10 - Clinical applications

Question 1

Namme 3 mecanisms of IP

Answer 1

1) ↓ expression of polymorphic MHC-1a molecules = ↓ immune response
2) ↑ MHC-1b monomorphic molecules = prevent recognition as a foreign cell
3) ↑ Immunosuppresive cytokines (TGF-B)
4) Surface molecules that inhibit the complement pathway
5) Expression of Fas-L that control the entry of Fas-expression lymphoid cells
6) Isolation by physical barriers

Question 2

Name 4 IP mecanisms of the eye (lens, cornea)

Answer 2

1) No adaptive immune cells
2) Lens has no immune cells
3) Lack of lymphatics
4) ↑ TGF-B
5) Blood-occular-barrier
6) Abscence of mature APC’s (MHC-2). There are only DC’s in the cornea
7) Lack of MHC-1a on tissue cells = negates CD8+ Tcells)
8) Presentation of MHC-1b cells - modulates NK response

Question 3

If the cornea is not vascularised, how does it activate immune response?

Answer 3

CALT (Conjunctive associated lymphoid tissue) = vascularised tissue surrounding the cornea that recruits adaptive immune cells when actived by Langerhans cells

Question 4

Explain the mecanisms that contribute to Corneal graft rejection

Answer 4

Corneal tissue contains resident MHC-2 molecules but no lymphatics = they can’t be activated.

However, recipient CD4+ cells can target these MHC-2 from the donor and the rejection of the graft will happen gradually and slowly. It ressembles chronic inflammatory disease

Question 5

Explain 3 mecanisms that explain maternal tolerance of the fetus

Answer 5

1) Lack of HLA-A (MHC-1a) moleculles = negate Tcell response
2) Trophoblaste expresses of HLA-G = negate maternal NK cell response
3) Regulatory CD4/25 that dampen immune response and also help prevent spontaneous abortion
4) Lowered complement activity

Question 6

What HLA molecules are expressed in the fetus, placenta and mother’s body (compare father and mother)

Answer 6

1) Fetus = 50m/50p HLA of all types
2) Placenta = 50p/50m HLA-G
3) Mother = 100 HLAm of all types

Question 7

Name the 3 functions of HLA-G

Answer 7

1) cellular adhesion of blastocyste to the endometrium
2) Modulation of angiogenesis in uterine tissue and maternal spinal arteires
3) interaction with mother’s imm cell R to negate NK signaling