Fig. 2: Generation of vaccine-specific immunity and potential mechanisms of alteration in kidney failure.

a | Impaired vaccine-induced immunity in patients with kidney failure is multifactorial. To identify possible underlying mechanisms of alterations, it is important to review the single steps within the generation of vaccine–specific immune response. Pathogen-derived proteins are taken up by antigen-presenting cells (APCs), processed into peptides and presented on MHC molecules on the cell surface. Adjuvants are commonly added to vaccines to promote APC activation, thereby enhancing antigen uptake and presentation. These compounds act as danger signals by engaging pattern recognition receptors (PRRs). Following activation, APCs migrate to local lymph nodes where they present their MHC–peptide complexes to T cells. Kidney disease-induced factors such as uraemia and immunosuppressive drugs such as corticosteroids can impair APC activation and therefore compromise vaccine-induced immunity. b | Binding of a cognate T cell receptor (TCR) to an MHC–peptide complex, in combination with co-stimulatory signals provided by binding of CD80 and/or CD86 on APCs to CD28 on T cells, induces T cell activation. Activated CD4⁺ T cells provide help to B cells, to promote their differentiation into effector B cells and the production of antibodies with high affinity for the vaccine antigens, which are key components of humoral immunity. Some activated B cells differentiate into memory B cells to enable a long-term memory immune response, whereas others become plasma cells that actively secrete antibodies. Effector CD4⁺ T cells and CD8⁺ T cells activated by migrating APCs proliferate and produce effector cytokines and cytotoxic molecules that contribute to the elimination of infected cells and therefore drive cellular immunity; some of these cells also differentiate into memory T cells. Almost every step during the generation of immune response can be affected by immunosuppressive drugs or factors associated with kidney failure-induced immune alterations, such as premature ageing and low-grade inflammation.