MHC recognition and immune tolerance

LO: Discuss the role of the major histocompatibility complex (MHC) in pathogen recognition

Major histocompatibility complex (MHC) = human leukocyte antigens (HLA)

MHC proteins provide a conveyer belt to present peptides normally inside the cell to the immune system
MHC presents pathogen peptides to T cells
Allows MHC to present virus peptides to T cell - allows T cell to see inside to find the virus
Conveyer belt loads self peptides onto MHC/HLA proteins
T-cell recognises MHC + self peptide but do not respond
If peptide or MHC wrong, T-cell activated
Occurs during infection and tissue rejection
Recognition of MHC peptide complexes by TCR triggers signal transduction pathways in the T-cell
Generates cytokines, cell adhesion molecules to kill infected cells (perforin)

T_h2 T-cells secrete cytokines to aid B-cell differentiation, isotype switching and antibody production

T_h2 T-cells also activate eosinophils and mast cells

T_h1 T-cells secrete INF $γ$ to promote the activity of antigen presenting cells

HLA/MHC defines 'self'
MHC/HLA varies greatly between individuals
HLA genes define a genetic locus that varies between individuals
A person can express up to 12 different HLA antigens (6 class I and 6 class II)
T-cells recognise cells as non self, not the proteins - thinks tissue if infected

T cells made in the bone marrow and educated in thymus
T-cells leaving thymus have rearranged T-cell genes and do not recognise self
Self-reactive T-cells are removed in the thymus before getting to lymph node
If immature T-cells have weak binding for MHC self-peptide they survive, this is positive selection
If immature T-cells have strong binding for MHC self-peptide they die, this is negative selection
This elimination of self-reactive T cells in the thymus is called central tolerance
Some self-reactive T-cells can escape the thymus

B-cells that make a self-reactive B-cell receptor cannot leave bone marrow and die