Lecture 22 Flashcards
Why should sperm be immunogenic to the male producing that sperm?
Despite having continuous production throughout life sperm production only begins during puberty, after the major period of central tolerance development suggesting that males should react to their own sperm
Why do sperm not induce an autoimmune response despite sperm being immunogenic?
They are an immunologically privileged site with the seminiferous tubules creating a blood/testes barrier through the tight junctions between adjacent sertoli cells
What can lead to the tolerance of a male to his own sperm?
This occurs when the barrier between the sperm and the immune system is broken, this occurs with testicular trauma, vasectomy and infection
These lead to the production of autosperm antibodies
What are the mechanisms of antisperm antibodies?
They agglutinate sperm
Interfere transport in the female reproductive tract
And can block fertilization
When do oocytes develop?
Oocytes enter during meiosis during fetal life then arrest until just before ovulation until the full complement of oocytes is present at 6 months gestation
As this is occurring during the same phase as central tolerance there is no need for a blood ovarian barrier
What is premature ovarian failure?
This is when menopause occurs before 40 and is suffered by 1% of women
In this condition either follicles are present but are unable to mature or there is immunity to primordial follicles which leads to total loss of follicles
What are the antigenic targets responsible for mediating premature ovarian failure?
Not all of these are known however several steroid hormone metabolizing enzymes have been implicated includingP450 side chain cleavage, 17ahydroxylase and 3b hydroxysteroid dehydrogenase
These can also induce disease in other organs such as addisons disease where there is an attack on the adrenal glands
What are the animal models of ovarian failure?
A neonatal thymetomy 2-5 days post birth can cause autoimmune disease including POF in some strains of Mice like balb/c
Immunisation with ovarian antigens such as ZP3
What are the different components of the placenta?
The villus placenta which is the main body of the placenta
The syncytiotrophoblast which is the outer layer of the placenta and is a continuous multinucleated epithelium
How does the syncytiotrophoblast cause the mother to have immunological tolerance to the implanted fetus?
The syncytiotrophoblast is the structure in contact with maternal blood and this does not produce any MHC molecules
It can be shown that this is what provides protection as breaches lead to maternal responses such as villitis
What are the leucocytes present in the decidua?
70% are NK like cells
20% are macrophages
10% are T cells
There is almost no B cells
What is the difference between uterine NK like cells and traditional NK cells?
pbNK cells are CD16+ and use FcgammaRII for antibody dependent cell killing
Uterine NK cells howevere are CD16 negative and CD56 bright their origin in humans is not clear bit they appear in the decidua during the menstrual cycle and are present in large numbers during the first half of pregnancy and have intimate contact with the syncytiotrophoblast but as they only kill if IL-2 is supplied they do not attack it
What is the role of MHC/HLA molecules in pregnancy immunology?
Invasive trophoblasts do not express HLA-A or HLA-B but do express HLA-G, HLA-E and HLA-C
HLA-C seems to be particularly important in compatibility between parents for pregnancy
What is the role of HLA-G in pregnancy immunology?
HLA-G is functionally very limited polymorphism and is expressed almost exclusively EVTs They are structurally different to classical class I proteins and have 6 isoforms with only HLA-G being expressed at the cell surface It may also interact with inhibitory receptors on NK cells to prevent cytolysis of the invasive trophoblast
What are the three receptors that NK cells express relevant to pregnancy immunology?
C-type lectin CD94/NKG2A this is only expressed on uNK and use HLA-E as a ligand which preferentially presents peptides from the leader sequences of other HLAs particularly HLA-G
ILT Immunoglobulin like transcripts these are promiscuous receptors that have low levels of ILT-2 being expressed by uNK
KIR Killer inhibitory receptors which recognize HLA-C these are expressed by a higher proportion of uNK cells than pbNK cells for mthe same woman, they are activating receptors which lead to cytokine secretion by not cytotoxicity
