BIOL 1010U Lecture Notes - Lincoln Near-Earth Asteroid Research, Hapten, Antibody

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30 Jan 2013
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ANTIBODY STRUCTURE AND FUNCTION
INNATE ADAPTIVE IMMUNITY
genetically hardwired plastic – involves shuffling DNA
germline evolution somatic
stereotypic response varied
primary defense delayed BUT efficient
Innate immunity cannot protect against bacterial evasion mechanisms (capsulation)
innate only recognizes features common (LPS) to certain pathogens
Innate response is essential for adaptive response
MAJOR PLAYERS
B Cells – differentiate and cab secrete antibodies
secreted antigen receptor = antibody
membrane bound are involved in B cell differentiation to PLASMA cells
(T cells also help mediate differentiation)
secreted antibodies
- neutralization (toxins/viruses)
- OPSONIZATION (promotes phagocytosis upon pathogen
binding)
- COMPLEMENT assistance (leads to pore formation in
pathogen)
T cells – recognize antigens presented of SURFACE of infected cells
CLONAL SELECTION THEORY
1. B cells generate antibody diversity AT RANDOM
2. an antigen encounter leads to PROLIFERATION AND DIFFERENTIATION
3. progeny have IDENTICAL antigen recognition
4. self-responsive antibodies are deleted (TOLERANCE)
LAG period between encounter and primary response
proliferation takes time
memory cells are produced which mediate secondary response
more cells that recognize antigen to start with heightened response
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STRUCTURE – (IgG)
PAPAIN cleavage – 3 fragments
2 identical Fab’s
1 Fc
PEPSIN cleavage – 1 fragment (Fab2)
Heterogeneous response to infection – “polyclonal”
MYELOMA’s – huge homogeneous production of antibodies;
“monoclonal”
Hybridomas – fuse antibody producing B cells (from spleen) to myelomas
can screen for desired antibodies
led to antibody AA sequencing
SECONDARY STRUCTURE
“beads on a string”
every chain divided into 100 AA domains (V = variable; C =
constant)
V – binds antigen
C – invariant among antibody class
effector role
light chain – 2 domains (1V, 1C)
heavy chain – 4 domains (1V, 3C)
“superdomain” = overlap of heavy and light variable chains
heavy and light chains stitched together by sulfhidryl linkages
flexible hinge/elbow
proven by DNP/EM studies
hinge – 180 degrees flexion/ 180 rotation (between C1 and C2)
elbow – 50 flesion/ 0 rotation (between V and C1)
**increases antigen recognition variablity**
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