Download type III

There are four types of hypersensitivity reaction
mediated by immunological mechanisms that cause
tissue damage
Types I, II and III are antibody-mediated and are distinguished by the different
types of antigens recognized and the different classes of antibody involved.
Type I responses are mediated by IgE, which induces mast-cell activation,
whereas types II and III are mediated by IgG, which can engage Fcreceptor and complement-mediated effector mechanisms to varying
degrees, depending on the subclass of IgG and the nature of the antigen
involved.
Type II responses are directed against cell-surface or matrix antigens, whereas
type III responses are directed against soluble antigens, and the tissue
damage involved is caused by responses triggered by immune complexes.
Type IV hypersensitivity reactions are T cell-mediated and can be subdivided
into three groups. In the first group, tissue damage is caused by the
activation of macrophages by TH1 cells, which results in an inflammatory
response. In the second, damage is caused by the activation by TH2 cells of
inflammatory responses in which eosinophils predominate; in the third,
damage is caused directly by cytotoxic T cells (CTL).
IPERSENSIBILITA’ DI TIPO II
• È MEDIATADA ANTICORPI DIRETTI VERSO ANTIGENI
PRESENTI SULLA SUPERFICIE CELLULARE O SULLA
MATRICE EXTRACELLULARE
• Antigene intrinseco della membrana cellulare oppure
della matrice
• Antigene esogeno (metabolita di farmaci adsorbito sulle
superfici cellulari o sulla matrice
IPERSENSIBILITA’ TIPO II
Schematic illustration of the three major mechanisms of antibody-mediated injury.
A, Opsonization of cells by antibodies and complement components and ingestion by
phagocytes.
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B, Inflammation induced by antibody binding to Fc receptors of leukocytes and by complement breakdown
products.
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C, Antireceptor antibodies disturb the normal function of receptors. In these examples, antibodies against the
thyroid stimulating hormone (TSH) receptor activate thyroid cells in Graves disease, and acetylcholine (ACh)
receptor antibodies impair neuromuscular transmission in myasthenia gravis.
Stimolazione
Inibizione
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Effector mechanisms of antibodymediated disease.
A. Antibodies opsonize cells and may
activate
complement,
generating
complement products that also
opsonize
cells,
leading
to
phagocytosis of the cells through
phagocyte Fc receptors or C3
receptors.
B. Antibodies recruit leukocytes by
binding to Fc receptors or by
activating complement and thereby
releasing
by-products
that
are
chemotactic for leukocytes.
C. Antibodies specific for cell surface
receptors
for
hormones
or
neurotransmitters may stimulate the
activity of the receptors even in the
absence of the hormone (left panel) or
may
inhibit
binding
of
the
neurotransmitter to its receptor (right
panel).
TSH,
thyroid-stimulating
hormone.
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MALATTIA EMOLITICA DEL NEONATO
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Test di Coombs
Usato per rilevare la presenza di Ab sugli eritrociti dei pazienti
Se ci sono anticorpi gli eritrociti sono agglutinati
dall’aggiunta di anti-immunoglobuline umane
Reazioni verso antigeni dei gruppi sanguigni si verificano nelle anemie
emolitiche autoimmuni
Il Test di Cooms può dare informazioni utili e può darle anche nei casi di Ab sui
globuli rossi indotti in trasfusioni non compatibili e nella malattia emolitica del
neonato
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IPERSENSIBILTA’ TIPO III
• I COMPLESSI ANTIGENE-ANTICORPO PRODUCONO
DANNI TISSUTALI SOPRATTUTTO PROVOCANDO
INFIAMMAZIONE NEI SITI DI DEPOSITO
• La presenza di complessi Ag-Ab in circolo non implica la
presenza di malattia;
• Due tipi di Ag provocano lesioni da Immunocomplessi:
– Ag esogeno (batterio, virus)
– Ag endogeni (self)
• Malattie da immunocomplessi possono essere
– Generalizzate o localizzate
IPERSENSIBILITA’ DI TIPO III
Schematic illustration of the three sequential phases in the induction of systemic immune
complex-mediated disease (type III hypersensitivity).
