The Immune System in Early Life Flashcards
List 8 characteristics of the immune system at birth.
1 - Immune responses to protein antigens is almost normal.
2 - Opsonic activity and complement is reduced to 65% of normal levels.
3 - Phagocyte function is reduced.
4 - Monocyte motility is reduced.
5 - There are higher numbers, but poorer function, of lymphocytes.
6 - Antigen presenting cell function is reduced.
7 - B cell activation is poor.
8 - Epithelial and mucosal surfaces are the first lines of defence.
Why does the immune system at birth have higher numbers, but poorer function, of lymphocytes?
Due to:
1 - Low levels of IL-2, IL-4, IL-5, IL-12 and IFN-g.
2 - Reduced activation of the humoral immune response.
To which other organ systems is immune development linked?
Cardiovascular and bone marrow development.
List 3 anatomical sites at which haematopoietic stem cells form during embryogenesis.
1 - The yolk sac.
2 - The aorta-gonad mesonephros region (AGM).
3 - The placenta.
At which stage in life do haematopoietic stem cells colonise the bone marrow?
At birth.
At which stage in life do macrophages start to develop?
At 3 weeks of gestation.
At which stage in life do thymocytes start to develop?
At 7 weeks of gestation.
At which stage in life do follicular dendritic cells start to develop?
At 17 weeks of gestation.
At which stage in life do follicular B cells start to develop in the spleen?
At 19 weeks of gestation.
At which stage in life do T regulatory cells start to develop?
At 14 weeks of gestation.
At which stage in life do B regulatory cells start to develop?
At 24 weeks of gestation.
At which stage in life do neutrophils start to develop?
At 30 weeks of gestation.
How do the numbers of NK cells change with age from gestation to adulthood?
- NK cells increase with gestational age.
- After birth they are higher than at any subsequent time in life but have reduced cytotoxicity.
- Numbers reduce to normal adult levels by 5 years of age.
At which age are complement levels normal?
By the first few years of age.
At which stage in life does the spleen develop?
At 5 weeks of gestation.
From which anatomical site do the cells required for the haemopoietic function of the spleen arise?
The yolk sac wall.
At which stage in life does the spleen generate both red and white cells?
The 2nd trimester of gestation.
At which stage in life do haematopoietic stem cells migrate to the foetal liver?
At 5 weeks of gestation.
At which stage in life are B cells present in the liver?
At 12 weeks of gestation.
From which anatomical structure does the thymic epithelium develop?
The 3rd pharyngeal arch.
At which stage in life does the thymic epithelium develop?
At 6 weeks of gestation.
From which embryological tissue layers do the cortex and medulla of the thymus develop?
- The cortex develops from the ectoderm.
- The medulla develops from the endoderm.
At which stage in life do lymphocytes migrate to the thymus?
At 8-9 weeks of gestation.
At which stage in life is positive and negative thymic selection possible?
Very early in utero.
How does the mass of the thymus change with age?
- At birth, it is 10-15g.
- It grows to 30-40g by the age of puberty.
- After puberty, involution occurs and it is replaced by adipose tissue such that by middle age, it is approximately 10g.
What is DiGeorge syndrome?
A heterozygous chromosomal deletion which causes a defective development of the pharyngeal pouches and a subsequent T cell deficit due to a reduced size of the thymus.
What might be found on a full blood count of a person with DiGeorge syndrome?
A range from slightly reduced T cell numbers to severe combined immunodeficiency.
Give an example of an organ other than the thymus that reduces in size due to DiGeorge syndrome.
The parathyroid gland.
What causes the initiation of expression of toll-like receptors in the intestines?
The gut microbiome bacteria stimulating gut lymphoid tissue.
List 7 anatomical sites in which intraepithelial lymphocytes can be found.
1 - The intestines.
2 - The biliary tract.
3 - The oral cavity.
4 - The lung.
5 - The upper respiratory tract.
6 - The reproductive tract.
7 - The skin.
How do levels of intraepithelial lymphocytes change?
- Greatest at birth.
- Slowly decreases with age until old age.
What is the primary function of intraepithelial lymphocytes?
They play an important role in gut tolerance of food and the microbiota.
List 3 immunological causes of miscarriage.
1 - Systemic lupus erythematosus (due to autoantibodies).
2 - Thyroid disease (due to autoantibodies).
3 - NK cell abnormalities.
List 3 maternal immune cells that are present at the endometrium.
1 - NK cells.
2 - Macrophages.
3 - T regulatory cells.
List 5 processes that allow the foetus to tolerate the maternal immune system.
1 - Synthesis of immunosuppressive molecules by the placenta.
2 - Downregulation of MHC class I to reduce cytotoxic responses.
3 - Repression of paternal MHC class II in trophoblast cells.
4 - Depletion of tryptophan by IDO and subsequent inactivation of T cells.
5 - Downregulation of TNF superfamily.
List 6 immunosuppressive molecules produced by the placenta.
1 - Progesterone.
2 - PGE2.
3 - Anti-inflammatory cytokines.
4 - IL-4.
5 - IL-10.
6 - Complement regulatory proteins.
List 3 main immunological defence mechanisms of newborn children.
1 - Innate immune system.
2 - Mucosal immunity by colonisation of the gut by commensal bacteria.
3 - Passively acquired transplacental antibodies.
Which antibody crosses the placenta?
IgG.
What is the half-life of IgG?
21 days.
What is hypogammaglobulinaemia of infancy?
An immune immaturity of IgG (gamma globulin) as levels come up more slowly during gestation.
What causes haemolytic disease of the newborn?
Where a foetus has both a different blood type and Rh factor (a surface protein on erythrocytes).
Which disease occurs due to differing Rh factor between a mother and a foetus?
Rhesus incompatibility.
What proportion of pregnancies involve rhesus incompatibility?
10%.
List 4 signs of haemolytic disease of the newborn.
1 - Haemolysis.
2 - Jaundice.
3 - Swollen liver.
4 - Liver failure.
How is neonatal lupus caused?
When maternal IgG antibodies cross the placenta and attack the myocardial conduction system.
List 3 signs and symptoms of neonatal lupus.
1 - Skin rash.
2 - Hepatitis.
3 - Thrombocytopenia.
List 3 signs of transplacental toxoplasmosis (a parasitic disease).
1 - Chorioretinitis (inflammation of the choroid and retina).
2 - Intracranial calcifications.
3 - Hydrocephalus.
List 5 signs of transplacental rubella infection.
1 - Deafness.
2 - Cataracts.
3 - Heart defects.
4 - Intellectual disabilities.
5 - Liver damage.
List 3 signs of transplacental cytomegalovirus infection.
1 - Low birth weight.
2 - Jaundice.
3 - Enlarged liver.
List 3 immune characteristics of breast milk.
1 - Antimicrobial.
2 - Anti-inflammatory.
3 - Immune-modulatory.
List 3 antibodies that are transferred in breast milk.
1 - IgG.
2 - IgA.
3 - IgM.
Give an example of a bactericidal protein that is transferred in breast milk.
Lactoferrin.
