12b – Neonatal Immunity

Question 1

Immune system in neonatal animals:

Answer 1

-immature
-mucosal immune system is maturing
-regulatory environment/Th2-bias of the immune system
-reduced number of APC and CD4+ T helper cells
*ineffective immune responses

Question 2

Ability to respond to an infection (vaccination):

Answer 2

-impaired
-type of immune response (difficult to induce Th1)
-short-term duration
-interference with maternal antibodies

Question 3

Characteristics of neonatal environment:

Answer 3

-Treg (fetus)/Th2-biased (mother) immune system
-high levels of IL-10 and high numbers of Treg
-high levels of corticosteroids at end of pregnancy
-inability to mount effective IFNg responses (need for Th1)
-varying levels of passively transferred immunity
-mucosal immune system functional but still developing

Question 4

Varying levels of passively transferred immunity:

Answer 4

-maternal antibodies
-cytokines and chemokines
-lymphocytes

Question 5

Parturition:

Answer 5

-triggered by ‘stress’ of the fetus (high steroid levels)
>can result in decreased immune functions

Question 6

For first 3 days of life:

Answer 6

-circulating levels of corticosteroids are immunosuppressive

Question 7

Human babies and immune response:

Answer 7

-takes a year before they mount a response similar to adults

Question 8

What largely drives the development of the newborn immune system?

Answer 8

-intestinal microbiota
>exposure to new antigens
>maturation of immune cells
>differentiation into specific immune cells
>immune training

Question 9

Absence of intestinal microbiota:

Answer 9

-‘germ-free’
*fail to fully develop their mucosal lymphoid tissue

Question 10

Immunity in new born:

Answer 10

1. Passive
2. Active

Question 11

Passive immunity:

Answer 11

-Ab (immunoglobulin) transferred from the mother to offspring

Question 12

Active immunity:

Answer 12

-response to vaccination or infection

Question 13

Susceptibility to infections in neonate:

Answer 13

-at first: high maternal Abs, gradually decrease
-middle: low maternal Abs and low neonatal Abs *MOST SUSCEPTIBLE
-later on: neonatal Abs reach ‘protection’ levels and higher

Question 14

The route of passive transfer of maternal immunity:

Answer 14

-determined by nature of placenta

Question 15

Endotheliochorial passive transfer:

Answer 15

-endothelium of mother is in contact with chorionic epithelium
-dogs and cats
-allows transfer of LOW amounts of IgG only
-newborns: 5-10% of maternal IgG levels

Question 16

Syndesmochorial passive transfer:

Answer 16

-chorionic epithelium is in contact with uterine tissues
-ruminants
-NO transfer of maternal IgG prior to birth

Question 17

Epitheliochorial passive transfer:

Answer 17

-fetal chorionic epithelium is in contact with intact uterine epithelium
-pigs and horses
-NO transfer of maternal IgG prior to birth

Question 18

Transfer of maternal Abs via:

Answer 18

1. Colostrum: ‘systemic’ and ‘local’ immunity
2. Milk: ‘local’ immunity

Question 19

Colostrum:

Answer 19

-first milk
-concentrated serum from the mother (yellow)
-very rich in maternal Ig
-only be absorbed within 6-24 hors after birth
-transported from the intestine into the serum of the new born

Question 20

Colostral IgG concentrations:

Answer 20

5-10x higher than maternal serum
*active hormone-regulated transport of IgG into colostrum via FcRn on mammary epithelial cells

Question 21

Colostrum consumption results in:

Answer 21

-serum Abs from mother ended up in serum of the offspring
>can be transported to other organs and surfaces

Question 22

Colostrum consumption outcome:

Answer 22

-Abs against whatever mom had in her serum are transferred to serum of newborn
-preparing newborn for same environment and systemic infections as the mother

Question 23

Drink colostrum within first 6-12/24 hours:

Answer 23

-intestinal epithelium of neonate non-selectively allows absorption of intact immunoglobulin directly into lymph and bloodstream
>transported to all sites in body (Ex. mucosal sites)

Question 24

Epithelial layer is ‘open’:

Answer 24

-tight junctions between the cells is not established
-within hours this changes and the intact proteins are no longer absorbed

Question 25

Gut absorption of IgG:

Answer 25

-declines rapidly after birth

Question 26

‘system’ and ‘local’ protection of colostrum:

Answer 26

-maternal IgG circulate in blood of newborn
-receptors on mucosal epithelial cells for Fc portion of IgG allow RE-SECRETION (TRANSUDATE) IgG from blood onto all mucosal surfaces

Question 27

Calf that receives 100g of colostral immunoglobulin:

Answer 27

-re-secretes 2-4g/day of functional immunoglobulin into the gut

Question 28

Goal of colostrum:

Answer 28

-transfer sufficient levels of maternal immunoglobulin to protect from
>septicemia and viremia
>enteric infections
>respiratory infections

Question 29

Newborns with low levels of maternal immunoglobulin in serum:

Answer 29

-have “failure of passive transfer’ (FPT)
>measured this at 24hrs of life

Question 30

Colostrum is more than immunoglobulin:

Answer 30

-also has immune cells and biologically active metabolites

Question 31

Cells/molecules in colostrum that provide “nonspecific” protection:

Answer 31

-lactoferrin
-lactoperoxidase
-lysozyme
*either inhibit growth or direct lytic effects both locally and systemically

Question 32

Other ells/molecules in colostrum roles:

Answer 32

-regulate development of gut epithelial cells
-stimulate cell growth and division
-stimulate protein synthesis

Question 33

Other cells/molecules in colostrum examples:

Answer 33

-insulin-like GF
-epidermal GF
-alpha lactalbumin
-TGF-beta, IL-1, CSF, IL6 and others

Question 34

Milk:

Answer 34

-contains Abs produced by plasma cells in the mammary gland
>migrated from mother’s intestine into mammary gland at the end of gestation
*local immunity in the gut

Question 35

Ruminant milk Ab composition:

Answer 35

-predominately IgG

Question 36

Non-ruminant milk Ab composition:

Answer 36

-mainly IgA

Question 37

Most Ig in milk is:

Answer 37

-local produced in mammary gland
>not derived from serum

Question 38

How much ruminant IgG in milk is from serum:

Answer 38

-only about 30%

Question 39

Milk consumption results in:

Answer 39

-offspring getting intestinal (local) immunity from the mother through the milk into its own gut
*whatever mom has been dealing within the gut is now transferred to gut of offspring
>assumes neonate needs to deal with same pathogens and microbes as mom

Question 40

Lactogenic immunity:

Answer 40

-continued protection by binding to pathogens and neutralizing them before they can attach/invade intestinal cells
-depends on IgA (IgG in ruminants)

Question 41

What mediates migration of Ig in lactogenic immunity?

Answer 41

-chemokine (CCL28)

Question 42

Maternal antibodies and active immunization:

Answer 42

-maternal antibodies provide protection for neonate for first few months of life
*interfere with active immunization
>bind to vaccines and neutralize/destroy the vaccine

Question 43

Multiple immunizations for neonates:

Answer 43

-immune system is immature early on and needs time to mature
-maternal Abs interfere with vaccines

Question 44

Time of effective vaccination of the young:

Answer 44

-inversely correlated to the titre of Ab found in the mother (levels of colostral protection)
>don’t always get titres, so we just vaccinate multiple times

Question 45

Multiple puppies multiple times:

Answer 45

-1st: didn’t work
-2nd: likely worked
-3rd: booster