Documentos de Académico
Documentos de Profesional
Documentos de Cultura
Inmunología Básica
Mayo, 2011
Persio D. López
Persio D. López
Common
myeloid
precursor
Megakaryocytes
Stem cell
Lin– Granulocyte–
monocyte Granulocytes
Sca1+
cKit+ ? progenitor
Thy1low
CD34low/+ Lin–
Sca1–
cKit+ Resident Macrophages
Thy1– monocytes and DCs
CD34+
CD16+
Common lymphoid CD32+
precursor
Inflammatory
monocytes
DC precursors DCs
La familia y la casa
the migration of monocytes. Nat Rev Immunol.
common myeloid precursor cell. At this stage, they express CD16 and CD32 on2004;4:432-444.
the cell surface andFigure
enter the
1, terminal-
Origin and haematopoietic
differentiation stage, which leads to differentiation into granulocytes and monocytes that subsequently exit from the bone
differentiation of myeloid antigen-presenting cells; p. 433.
marrow into the blood. After recruitment to peripheral tissues, monocytes can then further differentiate into dendritic cells
(DCs) or macrophages. This plasticity in differentiation pathways contrasts with circulating DC precursors, which can only
differentiate into myeloid or lymphoid DCs. NK, natural killer.
Thursday, May 12, 2011
Ontogenesis Primary lymphoid organs Secondary
lymphoid organs
Progenitor cell
Medulla
Epithelium
IL-1
IL-2
Dendritic IL-6 Spleen
cells IL-7
Cortex Macro-
phages T lymphocytes
Fetal liver
'()*+,#)-+. /$%)0%1.#2
Thymus T lymphocytes
Myelopoietic
progenitor cell
Pluripotent
stem cell
?
"
Bone marrow B lymphocytes Lymph nodes
Lymphatic
progenitor cell
Progenitor cell
Sinus
IL-1
IL-6
IL-7
Erythron Stroma
Mucosa-associated
B lymphocyte
lymphoid tissue
A. Structure of the lymphoid system
Burmester G-R, Pezzutto A, Ulrichs T, Aicher A. Color atlas
Defensa innata
and at intracellular compartments. After ligation of TLR ligands either
accessory molecules such as CD14, MD2 (also known as LY96) and CD36,
directly
cancer. Nat or
Physiological
withCancer.
Rev
functions
TLRs dimerize
the help 2009;9:57-63.
andof transmit
of induction)Figure
in tissue1,strom
Toll-like receptors (TLRs); p. 58.
ulation of anti-apoptotic
signals throughout the cell by means of adaptor molecules such as myeloid differentiation factor 88
(MYD88) and TRIF. This leads to the activation of multiple cellular phenomena, the best-described of signals to keep both dif
which being the activation signal transduction to the nucleus (such as through activation of nuclear progenitor cells within t
Thursday, May 12, 2011 factor-KB (NF-KB), MAPKs and interferon regulatory factors (IRFs). TLR activation leads to regulation In the nervous system
van Kooyk Y, Geijtenbeek TB. DC-SIGN: escape mechanism
secundarias
Figure 1.6; p. 13.
secundarias
Figure 1.6; p. 13.
específicas
Figure 1.7; p. 14.
Number of thymocytes
(TReg cell). A CD4+ T cell that
Positive cytes that were not specific for th
expresses high levels of CD25
selection
(also known as the α-chain of Negative selection: and other reasons, many investi
the interleukin-2 receptor), is clonal deletion the use of TCR-transgenic mice
naturally anergic and requires receptor editing cognate antigen of the TCR as
stimulation through the T-cell anergy
receptor for induction of its antigen for the modelling of n
cell-mediated suppressive thymocytes by clonal deletion.
function. The role of this A classic model of this type i
subset of T cells is to maintain which CD8+ T cells that express
self-tolerance.
is specific for the male antigen
CD8αα+ INTESTINAL Affinity selected in female mice but del
EPITHELIAL LYMPHOCYTE TCR-transgenic mice tend to fal
Agonist
A type of T cell that is found in of clonal deletion: those that del
the intestinal epithelium. The selection:
TReg cells in development (that is, at the d
CD8 molecule that they express
is a homodimer of CD8α, CD8αα+ IELs to double positive (DP) stage); a
NKT cells thymocytes late (that is, at the D
rather than the CD8αβ
heterodimer that is expressed (SP) stage). Sometimes these are
by conventional CD8+ T cells in Lymph node and medullary deletion, respectiv
the lymph nodes. It has been
proposed that these cells are
DP progenitors reside in the corte
self-reactive T cells that have area of the thymus) and SP prog
Provide immune Regulate
regulatory properties. responses to immune medulla (which is the inner area)
foreign antigens responses TCR-transgenic mice that have b
NATURAL KILLER T CELL
Figure 1 | Central-tolerance mechanisms. The affinity of
32 have been used to model clon
(NKT cell). A T cell that
expresses both natural killer the T-cell receptor (TCR) for self-peptide–MHC Hogquist the Baldwin half
ligands isKA, of these,SC.thymocytes
TA, Jameson are dele
Central tolerance:
Tolerancia a lo propio
(NK)-cell receptors and an
αβ-T-cell receptor (αβ-TCR).
crucial parameter that drives developmental outcomelearninginself-control
the inment, and in about
the thymus. Nat Revhalf, thymocy
Immunol.
