CLASIFICACIN DE ENFERMEDADES

INMUNOLGICAS POR HIPERSENSIBILIDAD

TIPO Gell y Coombs
I. Inmediata

II. Mediada por anticuerpos

III. Mediada por complejos inmunes

IV. Mediada por linfocitos

CLASIFICACIN DE ENFERMEDADES INMUNOLGICAS
TIPO MECANISMO IMUNOPATOLGICO

I. Inmediata Anticuerpo IgE

II. Mediada por Ac Anticuerpos IgM, IgG

contra tejidos o clulas

III. Mediada por c.i. Complejos inmunes de

antgenos circulantes y IgM - IgG

IV. Mediada por L a) LT CD4+ Hipersensibilidad tipo

retardado (DTH)
b) LT CD8+, CTLs, Citlisis
 CLASIFICACIN DE ENFERMEDADES INMUNOLGICAS
TIPO DAO TISULAR Y ENFERMEDAD
I.
Inmediata Clulas cebadas y sus mediadores

II.
Mediada por Activacin de C
anticuerpos Aumento y activacin de PMN y macrfagos
Funcin anormal receptores

III.
Mediada por Activacin de C
complejos inmunes Aumento y activacin de leucocitos PMN

IV.
Mediada por CD4+ Activacin de macrfagos, citoquinas
CD8+ Lisis directa, citoquinas
 Hipersensibilidad Tipo I

Anafilctica, reagnica, inmediata

Anticuerpos IgE
Individuos atpicos
Alergenos:
Protenas: Polenes: Drogas: Alimentos:
-sueros -pasto -penicilinas -nueces
-vacunas -sulfonamidas -arvejas, porotos
-anestsicos locales -leche
-salicilatos -huevos
-mariscos

Productos de insectos:
-veneno de abejas
-veneno de hormigas
-caros del polvo
Hipersensibilidad Tipo I

La reaccin iniciada por la estimulacin de los

mastocitos dependiente de IgE es uno de los ms
poderosos mecanismos efectores del sistema inmune

Rpida liberacin de mediadores que causan:

--Aumento permeabilidad vascular
--Vasodilatacin
--Contraccin del msculo liso bronquial y visceral
--Inflamacin local
Receptor
de alta
afinidad
para IgE
FcRI

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Hipersensibilidad Tipo I
 IgE
Mastocito Antgeno

FcRI

Edema
Liberacin de
Broncoespasmo
mediadores
Vasodilatacin
inflamatorios
Anafilaxia
 Figure 19-1 Sequence of events in immediate
hypersensitivity reactions. Immediate
hypersensitivity diseases are initiated by the
introduction of an allergen, which stimulates
TH2 reactions and IgE production. IgE
sensitizes mast cells by binding to FcRI, and
subsequent exposure to the allergen activates
the mast cells to secrete the mediators that are
responsible for the pathologic reactions of
immediate hypersensitivity.

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Figure 19-3 Mast cell activation. Antigen binding to
IgE cross-links to FcRI molecules on mast cells,
which induces the release of mediators that cause
the hypersensitivity reaction (A, B). Other stimuli,
including the complement fragment C5a, can also
activate mast cells. A light photomicrograph of a
resting mast cell with abundant purple-staining
cytoplasmic granules is shown in C. These granules
are also seen in the electron micrograph of a
resting mast cell shown in E. In contrast, the
depleted granules of an activated mast cell are
shown in the light photomicrograph (D) and
electron micrograph (F). (Courtesy of Dr. Daniel
Friend, Department of Pathology, Brigham and
Women's Hospital and Harvard Medical School,
Boston, Massachusetts.)

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 Figure 19-5 Biochemical
events of mast cell
activation. Cross-linking of
bound IgE by antigen is
thought to activate protein
tyrosine kinases (Syk and
Lyn), which in turn cause
activation of a MAP kinase
cascade and a
phosphatidylinositol-specific
phospholipase C (PI-
PLCgamma). PI-PLCgamma
catalyzes the release of IP3
and DAG from membrane
PIP2. IP3 causes release of
intracellular calcium from the
endoplasmic reticulum.
Calcium and DAG activate
PKC, which phosphorylates
substrates such as myosin
light chain protein and
thereby leads to the
degradation and release of
preformed mediators.
Calcium and MAP kinases
combine to activate the
enzyme cytosolic
phospholipase A2 (cPLA2),
which initiates the synthesis
of lipid mediators.

