Immunity in foetus and newborn Flashcards
what makes up the innate system
NK cells, macrophages, grnaulocytes dendritic cells
what does the innate system recognise
recognize a limited number of PAMPs
what makes up the adaptive system
T and B cells
what does the adaptive system recognise
recognize millsions of different antignes
what is in the
- blood lymph interstitial spaces
- epithelial surfaces
- cytoplasmic
- vesicular
– antibodies, complement, phagocytosis
– antibodies IgA, antimicrobial peptides
- cytotoxic T cells, NK cells
– T cell dependent macrophage activation
what are the CD4 cells that the naive THO cells can differentiate into
TH1
TH2
TH17
TREGS
what response does TH1 have
cell mediated response
what response does TH2 have
humeral response
what is the B cell activated by and what helps it become a plasma cell
- B cell is activated by antigen
- T cell helps it turn into the plasma cells
what is the first body produced
Intially IgM is produced then IgA, IgG, IgE antibody switching
what does overproduction of IL4 drive
allergies and asthma
describe how overproduction of IL4 drives allergies and asthma
IL4 activates TH2 produce IL4 – postivie feedback loop
IL4 produces IgE this binds to mast cells and arm the mast cells
2nd exposure - causes grnaulsoa of the mast cells and an allergy reaction
what produces TH1
- IL12 cause the production of TH1
- this then causes the production of IFN gamma and TNF alpha
what are the properties of MHC genes
polygenic
polymorphic
what does polygenic mean
There are different version of these
what does polymorphic mean
this is in the population there is many different veriosn of these molecules, likely hood that mother and father will have different MHC genes so we inherit these different genes, thus we are most likely be heterozygous for these
what does MHC polymorphism lead to
- means that allografts are usually like to be rejected
- this is due to immune recognition of MHC antigens that are present in the donor but not in the recipient
when was the first successful kidney transplant
First successful kidney transplant in 1954 between twin brothers
describe the problem of MHC and babies
- baby gets half MHC from mother and half from father
- thus it does not match mothers MHC
why is the foetus not usually rejected
- this is because the trophoblast in the placenta has protective features
- There are HLA G molecules inhibits NK cells from working
- Lot of production of antiinflammation cytokines such as TGF beta IL10
- No classic MHc moelcules leads to lack of T cell recognition
- IDO – this depeletes tyrptohan which inhibits T cell activation
- Sometimes these meahcnisms don’t work and lead ot rejection and may contribute to repeated pregnancy loss
where do all of the immune cells come from
All of the immune cells come from haemopiotic stem cells, give rise through the differentiation process and become progressively more committed to different fates
describe the changes in the site of haematopoiesis through development
- start in the yolk sac
- fetal liver and spleen
- bone marrow
where does adult haematopoiesis happen
happens mainly in bone marrow of: skull, ribs, sternum, spine, pelvis & femurs
what are the cellular components of the immune system that humans are born with
- Abundant naïve T cells and B cells in lymph nodes and spleen
- Few plasma cells or memory T cells – usually little exposure to antigens in utero
when does T cell production occur
T cell production begins early in gestation (8 weeks).
removing the thymus of a baby at birth …
Removing the thymus of a baby at birth (eg heart surgery) cause no great problems as the thymus has already produced enough T cells– already sufficient cells
what are the characteristics of innate immunity in early life
- Lower responses to PAMPs
- Reduced DC numbers and function
- Hypo-responsive NK cells
- Lower complement activity
what are the characteristics of adaptive immunity in early life
Skewing to Th2 responses (& Treg) instead of TH1 responses
Poor antibody responses:
- Poor response to T cell help that B cells need to make antibodies
- Reduced plasma cell survival
why is there poor antibody responses
- Poor response to T cell help that B cells need to make antibodies
- Reduced plasma cell survival
describe the serum antibody level changes with age
Newborns are born with lots of antibody which then disappear but then begins to reappear with childhood
IgG higher in newborn
IgM and IgA are lower and rise
how is IgG passively transferred
Maternal IgG antibodies are able to cross the placenta to protect the foetus/newborn
what is the window of injection
As maternal antibodies decay away there is a ‘window’ before the child’s own IgG production starts - risk of infection
describe the characteristics of premature babies and immunological maturity
lower IgG and longer to immunological maturity
at brith the levels of serum IgG are ..
