Specific immune response, known as the adaptive immunity provides a more sophisticated defence strategy through highly specific interactions with the pathogen. These responses improve with each successive exposure to an antigen. Adaptive responses comprise of B lymphocytes, T lymphocytes and antibodies. B lymphocytes develop in the bone marrow and express immunoglobulins on their surface (Igs). Whereas, T lymphocytes travel from bone marrow to thymus for maturation and express T cell receptors on their surface. These surface receptors provide immense specificity as unlike innate receptors, they can recognise between non-selves. The genes encoding these receptors are the product of gene recombination which produces a large number of unique receptors by rearranging, splicing and linking a finite set of adjacent genes. Adaptive responses are generated in the secondary lymphoid tissues where proliferation of antigen- specific B and T cells occur upon binding of surface receptors to antigen. This proliferation is initiated when antigen- presenting cells display the antigen to B and T lymphocytes, where B lymphocytes secrete antibodies and T cells help B cells produce antibodies, activate macrophages and kill infected cells. 4,11
There are two types of adaptive responses, humoral immunity which is mediated by B lymphocytes and their products and cell- mediated immunity which is mediated by T lymphocytes. T cells have antigen binding receptors on their surface referred to as T cell receptors. Molecules which are recognised by T lymphocytes are either class I MHC bound which are endogenously produced and present on all nucleated cells, or class II MHC bound which are exogenously produced and present peptides from phagocytosed proteins on APCs. T cells are divided into two types depending on their functions and cell surface markers present: Cytotoxic T lymphocytes (TC) which express CD8 marker and T helper lymphocytes (TH) which express CD4 marker. Cytotoxic cells containing CD8 recognise antigens presented on MHC I molecules and release perforins which create pores in the membrane and granzymes which digest proteins to induce apoptosis in cells displaying the antigen. Helper T cells containing CD4 markers recognise antigens presented on MHC II molecules on APCs such as macrophages, dendritic cells and B cells. Upon recognition, they release cytokines and specific effector functions are chosen depending on which cytokines are released 4,11.
TH1 lymphocytes secrete INF-g, IL-2 and lymphotoxin a promoting phagocytosis, cell-mediated responses through increased CD8+T cell proliferation and antagonising humoral responses 7. TH2 release IL-4, IL-5, IL-9, IL-10, IL-13 and IL-25 to enhance extracellular parasitic elimination. IL-4 induces antibody switching from IgM to IgE and increases other proinflammtory mediators such as IL-6, GM-CSF and VCAM-I. IL-5 and IL-13 activate the function of eosinophils and IL-9 activates mast cells, B cells, neutrophils and also eosinophils 8. IL-10 is an anti-inflammatory cytokine which inhibits TH1 cells and other innate immune system cells after pathogen clearance to achieve homeostasis 6. IL-25 promotes TH2 responses which include activation of eosinophils, mucus production, IgE switching and enhanced immunoglobulin secretion 6. TH17 cells release IL-17, IL-21 and IL-22 which play an important role in defence against bacteria and fungi in mucosal surfaces. IL-17 induces production of proinflammatory cytokines IL-6, IL-1 and TNFa 9. The selection of different effector functions depends on the coreceptor signalling, the nature of the antigen and the cytokine environment. IL-21 functions include activation of B cells to differentiate into plasma and memory cells, natural killer cells as well as T cell activation 5,10
Humoral immunity is mediated by B lymphocytes and their products, immunoglobulins. These Immunoglobulins on the surface of B cells recognise extracellular antigen presented which leads to proliferation and differentiation of B cells into plasma cells and memory cells in humoral responses. Memory cells remain the system for a long period of time and provide a faster and stronger response upon next exposure to the antigen. This proliferation is caused by TH1 and TH2 cells as they present the specific antigen to B cells and induce heavy chain isotype switching and affinity maturation. Plasma cells further differentiate and secrete antibodies specific to the antigen which have several effector functions to eradicate pathogen. Different antibody isotypes perform different functions for example, the IgM isotype agglutinates or clumps the pathogen which provides easy removal of the pathogen. The function of the IgG isotype is antibody dependent cell-mediated cytotoxicity in which binding of the antibody to the antigen flags the pathogen for phagocytosis by cells with Fc receptors such as natural killer cells and macrophages. IgA binding to a pathogen neutralises the pathogen as this binding prevents latter function of the pathogen such as viral attachment and uncoating and bacterial colonisation as well as agglutination function of IgA. IgE binds to mast cells and the cross-linking between mast cells, IgE and antigen causes mast cells to secrete granules which contains inflammatory mediators. Lastly, one of the most important function of the antibodies is activation of the complement cascade. This is caused by binding of IgM and IgG to the antigen. 4. B lymphocytes also express CR2 receptors and the specific antigen and the bound C3d is recognised through the CR2 receptor which enhances the effector functions of B cells 2. This is one of the ways in which innate immune responses enhance adaptive immune responses.