CH 5

antibody

glycoproteins found in the serum portion of blood
approx 20% of plasma

gamma band

gamma

gamma globulin

antigen recognition of biological activities related to immune response
ex. Opsonization and complement activation

heavy chain
IgG, IgM, IgA, IgD, IgE

the regions that make up abs. (approx 110 aa)

tetrapeptide

2 heavy (H) chains and 2 light (L) chains

noncovalent forces and disulfide interchain bridges

no antigen-binding ability
represents halves of 2 H chains that are held together by S-S bonding

effector functions of Abs. (like opsonization and complement fixation)

Fab fragments (2)

able to form a cross-linked complex with antigen

1 L chain and 1 H chain held together by disulfide bonding

cleaves IgG at carboxy-terminal side of interchain disulfide bonds
separates Fab from Fc?

L chains being secreted by malignant plasma cells
made it possible to isolate L chains

Kappa chains
lambda chains

the same sequence of amino acids on both kappa and lambda chains (L chain)

amino terminal of L chain

no

constant regions of H chain

H chain is unique to each immunoglobulin class

genetic variations in the constant regions

variable portions of each chain that are specific to abs. molecule and give abs. specificity

essential in formation of antigen-binding site; serves as antigen-recognition unit]

between Ch1 and Ch2 of H chain

proline and hydrophobic residues

allows for flexibility; allows Fab arms to cover more territory
& initiation of complement & binding to cells with specific Fc receptors

gamma, delta, alpha

mu and epsilon

carbohydrate portion
(localized between Ch2 and 2 H chains)

1. increasing solubility of abs.
2. providing protection against degradation
3. enhancing functional activity of Fc domains

binding region that helps capture antigens

small number of aa can create immense diversity (?)

IgG (70-75% of total serum abs.)

IgG1, IgG3, IgG4

IgG2

1. provide immunity for newborn
2. fixing complement
3. coats ag for opsonization (phagocytosis)
4. neutralizing toxins and viruses
5. agglutination and precipitation reactions

response to protein ags

polysaccharide ags

enhances contact between antigen and phagocytic cells, to increase phagocytosis

initiating phagocytosis (bc bind most strongly to Fc receptors)

high diffusion coefficient that allows it to enter extravascular spaces more readily than another abs.

precipitation involves small soluble particles, more easily brought together by relatively small IgG molecule

IgM (bc its larger)

J or joining chain

glycoprotein that serve as linkage points of disulfide bonds between 2 adjacent monomers

initiate polymerization by stabilizing Fc so that crosslinking can occur
and facilitates secretion at mucosal surfaces

10

primary response antibody

IgM

presence indicates primary exposure to ag

long lag phase, slow increase in abs., short lived response

shortened lag period, faster rise in abs., higher serum levels for longer period of time

larger number of ag-specific memory T and B cells generated during primary response

1. complement fixation
2. agglutination
3. opsonization
4. toxin neutralization

single molecule can initiate the reaction as a result of multiple binding sites

classifies lymphocytes as immature B cells

makes IgA2 more resistant to some bacterial proteinases that are able to cleave IgA1

anti-inflammatory

IgG-mediated phagocytosis
chemotaxis
bactericidal activity
cytokine release

respiratory, urogenital, and intestinal mucosa
breast milk, colostrum, saliva, tears, sweat

because its found in mucosal surfaces

polymerization and secretion of IgA

attached to Fc region around the hinge portion of alpha chains

from secretory precursor on epithelial cell and goes through transcytosis

When IgA and SC precursor taken inside the cell together and released to opposite surface

facilitates transport of IgA and makes dimer more resistant to enzymatic digestion

patrol mucosal surfaces (act as first line of defense)

neutralizing toxins by microorganisms and prevent bacterial and viral adherence to mucosal surfaces

through breastfeeding; helps maintain healthy newborns by passively transferring abs.

no

helps clear antigen without triggering inflammatory response (minimize tissue damage)

multiple myeloma

surface of immunocompetent but unstimulated B cells

B cell activation

respond to T cell help
and switching synthesis of IgG, IgA, or IgE
and regulating B cell maturation and differentiation

long hinge region

no

ability to activate mast cells and basophils

IgE

results in conformational changes and loss of ability to bind target cells

attach to basophils, Langerhans, eosinophils, and tissue mast cells

results in degranulation of mast cells, releasing histamine and heparin

release of mediators (histamine and heparin)

triggering acute inflammatory reaction that recruits neutrophils and eosinophils to area

constant and variable portions of antibody chains are actually coded for by separate genes

through random selection process

H genes - chromosome 14
k - chromosome 2
lambda - chromosome 22

needed for genes to become functional abs

if the first rearrangement is non-productive, then rearrangement of the second set occurs until successful

V D J

C

D and J

join variable region (V)

early in B cell development on pro-B cell

RAG-1 RAG-2

needed to initiate process; recognize recombination signal sequences

V J D not always are a fixed position, leading to more diversity

looping out and deletion of C regions

V J and then Ck (constant)

removed during RNA splicing

derived from a single parent ab-producing cell that has reproduced many times, forming a clone

fusion of activated B cell with lab grown myeloma cell that cannot make own DNA (missing HGPRT)

permanent and uniform supply of monoclonal antibody that reacts with a single epitope