???? ?????? ???????????? ???
  ????????????? ?? ?????????? ?????? ????? ?? ???
• ?????? ?? ??????????? ??? ???? p ?????????????
  ?????? ????????? ???? ?? ???? ???? ???? ????????
  ?? ???? ???? ?? ????

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Mediators
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Biogenic amines

• ?????? ?? ????? ???????? ???? ???? ???? ???? ??
  ???? ??????? ??????? ?? ?? ????????? ??????????
  ????? ? ???? ?? ???? ????? ?? ???
• ??? ??????? ????????? ????? ?? ? ????? ?? ????
  ????? ?????
• ?? ????? ??????? ??????? ?? ??? ???? ?????????
  ??? ?? ??????? ???????? ?? ????.
• ???????? ?? ???? ?????? ??? ???? ??? ?????
  ??????? ????? ??? ?? ???
• ??? ???????? ????? ??? ??? ?? ????? ???? ?????
  ??? ?????? ??????? ???? ?? ???? ?? ???? ??? ?? ???

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• ????? ???????? ?? ??????????? ???? ?????? ???
  ?????? ??????? ????????? ???? ? ???? ?????? ??
  ???? ?? ???.
• ???????? ?????? ??????? ??????? ????????? ????
  ???? ???????????? ? ?????? ????? ? ?? ????? ?????
  ???? ?? ???
• ??? ????? ???????? ??? ?? ???? ????? ? ????
  (Wheal and flare) ?? ?????? ?????? ???? ?? ???
• ???? ?????? ??? ?????? H1 ???????? ?? ?????????
  ???? ???? ????? ? ???? ???? ?? ???????? ????
  ????? ???

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histamine

• ???????? ?????? ?? ????? ???? ?????? ???????
  ?????? ?? ??? ??????? ? ???? ?? ??????????? ????
  ?????? ????? ???? ???? ?? (Peristalsis) ???????
  ??????? ?? ????? ?????? ?? ???????? ???????? ?
  ?????? ?? ????.

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Granule enzymes

• ?????????? ???? ??? ??????? ? ????? ?? ??????
  ???? ??????? ??? ????? ?? ????????? ???? ???? ??
  ???????? ??????? ????? ?? ?????? ?????? ???? ???
  ?????.
• ????????? ????? ????????? ????? ???? ??????? ????
  ???? ????? ?? ??? ?? ?????? ??????????????? I ??
  ?? ?????????? II ????? ???? ? ??? ??? ????
  ??????? ??????? ???? ????? ????? ???? ????? ??
  ???.
• ??????? ??????? A ? ??????? G ?????? ????????
  ??????? ?? ???? ??????
• ?? ????????? ?? ???? ????????? ???????? ???????
  ???? ????? ?????? ????? ?????????? ?? ?????
  ??????? ???? ????(major basic protein)
  ?????????????? ???.

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Granule contents

• ???????????????? ??? ?????? ? ?????????? ??????
  ??? ?? ???? ???? ??????? ????? ?? ????????? ????
  ? ???????????
• ??? ???????? ????? ???? ??? ?????? ?????? ??????
  ????? ????????????????? ???? ?? ??? ???? ??? ??
  ?????? ?? ????
• ?????????????? ???? ???????? ?????? ????? ?????
  ?? ??????? ????? ?????????? ? ?? ??? ???? ??
  ?????? ?? ?????? ???? ?? ???? ???? ??????? ??
  ????.

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Lipid mediators

• ?? ???? ??? ???? ???? ?????????A2 ????????????
  ????? ?? ???????? ???? ? ?????????? ???? ????? ??
  ???.
• ?????????? ???? ??? ????? ??????????????????????
  ??? ? ?????????????D2 (PGD2) ????? ?? ???.
• PGD2 ?? ?????? ??? ??? ?? ??? ??????? ?????? ??
  ??? ???? ??? ??????? ????????? ???? ? ?????
  ????? ??????? ??? ?? ????.
• PGD2 ?????? ???? ???????? ??????????????? ???? ??
  ??? ?????? ?? ????

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Lipid mediators

• ???????? ?? ??????????? ????? ?? ??? ?????
  ???????????? ?? ?????????? ???? ????? ?? ???? ???
  LTC4 ? ??????? ???? ?? ????? ?? LTD4 ? LTE4
• LTC4 ???? ???? ????? ????? ? ????????? ????? ??
  ????.
• ????????? ?? ?????? ??? ??? ??? ??????? ?????? ??
  ??? ???? ??? ????? ?????? ?????? ??????? ?? ????
• ???? ?? ????????? SRS-A ???? ?? ?????????? ????
  ?????? ??????? ?? ??? ???.

