Antibodies and Antigens Flashcards
What are antibodies?
Circulating proteins that are produced in vertebrates in response to exposure to foreign structures known as antigens. Mediators of humoral immunity against all classes of microbes
diverse and specific
What term is often used interchangeably with Abs?
Immunoglobulins
How were antibodies first discovered?
In serum as serum molecules that provided protection against diphtheria toxin, and thus termed antitoxins
What are the three classes of molecules used by the adaptive immune system to bind antigens?
Antibodies
MHC molecules
T cell antigen receptors
What are antibodies only synthesized by?
Cells of the B lymphocyte lineage
What are the two forms antibodies exists as?
Membrane-bound antibodies on the surface of B lymphocytes: function as antigen receptors
Secreted antibodies: neutralize toxins, prevent entry and spread of pathogens, and eliminate microbes
What do membrane bound antibodies on naive B cells do?
When the antibody recognizes antigen, it activates these lymphocytes and initiates a humoral immune response
Where are secreted forms of antibodies present?
In the plasma, mucosal secretion, and the intersitial fluid of tissues
What happens to secreted antibodies during the effector phase of humoral immunity?
The secreted antibodies bind to antigens and trigger several effector mechanisms that eliminate the antigens
What are the effector properties of Abs?
Toxin neutralization Activation of complement system Opsonization Immunomodulation-> reduced damage to host from inflammatory response->organized T-cell response Direct antibacterial activity
Define serum
Is the component that is neither a blood cell nor a clotting factor; It includes all proteins not used in blood clotting including antibodies
When blood or plasma forms a clot, where are the antibodies?
They remain in the residual fluid, which is called serum
Define antiserum
Any serum sample that contains detectable antibody molecules that bind to a particular antigen
Define serology
The study of antibodies and their reactions with antigens
How many antibodies does a healthy adult human produce? What is the type of the majority of antibodies produced?
2 to 3 g everyday
2/3 is IgA: produced in the walls of gastrointestinal and respiratory tracts
How can plasma or serum proteins be physically separated?
By solubility characteristics into albumins and globulins
And may be more precisely separated by migration in electrophoresis
Plasma or serum proteins are divided into migrating groups in electrophoresis. What are the groups? Which group are most antibodies found?
Albumins, alpha 1-, alpha 2- (alpha1 and 2 count as one), beta-, and gamma-globulins
Most antibodies are found in the third fastest migrating group of globulins, named gamma globulins for the third letter of the Greek alphabet
What term is used to refer to the immunity-conferring portion of the gamma globulin fraction?
Immunoglobulin
How does each antibody differ?
All antibody molecules share the same basic structural characteristics but display variability in the regions that bind antigens
The effector functions and common physiochemical properties are associated with the non-antigen binding portion-few variations
An antibody molecule has a symmetric core structure composed of what?
Two identical light (L) chains and two identical heavy (H) chains
=four polypeptide chains
The repeating homologous units in both the light chains and heavy chains fold independently in a globular motif called what?
Ig domain
What does an Ig domain contain?
Two layers of beta-pleated sheets held together by a disulfide bridge
Both H and L chains have ________ every 90 amino acid residues, which creates _________ domains, of 110 amino acids
Intrachain disulfide bridges
polypeptide loops
What are the antigen-binding sites formed by?
Juxtaposition of VL and VH domains
ABS have a basic unit of how many polypeptide chains?
4
What are the two light (L) chains and heavy (H) chains bound together by?
Covalent disulfide bridges as well as by noncovalent interactions
Abs can be proteolytically cleaved to yield what?
two Fab fragments and an Fc fragment
What are both H and L-chains divided into?
V and C regions
How many domains are in the V and C regions of heavy chains?
V region is composed of one Ig domain and the C region is composed of three or four Ig domains
How many domains make up the V and C regions of light chains?
Each light chain is composed of one V region Ig domain and one C region Ig domain
What regions participate in antigen recognition and binding?
V regions
What regions participate in determining the fate of the Ag and mediate effector functions?
C regions
Paired VL and VH domains retain the ability to bind antigen and are called ______ fragment
Fab
VL-CL associated with VH-CH1
Two identical disulfide-linked peptides, each containing the heavy chain CH2 and CH3 domains have the propensity to self-associate and to crystallize into a lattice and are called ____ fragment
Fc (fragment, crystallizable)
There are five different kinds of H-chains referred to as what?
γ, δ, α, μ and ε
What type of H-chain determines IgM?
μ
What type of H-chain determines IgD?
δ
What type of H-chain determines IgG?
γ
What type of H-chain determines IgE?
ε
What type of H-chain determines IgA?
α
What are the two types of L-chains that have a MW of 23 kDa each?
κ and λ
Each Ab unit can have only (fill in blank) but not both
Only κ or λ L-chains
The domains of the V and C regions are referred to as what?
VH, VL, CH1, CH2, CH3 etc
What do heavy chain C regions end in?
Tail pieces
True or False?
The location of complement - and Fc receptor-binding sites within the heavy chain constant regions are accurate
False: they are approximations
Compared to a secreted IgG, membrane-bound IgM on B cells have ____ more CH domain(s) than IgG has
One
Membrane-bound IgM on B cells have C-terminal ________ and ______ portions that anchor the molecule in the plasma membrane
Transmembrane and cytoplasmic portions
When papain is used with IgG, the enzyme acts on what region?
It cleaves at the hinge region
What does papain digestion allow?
THe separation of two Fab fragments and complement- and Fc receptors-binding the Fc fragment
Where does pepsin cleave IgG?
Distal to the hinge region
What does pepsin generate from IgG?
A single bivalent antigen-binding fragment, F(ab’)2
How can Abs bind to both widely spaced cell surface determinants and closely spaced cell surface determinants?
Because the hinge region allows flexibility between the CH1 and CH2 domains
A large group of cell surface and soluble proteins that are involved in the _____, ______, or ______ processes of cells belongs to the immunoglobulin superfamily.
recognition, binding, or adhesion
What are 6 examples of Ig superfamily proteins in the immune system?
membrane-bound IgG molecule T cell receptor; TCR MHC class I molecule CD4 coreceptor of T cells CD28: costimulatory receptor on T cells Adhesion molecule ICAM-I
Proteins that contain domains with an Ig fold structure (two adjacent beta-pleated sheets held together by a disulfide bridge) belong to what family?
Ig superfamily
Most of the sequence differences and variability among different antibodies are confined to what?
Three short stretches in the V region of the heavy chain and three stretches in the V region of the light chain
What are segments of the greatest diversity known as?
Hypervariable regions; also called complementarity-determining regions (CDRs)
How many CDRs are in the Ag-binding site of T cell receptors?
Three CDRs in V-alpha and three CDRs in V beta domains
What types of Ag may be bound to immunoglobulins?
Proteins, lipids, polysaccharides and small chemicals
What types of Ag may be bound to T cell receptors?
Peptide-MHC complexes
What antigenic determinants are recognized by immunoglobulins?
Linear and conformational determinants of various macromolecules and chemicals