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

Major histocompatibility complex (MHC) (1)

• Region is located on chromosome 6
• Consists of approximately 140 genes
• Peptides generated by the degradation of fragmented microorganisms bind to various MHC molecules
• Presented to T cells for recognition and immune stimulation
• Two groups: class I and class II

Class I (1)

• Present on the surface of every nucleated cell
• Area that can form interactions with molecules called CD8
• CD8 produced by cytotoxic T cells - called CD8-positive/CD8+
• Antigen presentation via MHC-I molecules will be directed to CD8+ (cytotoxic) T lymphocytes only
• MHC-I molecules tend to bind and present endogenous antigens - antigens manufactured intracellularly
• Every person has approximately six different class I and II MHC gene products
• Peptide-binding groove in MHC molecules makes it unlikely that no peptides from any microbe would fit in the groove of an MHC molecule

Class II (1)

• Found mainly on immune cells
• Area that can form interactions with molecules called CD4
• CD4 produced by helper T cells - called CD4-positive/CD4+
• Antigen presentation via MHC-II molecules will be directed to CD4+ (helper) T lymphocytes only
• MHC-II molecules tend to bind and present exogenous antigens - antigens from the extracellular space

Class III (1)

• Encode for other immune components not related to antigen presentation
• Complement, cytokines

Pathogen recognition (2)

• T cell receptors can recognise a foreign antigen only if it is presented as a complex with an MHC molecule
• MHC alleles different among individuals so some can be more susceptible to a microbe than others

LO: Discuss the role of the major histocompatiblity complex (MHC) in the concept of immune tolerance and how this relates to autoimmunity

Major histocompatibility complex molecules = human leukocyte antigens (HLA)

Tolerance (2)

• Specific immune non-reactivity against a certain substance
• Should be tolerant of own body components (self-tolerance)
• Foreign antigens introduced within a few hours of birth are usually tolerated (neonatal tolerance)
• Immunisation schedules in adults may induce tolerance rather than immunity (acquired tolerance)

T cell self-tolerance breakdown (2)

• Unusual expression of human leukocyte antigen (HLA) molecules/other ligands
• T cells may not be deleted or anergised against peptides made only in that cell type
• Cross reaction of microbial peptides with uncommon self-peptides
• HLA molecules present self and foreign peptides

Hypersensitivity (1)

• Side effects of normal immune response

Type 2

• Occurs when antibodies attach to determinants on self-structures (auto-antibodies)
• Tissues damaged by classical complement activation, phagocytosis/killer activity
• Originally used to describe antibodies against blood cells, now includes antibodies against other tissues

Type 3

• Antigen-antibody immune complexes, with or without complement, cause damage to neighbouring tissue.
• Antigen may be self
• Effects can be local or systemic

Type 4

• Damage associated with the interaction between activated helper T cells and activated macrophages, or activated cytotoxic T cells and natural killer cells (delayed type hypersensitivity, DTH)

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Reference

1. Yeatman Nigel,Riva Antonio,Martin Joanne, 6 - Infection, immunology and pathology, Medical Sciences (Fourth Edition), edited by Syndercombe Court Denise MIBiol CBiol FIBMS CSci DmedT FCSFS PhD,Kadri Alice BSc MBBS MSc MFPH,Xiu Philip MA (Cantab) MB BChir MRCP MRCGP MScClinEd FHEA MAcadMEd RCPathME, 2025, Pages 237-315, ISBN 978-0-7020-8239-9, http://dx.doi.org/10.1016/B978-0-7020-8239-9.00015-7. (https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702082399000157)

2. Helbert Matthew MBChB FRCP FRCPath PhD, Chapter 3 - Introduction to Antigen Recognition, Immunology for Medical Students (Third Edition), edited by Helbert Matthew MBChB FRCP FRCPath PhD, 2017, Pages 14-17, ISBN 978-0-7020-6801-0, http://dx.doi.org/10.1016/B978-0-7020-6801-0.00003-2. (https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702068010000032)