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Lipid mediators

• PAF(Platelet-activating factor) ??? ???? ??
  ?????????? ?????? ???.
• PAF ???? ?????? ??????? ?????? ???? ?? ??? ???
  ??? ?????? ????? ????? ???? ????????????????
  ????? ?? ???.

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Cytokines

• ???? ???? ? ????????? ??????????? ?????? ????? ??
  ?????? ?? ?????? ??????(??? ??????) ??? ???????
  ?????? ?? IL-4,5,6,13,3 ?GM-CSF ????? ???
• ????? ?? ??? ?????????? ? TNF ??? ??? ?? ???? ???
  ???? ???? ?? ???????? ???? ?? ???
• ??????? Th2??? ?? ?? ??? ????? ?????? ?????????
  ?? ???? ???? ?? ??? ?????????? ?? ????? ?? ????.
• TNF ???? ????? ???? ????????? ????? ?? ???
  ??????? ????????? ?? ??? ? ????? ?? ?????????
  ???? ????????????? ?????????? ????????? ?? ???.

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Eosinophils

• ???????????? ?? ????????????? ???? ?? ??? ???????
  ???? ?? ???????? ????? ?????????? ?????? ???????
  ?????? ???? ?? ????? ?? ?????? ?? ????? ???
  ????????? ?? ????????? ?????? ??? ?????.
• GM-CSF,IL-3,IL5 ?? ???? ??? ?????? ?? ??????? ???
  ??? ??? ?????.
• ?? ??????? ????? ? ????? ?? ???? ??? ????? ?????
  ? ???? ? ?????? ?????? ?????? ???? ????? ????
  ????? ??? ???????? ?????? ?? ?????
• ??????????? ???? ?? Th2 ???? ???? ??? ? ????????
  ?????????????? ??? ?????? ?????? ?? ????.
• ???????? ???????????? ?? ??? ?????? ??? ?????
  ????????? ????? ?? ??? ??????????? ????????????
  ??? ?? ?? ??? ??? ???????? ????? ?? ???? ???
  ?????? ???? ????. CCL11 ?? ????????? ?? ???
  ??????? ??? ????? ? ?????? ?? ?? ??? ????????????
  CCR3 ?? ????.

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Eosinophils

• ????????? ????? ?? ???????????? ???? ????? ???
  ????????? ??????????? ??? ??????????? ??? Major
  Basic Protein(MBP) ? Eosinophil cationic
  protein(ECP) ??? ?? ???? ????????? ? ?????? ???
  ???
• ???? ??? ???????????? ????? ???? ???? ? ?????????
  ???? ?? ???? ???? ?????????? ?????? ???
  PAF,PG,LT ?? ??? ? ?? ???? ????? ?? ????? ???
  ?????? ?? ??????

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Immediate hypersensitivity

• ?? ???? ????? ? ??????? B ?? ????????? ??? ??
  ???? ??? ? ???? ???? IgE ???? ?????? .

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Mast cell activation
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??Clinical and pathologic features

• Hay fever(allergic rhinitis)
• Increased peristalsis
• Bronchial asthma
• Anaphylaxis

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Wheal and Flare reaction
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Skin test(PK test)
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Therapy

• Inhibiting mast cell degranulation
• Antagonizing the effects of mediators
• Reducing inflammation
• Desensitization

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Anti IgE as a therapy
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RAST test or radioallergosorbent

• expensive
• considered as accurate as food challenges
• they are considered a very safe way to test for
  food allergies
• less sensitive than skin prick tests
• a positive RAST test will be often be confirmed
  with a food challenge

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RAST test

• The suspected allergen is bound to an insoluble
  material and the patient's serum is added. If the
  serum contains antibodies to the allergen, those
  antibodies will bind to the allergen.
  Radiolabeled anti-human IgE antibody is added
  where it binds to those IgE antibodies already
  bound to the insoluble material. The unbound
  anti-human IgE antibodies are washed away. The
  amount of radioactivity is proportional to the
  serum IgE for the allergen.
• RAST are often used to test for allergies when
  a physician advises against the discontinuation
  of medications that can interfere with test
  results or cause medical complications a
  patient suffers from severe skin conditions such
  as widespread eczema or psoriasis or a patient
  has such a high sensitivity level to suspected
  allergens that any administration of those
  allergens might result in potentially serious
  side effects.

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RIST(radiolabeled Immunosorbent test)

• a radioiummunoassay technique for measuring serum
  IgE concenration, using radiolabeled IgE and
  antihuman IgE bound to an insoluble matrix.
• The patient's IgE competes with the radiolabeled
  IgE attached to the matrix, so that the decrease
  in radiolabel remaining attached to the matrix
  can be used to determine the total concentration
  of serum IgE in the patient

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