No antibodies are detected in the fetus until the second trimester when low levels of IgM are reported.
Maternal, but not fetal, IgG is found in fetal blood.
The newborn infant has initial antibody levels similar to that in adults because of active transplacental transport of IgG.
As this IgG is catabolized, antibody levels gradually decrease until the infant begins to produce IgG itself, at about six months of age. Thus in fetal and neonatal life only a small amount of IgM is produced by the developing individual.
This IgM antibody has low affinity, confers no memory and is responsive to only a limited range of antigens. The T cell compartment of the immune system is also functionally immature at late stages of gestation and in neonates.
Although comprehensive capacity to respond to a range of antigens develops during the first one to five years, full immuno-competence is only achieved in adolescence.
During embryogenesis the cells of the immune system develop in the primary lymphoid organs, namely the fetal liver, spleen & bone marrow, and the fetal thymus. They derive from undifferentiated, self-renewing haematopoietic stem cells which differentiate under the influence of various growth factors and give rise to the cells which comprise the 'innate' and 'acquired' immune system.
Cells of the 'innate' immune system are dendritic cells, macrophages, neutrophils, eosinophils, basophils etc. Cells of the 'acquired' immune system that recognise and respond specifically to antigen are T and B lymphocytes.
B cells develop into immunocompetent lymphocytes in the fetal liver, spleen and bone marrow, T cells in the thymus.
Mature T and B lymphocytes migrate from primary lymphoid organs into secondary [or peripheral] lymphoid tissues, e.g., lymph nodes, spleen, tonsils, adenoids, Peyers patches and mucosal lymphoid aggregates. Within secondary lymphoid tissues T and B cells are segregated into distinct anatomical compartments.
Responses to invading pathogens occur in secondary lymphoid tissue.
The immune system develops relatively late in fetal life. The fetus is protected against infection by its isolation within the uterus and by maternal IgG antibodies that are transported from mother to fetus across the placenta.
Pathogens that do penetrate these barriers and cross the placenta are largely unchallenged and may cause severe disease or death of the developing infant.
Cells of the immune system are constantly replenished, after birth and throughout adult life. In adults, the thymus retains its function producing T cells 'on demand', to be seeded to the secondary lymphoid tissues.
The bone marrow takes over from liver, and produces naive, immuno-competent B-lymphocytes which also migrate to secondary lymphoid tissues. Responses to foreign antigens take place in secondary lymphoid tissues.
A process of stem cell proliferation, maturation and differentiation occurs in B cell development in the fetal liver and adult bone marrow. The diversity of receptor specificites is generated by random rearrangement of germ line immunoglobulin [Ig] gene segments to generate diverse Ig receptor molecules on mature B cells.
Cells with non-productive gene rearrangements die [by apoptosis]. Self-reactive cells are also deleted. This ensures that mature, antigen specific, self-tolerant B cells are seeded, via the circulation, to the secondary lymphoid tissues.
In embryogenesis, the thymus develops as an epithelial rudiment of endodermal origin. The rudiment is seeded by a small number of stem cells. Once there, the thymic epithelial microenvironment provides stimuli that induce massive cell proliferation, maturation and differentiation.
The majority of the T lymphocytes (T cells) generated DIE in the thymus, by a process of programmed cell death [apoptosis].
Why generate T cells in order to kill them?
As is the case for B cells, pre-T cells possess an identical collection of small gene segments in their germ line DNA. As each cell matures in the thymic environment, it selects at random some of these gene segments and rearranges them to build an antigen specific receptor [TCR] with a variable region specific for one antigen [epitope]. Other random selections generate other specificities.
Cells with non-productive receptor gene rearrangements die. Selection of functional T cell receptors is complicated by the fact that the TCR binds antigenic peptides associated with self MHC molecules [Major Histocompatibilty Complex molecules or HLA molecules] on other cells. The cells that present the antigenic peptides are called Antigen Presenting Cells (APCs).
Therefore during the maturation of T cells in the thymus, the differentiating cells must be 'educated'.
Those with a TCR that binds self MHC too weakly are eliminated [to generate MHC restriction of the TCR], those that are too strongly self-reactive are also eliminated [to generate self tolerance], and, therefore, those that survive recognise and bind to foreign antigens in the context of self MHC molecules.
These mature, naive, non-self-reactive T cells are seeded to secondary lymphoid tissues where they are activated to become effector and memory T lymphocytes in response to antigenic challenge.
Roitt, I., Brostoff, J., Male, D., (eds.), 2001, Immunology, 6th edition, Mosby, Edinburgh ; New York.
- Refer to chapters discussing T cell and B cell maturation.
- An excellent, short overview of the development and functions of the immune system
- An excellent, short overview of the development and functions of the immune system