An exploration of immunity, immune function, and immune response from the fetus to the elderly. 

 

Fetal Immune Function

The fetus develops in a sterile environment and therefore has no exposure to antigens by which to develop immunologic responses. Additionally, the fetal immune response is blunted to allow co-existence with the mother.

Most of the immunoglobulins are from passive placental transfer of maternal immunoglobulin G (IgG) during the third trimester of pregnancy.

By the end of the 1st trimester (12 weeks gestation), all of the major antigen presenting cells (APCs), including dendritic cells, monocytes/macrophages, and B-cells, are present.

At birth, the outside world exposes the newborn to bacteria, virus, fungi, and parasites, provoking the newborn immune system to develop immune capabilities ("acquired" or "adaptive" immunity) during these antigenic experiences.

Newborns, however, must initially rely on their innate immunity for protection against infection,

 

Newborn Immune Function

INNATE IMMUNITY

Present at birth, the innate immunity has both cellular and extracellular components at sites such as the skin, spleen, and mucous membranes, as well as in tissue fluids, blood, and secretions, such as tears and saliva.

Antigen-presenting cells (APCs), including dendritic cells, monocytes/macrophages, and B cells, are present.

Cellular components: The various functions of these cells include antigen presentation, phagocytosis, and cytotoxicity.

• dendritic cells, which stimulate the cooperation between the innate and adaptive immune systems;
• monocytes and macrophages,
• neutrophils, and
• natural killer cells.

T-cell function is partially intact at birth to help newborn B-cells for antibody production, but not functional enough to adequately fight pathogenic viruses with cytotoxicity.

The primary tissues responsible for the initial generation of B- and T-cell lymphocytes are the bone marrow and thymus, respectively.

Extracellular components: Humoral (B-cells and Immunoglobulins)

Compliment: matures in the fetus and reaches adult mature levels between 6-18 months.

B-cells: Normal-term newborns have adult levels of B-cells IgG: (mostly) from the mother;

Other extracellular components include Mannose-binding lectin, fibronectin, adenosine and acute-phase proteins, and antimicrobial proteins and peptides (AMPs).

ADAPTIVE IMMUNITY

The first 3 months see an explosion of acquired immunity, but while this is happening, the newborn depends on the innate (antigen-independent) immune system (phagocytes, natural killer cells, antigen-presenting cells--APCs, complement, and other mediators of inflammation of the humoral immune system).

B- and T-cell Lymphocytes:

The extracellular spaces are protected by the humoral immune response, in which antibodies produced by B-cells cause the destruction of extracellular microorganisms and prevent the spread of intracellular infections. The activation of HUMORAL B-cells and their differentiation into antibody-secreting plasma cells is triggered by antigen and usually requires helper T-cells.

T-cells: Some lymphocytes from the bone marrow travel to the thymus where they develop into T-cells with different functions in the immune response (primarily cell-mediated immunity). T-cells help stimulate B-cells.

B-cells: Others go to lymphoid tissues like lymph nodes and the spleen, where they develop into B-cells (for primarily humoral immunity).

The overall immune system in early life is diminished, so very young infants are more susceptible than older infants to serious bacterial infection, especially from increased exposure to:

• group B strep,
• E. coli,
• herpes simplex--HSV,
• varicella-zoster-VZV,
• respiratory syncytial virus--RSV, and]
• Candida yeast.

Certain clinical scenarios, such as recurrent severe infections, chronic diarrhea, and failure to thrive, should prompt immediate evaluation for immunodeficiency states.

 

From Mother to Infant

Term newborns have adult levels of their own B-cells, but few plasma cells and virtually no synthesis of serum or secretory antibodies.

Most of the newborn's serum immunoglobulins are derived from the transfer of maternal immunoglobulin G (IgG) across the placenta during the third trimester of pregnancy. This passively acquired IgG includes vaccine antibodies as a result of maternal immunizations given before or during pregnancy.

