HYPERSENSITIVITY REACTIONS

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HYPERSENSITIVITY REACTIONS
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TYPE 3 HYPERSENSITIVITY REACTION

• Type III hypersensitivity is also known as immune
  complex hypersensitivity
• Reaction may be general (e.g., serum sickness) or
  may involve individual organs including skin
  (e.g., systemic lupus erythematosus, Arthus
  reaction), kidneys (e.g., lupus nephritis), lungs
  (e.g., Aspergillus), blood vessels (e.g.,
  Polyarteritis), joints (e.g., rheumatoid
  arthritis) or other organs
• This reaction may be the pathogenic mechanism of
  diseases caused by many microorganisms

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• The reaction may take 3 - 10 hours after exposure
  to the antigen (as in Arthus reaction)
• They are mostly of the IgG class, although IgM
  may also be involved
• The antigen may be exogenous (chronic bacterial,
  viral or parasitic infections), or endogenous
  (non-organ specific autoimmunity e.g., systemic
  lupus erythematosus, SLE)

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• Primary components are soluble immune complexes
  and complement (C3a, 4a and 5a)
• The damage is caused by platelets and neutrophils
  
• The lesion contains primarily neutrophils and
  deposits of immune complexes and complement
• Macrophages infiltrating in later stages may be
  involved in the healing process

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• A local type III hypersensitivity reaction can be
  triggered in the skin of sensitized individuals
  who possess IgG antibodies against the
  sensitizing antigen.
• When antigen is injected into the skin,
  circulating IgG antibody that has diffused into
  the tissues forms immune complexes locally.
• The immune complexes bind Fc receptors on mast
  cells and other leukocytes, which creates a local
  inflammatory response with increased vascular
  permeability.

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• The enhanced vascular permeability allows fluid
  and cells, especially polymorphonuclear
  leukocytes, to enter the site from the local
  vessels.
• This reaction is called an Arthus reaction
• The immune complexes also activate complement,
  releasing C5a, which contributes to the
  inflammatory reaction by ligating C5a receptors
  on leukocytes

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• A systemic type III hypersensitivity reaction,
  known as serum sickness, can result from the
  injection of large quantities of a poorly
  catabolized foreign antigen
• This illness was so named because it frequently
  followed the administration of therapeutic horse
  antiserum

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• Serum sickness occurs 710 days after the
  injection of the horse serum, an interval that
  corresponds to the time required to mount a
  primary immune response that switches from IgM to
  IgG antibody against the foreign antigens in
  horse serum
• The clinical features of serum sickness are
  chills, fever, rash, arthritis, and sometimes
  glomerulonephritis
• Urticaria is a prominent feature of the rash,
  implying a role for histamine derived from
  mast-cell degranulation
• In this case the mast-cell degranulation is
  triggered by the ligation of cellsurface Fc?RIII
  by IgG-containing immune complexes

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• An injection of a foreign protein or proteins
  leads to an antibody response. These antibodies
  form immune complexes with the circulating
  foreign proteins. The complexes are deposited in
  small vessels and activate complement and
  phagocytes, inducing fever and the symptoms of
  vasculitis, nephritis, and arthritis. All these
  effects are transient and resolve when the
  foreign protein is cleared.

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TYPE 4 HYPERSENSITIVITY REACTION

• Type IV hypersensitivity is also known as cell
  mediated or delayed type hypersensitivity
• The classical example of this hypersensitivity is
  tuberculin (Montoux) reaction which peaks 48
  hours after the injection of antigen (PPD or old
  tuberculin)
• The lesion is characterized by induration and
  erythema

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• Type IV hypersensitivity is involved in the
  pathogenesis of many autoimmune and infectious
  diseases (tuberculosis, leprosy, blastomycosis,
  histoplasmosis, toxoplasmosis, leishmaniasis,
  etc.) and granulomas due to infections and
  foreign antigens
• Another form of delayed hypersensitivity is
  contact dermatitis (poison ivy (figure 6),
  chemicals, heavy metals, etc.) in which the
  lesions are more papular
• Type IV hypersensitivity can be classified into
  three categories depending on the time of onset
  and clinical and histological presentation

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DELAYED HYPERSENSITIVITY REACTION- 3 types
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• Mechanisms of damage in delayed hypersensitivity
  include T lymphocytes and monocytes and/or
  macrophages
• Cytotoxic T cells (Tc) cause direct damage
  whereas helper T (TH1) cells secrete cytokines
  which activate cytotoxic T cells and recruit and
  activate monocytes and macrophages, which cause
  the bulk of the damage
• The delayed hypersensitivity lesions mainly
  contain monocytes and a few T cells
• Major lymphokines involved in delayed
  hypersensitivity reaction include monocyte
  chemotactic factor, interleukin-2,
  interferon-gamma, TNF alpha/beta, etc.

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• Diagnostic tests in vivo include delayed
  cutaneous reaction (e.g. Montoux test (figure 5))
  and patch test (for contact dermatitis)
• In vitro tests for delayed hypersensitivity
  include mitogenic response, lympho-cytotoxicity
  and IL-2 production

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