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 Hipersensibilidad Tipo I

Predisposicin gentica
Comienzo minutos despus del contacto con el
alergeno
Sistmica: Anafilaxis
Local: Atopia, alergia
Ejs.: rinitis alrgica, fiebre del heno, asma,
urticaria, eczema alrgico, alergia alimentos
 Figure 19-6 Biologic
effects of mediators of
immediate
hypersensitivity. Mast
cells and basophil
mediators include
biogenic amines and
enzymes stored
preformed in granules
as well as cytokines
and lipid mediators,
which are largely newly
synthesized on cell
activation. The
biogenic amines and
lipid mediators induce
vascular leakage,
bronchoconstriction,
and intestinal
hypermotility, all
components of the
immediate response.
Cytokines and lipid
mediators contribute to
inflammation, which is
part of the late-phase
reaction. Enzymes
probably contribute to
tissue damage.
Activated eosinophils
release preformed
cationic proteins as
well as enzymes that
are toxic to parasites
and host cells. Some
eosinophil granule
enzymes probably
contribute to tissue
damage in chronic
allergic diseases. Downloaded from: StudentConsult (on 31 August 2008 05:25 AM)
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 Figure 19-7 The immediate and late-phase reactions. A. Kinetics: The immediate vascular and smooth muscle
reaction to allergen develops within minutes after challenge (allergen exposure in a previously sensitized individual),
and the late-phase reaction develops 2 to 24 hours later. B, C. Morphology: The immediate reaction (B) is
characterized by vasodilation, congestion, and edema, and the late-phase reaction (C) is characterized by an
inflammatory infiltrate rich in eosinophils, neutrophils, and T cells. (Courtesy of Dr. Daniel Friend, Department of
Pathology, Brigham and Women's Hospital, Boston, Massachusetts.)

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 Figure 19-8 The wheal and flare
reaction in the skin. A. In response to
antigen-stimulated release of mast cell
mediators, local blood vessels first dilate
and then become leaky to fluid and
macromolecules, which produces
redness and local swelling (a wheal).
Subsequent dilation of vessels on the
edge of the swelling produces the
appearance of a red rim (the flare). B.
Photograph of a typical wheal and flare
reaction in the skin in response to
injection of an allergen. (Courtesy of Dr.
James D. Faix, Department of
Pathology, Stanford University School of
Medicine, Palo Alto, California.)
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 Figure 19-9 Histopathologic features of bronchial asthma. Atopic bronchial asthma results from repeated immediate hypersensitivity
reactions in the lungs with chronic late-phase reactions. A cross-section of a normal bronchus is shown in A; a bronchus from a patient
with asthma is shown in B. The diseased bronchus has excessive mucus production, many submucosal inflammatory cells (including
eosinophils), and smooth muscle hypertrophy. (Courtesy of Dr. James D. Faix, Department of Pathology, Stanford University School of
Medicine, Palo Alto, California.)

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 Figure 19-10 Mediators
and treatment of
asthma. Mast cell-
derived leukotrienes
and PAF are thought to
be the major mediators
of acute
bronchoconstriction.
Therapy is targeted
both at reducing mast
cell activation with
inhibitors such as
cromolyn and at
countering mediator
actions on bronchial
smooth muscle by
bronchodilators such
as epinephrine and
theophylline. These
drugs also inhibit mast
cell activation. Mast
cell-derived cytokines
are thought to be the
major mediators of
sustained airway
inflammation, which is
an example of a late-
phase reaction, and
corticosteroid therapy
is used to inhibit
cytokine synthesis.
Cytokines are also
produced by TH2 cells
(not shown).

