Inmunobiología

DRA. MA. DE LA SOLEDAD LAGUNES CASTRO

Inmunidad innata: Reconocimiento de antígeno
Toll-Like Receptors (TLRs)

TLRs are the first identified and the best

characterized receptors among the signaling
PRRs. Signaling by these receptors initiate key
inflammatory responses and also shape adaptive
immunity.

All TLRs (10 in humans and 11 in mice) are type I transmembrane proteins characterized by an extracellular leucine-rich
domain and a cytoplasmic tail that contains a conserved Toll/IL-1 receptor (TIR) domain (PDB-101).
TLRs recognize a variety of PAMPs from bacteria, fungi,
parasites, and viruses, including lipid-based bacterial cell
wall components such as lipopolysaccharide (LPS) and
lipopeptides, microbial protein components such as
flagellin, and nucleic acids such as single-stranded or
double-stranded RNA and CpG DNA.

They also activate interferon regulatory factors leading to the production of type I interferons.
Nod-Like Receptors (NLRs)

NLRs constitute a family of intracellular

pattern recognition receptors (PRRs), which
contains more than 20 members in mammals.

NLRs are characterized by a tripartite-domain

organization with a conserved nucleotide
binding oligomerization domain
(NACHT/NOD), leucine-rich repeats (LRRs)
involved in microbial sensing and an N-
terminal effector region comprising a protein-
protein interaction domain such as the CARD,
pyrin or BIR domain.
NLR´s

Although the ligands and

functions of many of these
receptors are not known, their
primary role is to recognize
cytoplasmic pathogen-
associated molecular patterns
(PAMPs) and/or endogenous
danger signals, inducing
immune responses.
RIG-I-Like Receptors (RLRs)
and Cytosolic DNA Sensors
(CDS)

RLRs constitute a family of

cytoplasmic RNA helicases that
are critical for host antiviral
responses. The RLRs include the
RNA sensors RIG-I, MDA-5 and
LGP2, which when activated lead
to the activation of transcription
factors that also control the
transcription of genes encoding
interferons and other cytokines.
C-Type Lectin Receptors (CLRs)

CLRs, also called the C-type lectins,

encompass a large family of proteins
that act as phagocytic receptors that
bind carbohydrate moieties of various
pathogens.

Type C Lectin
Funciones
Interferón tipo
I
interferon-stimulated response element (ISRE)
Gamma-activated sequence (GAS).
Interferon-stimulated gene, ISG
La mayoría, si no todas, las
células en humanos y
ratones expresan el receptor
para interferones tipo I
(IFN).

Los IFN tipo I son importantes

para la defensa del huésped contra
los virus, a través de la inducción
de moléculas efectoras antivirales
que están codificadas por genes
estimulados por IFN.

Estos IFN puedencausar inmunopatología en infecciones virales agudas. Por el contrario, pueden provocar
inmunosupresión y pérdida del control del virus durante las infecciones virales crónicas.
• Durante las infecciones bacterianas, es posible que
se requieran temprano niveles bajos de IFN de tipo I
para iniciar respuestas inmunitarias mediadas por
células.

• En las infecciones bacterianas, las altas

concentraciones de IFN tipo I pueden bloquear las
respuestas de las células B o pueden conducir a la
producción de moléculas inmunosupresoras como la
interleucina-10.

• Los IFN tipo I también antagonizan la acción del

IFN tipo II (es decir, IFNγ) al reducir la capacidad
de respuesta de los macrófagos a la activación por
IFN tipo II. Otro antagonismo importante es entre
los IFN tipo I y la interleucina-1.
Deficiencias en la expresión de genes IFN tipo I
 Procesamiento y presentación de antígenos

•Both macrophages and dendritic cells (DCs) are considered professional antigen-presenting cells, although DCs
possess the unique capacity to activate naive T cells.
•DCs phagocytose
antigens and whole
microorganisms and place
them into membrane-
delimited compartments
termed phagosomes.
These structures are
modified over time and
ultimately fuse with
lysosomes to form
phagolysosomes.
MHC
Regulación de MHC Clase II
Regulación de MHC Clase I
MHC Clase I
Vía Citosólica
MHC Clase II
Vía Endocítica
Presentación
cruzada
Reconocimiento
de antígeno por
Linfocitos T
Coestimulación