L16 ANTIBODY CLASSES AND T CELL-MEDIATED IMMUNITY

Antibody classes

IgG, IgA, IgM, IgE, IgD

IgA

Most abundant in humans predominately in sero-mucus secretions

Dimer structure, so valency of 4 and effective opsoniser

Protecting external body surfaces + mucosal by preventing harmful material from getting through the gut, respiratory tract, and genitourinary tract

15-20% of human blood Abs and produced after birth

IgD

Found almost exclusively on the surface of naive B cells as a triggering receptor (delivers an activation signal through antigen binding)

Only trace amounts in blood and other bodily fluids

IgE

Small amounts in the blood, but generally in the first line barriers

Important in allergies and some parasitic infections

Bind strongly to mast cells via its Fc region, binding to Fcεr and acts as a trigger for rebinding of antigens = release of histamine and other enzymes

Reduction in IgE levels reduces severity of allergies

IgG

Monomer and 70 - 75% of the Ig pool in the blood, and diffuses readily into tissues

Potent anti-toxin antibody (Neutraliser), effective barrier against viral infections, and actively transported across the placenta

Ig1, Ig2, Ig3, and Ig4 which all have different Fc regions

Ig1 and Ig3

Excellent at activating phagocytic cells and enhancing phagocytosis (opsonisers) due to an aa sequence in the Fc region having higher affinity to C_1Q and Fcγr

IgM

Pentamer with a valency of 10, mostly confined to blood and lymphatics, 10% of the Ab pool

First in primary antibody response, as it is an efficient complement activator and opsoniser

Important defence against blood-borne spread but not transported across the placenta; therefore, produced in utero > 5 months

First Ab that activated B/early plasma cells release before class switching to IgG

Antigen presentation to T-cells

Antigens (9 - 17 aa)must be processed and presented to T-cells

Vast clonal repertoire (>100mil) due to different TCRs (larger CR = more antigens we can respond to)

B-cell immunity

Antibodies

Effective against extracellular antigens

Good at neutralising virus attachment, opsonisation, enhance phagocytosis, and driving ADCC

Cell mediated (T-cell) immunity

No antibodies

Effective against extracellular and intracellular antigens

Major regulators

Good against virus-infected cells, tumour cells, and transplanted organs

T lymphocytes

All have CD3 (part of the TCR complex) and TCRs, which can be used to identify T-cells

Can be CD8 (Cytotoxic T-cells) or CD4 (Helper T-cells)

CD8/4 and TCR interact with HLA

TCR interact with antigen

CD8 T-cells

Responds to Class 1 HLA

CD4 T-cells

Responds to Class 2 HLA

Mediate cell-cell communication using cytokines

HLA genes

Class I and Class II with combined > 44,000 known alleles

HLA is synthesised inside the cell and trafficked to the cell surface with peptide antigen present in HLA groove

Class 1 HLA

>30,000 alleles

HLA-B, HLA-C, HLA-A containing ß₂-microglobulin, α and ß subunits

Found on nucleated cells

Co-dominant

Highly polymorphic

Presents to CD8

Class 2 HLA

>14,000 alleles

HLA-DP, DQ, DR containing α and ß subunits

Found on specialised APCs and B cells

Co-dominant

Polymorphic

Presents to CD4

Antigen presentation in Class 1 HLA

Viral proteins synthesised in the cell will be cleaved, then incorporated into and presented by class 1 HLA, then trafficked to the membrane for presentation

Antigen presentation in Class 2 HLA

Peptides from phagocytic pathways are then incorporated into and presented by class 2 HLA, and then trafficked to the membrane for presentation

T-cell clonal activation

In 2^o lymphoid organs

Antigen-presenting cells present the right antigen to the right T-cell → Helper signals from CD4 T-cells → Proliferation and differentiation → CD8 T-cells + memory cells