Development of fetal and neonatal immune system 9[1].1.10

Development of Fetal and

Neonatal Immune System

Benita Nancy Reni.M

Immune system…..

• Complex array of organs, cells, chemicals.

• Determine self from non-self.

• Identify potential dangers to the body.

& Elimination – by immune response.

Development of Immune System…

Starts early in the embryo stage.

Continues during fetal life.

& is completed – several years after

the birth.

Fetal immune system….

Hematopoietic stem cells

↓

Originate in the yolk sac

(3rd-4th week of gestation)

↓

Migrate to the liver & spleen

(5th-12th week)

↓

Ultimately, reach the bone marrow. (2nd-3rd trimester of gestation)

The thymus → first immune organ to develop.

followed by,

The development of secondary immune organs.

Development of immune system in calf…

T CELLS

• Differentiation initiates in the thymus after the 7th week of gestation.

• T-cells only colonize the fetal liver, spleen & bone marrow after the

13th week.

• Helper and suppressor activities of fetal thymocytes and

splenocytes are acquired between the 12th and the 16th week.

T-cells migrate and appear in

tissues with development

and increase in number throughout Gestation.

B-CELLS…

• FIRST appear in immature state – yolk sac, Liver (at 7 weeks), &

then in bone marrow.

• LATER –appear mature by 14-20 weeks.

• B-cell maturation → antigen independent.

NATURAL KILLER CELLS…

• First appear in fetal bone marrow around 13 weeks gestation.

• Found throughout body.

• NK cells have diminished activity before birth compared to adult

• Stimulated by interferon after 27 weeks.

HLA antigens are first detected in the lymphocytes at the beginning of the second trimester.

COMPLEMENT PROTEINS…

• Arise from liver • First detected → 5-6 weeks gestation • Increase gradually in concentration. • At about 28 weeks complement proteins around 2/3 that of adult concentrations. 

Maternal/Fetal Interactions…

The developing fetus - histoincompatible graft.↓

Recognized as foreign by the mother's immune system, but, not get rejected.

Reasons are,…

▪ Placenta-filter for anti-HLA antibodies.

▪ Coating of antibody on paternal antigens present in the placenta

→"hide" the foreign HLA antigens → from cell-mediated immune

response.

▪ trophoblast, do not express the HLA Class I protein.

▪ The state of pregnancy induces a state of moderate

immunosuppression of the mother

MATERNAL-FETAL EXCHANGE…..

Neonatal immune system…Neonatal age − adaptation from intra- to extra-uterine life.

Neonates – have to defend against hostile microbes in the surroundings.

• At birth -Immune system is naive,…. Although, it is

responsive.

• Physiological immaturity of the immune function.

• At time of birth, baby will have large numbers of circulating antibody passed across

the placenta from mother – protect against some infections

• They rely on passive transfer of maternal antibodies in breast milk.

• human babies don’t have a porous stomach (like calves do) in order to absorb the

antibody.

• Immunological components in breast milk will work in protecting pathogens crossing

the oral cavity.

Functional differences during immune system development ….

Monocytes, macrophages and dendritic cells…

activity depends on the secretions of cytokines, mainly IFN-γ, IL-12

and IL-18

The reduced synthesis of these cytokines →increased susceptibility

to infection by

intracellular bacteria.

Neutrophils…Compromised Neutrophils storage pool

T cell…•Significant phenotypic differences b/w neonatal & adult T-cells•The percentage of CD4+ T cells is higher,•Th 1 like response is more compromised.

• B cell…

• Several differences in surface phenotype…

• Increased CD10 & CD18.

• Reduced CD21,CD32, adhesion molecules & class װ MHC expression.

• class switching – delayed.

• reduced cytotoxic response

during fetal life,

• poor T lymphocytes response

to mitogens,

• immaturity of T and B

lymphocytes,

• inadequate cytokine synthesis,

• marked deficiency of antibody

production

• reduced Neutrophils,

complement and natural killer

cell activity

In conclusion…

Complex deficiency of immunological function

increased susceptibility to various infections.

reduced clearance of intracellular pathogens

Pluripotent stem cells

THANK YOU…