ag+mhc
TRANSCRIPT
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Inmunogenicidad vs antigenicidad
Inmunogenicidad…….Inmunógeno
-Es la capacidad de una sustancia para inducir una respuesta inmunitaria humoral, mediada por células o ambas.
Antigenicidad………..Antígeno
-Es la capacidad para combinarse en forma específica con anticuerpos, receptores de superficie celular o ambos.
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Endovenosa poco inmuno-génica vs subcutánea: se reclutan macrófagos + adyuvantes expresión de moléculas coestimulatorias
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Grupo sanguíneo
Antígenos en la membrana de los glóbulos
rojos
Anticuerpos en el plasma
A
B
AB
0
Antígeno A
Antígeno B
No antígenos
Antígenos A y B
Anti‐A
Anti‐B
Anti‐A y Anti‐B
No anticuerpos
Genotipo Fenotipo o grupo sanguíneo
AA
A0
B0
BB
AB
00
A
B
AB
0
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Moléculas del CMH Iy IIcaracterísticas comunes
• 1-Hendidura extracelular de unión a péptidos, seguida de dominios similares a Igs, anclaje a la célula por dominios transmembrana y citoplasmáticos.
• 2- Aminoácidos polimorfos están y son adyacentes a la hendidura. Debido a esta variabilidad diferentes moléculas del CPH se unen a diferentes péptidos a ser luego reconocidos por LT.
• 3- Dominios similares a Igs contienen sitios de unión a LTCD4 y LTCD8.CD4 unión selectiva a moléculas del CPH clase II (LTh)CD8 unión selectiva a moléculas del CPH clase I (LTc)
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Moléculas del CMH I
Hendidura: fija péptidos de 8-10 aa y los extremos están cerrados. Proteínas globulares deben ser procesadas. EspecificidadPunto de unión a CD8 α3.restriccion de LT
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Moléculas del CMH II
Hendidura: extremos abiertos, entran péptidos de 30-40 aa. Especificidad.Punto de union a CD4 β2. Restricción de LT.
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El reconocimiento Ag-Ac implica una unión reversible no covalente.
Zona de equivalencia in vivo: inmunocomplejos circulantes que atrapados o en los tejidos … reacción inflamatoria.
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• Afinidad: fuerza de la unión entre la zona de fijación de Ac y el epitopedel Ag. 1determinante antigénico +1 punto de unión
• Equilibrio de la reacción Ag + Ag ……… Ag-Ab• Ka=Ag-Ab Unido/Ag libre x Ab libre.
• Constante de disociación (Kd ): La concentración Molar de ag. a la quela mitad de las moléculas de Ab estén unidos a él y la otra mitad libre.para los Ab es de 10-7 a 10-11 M. 1/Ka
• IgG-IgE región bisagra (flexible) para unión a Ag multivalente por masde un punto de unión. 2 lugares de unión Fab.
• IgM pentamérica (2 Fab x5) 10 sitios de unión.
• Avidez: fuerza de unión global; es mayor a la afinidad pues tiene encuenta la fijación de los lugares a todos los epitopes disponibles.Anticuerpo polivalente + antìgeno polivalente
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Ac. Penicilinico + proteìna del suero
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Reacciòn cruzada
• Interacciòn de dos antìgenos diferentes con un mismo anticuerpo especìfico para uno de ellos. Debido a la presencia de determinantes antigènicos compartidos.
Determinante antigénico COMPARTIDO
BVD PPC
Determinantes antigénicos
DIFERENCIALES
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Contexto del reconocimiento antígeno por LT y LB
Heterodímero: cadena a y b (g y d) unidas por S-Sc/u posee dominios: Variable, Constante, región transmembrana y citoplasmática.Regiones V: secuencias de aa variabilidad …regiones hipervariables.
Proteínas DC3 y ζ se asocian no covalentemente y trasducen señales.
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Compuesto por dos cadenas pesadas y dos livianas.
Hay dos componentes secundarios asociados estrechamente para acoplar señales intracelulares.
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Receptor B reconoce regiones de la “superficie” del antígeno
Receptor T reconoce péptidos lineales cortos del antígeno
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Nominal antigens & superantigens
Nominal antigens
Require processing to peptides
TcRα and β chains are involved in recognition
>1 in 105 T cells recognise each peptide
Recognition restricted by an MHC class I or II molecule
Almost all proteins can be nominal antigens
Superantigens
Not processed
Only TcR β chain involved in recognition
2-20% of T cells recognise each superantigen
Presented by almost any MHC class II molecule
Very few antigens are superantigens
Suggests a strikingly different mechanismof antigen presentation & recognition.
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Electoforesis: PI 4,9 (Albúmina) y 7,4 (Gamma-globulinas).Con un tampón depH = 8,6, todas las proteínas del suero tendrán carga negativa. La albúmina, al tener el puntoisoeléctrico más alejado del pH, tiene más carga negativa y avanza más rápido, quedando más cerca del polo positivo que las gamma-globulinas, que migran muy poco por ser el pH próximo a su pI. Lasrestantes proteínas séricas quedan situadas entre estas dos.
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Extremo N terminal de las cadenas L y H: sitio de combinación del Ac.
Extremo C terminal, dominios constantes de las cadenas H permite cumplir con funciones efectorasDominios Ig: 110 aa bucle.VH: 1 CH:3-4VL:1 CL:1
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distal
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