12 Reproductive Immunology

Question 1

what are the events in mammalian reproduction

Answer 1

• production of gametes
• mating
• fertilisation
• implantation
• pregnancy
• parturition
• lactation

Question 2

what is the production of gametes

Answer 2

gametes develop in an immunologically privileged environment

Question 3

what happens in mating process

Answer 3

involves internal exchange of fluid

Question 4

what happens in fertilisation

Answer 4

male and female gametes are genetically dissimilar

Question 5

what happens in implantation

Answer 5

conceptus is half paternal (an ‘allograft’)

Question 6

what is the effect of events in mammalian reproduction

Answer 6

all involve ‘genotypic confrontation’ - combination or potential interaction of different genotypes

Question 7

what do all mammalian reproduction events have the potential for

Answer 7

immunological confrontation

Question 8

effect of immunological self/non-self-identity established perinatally

Answer 8

• establishment of class I MHC antigens unique to the individual, on all nucleated cells
• clonal selection of T cells (by thymus gland) which don’t react to self but will react to non-self

Question 9

what do antigen-antibody reactions lead to

Answer 9

activate the complement cascade

Question 10

where do sperm develop

Answer 10

develop in immunologically privileged environment

Question 11

where is sperm made

Answer 11

Sertoli cells

Question 12

what is the complex membrane

Answer 12

(5/6 layers of complexity) – tubules don’t talk to anyone else

Question 13

what does privileged mean for sperm

Answer 13

semen never contacts the blood (no AB for sperm)

Question 14

what is the blood-testis barrier

Answer 14

Capillaries do not cross the membrane – sperm develop away from direct contact of blood = ‘blood-testis barrier’

• no entry of blood into seminiferous tubule
• no lymphocytes at site of sperm production

Question 15

where is sperm released

Answer 15

externally

into epididymis

Question 16

what can cross the ST membrane

Answer 16

IgG are small enough

Question 17

what is the immunological significance of sperm

Answer 17

Recognition of self/non-self occurs perinatally, by actions of the thymus glans
Sperm not made until puberty

Question 18

what is the medical significance

Answer 18

normally, sperm external to immune system

Question 19

what can the blood-testis barrier breakdown

Answer 19

• testicular disease
• injury or trauma
• damage during vasectomy or vasectomy reversal

Question 20

what leads to infertility

Answer 20

1. damage to blood-testis barrier allows sperm or sperm proteins to enter circulation
2. sperm are recognised as non-self: immune response occurs
3. anti-sperm AB pass from blood into S.T.
4. sperm inactivated by AB

Question 21

what causes the infertility

Answer 21

AB is anti-sperm AB made – immune system is able to make AB

If have anti-sperm AB = infertile

Question 22

what are the consequences of breaking down the blood-testis barrier

Answer 22

• azoospermia or low motile sperm count
• infertility or reduced fertility
• ineffective vasectomy reversal, despite reconnected vas deferens

Question 23

where do trophoblasts invade

Answer 23

endometrium – implants

Question 24

what does trophoblast form

Answer 24

placenta, adjacent to maternal capillaires

Question 25

what is the conceptus

Answer 25

= zygote --> embryo + placenta half maternal and half paternal - contains non-maternal genes and expresses non-maternal antigens

Question 26

what is the maternal immune system to exposed to

Answer 26

not exposed directly to fetal T cells, macrophages or other fetal APCs

Question 27

what MHC are expressed in trophoblasts

Answer 27

``` class I trophoblast cells expresses monomorphic, species-specific MHC class I antigen ```

Question 28

what are trophoblasts recognised by

Answer 28

maternal immune system, despite presence of paternal antigens

Question 29

what would be the effect if MHC class I not present in trophoblasts

Answer 29

trophoblast cells would be attacked by maternal NK cells

Question 30

what is the effect of late MHC class I expression for cattle

Answer 30

specific MHC class I expressed in trophoblast cells in last third of pregnancy, so rejection may contribute to parturition

Question 31

what is the effect of trophoblasts not expressing MHC II

Answer 31

can’t act as an APC – don’t present fetal antigens to maternal T cells

Question 32

what does the placenta secrete

Answer 32

range of hormones and prohormones

Question 33

what does the placenta do

Answer 33

disguise self as parasite

Question 34

what is secreted with hormones in placenta

Answer 34

secreted with phosphocholine attached to aspartate residues

Question 35

what does phosphocholine used by

Answer 35

used by parasitic nematode worms to protect themselves from host immune system

Question 36

what is the placenta hypothesis

Answer 36

placental cells cover themselves in phosphocholine and avoid attack by maternal immune cells

Question 37

what are the two local alteration of immune cell activity

Answer 37

monocytes | T regs

Question 38

what does implantation require - Local alteration of immune cell activity: monocytes

Answer 38

immunologically receptive endometrium

Question 39

what does early deciduum contain

Answer 39

contains abundant monocytes (tissue macrophages)

Question 40

what do monocytes secrete

Answer 40

interleukins (types 1, 2, 6, 8, 10) and TGF-beta

Question 41

what are monocyte secretions involved in

Answer 41

local immune suppression and in parturition

Question 42

what does Prostaglandin E2 do in Local alteration of immune cell activity: monocytes

Answer 42

Endometrium has abundant NK (CD56+) cells, but these are non-cytotoxic, probably due to inhibition by PGE2

Question 43

what happens if Treg contacts antigen

Answer 43

If Treg contacts the antigen = proliferate and generate lots | T cell presence major event for downregulation

Question 44

what are memory regulatory T cells specific for

Answer 44

specific to paternal antigen, already exist in maternal circulation

Question 45

what antigen does the fetus express

Answer 45

paternal

Question 46

what can rapid proliferation of antigen-specific regulatory T cells explain

Answer 46

- may explain reduced incidence of pre-eclampsia in second and subsequent pregnancies - tolerance of paternal antigen

Question 47

what do the high numbers of regulatory T cells may explain

Answer 47

why autoimmune diseases (e.g. arthritis) are often ameliorated temporarily during pregnancy

Question 48

trophoblast invasion for pig placenta

Answer 48

complex for AB to pass

Question 49

trophoblast invasion for ruminants

Answer 49

not too easy

Question 50

trophoblast invasion for carnivores

Answer 50

simpler as closer

Question 51

trophoblast invasion for primates and rodents

Answer 51

easy

Question 52

what can the fetus receive from mother

Answer 52

IgG

Question 53

what is rhesus antigen

Answer 53

proteins expressed exclusively on surface of erythrocytes

Question 54

what is rhesus antigen for

Answer 54

Used for blood grouping (in addition to A, B, O)

Question 55

what do individuals express - rhesus

Answer 55

Individuals either express antigen (Rh+) or do not (Rh-)

Question 56

how is rhesus determined

Answer 56

Rh+ or Rh- refers to the presence or absence of D antigen

Question 57

does rhesus matter

Answer 57

yes if mother has anti-Rh IgG, can cross placenta | if fetus Rh- is fatal

Question 58

what is anti-IgG

Answer 58

- removes any fetal RBCs from mother’s circulation | - prevents mother from developing immune reaction to Rh