•I grandi complessi formati da importante eccesso di Ag sono rapidamente rimossi
•Dalla circolazione da parte dei fagociti mononucleati e quindi sono relativamente innocui
I complessi più “pericolosi” sono di piccole e medie dimensioni, formati da lieve eccesso di Ag,
che legano meno avidamente le cellule fagocitarie e quindi circolano più a lungo.
FATTORI CHE INFLUENZANO IL DEPOSITO DEGLI IMMUNOCOMPLESSINEI TESSUTI
Carica degli immunocomplessi, valenza dell’antigene, avidità dell’Ab affinità dell’Ag per le varie
Componenti tissutali, struttura tridimensionale dei complessi e fattori emodinamici
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Pathogenesis of immune complex-mediated tissue injury.
The morphologic consequences are depicted as boxed areas.
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MALATTIA DA SIERO ACUTA
Prototipo della malattia sistemica da immunocomplessi
Serum sickness is a classic example of a transient immune complex-mediated
syndrome. 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.
Figure 6-17 Immune complex vasculitis. The necrotic vessel wall is replaced by smudgy, pink "fibrinoid" material.
(Courtesy of Dr. Trace Worrell, Department of Pathology, University of Texas Southwestern Medical School,
Dallas, TX.)
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Il tempo di reazione è quello
che distingue il fenomeno di Arthus
dalla reazione di tipo I
Sequence of immunological responses in experimental acute serum sickness. Injection of
bovine serum albumin into a rabbit leads to the production of specific antibody and the formation
of immune complexes. These complexes are deposited in multiple tissues, activate complement
(leading to a fall in serum complement levels), and cause inflammatory lesions, which resolve as
the complexes and the remaining antigen are removed. (Adapted from Cochrane CG. Immune
complex-mediated tissue injury. In Cohen S, PA Ward, and RT McCluskey [eds]. Mechanisms of
Immunopathology. Werbel & Peck, New York, 1979, pp 29-48. Copyright 1979, Wiley-Liss, Inc.)
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Types of antibody-mediated diseases.
Antibodies may bind specifically to tissue
antigens (A), or they may be deposited as
immune complexes that are formed in the
circulation (B). In both cases, the
deposited antibodies induce inflammation,
leading to tissue injury.
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Pathologic features of antibody-mediated
glomerulonephritis.
A. Glomerulonephritis induced by an
antibody against the glomerular basement
membrane (Goodpasture's syndrome): the
light
micrograph
shows
glomerular
inflammation and severe damage, and
immunofluorescence shows smooth (linear)
deposits of antibody along the basement
membrane.
B. Glomerulonephritis induced by the
deposition of immune complexes (SLE): the
light
micrograph
shows
neutrophilic
inflammation, and the immunofluorescence
and electron micrograph show coarse
(granular) deposits of antigen-antibody
complexes along the basement membrane.
(Immunofluorescence
micrographs
are
courtesy of Dr. Jean Olson, Department of
Pathology, University of California San
Francisco, and the electron micrograph is
courtesy of Dr. Helmut Rennke, Department
of Pathology, Brigham and Women's
Hospital, Boston.)
Tipo II
Tipo III
(Immunofluorescence micrographs are courtesy of Dr. Jean Olson, Department of Pathology, University of
California San Francisco, and the electron micrograph is courtesy of Dr. Helmut Rennke, Department of
Pathology, Brigham and Women's Hospital, Boston.)
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IPERSENSIBILITA’ DI TIPO IV
Cellulo-mediata
Mechanisms of T cell-mediated (type IV) hypersensitivity reactions. A, In delayed type
hypersensitivity reactions, CD4+ T cells (and sometimes CD8+ cells) respond to tissue antigens
by secreting cytokines that stimulate inflammation and activate phagocytes, leading to tissue
injury. B, In some diseases, CD8+ cytolytic T lymphocytes (CTLs) directly kill tissue cells. APC,
antigen-presenting cell.
