Male
Immunological
Infertility
田美策 孙钦辉 魏源 魏艳 王思宇
Sir Frank Macferlane Burnet
Clonal Selection Theory
There are various lymphocyte clone,each of them bears a single type of Ag receptor of unique specificity.
Ag receptor—Ag’s specific interactions lead to lymphocytes activation (proliferated ), then produce both Ab and memory cells.--- Clone selection
Those clones whose receptor can recognize self will be destroyed or learn to tolerance to self Ags (forbidden clones) at early stage.—Clone deletion
forbidden clones can be revival and cause antoimmunity
Clonal Selection Theory
For male, spermatogenesis commences( 发生 ) well after the development of neonatal (new born) immune tolerance
And for female, sperm is definitively “non-self”
Mechanisms normally in place to modify the immune response and prevent immune reaction Blood-testis barrier Sperm plasma immunosuppressive
factors ( 精浆免疫抑制因子 )
The barriers may be disrupted, result in the exposure of sperms to the immune system.
And thus the production of antibody
research on sperm as an antigen has been making little progress
So what do we know about sperm as an antigen?
MostlyMembraneproteins
Spermatogenic cells
Sustentacular cells
Deputy gonadal components
( 副性腺成分 )
Mechanism of anti-sperm antibody causing infertility
Direct binding influence
Function impairment of antigen molecules
Direct binding influence1.Occlude the
sperm penetration through the cervical mucus
2.Accelerate the clearance of sperms in the female genital canal (mainly carried out by complements)
Antigen function impairment
Inhibit fertilization
AsAb binds to Ag P36 and P18, manifesting a reduction of penetration through zona pellucida and oval membrane.
Induced spontaneous acrosome( 顶体 ) activation and acrosomal enzyme lost
Failure of fertilization………
Diagnostic techniques
Traditional methods sperm membrane extract( 膜提取
物 ) or motile sperms( 活动精子 ) as antigen to detect AsAb
Being questioned for deficiency and uncertainty
Diagnostic techniques
According to WHO
Diagnostic basis the surface of motile sperm is
attached by immunoglobulin positive result of IBT or MAR
IBT----immunobead test( 免疫珠试验 )
Utilize polyacrylamide beads( 聚丙酰烯胺珠 ) coated with Ig to human IgG, M and A to detect AsAb.
MAR----mixed agglutination reaction( 混合凝集试验 )
Uses anti-human Ig to mediate agglutination between latex( 胶乳 ) beads or SRBC labeled with human Ig and viable sperms ( 活性精子 )
Standard of IBT and MAR
The percentage of viable sperms attached by AsAb among all viable sperms
Detect not only the existence of Ig, but also the position of attachment
Clinical therapy
Different percentage and site of attachment have different clinical significance
It is recommended to choose different methods according to the percentage of sperms attached by AsAb, particularly to their heads.
From the lowest highest
We choose IUI IVF ICSI
Clinical therapy
IUI----intrauterine insemination
Send sperms directly into the uterine cavity
First choice for male immunological infertility
IUI----intrauterine insemination
IVF---- in vitro fertilization Not only overcomes the
difficulty of AsAb-attached sperms penetrating the cervical mucus, but also make sure there are enough sperms contacting with ovum.
IVF---- in vitro fertilization
ICSI----intracytoplasmic sperm injection The most
effective method for severe immunological infertility
But with the highest cost
tens of thousands of dollars!
Other options
Isolation therapy (using condom) Immune inhabitation (large-dose-glucocorticoid
injection)
…….
There are questions remaining to be answered!!!
Acknowledgements
Sperm antigen---------------------- 魏艳 Production of AsAb---------------- 魏源 Mechanism of infertility----------- 田美策 Diagnostic techniques------------ 孙钦辉 Clinical therapy--------------------- 王思宇
Thanks all !