Neonatal immunity (Path)

Question 1

Foetal immunity to neonate

• 1st organ
• does fetus require it?

Answer 1

1. thymus first organ identified
2. Cell mediated immunity develops at same time Ab production
3. foetus doesn’t require a functional immune system
4. Neonate in most species has a well developed immune system, just not 100% functional
5. development completely required antigen stimulation- no antigen exposure = no final development
6. MDA are essential

Question 2

Phagocyte development in neonate

Answer 2

• Circulating levels of macrophage, neutrophils (phagocytes) etc are normal but functional in neutrophils impaired

Believe could be due to:
1. Maternal hormones which flood the system at birth provoke an anti imflammatory effect, imprinting a non responsive effect in neonatal neutrophils. Also N are short lived (half life 8 hrs)

2. At birth complement isn’t fully functional and for correct neutrophil function we need a fully functional complement system. Could cause this reduced neutrophil function

Question 3

Risks of intrauterine infection

Answer 3

o Pathogens exploit the underdeveloped/developing foetal immune system.

Question 4

Risk to unborn animal to neospora canium

Answer 4

Infected in ……

1. 1st Trimester – Foetal not developed = absorption of mummified foetus.
2. 2nd Trimester – Foetal not developed/ see large degree Maternal Inflammation which causes abortion due to rupture across placental structures
3. 3rd Trimester – Foetus immunocompetent (almost fully developed); parasite invasion/distribution limited = congenital infection (we see some necrosis but much more limited as parasite invasion is limited – to CNS and liver – live calf but is congenitally infected)

Question 5

Talk about Bovine Viral Diarrhoea virus (BVD)

Talk about the 2 stains effect on gestation

Answer 5

2 stains of virus:

1. Non cytopathic (doesn’t kill cells)
   - Infection up to mid way through gestation = tolerance and persistent infection. So becomes established within foetus but both mother and calf become tolerant
   - If later in gestation, as calf begins to have own fully developed immune system = born normal. No tolerance and somewhat clear of infection.
2. Cytopathic (kills cells)
   - Highly pathogenic.
   - Same pattern as with neospora caninum – up to almost 3rd trimester we see abortion, mummification, late 2nd, early 3rd we see malformations
   - Late 3rd trimester = normal animal born due to foetal competence

Question 6

Risk to unborn animal to Bovine Viral Diarrhoea virus (BVD) - what does tolerance to BVD mean to calf?

Answer 6

1. been challenged with NON cytopathic BVD = tolerant or persistently infected calf between 0 and mid gestation. (if after than normal)
2. Tolerant calf - When later challenged later with cytopathic BVD – severe disease. NO benefit from previous immune exposure
   • Infection in utero means calf will succumb if challenged – poor response
   • By 3rd trimester foetus preventing abortion, death or persistent infection but sees no benefit in terms of later life infection

Question 7

The need for passive transfer and MDA

Transfer of immunity to offspring colostrum and placenta…..

Answer 7

• Neonatal immunity is always a primary response (first time immune system has seen those antigens. No secondary immune response therefore: need MDA

1. Primates placental transfer occurs (IgG only)
2. dogs and cats 5% placental, 95% colostrum
3. Ruminants, pigs, horses 100% colostrum NO IN UTERO Ab transfer

Question 8

Relative components of colostrum

Answer 8

1. Colostrum is produced in mammary glands in last few weeks of pregnancy
2. Due to hormonal changes there is an active uptake
   of Igs from blood to mammary gland under hormonal influence (oestrogen & progesterone) + local production
   • Main colostral antibody isotype is IgG in first few hrs
   • As colostrum changes to milk get reduced IgG content; proportionally more IgA
   • Colostrum content – all IgG, most IgM and half IgA are derived from serum
   • Colostrum also contains growth factors (cytokines) and other hormones

Question 9

Describe process that governs transfer of colostrum

Answer 9

• Colostrum ingested and passes into GI tract where enzyme levels are low/blocked so that proteins can reach small intestine
o Newborns have specialised Fc receptor (FcRn) on intestinal epithelia (only briefly for about 24hrs)
- FcRN reaches peak expression in ruminal intestinal epithelia 6 hrs after birth so IgG bulk must be in by 6 hrs!
• In GI tract, Igs are bound, actively pinocytosed and quickly reach lymphatics and circulation
• So, in first few hours of life, newborn receives large amount of Igs from mother – rapidly seen in plasma Ig levels as maternally derived antibodies (MDA) = gets a lots of IgG into circulation
• Intestine is only permeable for short period, declines after 6 hrs. By 24hrs almost nil absorption.

Question 10

Species differences in colostrum

Answer 10

1. new born calf is a temporary monogastric
   • Horse and pig: IgG and IgM selectively absorbed to blood; IgA stays in intestine
   • Ruminants: all Igs (Ab) go into blood
   • Calves and foals need minimum 1L colostrum within 6 hrs of birth
   • Cow has oesophageal groove at birth (for 20 days) to divert colostrum and milk straight to abomasum, avoiding rumen and omasum. Thus, colostrum/milk avoids souring in rumen and is readily absorbed, including Igs.

Question 11

When is the peak level of circulating Ab?

What deos igG prevent and IgA

Answer 11

12-24 hrs after birth

IgG prevents septicaemia
o IgA prevents enteric disease (diarrhoea induced by crypto spiridium)

Question 12

Examples of how failure of passive transfer can occur

Answer 12

1. production - premature alctation/ dripping
2. Ingestion - multiple births, damaged tear
3. Absorption, esp horses. 25% foals fail to upregulate FcRn so can’t acquire enough colostrum Ab across intestine

Question 13

How to diagnose failure of passive transfer

Answer 13

• Hydrometer/Colostrometer
• Measures specific gravity.
• Correlates with:
• Protein
• IgG content

Question 14

Treatment failure passive transfer

Answer 14

1. additional colostrum by bottle of nasogastric tube IF < 15 hrs
   6-12 hr window post birth for active transport of MDA across intestine due to FcRn receptor on intestinal epithelia.
2. Over 15 hrs use IV plasma with high specific Ab titres
3. DANGER = o Both must be free of anti-erythrocyte antibodies (anti RBC Ab)
    No mismatch of donors
   o Northern Ireland example showing the danger of passive transfer – infectious anaemia outbreak based on donor bank.

Question 15

Relationship between vaccine and MDA

Answer 15

1. MDA via passive immunisation inhibits development of immune response
2. if vaccinated and MDA too high or Ab in general too high (e.g. after infection) then vaccine destroyed

Question 16

Why do Non-suckled calves make antibodies sooner than suckled calves

Answer 16

o Maternally derived antibodies (MDA) in suckled calf inhibit Ab production

Question 17

What are the key issues concerning vaccination efficacy in very young animals?

Answer 17

• MDA inhibit endogenous neonatal Ig synthesis in neonate
• Prevent successful vaccination of young animals
• Window of susceptibility is 2-3 week when the mothers Ab in pup stops being protective, continues to drop, below level at which it no longer interferes with protective effect of vaccination
• Only become significantly low by 10-12 weeks before window definitely gone – keep pup indoors and away from other dogs. Until first vaccine
• Remember there is no limit to the amount of antigens we can expose a neonate to due to the diversity of T and B cell receptor
• Neonate in good health = no reason why T and B cells cant handle exposure