Immunology Flashcards
Describe the sterility of the uterus
Sterile except when cervix opens in oestrus
Outline the immunological challenges of the female reproductive tract
- Commensal flora
- Infectious agents
- Sperm
- Semi-allogenic foetus
- Seminal plasma
- Oestrogen
- Progesterone
What does semi-allogenic mean?
From the same species but sharing half the genetic material
Describe seminal plasma as a challenge to the female reproductive tract
- Induces local inflammatory changes
- To protect agains infectious agents introduced during intercourse
- Inflammatory response when semen comes into contact with vagina, cervix and uterus
Describe oestrogen on terms of female reproductive tract immunology
- Influx of leukcocytes at oestrus
- Pro-inflammatory factors prior to implantation in association with pre-implantation surge of E2
- Insemination: infectious material cleared rapidly
- Th1 dominant (CD4 Th, IFNy and CMI)
- Pro-inflammatory
Describe progesterone in terms of female reproductive tract immunology
- Anti-inflammatory
- INduction of immunoregulatory protein
- When binds to immune cells, produce factors that are immuno-suppressive
- Th2 dominant (CD4 Th producing IL-4, -5, -9, -13)
- Pregnancy has bias towards Th2 (anti-inflam) immunity
Explain the concept of the foeto-placental allograft
- Foetus and trophoblasts expressing antigens (MHC I) from father, but not rejected by mother
- The conceptus can be considered as 2 grafts - foetus and trophoblast
- Trophoblast is the first barrier to maternal immunity
List mechanisms by which the foetus may avoid maternal immuno-rejection
- Trophoblast as first barrier to maternal immune response
- Decidua and endometrium
- Greater number of layers between maternal and foetal blood (more layers = less challenge to immune system)
Describe the formation and function of the decidua and endometrium in relation to foetal avoidance of maternal immuno-rejection
- Formed in response to progesterone
- Prepares uterus for embryo
- Secretory phase
Describe the development of the decidua in primates and rodents prior to pregnancy
- Increases glandular epithelial secretions (oedema) at secretory cells
- Promotes formation of spiral arterioles
- Shed when progesterone declines
Describe the development of the endometrium in farm animals prior to pregnancy
- Increase in glandular secretions
- Increase in blood vessels and blood flow
- Re-absorbed when progesterone declines
- No menstruation
Explain why the trophoblast is antigenically unusual
- Does not express some of paternal antigens easily recognised by maternal immune system
- E.g. MHC class I
- Makes placenta resistant to recognition and attach by maternal immune cells
What does the type of immune cells present in uterus depend on?
- Differs between species
- Presence of decidua or endometrium
- Degree of trophoblast invasion
Describe the immune cells in species with decidua
- Human and non-human primates
- NK cells 75% of decidual leuckocytes
- Interact with placental antigens
- Normally result in production of local factors supportive of pregnancy e.g. immunosuppressive
Describe the immune cells in species with endometrium
- Includes domestic animals
- No uterine NK (except pigs)
- Macrophages
- Specialised T cells (sheep, horse)
- Immunosuppression, growth enhancement, placental detachment at parturition
Describe the immunological features of binucleate cells in ruminants
- Uni-nucleate trophoblast cells have very little, if any MHC-I
- Increased expression as BNCs migrate
- Foreign antigens deliberately upregulated
Explain the immunological implications of the binucleate cells in ruminants
- Migrate and fuse with maternal cells
- Upregulation of MHC-I
- Exposure and prime maternal immune system so that system recognises pregnancy and responds in beneficial way
Compare the antigens expressed on chorionic girdle cells vs endometrial cups
- Cells: MHC-I positive
- Cups: MHC-I negative
Explain the immunology of the formation of the endometrial cups, and its role in maternal recognition of pregnancy
- Chorionic girdle cells are MHC-I postive
- Trophoblast cells are MHC-I negative
- Endometrium is MHC-I positive
- When the girdle cells invade, switch from MHC-I positive to negative as become endometrial cup cells
- Following invasion, only the endometrial cells are MHC-I positive
- Invasion sends signal to mother that she is pregnant and needs to adapt her immune response
Describe the maternal immune response to the invasion of the endometrial cup cells
- Accumulation of maternal leukocytes around base of cups
- Mononuclear cells invade between cup cells
- Immunce cells detroy cup cells (do not know hwat the target of these is)
- Pregnancy induces local cell mediated immune response
What type of leukocytes accumulate around the endometrial cups?
- Mainly T cells
- Some B cells
What antibodies are prodced by most maiden mares in their first pregnancy in response to the girdle cell invasion?
Cytotoxic antibodies to the antigens expressed on girdle cells
During pregnancy and locally in the pregnant uterus, what is the conceptus protected by in the mare?
- Modified and protective maternal immune response
- Factors secreted by trophoblast dampen damaging immune response
- Factors secreted by pregnant endometium that also dampen any damaging immune response
What are the immunological implications of the cups?
- Modulation of local vs systmic immune responses
- Split tolerance between systemic and local immune respnse
- Important as mare needs to be able to respond to pathogens, but not damage foetus
