Chapter 25
Hypersensitivity (Type III)
Trai-Ming Yeh, Ph.D.
Department of Medical Laboratory Science
and Biotechnology
College of Medicine
National Cheng Kung University
Diseases caused by immune complexes can be divided into
three groups.
Persistent infection with a weak antibody
response can lead to immune complex disease
Renal artery
FITC (green)
anti-HBsAg
Rhodamine (red)
anti-IgM
Immune complex disease is a frequent complication of
autoimmune disease
Immune complex following inhalation of
antigen: extrinsic allergic alveolitis
Precipitin antibody (P) present in the serum of a patient with pigeon fancier's lung
(3) is directed against the fungal antigen Micropolyspora faeni. Normal serum (N)
lacks antibodies to this fungus.
Immune complexes can trigger a
variety of inflammatory processes
Type II and type III
hypersensitivity cause damage
by similar mechanisms
Complement is an important
mediator of type III
hypersensitivity
Autoimmunity causes immune complex
disease in the NZB/NZW mouse
Experimental models demonstrate the main immune complex
diseases
Injection of antigen into the skin of presensitized
animals produces the Arthus reaction
Type I
15 min
Type III
(Arthus reaction)
5-12 h
Type IV
214-48 h
CR1 on RBC readily binds
immune complexes
Immunocomplexes are transported to the liver and
spleen, where they are removed by fixed tissue
macrophages
I-125 lable BSA /anti-BSA
removed in liver
Complement solubilization of
immune complexes in vitro
Complement can
rapidly resolubilize
precipitated complexes
through the alternative
pathway.
1. Non-erythrocyte-bound
complexes are taken up rapidly
by the liver (but not the spleen)
and are then released to be
deposited in tissues such as
skin, kidney, and muscle,
where they can set up
inflammatory reactions.
2. Complement deficiency
impairs clearance of
complexes.
The size of immune complexes
affects their deposition
1. Larger immune
complexes are rapidly
removed
2. Phagocyte defects
allow complexes to
persist
3. Carbohydrate on
antibodies affects
complex clearance
The class of immunoglobulin in an immune complex can
also influence its deposition: IgM to IgG2a in SLE mice
Ig classes affect the rate of
clearance
Immune complex deposition in the tissues
results in tissue damage-But what cause it to
deposit?
• The most important trigger for immune
complex deposition is probably an increase in
vascular permeability-vasoactive amine
antagonists, such as chlorpheniramine and
methysergide prevent tissue damage (Fig.
25.18).
• Immune complex deposition is most likely
where there is high blood pressure and
turbulence (Fig. 25.19)-kidney
Summary of Chapter 25 Hypersensitivity (III)
• Diseases caused by immune complexes can be
divided into three groups.
• Immune complexes can trigger a variety of
inflammatory processes.
• Experimental models demonstrate the main immune
complex diseases.
• Immune complexes are normally removed by the
mononuclear phagocyte system.
• The size of immune complexes affects their
deposition.
• Immune complex deposition in the tissues results in
tissue damage.
• Deposited immune complexes can be visualized
using immunofluorescence.
Chapter 26
Hypersensitivity (Type IV)antigen-specific CD4 T cells
Trai-Ming Yeh, Ph.D.
Department of Medical Laboratory Science
and Biotechnology
College of Medicine
National Cheng Kung University
THERE ARE THREE VARIANTS OF TYPE IV
HYPERSENSITIVITY REACTION
Contact hypersensitivity occurs at the
point of contact with allergen (haptan)
such as nickel, chromate…
1. Contact hypersensitivity is
primarily an epidermal
reaction, and the dendritic
Langerhans' cell, located in
the suprabasal epidermis, is
the principal antigenpresenting cell (APC)
involved
2. Birbeck granules, which are
organelles derived from cell
membrane and are
characteristic of Langerhans'
cells
3. Keratinocytes produce a
range of cytokines important
to the contact hypersensitivity
response
1. A contact hypersensitivity
reaction has two stagessensitization and elicitation
2. Sensitization (takes 10-14 days
in humans) stimulates a
population of memory T cells
3. Elicitation involves
recruitment of CD4+
lymphocytes and monocytes
Cytokines and prostaglandins are
central to the complex interactions
between Langerhans' cells, CD4+ T
cells, keratinocytes, macrophages,
and endothelial cells in contact
hypersensitivity
TUBERCULIN-TYPE
HYPERSENSITIVITY
1. The tuberculin skin test
reaction is an example of
the recall response to
soluble antigen
previously encountered
during infection which
involves monocytes and
lymphocytes
2. The tuberculin lesion
normally resolves within
5-7 days, but if there is
persistence of antigen in
the tissues it may develop
into a granulomatous
reaction.
GRANULOMATOUS
HYPERSENSITIVITY
• intracellular microorganisms such as M.
tuberculosis and M. leprae, which are able
to resist macrophage killing leads to chronic
stimulation of T cells and the release of
cytokines.
• The process results in the formation of
epithelioid cell granulomas with a central
collection of epithelioid cells and
macrophages surrounded by lymphocytes
Macrophages, lymphocytes, epithelioid
cell, and giant cells in granulomas
• Granulomas occur with chronic infections
associated with predominantly TH1-like T cell
responses, such as tuberculosis, leprosy, and
leishmaniasis, and with TH2-like T cells, as in
schistosomiasis.
• Epithelioid cells large and flattened with
increased endoplasmic reticulum (Fig. 26.11) are
derived from activated macrophage under chronic
stimulation
• Giant cells are formed when epithelioid cells fuse
to form multinucleate giant cells (Fig. 26.12)
Tuberculin-like DTH reactions are used practically in two ways:
confirms past or latent infection with M. tuberculosis or measure of
cell-mediated immunity
IFNγ is required for granuloma
formation in humans
TNF and lymphotoxin-α are
also essential for granuloma
formation during mycobacterial
infections
TNF is essential for the development
of epithelioid cell granulomas
Many chronic diseases manifest type
IV granulomatous hypersensitivity
borderline leprosy has
characteristics of both
tuberculoid and
lepromatous (no protection)
leprosy
tuberculoid-type reaction,
lymphocyte proliferation or
the release of IFNγ
following stimulation with
M. leprae antigens
Tuberculosis is caused by M.
tuberculosis
• The reactions are frequently accompanied by extensive fibrosis
and the lesions may be seen in the chest radiographs of affected
patients
• The histological appearance of the lesion is typical of a
granulomatous reaction, with central caseous (cheesy) necrosis
Summary of Chapter 26 Hypersensitivity (Type IV)
• DTH reflects the presence of antigen-specific CD4 T
cells.
• Contact hypersensitivity occurs at the point of
contact with an allergen.
• Tuberculin-type hypersensitivity is induced by
soluble antigens from a variety of organisms.
• Granulomatous hypersensitivity is clinically the most
important form of type IV hypersensitivity.
• Many chronic diseases manifest type IV
granulomatous hypersensitivity.
Important points needed to understand after class
• Understand the role of immune complex.
• Understand the role of immune complex in tissue
damage.
• Understand the role of type IV hypersensitivity on
diagnosis and treatment of various diseases.