Chap 25C - Infectious diseases

Describe IgG

• Common serum antibody

• Secreted after the plasma cell has undergone further development

• Plays an important role in neutralisation of pathogens and initiation of antibody-dependent cell-mediated cytotoxicity

• Only IgG can cross the placenta to confer passive immunity on foetus

State classes of antibodies

IgM, G, A, E, D

Describe functions of antibodies

1. Antibodies bind to pathogens and prevent them from infecting cells -> neutralising the pathogens

2. Antibodies coat (opsonise) pathogens and target them for phagocytosis, as phagocytes (neutrophils, macrophages) express Fc receptors specific to heavy chains of antibodies.

3. Antibodies can clump bacteria together to facilitate phagocytosis by macrophages (agglutination)
   

4. Antibodies binding to the surface of a pathogen can activate the proteins of the complement system (of innate IS)

Describe coding in light chains

• 2 gene clusters coding for the light chains of antibodies, found on ch 2 + 22

• Each cluster includes a series of variable (V) genes, (J) genes and constant (C) genes

• An individual B cell will express 1 of the 2 gene clusters to produce 1 type of light chain (NEVER both)

Describe coding in heavy chains

• 1 gene cluster coding for the heavy chains of antibodies, found on ch 14

• Includes a series of variable (V) genes, diversity (D) genes, joining (J) genes, constant (C) genes

Describe somatic recombination

• The V, (D) and J genes are assembled via somatic recombination OR V(D)J recombination during B cell development in the bone marrow

• Helps diversify the antigen binding sites of antibodies

Describe somatic recombination of light chains

• 1 of the V genes randomly recombines with 1 of the J genes at the DNA level to create a conjoined VJ pair catalysed by recombinase enzymes, with the intervening DNA removed and degraded

• Hundreds different VJ units can be generated in different B cells

• The rearranged light-chain gene cluster contains a short Leader (L) exon, intron, a joined VJ gene segment, a second intron, constant (C) exon region, and a promoter sequence lying upstream of the L segment

• Transcription begins at the L exon and continues through the C segment to the termination signal -> generates a light-chain pre-mRNA that undergoes splicing, which joins the VJ segment to the C exon to form the mature mRNA to be translated into the light chain polypeptide

Describe somatic recombination of heavy chains

• 1 of the D genes randomly joins to 1 of the J genes -> 1 of the V genes joins the rearranged DJ gene segment

• Intervening DNA is removed and degraded.

• Thousands of different VDJ units can be generated in different B cells

• Heavy chain pre-mRNA containing the VDJ gene segment and constant (C) exons is transcribed -> splicing joins VDJ gene segment to the C exons to form the mature mRNA to be translated into the heavy chain polypeptide

Describe post somatic recombination

• After light and heavy chain polypeptides have been translated at RER -> they are transported to GA for assembly into antibodies

• Assembled antibodies are embedded at cell surface membrane as B cell receptors (naïve B cells) OR secreted (plasma cells/effector B cells)