2005;5:772-782. Figure 1, Central tolerance mechanisms; p.
thymus. Progenitors that have no affinity or very773.low affinity die development. (For a complete li
In mice, these cells were first by neglect. This is thought to be the fate of most thymocytes. strains, see Models of negative se
identified by their expression If the TCR has a low affinity for self-peptide–MHC, then the
of the alloantigen NK1.1 (also
links box.) One determinant of
progenitor survives and differentiates, a process that is known
known as NKR-P1C). Some versus late clonal deletion is whet
Thursday, May 12, 2011
as positive selection. If the progenitor has a high affinity for self-
a
cTEC
Differentiation-
promoting
factor
T cell
Differentiation Apoptosis
b mTEC or DC
Hogquist KA, Baldwin TA, Jameson SC. Central tolerance:
learning self-control in the thymus. Nat Rev Immunol.
Linfocitos B
Figure 9.1; p. 188.
Linfocitos B
Figure 3.1, Structure of an antibody molecule; p. 48.
Linfocitos B 128.
.#$/+"-$0+' 12)$3)4'-,
VL Monomeric lgA
CL
SS
SS
SS
IgG1 65%
SS SS
SS
SS
SS
SS
SS
SS
SS
SS
SS
IgG2 23%
"
Secretory Membrane- Membrane-
lgA; dimer bound lgM bound lgD
SS
SS
SS
SS
Hinge
SS SS
SS SS SS
SS
region SS
SS
SS
SS
J
IgG3 8%
S
S chain SS
SS
SS
SS
Half-life
Homeland
23 6
Security:5
Burmester G-R, Pezzutto A, Ulrichs T, Aicher A. Color atlas
3
of immunology. Stuttgart 2.5 days
; New York: Thieme; 2003. Figure
Linfocitos B
14c, Immunoglobulin structure and features; p. 29.
C. Immunglobulin structure and features
✂
VH1 VH2 VH3 Vn
5' 3'
L1 L2 L3 Ln D1 D2 D 3 D 4 Dn J1 J2 J3 J4 J5 J6 Cµ C% C#3 C#1 C&1 C#2 C#4 C' C&2
Deletion Transcription
1#$2."+$0.' 3-)$4)5'+6
VDJ-rearrangement DJ-Cµ mRNA DJ-Cµ protein
VH1 VH2
Cleavage
5' 3' of L-coded
L1 L 2 D3 J 5 J6 Cµ C% C#3 C#1 C&1 C#2 C#4 C( C&2 sequence
"
n = ~35
V$1 V$2 V$3 V$n
5'
L1
Homeland Security:
L2 L3 Ln J$1 J$2 J$3 J$4 J$5
Burmester G-R, Pezzutto
3' A, Ulrichs T, Aicher
Chromosome 2 A. Color atlas
of immunology. Stuttgart ; New York: Thieme; 2003. Figure
15a, COrganization and rearrangement of immunoglobulin H
Linfocitos B
$
genes; p. 31.
B. Organization of ! light chain genes
Linfocitos B
1.4, Two forms of B cell activation; p. 7.
Linfocitos T p. 318.
Myeloid Lymphoid
progenitor progenitor
T-cell B-cell
Mega- pre- Thymus pre-
karyocyte Myeloblast Monoblast cursor cursor
Erythroblast
'()*+,#)-+. /$%)0%1.#2
Platelets
B
P lympho-
h cytes
Erythrocytes a
g o e s
c y t
T lympho-
cytes
"
Basophils
Generation of
Thursday, May 12, 2011 Natural killer cells specific receptors
Abbas AK, Lichtman AH. Cellular and molecular
T reg
5 9 b Helper T cell
C
3 CD iC3 C3a
C3 d
st 3
ce
Adaptive a, or CR differentiation
lls
C5 C
defense a 3dg T cells TH1>TH17 TH17>TH1
Activation/survival Polyclonal D59
DAF, C
Ab response response CD46 T cells
IgG Complement C3a, C5a
Autoimmunity Opsonization CD46, DA APC DC M'
h FcHR I,II,III F
FcHR Chemotaxis APC
C5a C
Interface - I1 I TCC lysis C5 5a C3a TLR
P I C5 b-8
Enhanced F, A or X in a ,9 Osteal tissue C5a activation
T ct b , C5 /C
activation and a m 2 C b 5 Synovial cells
F ro P- CD14 3a -8 a desA
phagocytosis Th AS a MBL C1 3a/ C ,9 rg
nt. M C5 TLR2 q desA
TLR4 C5a rg
Coagulation TLR9 C3a Bone marrow Cartilage and
bone resporation
Innate TLRs HSPC molbilization
Spread of DIC
s defense infection Immune cell
replenishment
and
Enhanced
inflammation Inflammatory Cell-dependent
antimicrobial
cytokine differential
functions
amplification regulation of
(phagocytosis,
IL-12 family
oxidative burst
and so on)
Paul WE. Fundamental Immunology. 6th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2008.
Roitt IM, Brostoff J, Male DK. Immunology. 7th ed. Edinburgh ; New York: Mosby; 2009.
Kindt TJ, Goldsby RA, Osborne BA, Kuby J. Kuby immunology. 6th ed. New York: W.H. Freeman; 2007.
Abbas AK, Lichtman AH. Cellular and molecular immunology. 5th ed. Philadelphia, PA: Saunders; 2005.