At birth, levels of serum IgG are higher in the neonate than in the mother
when can IgG be detected in foetal circulation
IgG detected in foetal circulation from ~13weeks rising steadily thereafter
Similar range of antigen specificities in mother & foetus
how is IgG transferred across the placenta
gG gets from the mother to the fetus – active process, passive antibody as it is not made by the fetus or baby, this uses a receptor called the neonatal FcR receptor
Transfers it across into the fetal cricualtion
The neonatal FC receptor is expressed in adults, has another really important function
What does FcRN do in adults
sequesters IgG from degradation in endothelial cells & prolongs antibody half-life
describe rhesus positive
Multiple Rhesus (Rh) blood group antigens
RhD is the most immogenic
People can be RhD+ (have the antigen on red cells) or RhD- (lack the antigen)
Potential issue when RhD+ fetus in RhD- mother (baby’s RhD comes from father)
can be a problem in secondary pregnancy as it causes the production of anti rhesus antibodies which can attack the babies red blood cell and leads to become being destroyed
how do you treat rhesus disease
Prophylaxis with antibodies to RhD (anti-D/RhoGAM)
Disease prevented if mother is passively transfused with anti-D antibodies during first and subsequent pregnancies – prevents activation of her B cells specific for RhD
how does Anti D work
One way RBC destruction rhesus postivie red cells, bidning of the antibody means that the red blood cells is degraded befor eit has a chancge
Epitope masking – hides the bits of it that will be recognized from the maternal immune system
Inhibition of signaling, anti D are detected by inhibitor detectors on the B cell which blocks the b cell from self responding to those – it has signaling motives cause ITAMS which act to inhibit the anti D
describe graves disease
- this is antibody mediated autoimmunity
- Signs of autoimmunity appear in the foetus due to transfer of maternal antibodies
how does graves disease resolve itself
Symptoms resolve with catabolism of maternal antibodies but in some situations damage has already occurred (eg heart damage in babies born to mothers with SLE or Sjörgen’s syndrome)
what does IgG protect
gives systemic protection but does not protect mucosal surfaces (eg the gut)
what antibody is in breast milk
IgA
what protection does IgA give
In adults, mucosal surfaces are protected by dimeric IgA antibodies secreted across the epithelium
what is secretory IgA
Poly Ig eceptor transfers and releases it to the lumen of the intestines, little bit of the polymeric Ig RECPETOR remains ttached to the igA prevents it being degraded by proteolysis, makes it hang around a bit longer
what does IgA do and not do
Does not:
activate complement
recruit inflammatory cells
opsonise for phagocytosis
Does:
Exclude
Agglutinate
what does IgA protect against and how much passes to the milk
- 25-0.5g/day pass from mother to baby in milk
- Mostly reactive to gut microbes
- Some uptake into rest of body
breastfeeding may…
protect against allergies
what are babies susceptible to infection
- when maternal antibodies are decaying and immune system hasn’t reached full function
what susceptibility to infection can cause mortality from what disease
influenza
what can cause the development of allergies
Skewing of CD4 T cell responses towards Th2 may favour development of asthma or allergy in some individuals
Effective shift towards Th1
responses in early life may protect
why don’t vaccines not work in the neonatal immune response
Immaturity of the infant
immune system
- Interfering effects of maternal antibody
- masking of epitopes
negative signalling
what is required for vaccinations to work in the neonate
Often a balance between obtaining optimal responses ( maturity of immune system/ decay of maternal antibodies) and minimising period of susceptibility
why is the immune system in the newborn the way it is
A ‘hangover’ from pregnancy and the need for the foetus to co-exist with non-inherited maternal antigens
To foster colonisation with commensal micro-organisms without a lot of inflammation
when does colonisation of bacteria begin
The foetus is sterile but bacterial colonisation begins at birth
Reach 1014 bacteria in large intestine (1011-1012 per ml) ~1Kg
what are the benefits of the colonisation of the neonate
Required for normal development of the immune system
Digest of complex carbohydrates
Compete with pathogens
the host immune response….
The host immune response can shape the composition of the microbiota
how is the immune system shaped by the microbiota
- peyers patch
- lymphocytes in villus
how to the maternal antibodies affect immune responses to colonising bacteria in early life
In the offspring colonization of the mother only there during pregncy, transfer of antibodies that recongise these organism innate immune system gets a bit of a boost and produces antimicrobial peptides which can be important in controlling microbiome whereas the adaptive immunity decreases
what is normal microbiota are associated with
- normal microbiota is associated with lots of good outcomes whereas a dysregulated micorbtioa leads to lots of inflammatory conditions
- Events early in life determine whether the microbiota are successful estbalised
