Related Subjects:
|Major Histocompatibility complex
|Immune response
|Complement
|Opsonisation
|Toll-like Receptors (TLRs)
|Immunoglobulins
|Immunology
|X linked Agammaglobulinaemia (Bruton)
|X-linked lymphoproliferative disease (Children)
|Chediak Higashi syndrome
|Common variable immunodeficiency
|Severe combined immunodeficiency disorders
|DiGeorge syndrome (thymic aplasia)
|Selective IgA deficiency
|Wiskott-Aldrich syndrome (Children)
|T lymphocytes
📖 About
- Major Histocompatibility Complex (MHC) = group of polymorphic glycoproteins coded on chromosome 6 (HLA complex in humans).
- Function: display antigenic peptides to T cells → distinguishes self vs non-self.
- Located on chromosome 6p21, subdivided into Class I, II, and III.
🧬 Class I MHC Molecules
- Expressed on all nucleated cells (not RBCs).
- Classical types: HLA-A, HLA-B, HLA-C.
- Associate with β2-microglobulin for stability.
- Antigen source: endogenous (e.g. viral proteins, tumour antigens).
- Peptides generated by proteasomes, transported to ER, loaded onto MHC I.
- Presented to CD8+ cytotoxic T lymphocytes → destruction of infected/malignant cells (perforins, granzymes, apoptosis).
- Mnemonic: “1 for 8” → MHC I → CD8 T cells.
🧬 Class II MHC Molecules
- Restricted to antigen-presenting cells (APCs): dendritic cells, macrophages, B cells, monocytes.
- Classical types: HLA-DP, HLA-DQ, HLA-DR.
- Antigen source: exogenous (phagocytosed pathogens, extracellular proteins).
- Peptides processed in endosomes → presented on cell surface with MHC II.
- Presented to CD4+ helper T cells → stimulates antibody production, cytokine release, delayed-type hypersensitivity.
- Mnemonic: “2 for 4” → MHC II → CD4 T cells.
🧬 Class III MHC Molecules
- Do not present antigens.
- Encode other immune proteins: Complement components (C2, C4, Factor B), and Tumour Necrosis Factor (TNF).
⚕️ HLA Associations with Disease
- Class I: HLA-B27 → ankylosing spondylitis, reactive arthritis, psoriatic arthritis, IBD-associated arthritis.
- Class II:
- HLA-DR4 → rheumatoid arthritis
- HLA-DR2 → multiple sclerosis, Goodpasture’s syndrome
- HLA-DR3 → type 1 diabetes, SLE, coeliac disease
- HLA-DR5 → pernicious anaemia, Hashimoto’s thyroiditis
💡 Teaching Pearl:
- MHC I presents intracellular peptides to CD8 T cells.
- MHC II presents extracellular peptides to CD4 T cells.
- Class III doesn’t present antigens at all.
Remember: “1 for 8, 2 for 4”.
