Células Dendríticas

Edgar Garavito, M.D.

 Tejidos

Sangre Linfa

Organos Linfoides
 Accessory Cells
(Professionals APC)
 Células de Langerhans
Células de Langerhans
Células de entran en el ganglio
Langerhans linfático donde se
Captura de antígeno abandonan la piel y convierten en células Las células dendríticas
por células de entran en el sistema dendríticas que B7 positivas estimulan
Langerhans en la piel linfático expresan B7 células T naive

Las células de Langerhans pueden capturar antígenos en la piel y migrar a los órganos linfoides
donde se los presentan a las células T
MHC Molecules
HLA Function and Expression
 HLA I Structure

1000
Conformational Complementarity

Electrical Affinity

Amino acid sequence

MHC Class I Presentation
 Proteasome

Intracellular
Proteins

Peptides
8 -11aa

aa
HLA II Structure

2.000
Human MHC Complex Map
Cellular MHC expression
 Cellular MHC expression

4 4 8 2 2 2

6x1000=6.000
22 40.000 100000
16x2000=32.000 peptides 1000000
Pathogens
Adherent splenocytes
(Macrophages) Peritoneal
Macrophages

Ac X

L Antibodies
B

T Help
 Accessory cells

Macrophages

Adherent New cells

splenocytes
 Ralph Steinman

For years dendritic cells (DCs) have

languished on the sidelines of
immunology research while
T lymphocytes have been given top
billing. Now, almost 30 years after
discovering them, Ralph Steinman is
seeing dendritic cells take center
stage.
 re v ie w a rtic le

De ndritic c e lls a nd the c o ntro l o f

im m unity
Ja c q u e s Ba n c h e re a u & Ra lp h M . S te in m a n 8
. . ... .. . ... ... . .. . .. .. .. .. . . ... . .. . .. . ... . .. . .. .. . . .. .. .. .. . . .. .. .. .. . .. .. . .. .. . .. . .. . ... . .. . ... ... . .. . ... .. . . .. . ... .. . . .. . ... .. .. . . .. ... .. ... .. ... .. .. .. . . ... .. .. ... . .. .. .. .. ... . . .. .. .. .. .. .. .. .. .. ... . . .. .. .. ... .. . .. .. ... .. .. .. .. ... .. .. . .. ... .. .. ..

B a n d T ly m ph o c y t e s a re the m e dia to rs o f im m un ity, bu t th e ir fun c tio n is un de r the c o ntro l o f de n dritic c e lls . De ndritic
c e lls in th e pe riphe ry c a ptu re a n d pro c e s s a ntig e n s , e x pre s s ly m pho c y te c o -s tim ula to ry m o le c u le s , m ig ra te to
ly m pho id o rg a ns a n d s e c re te c y to kin e s to in itia te im m u n e re s po n s e s . The y n o t o nly a c tiv a te ly m ph o c y t e s , th e y a ls o
to le riz e T c e lls to a n tig e ns tha t a re in n a te to th e bo dy (s e lf-a n tig e ns ), th e re by m inim iz in g a uto im m un e re a c tio n s . On c e
a n e g le c te d c e ll ty pe , de n dritic c e lls c a n n o w be re a dily o bta ine d in s uffi c ie nt qua ntitie s to a llo w m o le c ula r a n d c e ll
bio lo g ic a l a na ly s is . With kno w le dg e c o m e s th e re a liz a tio n th a t th e s e c e lls a re a po w e rful to o l fo r m a nipu la ti n g th e
im m u ne s y s te m .

