Pathways and Stages

Adaptive immune responses represent antigen-specific defense mechanisms, which take days or weeks to develop. These responses are orchestrated by the complex interactions and activities of a large number of various cell types involved in the processes. There are four pathways of adaptive immune responses depending on a pathogen type.


Simple B-cell-mediated responses to T independent antigens and/or molecular patterns belonging to extracellularly located pathogens proceed with the involvement of naïve B cells but with no aid from helper T cells. However, such a response leads to the production of IgM only, whereas other isotypes of antibodies and the long-term immunological memory do not occur.


Advanced B-cell-mediated responses to antigens derived from extracellularly located pathogens proceed with the participation of naïve B cells and type 2 helper CD4+ T (Th2) cells/ follicular helper T (Tfh) cells. Such a response results in the maturation of plasma cells, antibody switching (subsequently IgM, IgG, IgA, and even IgE) by a partial control of type 1 helper CD4+ T (Th1) cells, and producing long-term or even lifelong immunological memory to the antigen due to memory B cells, and a relatively short-term memory due to long-lived plasma cells.


The HLA II pathway of the T-cell-mediated response involves naïve CD4+ T cells that result in their clonal expansion and differentiation into effector CD4+ T cells with inflammatory potential. In the beginning, the same cells are type 1 helper CD4+ T cells. This immune response is required to eliminate some intracellularly located exogenous antigens by immune inflammation. Long-term or lifelong immunological memory CD4+T cells are established in any case.


The HLA I pathway of the T-cell-mediated response engages naïve cytotoxic CD8+ T cells, which are activated with the aid of type 1 helper CD4+ T cells. Subsequently, CD8+ T-cell clonal expansion proceeds and the cells mature until they become effector cytotoxic CD8+T cells to take part in the elimination of such endogenous (intracellular) pathogens like viruses. It is achieved by apoptosis in virus-containing target cells. Lifelong memory CD8+T cells are always formed.

There are six stages of adaptive immune responses, as follows:

   (1) Antigen endocytosis, processing and loading on Class I HLA or Class II HLA molecules for presentation to          lymphocytes.
   (2) "Dual recognition" of the antigen/HLA I molecule or antigen/HLA II molecule complexes and simultaneous          recognition of two other signals from costimulatory/coinhibitory molecules and cytokines.
   (3) Signal transduction (signaling) and activation of lymphocyte clones.
   (4) Clonal expansion, or proliferation of lymphocytes.
   (5) Differentiation of lymphocyte effector and memory cells.
   (6) Effector activity of lymphocytes and engaged cells.

Antigen-presenting cells (APCs), including dendritic cells, macrophages, and B cells, play crucial roles in the adaptive immune responses. They encounter a native antigen or several native antigens in the site of infection, endocyte them, then accumulate and carry to the secondary organs of the immune system.
Macrophages phagocyte large intracellularly located antigenic objects, e.g., infected cells, fungi, protozoans, while dendritic cells pinocyte viruses and proteins, and B cells internalize microbial toxins.