Ag recognition in adaptive immunity

MHC molecules

Major histocompatibility complex molecules

What is the process called for T cells to recognise antigens?

MHC restriction

How do T cells recognise antigens?

Processed into peptides by APCs breaking them down → Presented and loaded onto MHC molecules = peptide-MHC complex

CD4+ T helper cells

Exogenous antigens

MHC Class II

CD8+ cytotoxic T cells

Recognise endogenous antigens

MHC Class I

Why is MHC restriction important?

Ensures that T cells respond only to antigen in correct cellular context

MHC Class II APCs

Dendritic cells

Macrophages

B cells

TCR structure

Membrane-bound heterodimer

Composed of a and b chains, each has V and C regions

V regions - form single antigen-binding site that recognises p-MHC complexes

Short cytoplasmic tail

Relies on CD3 complex for signal transduction

What does CD3 do in TCRs?

Transmits intracellular signals via ITAM motifs → T cell activation

CD3 chains are required for cell surface expression of TCR-CD3 complex and signalling through the TCR - CD3 is a protein multi-subunit protein complex that is an essential signaling component of TCR complex

What does each antibody consist of?

2 identical heavy chains

2 identical light chains

Linked by disulfide bonds

What do the arms of antibody contain?

Variable regions of both chains that form the antigen-binding sites, specifically for particular epitopes (complementarity-determining regions (CDRs)

Constant region

Determines antibody’s class and effector function

2 main functional regions in antibody

Fab and Fc

Fab region

Responsible for antigen binding - V + C

Fc region

Mediates effector functions such as binding to Fc receptors and complement activation (opsonisation, antibody-dependant cellular cytotoxicity (ADCC) - signals immune cells to destroy

IgG

Most abundant in serum (80%)

Cross placenta = neonatal immunity

Dominates secondary responses

Reacts with FcR’s on phagocytic cells to promote opsonisation and are strong activators of classical complement pathway and placental transport

Monomer diffuses into tissues

Highly versatile - mediates opsonisation, ADCC, complement activation

IgA

Second most abundant In serum

Most abundant in external excretions

Exists as monomer in serum but predominantly as a dimer in secretions linked by J chain and associated with a secretory component that protects it from enzymatic degradation - saliva, tears, breast milk, gut

Primary defender on mucosal surfaces, preventing pathogens from adhering to epithelial cells, traps pathogens within mucus, allowing removal when secretions are expelled, neutralises viruses and toxins in mucosal environment

IgE

Very low concentration in serum

Fc region binds to Fc receptors on basophils and mast cells, causing degranulation and release of histamine = allergies and hypersentivity response

Cross linking of IgE by antigen induces degranulation = allergic reactions and defence against helminths

IgM

Expressed as a monomeric BCR

Secreted IgM found as a pentamer linked by J chain → pentameric structure gives IgM high avidity for Ag and makes it extremely efficient for activating complement

Large size means it largely confined to bloodstream and doesn’t cross placenta

3rd most abundant and 1st antibody produced in primary immune responses by b cells

IgD

Monomeric and low contractions in serum

Expressed as a membrane-bound receptor on naive cells alongside IgM

Functions less defined by BCR for b cell activation