Immunology has long been focused on antigens and lymphocytes, a frequency of 1/100,000 or less) through a TCR that has a low
but the mere presence of these two parties does not always lead to affinity (1 mM or less). Moreover, infected cells and tumours
immunity. A third party, the dendritic cell (DC) system of antigen- frequently lack the co-stimulator y molecules that drive clonal
presenting cells (APCs), is the initiator and modulator of the expansion of the T cell, the production of cytokines, and develop-
immune response. First visualized as Langerhans cells (LCs) in the ment into killer cells. DCs provide a means of solving these
skin in 1868, the characterization of DCs began only 25 years ago. challenges. Located in most tissues, DCs capture and process
It was known that ‘accessory’ cells were necessary to generate a antigens, and display large amounts of MHC–peptide complexes
primary antibody response in culture, but it was only once DCs were at their surface (Fig. 1). They upregulate their co-stimulator y
identified and purified from contaminating lymphocytes and molecules and migrate to lymphoid organs, the spleen and the
macrophages that their distinct function as APCs became apparent
(Box 1).
DCs are efficient stimulators of B and T lymphocytes1. B cells,
the precursors of antibody-secreting cells, can directly recognize
native antigen through their B-cell receptors. T lymphocytes,
however, need the antigen to be processed and presented to them
by an APC. The T-cell antigen receptors (TCRs) recognize fragments
of antigens bound to molecules of the major histocompatibility
complex (MHC) on the surface of an APC. The peptide-binding
proteins are of two types, MHC class I and MHC class II, which
stimulate cytotoxic T cells (CTLs) and helper T cells respectively.
Intracellular antigens, cut into peptides in the cytosol of the APC,
bind to MHC class I molecules and are recognized by CTLs, which,
once activated, can directly kill a target cell. Extracellular antigens
that have entered the endocytic pathway of the APC are processed
there and generally presented by MHC class II molecules to T-helper
cells, which, when turned on, have profound immune-regulatory
effects.
Some raisons d’être for a specialized DC system are now clear
(Fig. 1). The initiation of T-cell immunity is rather demanding.
Initially, peptides from infected cells located anywhere in the body
must be found and recognized by T cells that circulate in the blood
stream. The amounts of specific antigen –MHC complexes on
tumours and infected cells are typically small (one hundred or
less per cell), and must be recognized by rare T-cell clones (usually at Figu re 1 Affe re nt a nd e ffe re n t limb s o f imm unity tha t re s o lve s e ve ra l de m a nds of
a ntige n p re s e nta tion in vivo (s e e te xt). Antig e ns a re c a p ture d b y DCs in pe riphe ra l
tis s ue s a nd p roc e s s e d to fo rm MHC –p e ptid e c om ple xe s . The s e imm a tu re DCs
d e rive s uc c e s s ive ly from p rolife ra ting p ro ge nitors a nd non-p rolife ra ting pre cu r-
Bo x 1 De n d ritic c e lls a nd th e co n tr o l o f im m un ity s ors , the la tte r no t b e ing fully c o mm itte d to form DCs . As a c o ns e qu e nc e of
X S e ntine ls in vivo : in s itu d is trib utio n to o p tim ize a ntig e n ca p ture ; a ntige n de p os ition a n d infla m ma tion , DCs be gin to m a ture , e xpre s s ing m o l-
m igra tion into lymp h oid o rga ns to o ptimize c lona l s e le c tion o f ra re , e cu le s th a t will le a d to b inding a nd s tim ula tion of T ce lls in th e T-c e ll a re a s of
CD4 + a nd CD8 + T c e lls lymp hoid tis s ue s . If the a ntige n ha s a ls o be e n b o und b y B c e lls , the n b oth B a nd T
X Initia to rs of im m une re s p o ns e s : s timula tion o f quie s c e n t, na ive a nd c e lls c a n clus te r with DCs , a s s ho w n. Afte r a c tiva tio n , T (blue ) a n d B (ora nge )
m e m ory, B a nd T lymp h oc yte s b la s ts le a ve th e T-ce ll a re a . B b la s ts m o ve to the lining of th e inte s tin e , th e b one
X Po te nc y in s tim ula ting T ce lls : c a pa c ity o f s ma ll n um b e rs o f DCs a n d m a rro w, a nd othe r p a rts o f the lym pho id tis s u e , s uc h a s the me dulla o f lymp h
lo w le ve ls o f a ntig e n to in duc e s trong T-c e ll re s po n s e s n ode , with s om e b e c o min g a ntib ody-s e c re ting p la s m a c e lls . T bla s ts le a ve the
X Induc e rs o f to le ra nce : de le tion o f s e lf-re a c tive thymo cyte s , a nd b loo d a t the origina l s ite o f a ntige n de p o s itio n, re c o gn izin g c ha nge s in the
a n e rg y o f m a ture T c e lls in fla m e d blo od ve s s e ls a nd re s po nding vigoro us ly to c e lls tha t a re p re s e ntin g
a ntige n . Th is limits th e T-c e ll re s po n s e to the s ite o f mic ro bia l infe c tion .

Nature © Macmillan Publis hers Ltd 1998

NATURE | VOL 392 | 19 MARCH 1998 245