Eventos en el centro germinal tras la estimulacin con antgenos TIMO-DEPENDIENTES (proteicos)

Hipermutacin somtica Maduracin de la afinidad Cambio de isotipo (switch) Generacin de clulas de memoria

Interaccin entre linfocitos T y B

Tras la interaccin del linf. B con el linf. T tambin se induce la expresin de AID (desaminasa de citidina Inducida por activacin) y UNG (uracil-N-glicosilasa), enzimas que participan en: Hipermutacin somtica Y Cambio de isotipo

NEMO: Escencial Modulator NF B

Diferencia entre recombinacin e hipermutacin

Cambio de isotipo

-AID first deaminates C to U, and then uracil-DNA glycosylase removes U, leaving an abasic site. Subsequent steps generate single-strand breaks [17], which become substrates for mutagenic repair or recombination. Somatic hypermutation alters variable region sequence, and switch recombination joins a new constant region (C1) to the expressed variable region, producing an extrachromosomal DNA circle (bottom), which contains the deleted region. The final result is a heavy chain locus containing a mutated variable region (mutations are indicated by stars) and a chromosomal S/S1 junction (bottom).
--Somatic hypermutation is shown following switch recombination, but neither process is prerequisite for the other

Influencia de las citocinas en el cambio de isotipo clase de Ab.

Maduracin de la afinidad (hipermutacin y seleccin por las FDC)

Antes y despus de formarse el centro germinal

Centro germinal (good!)

Ulf Klein & Riccardo Dalla-Favera Nature Reviews Immunology 8, 22-33 (January 2008)

Antigen-activated B cells differentiate into centroblasts that undergo clonal expansion in the dark zone of the germinal centre. During proliferation, the process of somatic hypermutation (SHM) introduces base-pair changes into the V(D)J region of the rearranged genes encoding the immunoglobulin variable region (IgV) of the heavy chain and light chain; some of these base-pair mutations lead to a change in the amino-acid sequence. Centroblasts then differentiate into centrocytes and move to the light zone, where the modified antigen receptor, with help from immune helper cells including T cells and follicular dendritic cells (FDCs), is selected for improved binding to the immunizing antigen. Newly generated centrocytes that produce an unfavourable antibody undergo apoptosis and are removed. A subset of centrocytes undergoes immunoglobulin classswitch recombination (CSR). Cycling of centroblasts and centrocytes between dark and light zones seems to be mediated by a chemokine gradient, presumably established by stromal cells in the respective zones (not shown)14. Antigen-selected centrocytes eventually differentiate into memory B cells or plasma cells.

Subpoblaciones de linfocitos TH

Figure 1.Functional development and activity of Th cell subpopulations. Activation of dendritic cells (DC) follows interaction of pattern recognition receptors such as C type lectin receptors (CLR) or toll like receptors (TLR) with molecules on the surface of microorganisms. Antigen presentation to nave T cells results in the development of Th1, Th2 or Th17 cells depending on the cytokine milieu. Cells of the innate immune system, e.g. DC and NKT cells, are the source of promoting cytokines, IL-4, IL-6, TGF- and IL-12. IL23 promotes the expansion rather than the development of Th17 cells. The cytokines which are made would depend on the antigenic stimulus. The activity of Th cell subpopulations can be regulated by Tregs which may include naturally arising Foxp3expressing Tregs.

Respuesta inmune y linfocitos TCD8

Tarea: cmo se activa un linfocito TCD8? cmo lleva a cabo su funcin ?

Cuestionario:
1. Esquema de la sinapsis inmunolgica entre linfocito T y cel. Dendrtica 2. En qu consiste la seleccin positiva y la seleccin negativa para un linfocito T 3. A qu se debe la agammaglobulinemia de Bruton y cmo se puede diagnosticar 4. Qu enzima da lugar a la formacin del DAG e IP3 y cmo actan 5. Qu consecuencia hay por ausencia de la unin entre CD40-CD40L