Autoimmunity and transplantation

Question 1

Central tolerance

Answer 1

Elimination of strongly self-reactive T/B cell clones before maturation

Negative selection of T cells in the thymus (apoptosis) and B cells in the bone marrow (clonal deletion/receptor editing)

Question 2

Immune privileged sites

Answer 2

Eye, brain, uterus and testis

B and T cell ignorance of these tissue-specific antigens

Can be compromised by infection and injury

Question 3

Absence of co-stimulatory signals

Answer 3

Mechanism of peripheral tolerance

T cell recognises APC in absence of CD80/86 and CD40 leading to T cell anergy or activation-induced death

Question 4

APC inhibition by Treg cells

Answer 4

Treg cell binds antigen via TCR and CTLA-4 receptor binds CD80/86. Sends inhibitory signal to APC

One APC engages several different T cells (including Treg) and Treg cell inhibits activity of the other T cells (bystander suppression)

Question 5

Autoimmunity

Answer 5

Caused by failure of tolerance mechanisms

Can be caused by autoantibodies or self-reactive T cells, leading to cell lysis and organ damage

Question 6

Type I diabetes mellitus

Answer 6

Autoimmune disease affecting the pancreas. Insulin producing beta cells are attacked.

Leads to increased blood glucose levels

Question 7

Myasthenia Gravis

Answer 7

Motor end plate cells of skeletal muscles are destroyed.

Autoantibodies to acetylcholine receptors trigger complement-mediated lysis of cells

Progressive loss of muscle function

Question 8

Systemic lupus erythematosus

Answer 8

Systemic autoimmune disease
Autoantibodies to a wide range of tissue antigens, commonly proteins associated with self DNA/RNA

Characteristic butterfly rash on the face

Question 9

Multiple sclerosis

Answer 9

Auto-reactive T cells attack the myelin sheath of nerve fibres and spinal cord

Numbness, paralysis, loss of vision.

Question 10

Genetic factors for autoimmunity

Answer 10

MHC variants (HLA-B27 in ankylosing spondylitis)
Immune cell surface proteins (IL-2 receptor and CTLA4 in type I diabetes)
Innate immune signalling factors (TLRs in SLE)
Single mutations (FoxP3 in IPEX)

Question 11

Molecular mimicry

Answer 11

Foreign antigen shares sequence/structural similarities with self-antigen

Question 12

Transplantation grafts

Answer 12

Autograft is from one site on the body to another
Isograft is from one genetically identical twin to another
Allograft is from a donor to a recipient
Xenograft is from animal to humans

Question 13

Allograft donor matching

Answer 13

Major antigens must be matched including ABO blood type and MHC molecules (HLA)

MHC proteins are very polymorphic

Question 14

Allorecognition

Answer 14

Direct allorecognition is when the recipient T cell recognises MHC/peptide on the surface of the donor APC

Indirect allorecognition is when the recipient’s T cell recognises donor MHC peptide displayed by self-MHC on self-APC

Question 15

Neurological tissue immune privilege

Answer 15

Express CD200, FasL and TRAIL which regulate T cells.

Fas ligand (FasL) binds to Fas receptor to induce apoptosis

Question 16

Crohn’s disease

Answer 16

autoimmune disease causing inflammation of the gut mucosa

May be associated with mycobacterium subspecies paratuberculosis (map)