Development of the immune system Flashcards
Why is the immune system in children dampened compared to adults?
- immunosuppressive environment of the womb
= womb was sterile
= baby didnt need active immune system
- at birth baby is exposed to many antigens- having a reaction to all of them, would be harmful to baby
Why was the womb immunosuppressive?
- so maternal immune system doesn’t reject antigens of foetus AND VICE VERSA
When the baby is born why are they vulnerable to pathogens?
- dampened immune system
- not good response to vaccines when born
What is immunoessence in pneumonia?
- common in first few months of life
- common in elderly again
- immune system changes with age
- pneumococcal disease is an opportunistic infection
What are the 2 parts of the immune system?
- non antigen specific
- antigen specific
What is the non- antigen specific immune system made up of?
- barriers = skin/mucosal surfaces
- cellular components = neutrophils, monocytes, macrophages NK cells= PHAGOCYTOSIS
- soluble components = complements (opsonization) and cytokines (cell signalling)
Why do preterm babies have higher risk of infection?
bc thin skin
easy to penetrate barrier
How do monocytes, macrophages etc detect pathogens?
WBC have TLR which detect PAMP on bad guys
What is antigen specific immune system made up of?
B cells
T cells
What are B cells?
- have antibodies on them
- specific for antigen
- millions of B cells with diff antibodies respond to diff antigens
- can produce memory cells
What are the 2 types of T cells?
- CD4+ T helper
- CD8+ cytotoxic cells
What are CD4+ T helper cells?
- dendrites present antigens to these cells through their MHC
- immature T helper cells get activated
- help activate CD8+ T cytotoxic cells
- also help antibody class switching in B cells
- memory T helper cells produced
What are CD8+ cytotoxic cells?
- cells infected by viruses and bacteria present antigens to these
- leads to their activation
- chemicals from T helper cells help mature the cytotoxic T cells which can then attack infected body cells
What is a primary lymphoid organ?
- Thymus= in thorax, T cells develop
- Bone marrow= stem cells giving rise to blood cells (e.g. T and B lymphocytes)
What is a secondary lymphoid organ?
- SPLEEN
= filter blood
= remove old damaged RBC
= remove infec agents- use them to activate lymphocytes - LYMPH NODES
= in subcut tissue - PEYERS PATCHES
= in intestine
= filter out dead cells - LYMPHATIC VESSELS
= collect lymph fluid that has leaked out from blood into tissues
Why do people without a spleen have high infection rate and by what in particular?
- high infection risk by encapsulated bacteria
e. g. pneumococcus and meningococus
What are the phases the development of the immune system can be divided into? MHSM
- MESOBLASTIC
- HEPATIC
- SPLENIC
- MYELOID
What happens in the mesoblastic stage?
MESOBLASTIC:
- 10 weeks
- production of haematopoietic cells in the yolk sac
- haematopoeitic cells = precursors for all the blood cells including lymphocytes (B and T cells)
What happens in hepatic stage?
- happens in liver
- begin 6-8 weeks gestation
- continue till shortly after birth
What happens in the myeloid phase?
- happens in bone marrow
- 10-12 weeks gestation
- by 20 weeks its a major blood cell forming site
How do T cells develop?
- develop in bone marrow
- migrate to thymus
- go through gene rearrangement and becomes T cells
What happens in the thymus?
- T cells undergo gene arrangement
- develop specificity
What is the thymus and where is it derived from?
- organ
- derived from 3rd pharyngeal pouch
- located in thorax
- thymus has cortex and medulla
- cortex has THYMOCYTES (which are T lymphocytes)
- medulla has dendrites, macrophages, and the Hassall’s corpuscle (function unknown)
How does the thymus develop?
- 8 weeks gestation= thymus colonized by haematopoietic stem cells (precursors for blood cells like lymphocytes)
- 20 weeks of gestation= thymus completely developed
- 16-20 weeks gestation= T cells go from thymus to peripheral bodies
How are Th1 lymphocytes produced?
- Th1 lymphocytes are produced by exposure to IL12 and IL18
- secrete IFN gamma which activates macrophages to kill intracellular bacteria
What secetes Th2?
IL4
- activates macrophages
- kills parasitic worms
What produces Th17 and IL22?
- exposure to IL6 and TGFB
- which attract neutrophils and induces antimicrobial peptide production
What is Treg lymphocyte produced by?
- exposure to retinoic acid and TGFB
- inhibit immune responses through IL10
How do B cells develop?
- develop in bone marrow
- mature in bone marrow
- migrate to 2ndary organs
What do B cells express?
- immunoglobulins on cell surface membranes (antibodies) = specific to a certain antigen
- many diff types of B cells= many diff types of Ig
- done through gene rearrangement
What happens when an immature B cell encounters an antigen?
- once the immature B cell encounters an antigen which matches the Ig on top of it
- matures
- replicates
Newborns are deficient in self-generated antibodies and are thus in an immunosuppressant state- How do you sort this out?
- transplacental active transfer of maternal IgG antibody
= last trimester = active transport of IgG from mum to foetus
= IgG half life is a month
- Secretory IgA in breast milk
= important to coat mucosal surfaces= prevent things like gastroenteritis
When does the baby produce its own antibodies?
3 months
How do babies develop antibodies (in what order?)
- IgG production increases slowly with IgG 1 and IgG 3 2. IgG 2 and IgG 4
- IgA reaches adult levels the latest
At what week are cellular components of non antigen specific component of the immune system seen?
31 weeks gestation
Granulocytes are high in numbers in newborns but less effective than adults. Why?
- reduced motility (movement)
- cannot cross the blood vessels’ endothelial layer
- BUT their adherence and phagocytosis is similar to an adult
HIGH GRANULOCYTE NUMBER BUT LOW SUPPLY
Why are bacterial infections more likely in babies?
- increased susceptibility to bacterial infections such as group B streptococcus
- low qualitative and quantitative (less number low quality)
- AB deficiency
- complement protein deficient
- less phagocytic cells at infection site
Why are viral infections more likely?
- antibody deficient
- less NK cells
- low cytokines
- low macrophage activity
- low T cell cytotoxicity
How do we protect newborn infants?
- give antibiotics/antivirals at any sign of infection
- wash hands
- encourage breastfeeding- IgA
- give mother important vaccinations so antibodies are passed down to child
- give infant vaccinations when required
Why is breastmilk good in infants?
breast milk also contains:
- macrophages, neutrophils and lymphocytes
- complements which help with opsonization
- lysozyme which attacks bacterial cell walls
- lactoperoxidase which is an antistreptococcal agent
- lactoferrin which inhibits growth of bacteria
Why dont you give vaccinations to newborns?
- maternal Ig come in the way
- poorly developed immune system when born
Why do you give BCG vaccine at birth?
- for Tb
- elicits a cell mediated response
- babies have stronger cellular response than a humoral response (antibody response)