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Schematic illustration of the events that give rise to the formation of granulomas in cell-mediated
(type IV) hypersensitivity reactions. Note the role played by T cell-derived cytokines.
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The stages of a delayed-type hypersensitivity reaction.
The first phase involves uptake, processing, and presentation of the antigen by local
antigen-presenting cells. In the second phase, TH1 cells that were primed by a
previous exposure to the antigen migrate into the site of injection and become
activated. Because these specific cells are rare, and because there is little
inflammation to attract cells into the site, it can take several hours for a T cell of the
correct specificity to arrive. These cells release mediators that activate local
endothelial cells, recruiting an inflammatory cell infiltrate dominated by macrophages
and causing the accumulation of fluid and protein. At this point, the lesion becomes
apparent.
The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines
released by TH1 cells stimulated by antigen. Antigen in the local tissues is processed by
antigen-presenting cells and presented on MHC class II molecules. Antigen-specific TH1 cells that
recognize the antigen locally at the site of injection release chemokines and cytokines that recruit
macrophages to the site of antigen deposition. Antigen presentation by the newly recruited
macrophages then amplifies the response. T cells can also affect local blood vessels through the
release of TNF-a and TNF-b, and stimulate the production of macrophages through the release of
IL-3 and GM-CSF. Finally, TH1 cells activate macrophages through the release of IFN-g and TNFa, and kill macrophages and other sensitive cells through the cell-surface expression of the Fas
ligand.
•
Type IV hypersensitivity responses. These reactions are mediated by T cells and
all take some time to develop. They can be grouped into three syndromes, according
to the route by which antigen passes into the body. In delayed-type hypersensitivity
the antigen is injected into the skin; in contact hypersensitivity it is absorbed into the
skin; and in gluten-sensitive enteropathy it is absorbed by the gut
Mechanisms of T cell-mediated diseases. A. In delayed-type hypersensitivity reactions, CD4+
T cells (and sometimes CD8+ cells) respond to tissue antigens by secreting cytokines that
stimulate inflammation and activate phagocytes, leading to tissue injury. APC, antigen-presenting
cell. B. In some diseases, CD8+ CTLs directly kill tissue cells.
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Delayed hypersensitivity in the skin. A, Perivascular infiltration by T cells and mononuclear phagocytes. B,
Immunoperoxidase staining reveals a predominantly perivascular cellular infiltrate that marks positively with antiCD4 antibodies. (Courtesy of Dr. Louis Picker, Department of Pathology, University of Texas Southwestern
Medical School, Dallas, TX.)
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A section of a lymph node shows several granulomas, each made up of an aggregate of epithelioid cells and
surrounded by lymphocytes. The granuloma in the center shows several multinucleate giant cells. (Courtesy of Dr.
Trace Worrell, Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX.)
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Skin tests are carried out by introducing 0.02 ml of extract intradermally. With allergens such as pollen, cat, or dust mite, the positive
reaction is an immediate (i.e. within 20 min) wheal, which in some cases is followed by an indurated response occurring late (i.e. at 4-12
hours). Non-allergic individuals make no discernible reaction to testing with these allergens. A delayed skin response is the commonest
form of positive response to tuberculin, tetanus, and mumps, or to fungi such as Trichophyton and Candida spp. The skin typically shows
no reaction up to 12 hours and then gradually develops an erythematous, indurated, delayed hypersensitivity response, which is maximal
at 24-48 hours. Patch tests are performed by applying a gauze pad with allergen to a patch of skin that has been mildly abraded. This
procedure may give an immediate wheal response, but this is followed at 24-48 hours by an indurated, erythematous response, which
has many of the features of eczema. The patch test is not a diagnostic test, but has provided extensive information about the role of
allergens in atopic dermatitis.
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