Lecture 24 (Neonatal Immunity)

Question 1

why is a fetus considered a foreign antigen?

Answer 1

the sire has MHC molecules that are foreign and the dam is receiving those

Question 2

what are the 4 maternal mechanisms for achieving maternal-fetal tolerance

Answer 2

1. progesterone
2. increased complement regulatory proteins
3. TH2 response dominates (lower chance for TH1 mediated cytolysis of fetal tissues)
4. high levels of Tregs

Question 3

T-regulatory cells [heighten/dampen] your immune response

Answer 3

dampen

Question 4

is a TH2 response humoral immunity or cell-mediated immunity?

Answer 4

humoral immunity

Question 5

what are the 3 fetal mechanisms for achieving maternal-fetal tolerance

Answer 5

1. fetal cells down regulate MHC I (lowers expression of self-antigens)
2. TH2 cytokines are expressed
3. inhibit T-cells (progesterone & other cytokines)

Question 6

[MCH I/MHC II] is expressed on all nucleated cells

Answer 6

MHC I

Question 7

t/f: the adult is less able to combat infections than a fetus

Answer 7

false - the fetus is less able to combat infections than an adult

Question 8

reduced or absent adaptive immunity [decreases/increases] with fetal age

Answer 8

increases

Question 9

despite early population of lymphoid tissues, the adaptive response is limited at birth…why?

Answer 9

there is limited antibody and T-cell diversity, no memory cells, and reduced cytokines (haven’t flushed out the system with exposure to antigens yet)

Question 10

neonates have a slow and weak [innate/adaptive] response

Answer 10

adaptive

Question 11

since the fetus has a reduced adaptive response, that means it relies on what three things?

Answer 11

-innate immunity
-passive immunity
-physical barriers

Question 12

the adaptive immune response requires population of primary and secondary lymphoid organs in the ________ trimester

Answer 12

1st

Question 13

when does the adaptive immune response start to increase in the fetus?

Answer 13

after population of lymphoid organs

Question 14

due to reduced adaptive immunity, the fetus relies on what two things?

Answer 14

-its own innate immunity
-passive immunity from the dam

Question 15

the fetal innate response and developing adaptive response can be passively supplemented by maternal _________

Answer 15

antibodies

Question 16

placenta type where maternal epithelium is in contact with fetal tissues (fetal endothelium, CT, and epithelium)

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 16

a) epitheliochorial

Question 17

placental type where there is no maternal epithelium, and instead the endothelium is in contact with fetal tissues (fetal endothelium, CT, and epithelium)

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 17

b) endothelialchorial

Question 18

placental type where the fetal tissues (fetal endothelium, CT, epithelium) are in direct contact with maternal blood

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 18

c) hemochorial

Question 19

what type of placenta do horses, swine, and ruminants have?

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 19

a) epitheliochorial

Question 20

what type of placenta do dogs & cats have?

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 20

b) endothelialchorial

Question 21

what type of placenta do humans, primates, and rodents have?

a) epitheliochorial
b) endothelialchorial
c) hemochorial

Answer 21

c) hemochorial

Question 22

t/f: antibodies cannot pass through multiple layers of the placenta

Answer 22

true

Question 23

any species that maintains all 6 of the placental layers are completely dependent on _____________ for transfer of their passive immunity

Answer 23

colostrum

Question 24

what layers are lost in an epitheliochorial placenta?

Answer 24

none
*no maternal layers are lost

Question 25

what layers are lost in an endotheliochorial placenta?

Answer 25

-maternal epithelial cells -maternal connective tissue

Question 26

what layers are lost in a hemochorial placenta?

Answer 26

all three maternal layers: -maternal epithelial cells -maternal connective tissue -maternal endothelial cells

Question 27

which placental type allows for complete transfer of colostrum? a) epitheliochorial b) endothelialchorial c) hemochorial

Answer 27

c) hemochorial

Question 28

which placental type allows for partial transfer of colostrum? a) epitheliochorial b) endothelialchorial c) hemochorial

Answer 28

b) endotheliochorial

Question 29

what percentage of total neonate serum IgG is transferred via the placenta in cats and dogs

Answer 29

~5-10%

Question 30

fetal humans, rabbits, and rodents have complete transfer of which immunoglobulin via the placenta?

Answer 30

IgG

Question 31

in addition to placental transfer, all species can receive maternal antibodies post-fetally via ______________

Answer 31

colostrum

Question 32

what is colostrum?

Answer 32

milk produced late in gestation and early postpartum that is high in antibody content

Question 33

the maximum amount of colostrum that can be absorbed is within the first ___ hours in foals and calves and then rapidly declines

Answer 33

6 hours

Question 34

which immunoglobulin is the only one to pass through the placenta?