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 Hipersensibilidad Tipo II
Citotxica
Mediada por anticuerpos IgG o IgM
Fijacin de complemento
Clulas blanco
Lisis celular
Fagocitosis
Estimulacin o bloqueo de funciones
biolgicas
Fenmenos autoinmunes mediados
por autoanticuerpos
 TEJIDO

C
C ERITROCITO

Lisis
Fagocitosis
C Complemento Anticuerpo Antgeno
Hipersensibilidad Tipo II
Eritrocitos: transfusin de sangre incompatible
anemia hemoltica autoinmune
anemia hemoltica inducida por
drogas
enfermedad hemoltica del recin acido

Plaquetas: prpura trombocitopnica idioptica

prpura inducida por drogas

Rin y pulmn: sindrome de Good Pasture

Piel: trastornos penfigoides

Tiroides: hipertiroidismo

Placa neuromuscular: miastenia gravis

Hipersensibilidad Tipo III
Reaccin de Arths
Gran concentracin de anticuerpos
Formacin de complejos en lugar de entrada del
antgeno
Activacin del complemento
Anafilotoxinas
Factores quimiotcticos para neutrfilos
Degranulacin de neutrfilos
Agregacin plaquetaria
Vasculitis necrotizante
Ejemplos: Neumonitis por hipersensibilidad
Alveolitis alrgica extrnseca (aspiracin de
esporas de hongos)
 Hipersensibilidad Tipo III
Antgenos inducen IgG IgM
Comienzo a las 2-6 hrs del
contacto
con el Ag
Localizacin de complejos
inmunes en
tejidos
Inflamacin
Compromiso de neutrfilos,
monocitos, complemento
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Hipersensibilidad Tipo III
Enfermedad del suero
Complejos antgeno-anticuerpo circulantes
Depsito de c.i. en rion, piel, articulaciones, vasos
sanguneos
Activacin del complemento
Anafilotoxinas
Agregacin plaquetaria
Inflamacin
Dao tisular

Ejemplos: Glomerulopatas por complejos inmunes

Artritis inmunes
Vasculitis inmunes
Figure 18-4 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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 Figure 18-3 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.)

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Hipersensibilidad tipo IV

Ags proteicos
Atraccin e inmovilizacin de
Ags qumicos macrfagos, activados por citoquinas
que se unen a
protenas propias Infiltrado perivascular caracterstico:
macrfagos y linfocitos
Desarrollo a las 24 48 Edema
hrs. de contacto con el Granulomas:
Ag clulas gigantes multinucleadas
clulas epitelioides
Clulas T CD4+
sensibilizadas,
T CD8+
IL-2, IFN-, MIF, TNF-,
IL-8,
Hipersensibilidad tipo IV

Ejs:
Dermatitis de contacto
(nquel, sustancias
qumicas

Infecciones por patgenos

intracelulares (TBC)

Pruebas cutneas de
hipersensibilidad
(evaluacin inmune,
diagnstico)
Inmunologa de Kuby, 2002
Figure 18-5 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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 Reacciones de hipersensibilidad son reacciones inflamatorias
Resumen dentro de las respuestas humorales y celulares del sistema
inmune, que llevan a dao extenso de tejidos e incluso a la
muerte.

Tipo I. mediada por IgE, cuyo Fc se une a Rc en mastocitos o basfilos.

Entrecruzamiento por el alergeno lleva a la degranulacin y liberacin de mediadores
farmacolgicamente activos: contraccin del msculo liso y vasodilatacin.
Manifestaciones clnicas incluyen anafilaxis sistmica y respuestas locales como asma y
rinitis.

Tipo II. El anticuerpo reacciona con determinantes antignicos en la superficie de

clulas, llevando a dao celular o muerte por ADCC o lisis por C. Ejemplos son las
reacciones a las transfusiones y EHRN.

Tipo III. Mediada por la formacin de complejos inmunes y activacin de C.

Fragmentos de activacin de Cson los efectores que provocan vasodilatacin local y
atraen quimiotcticamente a neutrfilos. El depsito de c.i. en el sitio de entrada del Ag
provoca dao al tejido local por enzimas lticas liberadas por neutrfilos y por MAC.

Tipo IV. Respuesta celular. La activacin por el Ag de clulas TH1 induce liberacin de
citocinas que acumulan y activan macrfagos, liberando enzimas lticas que causan dao
tisular local.