Theme 5

Generation of diversity in immunoglobulin

Antibody repertoire - total number of antibody specificities available to an individual

Germline theory - each antibody is encoded by a separate gene

Somatic diversification - antibodies arise from gene segment rearrangement during B cell development

Mechanisms for generating antibody diversity

V(D)J recombination - genetic shuffling of V, D and J gene segments

Somatic hypermutation - point mutations in activated B cells increase affinity

Class switch recombination - switches the antibody constant region to change its class without altering specificity

V(D)J recombination

One D segment and J segment selected randomly, DNA in between is cut out, DJ join

One V segment is chosen and joined to previously formed DJ, DNA segments are cut using RAG-1 and RAG-2 enzymes

The VDJ sequence is transcribed into mRNA and gets translated into the variable region of the antibody

The variable region is then joined with constant C region

This determines antibody class

Apoptosis

Programmed cell death

Prevents the overaccumulation of lymphocytes

B cells that are not activated undergo apoptosis

Infected cells can self destruct to limit infection spread

Clonal selection

Specific B and T cells are selected and expanded when encountering antigen

Tolerance - immune system avoids self-reactivity

Clonal detection - self reactive cells are removed early in development

Agglutination

Antibodies cause antigens to clump together

Clumped microbes are easier to trap and remove

Phagocytes can ingest multiple pathogens at once

Example → wrong blood perfusion causes RBC agglutination

Opsonization

Antibodies coat the surface of a pathogen, Fc region of antibody sticks out

Phagocytic cells (like macrophages and neutrophils) have receptors for the Fc region

When they bind, they are stimulated to engulf and destroy the pathogen

Neutralization

Antibodies bind to viruses, toxins or bacteria and block their ability to bind to host cells

This neutralises toxins by blocking their active site

IgG

Complement activation

When antibodies bind antigens (especially IgG or IgM), they can activate the complement system → a group of plasma proteins

This complement forms membrane attack complex which punches holes in membranes to cause cell lysis

It can attract immune cells and enhances phagocytosis

T-cell and cell-mediated immunity

Targets intracellular antigens

Requires antigen presentation MHC

T Helper cells

Most are CD4+

Recognise antigen presented by antigen presenting cells like macrophages

Activates macrophages

Stimulate B cells and cytotoxic T cells

Cytotoxic T cells

Most are CD8+

Kill infected or abnormal host cells (cancer, transplant tissues)

Use perforin to create pores in the target cell → causes lysis

Undergo apoptosis when antigen is cleared

T-dependent vs T-independent antigens

T dependent → require helper T cells, stronger response, antigens are mainly proteins

T independent → do not require T cells, antigens are mostly polysaccharides with repeating subunits, weaker response

Antibody-dependent cellular cytotoxicity (ADCC)

Target cell is covered with antibodies (Fc portion sticks out)

Involves NK cells

Target organism is lysed by substances secreted by attacking cells (cytotoxic granules)

Used to destroy large organisms that cannot be phagocytosed

Overview