After 3 months:

The IgG level gradually falls as the maternal IgG is metabolized and then progressively increases as the infant’s own IgG synthesis becomes established.

(Premature infants have lower IgG concentrations due to diminished time for transfer and lower production levels.)

IgG: passively transferred to the fetus.

(IgA, IgM, IgD, and IgE do not cross the placenta.)

IgA increases gradually the first year, and breastfed infants receive maternal IgA antibodies to protect the infant's GI and respiratory tracts.

 

Breastfeeding Contribution to Immunity

The majority of the nutritional components of human milk include the following properties:

• Bacteriostatic and immune modulating properties, which are activated prior to and/or during the process of digestion.
• Anti-inflammatory.
• Growth promotion of cells in the infant's gut or other cells in the body.
• Aid in digestion.

Secretory immunoglobulin A (IgA) is synthesized in the mammary gland by plasma cells against specific antigens. They are major contributors to the protective nature of human milk.

Cells in breast milk include:

• macrophages,

capable of chemotaxis, phagocytosis, and secretion of complement, lysozyme and lactoferrin.

• lymphocytes,

Both B- and T-lymphocytes in human milk aid in protecting the infant's intestinal tract from invading organisms.

• neutrophils.

 

Immune Response in the Elderly

As the immune system ages and their capabilities decline, there is increased susceptibility to infections and cancer and an increased incidence of autoimmune disorders.

Aging affects both innate and adaptive immunity, although adaptive processes are affected more dramatically.

Adequate nutrition is probably important in improving immunity, and there are some data indicating that regular, moderate exercise is also important.

As people get older, the immune system becomes less effective: 

• Macrophages destroy antigens more slowly, increasing the risk of elderly population cancers.
• T-cells (which remember previously encountered antigens) now respond more slowly to them.
• Antibody production against newly encountered antigens is also affected, and the body is less able to remember new antigens to defend against them.

Antibody production, in general, is now less, and the antibodies are less able to attach to the antigen, rendering the elderly population's ability to fight off infections much less than that of a middle-aged adult.

Autoimmune Disorders: In the elderly, the immune system becomes less able to distinguish antigens from the body’s own healthy cells.

It is unknown whether aging causes immunity decline or immunity decline contributes to aging. Common herpesviruses, such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), may contribute to "immunologic exhaustion," so vaccinations against these may improve immunity in the elderly.

IRP:

The "immune risk profile" (IRP) is used to describe a combination of immunodeficiencies with aging: poor T-cell response, low B-cells, etc. High IRP has a higher mortality rate and families with longevity showed lower IRPs.

 

In the Field

In the field, your most likely encounters with the immune system should only involve consequences of newborn immaturity or age-related impairment of immunity.

Newborn/Infant:

• E. coli: Diarrhea and dehydration.
• Group B strep: Sepsis.
• Varicella: chickenpox/pneumonia. 
• Encephalitis: Reye syndrome (nausea and vomiting, headache, delirium, and combativeness, and coma).
• Herpes: 10% of neonatal HSV infections occur when a caretaker with active HSV infection, such as herpes labialis (cold sore), has close contact with the newborn infant.
• Sepsis--fever, dyspnea, DIC.
• CNS manifestations: seizures, lethargy, irritability, tremors, poor feeding.
• Skin lesions (present in 60 to 70%)
• Respiratory syncytial virus--RSV:
  • Cough
  • Runny nose
  • Conjunctivitis
  • Sinusitis
  • Otitis
  • Bronchospasm
  • Pneumonia
  • Acute respiratory failure
• Candida yeast:
  • Thrush
  • Invasive candidemia sepsis (fever, sepsis indistinguishable from bacterial sepsis).

Elderly:

• Infections:
  • Pneumonia
  • Influenza
  • Sepsis
• Complications of autoimmune disease:
  • Pain
• Complications of cancer:
  • Obstruction
  • Pain
  • Sepsis
  • General debilitation