Lecture #4: Adaptive Ag Recognition Flashcards
(32 cards)
Fab/Fc Fragments
Fab = fragment Ag binding
Fc = fragment crystallized)
Both have effector functions
Where are most Abs found in the globulins?
Third, slowest migrating group i.e. “gamma” globulins
Effector Properties of Abs
Immunomodulation
Reduce host damage from inflammation
Organized T cell response
Opsonization
Activate complement system
Toxin neutralization
Direct antibacterial activity
Papain
Cleaves IgG at the heavy chain into two Fab fragments and complement: Fc receptors binding the Fc fragment
Proteolysis of IgG by Pepsin
Generates a single bivalent Ag-binding fragment F(ab’)2
Five classes of Abs
IgM, IgD, IgG, IgE, IgA
Two different kinds of light chains:
K and delta
Ab unit can only have one or the other at one time
Ig Superfamily Proteins
T cell receptor MHC Molecules CD4 coreceptor of T cells CD28 ICAM-1
Properties of Secreted IgG
Ag-binding sites formed by juxtaposition of VL and Vh domains
Heavy chains C regions end in tail pieces
The locations of complement-Fc RC-binding sites within the heavy chain constant regions are approximation
Properties of Membrane-bound IgM on B cell
One more CH4 domain than IgG
Has C terminal transmembrane and cytoplasmic portions that anchor in the plasma membrane
Locations of Ab Hinges
Between Ch1 and Ch2 domains
Structure/function/concentration of IgA
Mainly dimer, also monomer, trimer
Mucosal immunity
3.5mg/ml
Structure/function/concentration of IgD
Monomer
Naive B cell Ag Rc
Trace
Structure/function/concentration of IgE
Monomer
0.05mg/ml
Defense against helminthic parasites, immediate hypersensitivity
Structure/function/concentration of IgG
Monomer
13.5mg/ml
Opsonization, complement, Ab dependent cell mediated cytotoxicity, neonatal immunity, feedback inhibition of B cells
Structure/function/concentration of IgM
Pentamer
1.5mg/ml
Naive B cell Ag receptor, complement activation
Ab Affinity
Lower in the primary response but higher in the memory response to Ags, they have a higher binding constant and are less likely to dissociate
Valence of an Ab
Max number of antigenic determinants with which it can react
Ex: IgG has two Fab regions that can two Ags, so it has a valence of 2
Increases the affinity
Avidity
Overall strength of an Ab-Ag complex
Dependent on:
- affinity of Ab for epitope
- Valence of both Ab and Ag
Steps in production of monoclonal Ab
Splenocytes from mouse immunized with known Ag isolated
Cells fused to myeloma cells with polyethylene glycol (myeloma cells don’t secrete own Ig)
Cells placed in HAT (hypoxanthine, aminopterin, thymidine) only they survive because they lack HGPRT
Aminopetrin
Blocks de novo purine synthesis during production of monoclonal Ab
Basic Structure of TCRs
Membrane bound, heterotrimeric with A and B chain
Each chain has one variable and one constant region
In V region, there are 3 complentarity-determining regions (CDR) each corresponding to a loop in V domain
Structure of the TCR Complex
A/B TCR non-covalently linked to the CD3 and zeta proteins which are the signal transducing subunits
Association mediated by charged residues in transmembrane regions
A/B chains carboxyl cyto tails 5-12 aa long
CD4 vs CD8 Co Receptor Structures
CD4: 4 extracellular Ig-like domains, hydrophobic TM region, basic cyto tail 38 aa long
CD8:
made of CD8a/b which have = Single extracellular Ig domain, hydrophobic TM region, basic cyto tail 25 aa long
