Neonatal Immunity

Question 1

Immature immune system of neonatal animals

Answer 1

• Mucosal immune system is maturing
• Regulatory environment/Th2-bas of the immune system
• Reduced number of antigen presenting cells and CD4+ T helper cells
• Ineffective immune responses

Question 2

Impaired ability to respond to infection

Answer 2

• Depends on immune response needed; difficult to induce Th1
• Short-term duration
• Interference with maternal antibodies

Question 3

Neonatal environment characteristics

Answer 3

• T reg (fetus)/Th2-biased (mother) immune system
• High levels of IL-10 and high numbers of Tregs
• High levels of corticosteroids at end of pregnancy
• Inability to mount effective IFN-g responses
• Varying levels of passively transferred immunity (maternal antibodies, cytokines, chemokines, lymphocytes)
• Mucosal immune system functional, but still developing

Question 4

High levels of corticosteroids in neonates

Answer 4

• Parturition is triggered by stress of the fetus (high steroid levels) which can result in decreased immune function
• For first 3 days of life, circulating corticosteroids are immunosuppressive

Question 5

Maturation of neonate immune system

Answer 5

Includes exposure to new antigens, maturation of immune cells, differentiation into specific immune cells, immune training
- Largely driven by intestinal mucosa

** Animals raised in a germ-free environment fail to fully develop their mucosal lymphoid tissues (lamina propria is essentially empty)

Question 6

Types of immunity in newborn

Answer 6

1. Passive
2. Active

Question 7

Passive immunity in newborn

Answer 7

Antibody transferred from the mother to the offspring

Question 8

Active immunity in newborns

Answer 8

The newborns immune response to vaccination or infection

Question 9

Susceptibility of neonates

Answer 9

Initially, mother is helping to protect the newborn through her antibodies

As the animal is weaned, the maternal antibodies will begin to decreases, while the neonates antibodies are increasing slowly
- There is a window where the neonate is more susceptible to infection when their antibodies have not increased enough yet and mothers have dropped

Question 10

Antibodies received by endotheliochorial animals (dogs and cats)

Answer 10

Receive low amounts of IgG only (about 5-10% of maternal IgG levels)

Question 11

Antibodies received by syndesmochorial animals (ruminants)

Answer 11

No transfer of maternal Ig pror to birth

Question 12

Antibodies received by epitheliochorial animals (pigs and horses)

Answer 12

No transfer of maternal Ig prior to birth

Question 13

Transfer of maternal antibodies via Colostrum

Answer 13

1. Colostrum is first milk (thicker, more yellow, concentrated serum from mother, rich in maternal Ig). Must be absorbed within 6-24hrs after birth
2. Transported from intestine to the serum of the newborn (non-selective passive absorption occurs directly into lymph and bloodstream)
3. Serum antibodies can then be transported to all organs and surfaces
   - Maternal IgG are received by receptors on mucosal epithelial cells (Fc portion) allowing for re-secretion (transudate) of IgG from the blood onto the mucosal surfaces
4. Outcome is that antibodies against whatever the mother had been in contact with was then passed on to the newborn which prepares the newborn for the same environment and systemic infections as the mother

Question 14

Transfer of maternal antibodies via milk

Answer 14

1. Plasma cells migrate from mothers intestines into mammary gland at the end of gestation
2. Milk contains antibodies produced by plasma cells in the mammary gland
3. Milk ingested my newborn, and antibodies enter the intestines. Provides intestinal immunity to offspring. Now whatever the mom was encountering in her gut, the offspring now has the same protection

Question 15

How do the antibodies end up in the colostrum?

Answer 15

Active hormone-regulated transport of IgG into the colostrum via specialized receptors (FcRn) on the mammary epithelial cells

Question 16

Colostral IgG concentrations

Answer 16

5-10x higher than maternal serum

Question 17

Why can non selective absorption occur in newborn for initial 6-12 hours?

Answer 17

Epithelial layer of intestine is open in the first few hours after birth
- Tight junctions are not established

After a few hours, the intestinal epithelia will change so intact proteins can no longer get through

Question 18

Calves colostral immunoglobin distribution

Answer 18

If a calf receives 100gms of colostral immunoglobulin, then it re-secretes 2-4 gms/day of functional immunoglobulin into the gut

Question 19

What is the maternal immunoglobulins main goal?

Answer 19

To protect neonate from:
1. Septicemia and viremia
2. Enteric infections
3. Respiratory infections

Question 20

Failure of passive transfer (FPT)

Answer 20

Newborns that have low levels of maternal immunoglobulin in serum at 24hours of life

Question 21

Colostrum feeding window

Answer 21

There is a short period of time in which the calf can absorb the maternal antibodies from the mother. Earlier colostrum feeding is best

• Serum IgG declined from over 14g/L to less than 10g/L

Question 22

Contents of colostrum

Answer 22

1. Immune cells
2. Biologically active molecules

Question 23

Examples of biologically active molecules that can be found in colostrum

Answer 23

Provide non-specific protection against infectious agents either by inhibiting growth or direct lytic effects
- Lactoferrin
- Lactoperoxidase
- Lysozyme

Regulate gut epithelial development, stimulate cell growth and protein synthesis
- Insulin-like growth factor
- Epidermal growth factor
- Alpha lactalbumin
- TGF-beta, IL 1, CSF, IL6 and more

Question 24

Antibody composition in milk

Answer 24

• Ruminant milk is predominantly IgG
• Non-ruminant milk mainly IgA

Question 25

Where is most of the immunoglobulin in milk produced?

Answer 25

Locally produced by plasma cells in the mammary gland (Not much derived from serum like colostrum)
- Plasma cells originally migrated from the intestines at end of gestation (chemokine stimulated)

Question 26

Lactogenic immunity

Answer 26

Provides continued protection by binding to pathogens and neutralizing them before they can attach/invade intestinal cells

Question 27

Vaccinating mom to protect offspring

Answer 27

Can vaccinate mom before neonate is born to increase the maternal antibodies present and decrease the susceptibility that the neonate experiences during the “window”

• Window: period where maternal antibodies are decreasing and neonates immune system is being developed

Question 28

Interference of maternal antibodies

Answer 28

Maternal antibodies provide protection of the neonate for the first few months of life but they also interfere with active immunization
- The maternal antibodies will bind and destroy the vaccines

Often need multiple immunizations in neonates because their immune system is immature early on and due to the maternal antibodies interference

Question 29

Effective vaccination time in neonates

Answer 29

• Time of effective vaccination of young is inversely correlated to the titer of antibody (level of colostral protection) found in the mother
• Often do 3 vaccines (one often doesn’t work, second will work, 3rd boosts). Ensures that the maternal antibody interference is not effected immunity