Fetal and neonatal immunity Flashcards
Immune system development
The thymus develops first, followed by secondary lymphoid organs
B cells appear soon after the spleen and lymph nodes have developed
Cell-mediated immune responses and antibody production are not usually found until late in fetal life, if at all
TCR diversity is limited in the fetus and neonate, low cytokine production
When born, basic immune components ready to go, but not working totally yet
Calf’s immune system development
Conception 41 days- thymus 45 days- blood lymohocytes 56- bone marrow and spleen 59 IgM positive cells 60 lymph nodes 130 serum iGm 135 igg positive cells 145 serum igG
The immune system and intrauterine infection
The fetus is less capable of mounting IR- adaptive immune system is not fully functional- cannot generate proper response from beginning
Mild or innaparent infections in the mother can be sever or lethal in fetus (blue tongue virus, infectious bovine rhinotracheitis, toxoplasmosis)
The response to infection is determined by the state o immunological development of the fetus
Bovine viral diarrhea: noncytopathic
Noncytopathic BVD: can result in tolerance and persistent infection; normal
If exposed in process of producing first T cells, T cells will think BVD is self
Pregnant cows infected with a non-cytopathic BVDV early in conception up to 120 days will give birth to calves that are tolerant to BVDV and persistently infected
Cows infected with a non-cytopathic BVDV between 120-200 days will give birth to normal calves
Bovine viral diarrhea: cytopathic
Cytopathic BVD is more pathogenic- can result in abortion, resorption, mummification; malformations; normal
Infection of pregnant cows with a cytopathic BVDV within the first 100 days of conception will lead to abortion, resorption or mummification of the fetus
Malformations may occur in calves originating from mothers infected with cytopathic BVDV between 100-150 days from conception
Calves from mothers infected with cytopathic BVDV after 150 days from conception may be born normal
Immune response on newborn mammals
Birth: animals move from a sterile environment to one with many pathogens
Capable of mounting innate and adaptive IR, however, adaptive mechanisms are not full functional- will respond but will be slow and ineffective
Any adaptive immune will be a primary response
-slow response and low concentrations of antibodies
-innate IR is critical for survival in the first weeks of life
The newborn relies on passive immune transfer from the mother
Innate immunity on Newborn mammals
Several antimicrobial molecules
TLR is working
Neutrophils- deficient bactericidal activity associated with high levels of cortisol at birth
Serum deficient in C3 and complement components-C3 in newborn piglets reaches adult levels by 14 days of age
Macrophages present but immature-capable of phagocytizing bacteria, but less efficient at killing, until after 7-10 days
Fewer NK cells- respond more strongly to IL-2 or IL-15 and are more cytotoxic- v effective
Adaptive immunity on newborn mammals
Responses tend to be predominantly Th2 based- more shifted toward Ab production instead of cell immunity
Delayed development of IL-12 producing DC1
Activities of IL-4 and IL-13 from CD2
Newborn foals are unable to express IFN-y at significant levels
-associated with placental damage
-6-12 months to reach adult levels
Higher lymphocyte counts than adults (dogs and cats)
-low CD8+ count
Immune response on newborn mammals
Born with immune system thats ready but not full effective yet
Transfer of maternal antibodies- dependent on the type of placenta
Hemochorial
Primates
Allows maternal IgG transfer (not IgM, IgA, or IgE)
Endotheliochorial
Dogs and cats
5% to 10% of IgG is directly transferred from the mother to the puppy or kitten,
Mostly through colostrum
Syndesmochorial
Ruminants and Epitheliochorial- horses and pigs
No transplacental passage of Ig molecules
Transfer entirely dependent on the colostrum
Composition of colostrum and milk
Ruminant colostrum will have high IgG as will ruminant milk
while nonruminant milk will have majority IgA
Colostrum absorption
Once Ig reaches SI they need a way to get internalized and to blood stream
Low protease activity in digestive tract
Ig reach the SI intact and bind with FcRn receptors on intestinal epithelial cells
Ig bound to FcRn are taken up by intestinal epithelial cells and transferred to the lacteals and possibly the intestinal capillaries- lymphatic circulation
Reaches the bloodstream
There are neonatal receptors but appear to stay through adult life- do other functions in adults.
Colostrum absorption: Selectivity of intestinal permeability
Horses and pigs
-absorb IgG and IgM; IgA remains in the intestine
Ruminants
-no selectivity