Answer 34

IgG

Question 35

what explains why absorption of colostral Abs is time sensitive? a) IgG is only produced by dams b) IgG is known to degrade within 6 hours c) FcR receptor expression falls off after 6 hours

Answer 35

c) FcR receptor expression falls off after 6 hours

Question 36

which immunoglobulin is predominant in ruminant milk?

Answer 36

IgG

Question 37

which immunoglobulin is predominant in non-ruminant milk?

Answer 37

IgA

Question 38

when is the maximum amount of colostrum absorbed from the neonatal intestine?

Answer 38

-first 6 hours in foals and calves -within the first 12-24 hrs in other species

Question 39

t/f: colostrum has low lymphocyte count

Answer 39

false - has high lymphocyte count

Question 40

why is it important to consider the timing of when to vaccinate neonates?

Answer 40

-maternal antibodies can inhibit neonate Ig production (FcγRIIB) -maternal antibodies can bind the vaccine antigen and block immune response (epitope masking, neutralization of live-attenuated viruses)

Question 41

when should you start vaccinating puppies and kittens?

Answer 41

6 wks of age then every 3 wks x3

Question 42

when should you start vaccinating foals and calves?

Answer 42

3-4 months of age then every 4 wks x3

Question 43

what are the negative aspects of passive immunity?

Answer 43

-maternal antibody may impair neonatal adaptive immune response -FcγRIIB receptor engagement reduces BCR activation → masks antigens; may bind epitopes and prevent appropriate response to neonatal vaccines -maternal antibodies may also recognize neonatal tissue (neonatal isoerythrolysis; Rh disease)

Question 44

what is neonatal isoerythrolysis?

Answer 44

when the mother has antibodies against the blood type of the newborn *when the newborn ingests colostrum, it has antibodies against it's own blood, causing destruction of RBCs

Question 45

what can you give to prevent neonatal isoerythrolysis?

Answer 45

artificial colostrum

Question 46

neonatal immunodeficiency can occur due to:

Answer 46

-can occur due to developmental failure examples: -innate response defects → trapped neutrophil syndrome (Border Collies) -adaptive response → RAG-1/2 mutations -can also occur due to failure of passive immunity transfer (vast majority)

Question 47

what is the most common source of immunodeficiency?

Answer 47

failure of passive immunity transfer (FPT)

Question 48

what is the major source of passive immunity?

Answer 48

maternal antibody transfer

Question 49

what are the 3 specific groups of causes of immunodeficiency?

Answer 49

-production failure → maternal (does not make antibodies) -ingestion failure → placental or neonatal -absorption failure → neonatal (major cause is lack of colostral transfer)

Question 50

discuss avian neonate immunity

Answer 50

-passive mechanisms of immunity transfer differ due to lack of placenta and lack of colostrum -hen actively transfers IgY (=IgG) from serum to yolk → contents absorbed into bloodstream of developing chick -IgM and IgA are secreted into the albumin in the oviduct (diffuse into amniotic fluid and swallowed by chick) → IgM and IgA in intestine (mucosal immunity)

Question 50

which of the following features promotes maternal-fetal tolerance? a) high maternal levels of estrogen b) high maternal complement expression c) high maternal levels of progesterone d) Th1 predominant immune response

Answer 50

c) high maternal levels of progesterone

Question 51

after maximum immunoglobulin consumption via colostrum, does the dam still provide immunity to the neonate?

Answer 51

yes, the dam continues to put immunoglobulin in colostrum (IgA) for mucosal immunity in the neonate

Question 52

in what species is failure of passive transfer most common?

Answer 52

horses

Question 53

list the 3 types of placenta

Answer 53

-epitheliochorial -endotheliochorial -hemochorial

Question 54

this receptor binds IgG at birth, protecting it from digestion and bringing it to circulation in neonate blood

Answer 54

fetal Fc receptor

Question 55

this receptor has high levels at birth and rapidly declines in number nearing 0 left by 24 hours

Answer 55

fetal Fc receptor

Question 56

t/f: you vaccinate an animal as maternal antibodies decrease and young animal's adaptive immunity response begins to develop

Answer 56

true

Question 57

fescue hay having an endophyte that potentially causes a failure to produce colostrum is an example of which type of failure of passive immunity transfer?

Answer 57

production failure

Question 58

this type of FPT can be placental (abnormal placenta that precludes normal transfer) or neonatal (foal that won't stand to nurse)

Answer 58

ingestion failure

Question 59

this type of FPT is mainly a cause of lack of colostral transfer such as taking in colostrum too late

Answer 59

absorption failure

Question 60

Hens actively transfer this antibody from serum to yolk that is equivalent to IgG

Answer 60

IgY

Question 61

_____ and ____ are two antibodies that are secreted into albumin in oviduct and diffuse into amniotic fluid and swallowed by the chick, ending up in the intestine

Answer 61

IgM and IgA