Module 2 Lesson 1: Antibodies

tetrapeptide

the four chain unit thats comon to all Ig

N-terminus

the end of the Ab that varies and changes

gives the idiotype

C-terminus

the end of the Ab that is constant

gives the isotype

heavy chain

the two inner, longer parts of the antibody

light chain

the two short, outer parts of an antibody

can either be Kappa or Lambda

how many of each chain does an Ab have?

two of each

what are the chains of an Ab held together by?

disulfide bridges

Fab region

“antigen binding”

The regions vary 

located in the N-terminus 

Fc region

part of the Ab that binds to the cell surface

helps create effector funcitons

located in the C-terminus

hinge region

gives an Ab its flexibility 

allows for antigen-independent binding and more coverage

located between CH1 and CH2

What does each domain of an antibody look like?

they have beta-pleated sheets

they fold into balloon shaped folds 

immunoglobulin folds

where the folds of the heavy and light chains meet and contain the hypervariable regions where antigen is captured

where are the hypervariable regions located?

Fab region

How many hypervariable regions are there on each chain?

3 each 

what are the functions of hypervariable regions?

determines antigen specificity 

How do hypervariable regions perform their function?

at least four complimentary determining regions (CDRs) are involved 

it also depends on the positioning of all 6 CDRs on a Fab arm 

Isotype

the heavy chain is the constant region

the class of Ig changes 

the amino acid sequence is identical for all Ab in that class type 

Idiotype

classified by unique structures in the variable region of both chains 

makes the Ab specific for an Ag

Allotype

genetic variants within the same species

having a lambda chain instead of a Kappa

structure of IgM

pentamer

four constant regions 

the largest→callled the macroglobulin"

5 monomer units held together by J chain

function of IgM

triggers the classical complement pathway

opsonization 

toxin neutralization

half life and potency of IgM

6 days

5-10%

which Ab is the only one that can pass through the placenta?

IgG

where are IgM found?

they are membrane bound to B cells as receptors

special characteristics of IgM

have no memory

the first Ig class produced 

is the most efficient Ab due to its many binding sites

structure of IgG

monomer 

3 constant regions 

4 different subtypes that differ based on # of disulfide bonds

functions of IgG

provide immunity to newborn

bind complement pathway 

opsonization 

antibody dependent cellular cytotoxicity 

agglutination 

half life and potency of IgG

23 days

70-75%

which subclass of IgG is the most efficient?

IgG3 because it has the largest hinge region 

special characteristics of IgG

high diffusion coefficient (can enter extravascular)

has memory response 

structure of IgA

either a monomer of dimer

3 constant regions 

2 subtypes (depends on location)

functions of IgA

partol mucosal surfaces

anti-inflammatory agent (downreg IgG)

where are the subtypes of IgA located?

IgA1 is mainly in serum (monomer)

IgA2 is found in secretions (dimer)

half life and potency of IgA

5 days

10-15%

whats special about IgA2?

it is produced by plasma cells

special characteristics of IgA

transported via transcytosis with Secretory component 

found in neutrophils, monocytes, macrophages

secretory component (SC)

a protein that attaches to the Fc region around the hinge of alpha chians

strucutre of IgD

monomer

3 constant regions 

unusually long hinge region 

function of IgD

found on B cells (maturation/differentiation)

also found in serum 

half-life and potency of IgD?

1-3 days

less than 0.001%

structure of IgE

monomer

4 constant regions 

functions of IgE

meidates histamine and heparin release from mast cells

allergic reactions 

anti-parasitic 

half life and potency of IgE?

2-3 days

0.0005%

special characteristics of IgE

bind to eos, basos, tissue mast cells, and langerhans cells

primary response 

First exposure to an antigen 

1. lag phase: no Ab detection and none in serum for several days

2. log phase: Ab titere increases 

3. plateau: Ab titer stabilizes and most B cells become plasma and some become memory 

4. decline: Ab are catabolized

what is the primary class of Ab in primary response?

IgM

secondary reponse

same four phases as primary

the response changes 

a subsequent exposure to the same antigen 

shorter lag phase 

longer plateau 

more gradual of a decline 

what Ab is the predominant one in the secondary response?

IgG 

creates a higher total concentration 

Erlich’s side-chain theory

1900s

certain cells have receptors for a specific antigen that appear before contact 

Those receptors will break off and circulate as Ab

Jerne and Burnet addition

1950s

lymphs are genetically preprogrammed to respond to one antigen (only one isotype)

Deryer and Bennett addition

1965

separate genes code Constant and variable regions of Ig

which chain rearranges first?

the heavy chain

where are the heavy chain genes found?

chromosome 14

what are the variable regions on the heavy chain?

V D and J

How does the heavy chain rearrange?

one choice for each region (VDJ and C) are chosen and commits to one specificity for a B cell 

where are the genes for the light chain found?

Kappa is found chromosome 2

lambda is found on chromosome 22

what are the variable regions for the light chain

V and J

which gene rearranges first on the light chain?

Kappa

how is lambda formed?

only if a nonfunctional product is produced on chromsome 2 (accounts for why Kappa is more prevalent)

what happens after light chain rearrangements?

The light chains combine with mu chains in maturing B cells to form IgM

how is class switching initiated?

by T helper cells and cytokines

how does class switching happen?

the C region is spliced off so another class combines with the same VDJ region 

what is the product of class switching?

a different class of antibody witht eh same specificity for an antigen (IgM for a antigen becomes IgG for the same antigen)

monoclonal antibodies

antibodies that are derived from a single plasma cell to produce identical antibodies 

what are the clincial applications of monoclonal anitbodies?

in vitro diagnostics

therapeutic treatments

autoimmune treatments