Part 2

Discussion Notes
Part 2

Start of September 8 Discussion

Antibody structure and function

Chapter 2 and selected images from Chapters 1, 4, 6, 7 (indicated in these Discussion Notes)

the cellular response (animation - click on Antibody-mediated Immunity in the bottom row of images)

1. pre-existing specific B-lymphocytes (fig 2.1 left) bind to epitope via specific surface receptors (fig 2.1 middle) - animation

2. receive help from stimulated T-helper cells (fig 6.36) - animation

3. cell division and differentiation into antibody-secreting plasma cells (fig 2.1 right) - animation

The antibody molecules themselves

"naming" the molecule

antibody - functional

immunoglobulin (Ig) - structural

two dimentional representation (fig 2.2) of three dimensional molecule (fig 2.5a; another image)

light & heavy chains (fig 2.2)

two heavy chains (~440 amino acids each)

two light chains (~220 amino acids each)

identical amino acid sequences in both H (H=H) and both L (L=L)

amino & carboxy terminal ends

interchain dilsufide bonds (H=H, H-L)

hinge region

variable and constant regions (fig 2.2)

papain cleavage (fig 2.3)

Fab

Fc

pepsin cleavage (fig 2.3)

F(ab')

antibody isotypes (fig 2.4)

constant portion of heavy chain (fig 2.2)

NOT involved in binding to epitope

physical properties (fig 2.28)

serum levels

half-life

biological properties (fig 2.29)

infectious diseases & exotoxins

neutralization - IgG, IgA, IgM

toxin neutralization (fig. 7.22 left and fig 7.22 right) - animation

viral neutralization (fig. 7.23 top/left and fig 7.23 top/right) - animation

prevent binding of bacteria (fig. 7.23 bottom) - animation

opsonization (fig 7.25 left and fig 7.25 right) - IgG (via Fc receptors for Fc of IgG on phagocytes) - animation

agglutination (clumping) of bacteria (image)

End of September 8 Discussion
Start of September 10 Discussion

complement activation (fig 7.32) - IgM, IgG - animation

NK cells (figs 1.11 & 1.9c) and ADCC (fig 7.28 left and fig 7.28 right) - IgG - animation

allergic reactions - IgE and mast cells (fig 7.26) - animation

does IgE do anything good? (response against parasitic worms)

placental transfer (7.19) - IgG

movement into tissues (across epithelial cell barrier, fig 7.17) - IgG

epitope receptor on B-lymphocyte surface - IgM (fig 2.23), IgD (fig 4.3 far right)

isotype switching (fig 2.27) - more details

receive help from stimulated T-helper cells (fig 6.36) - animation

enhanced response (figure 1.30) - secondary response

DISCUSSION (and clicker questions) about pneumonia vaccine, conjugate vaccine (using a toxoid vaccine as the protein), involvement of T-helper2 cell in assisting B-lymphocyte (cell replication, differentiation into plasma cells and isotype switching); need peptide (protein fragment) to stimulate T-cell

End of September 10 Discussion
Start of September 12 Discussion

which isotype? - influenced by cytokines produced by Th2 cells(fig 7.14)

J-chain and polymeric antibody molecules (figs 2.26, 2.30)

importance of secretory IgA (sIgA)

movement into intestinal lumen (across epithelial cell barrier, fig 7.17)

breast milk/nursing infants

tertiary structure

domains - structural subunits (fig 2.5)

beta sheet (fig 2.6)

"loops" (fig 2.6) in V domain important in specificity

Antibody specificity - epitope binding

hypervariable amino acids (fig 2.7 top, fig 2.7 middle)

form non-covalent, weak, short-range bonds with epitope (fig 2.8)

framework amino acids (fig 2.7 top, fig 2.7 middle)

position hypervariable amino acids (fig 2.8)

antibody affinity

cross reactions

End of September 12 Discussion
Start of September 15 Discussion

B-lymphocyte epitope receptor (fig 2.23)

monomeric IgM & IgD - specificity

alpha & beta chains

intracellular signaling (fig 7.2, a really "scary" image)

Generation of antibody and B-receptor diversity

somatic recombination - animation

limited gene pool - germline genes (fig 2.14)

heavy chain segments on chromosome 14

light chain segments on chromosomes 2 (kappa) and 22 (lambda)

use this gene pool to generate 10⁶-10¹⁶ different specificities

during development of B-lymphocytes (fig 1.11)

prior to encountering epitope

V,D,J & V,J gene segment regions (figs 2.14, 2.16)

random somatic recombination (fig 2.18) - animation

V_L (fig 2.15 V_H (fig 2.15)

allelic exclusion (only one chromosome used)

junctional diversity (fig 2.19) generates additional variability

VDJ then coupled with constant gene (M, D, G, A, E) (fig 2.20)

animation and Video (QuickTime format, also need audio)

VJ coupled with either kappa or lambda constant gene (depending on chromosome used)

epitope receptors (IgM, IgD) (fig 2.21)

secreted antibody (IgM, IgG, sIgA, IgE) (fig 2.24)

somatic hypermutation

after encountering antigen

End of September 15 Discussion
September 17 Discussion - Part 3 - Antigen Recognition by T-lymphocytes