Please enable JavaScript.
Coggle requires JavaScript to display documents.
IMMUNOGLOBINS, SANDHYA A 191822016 - Coggle Diagram
IMMUNOGLOBINS
DEFINITION
An antibody (Ab), also known as an immunoglobulin (Ig),is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.
-
FUNCTION
Neutralisation, in which neutralizing antibodies block parts of the surface of a bacterial cell or virion to render its attack ineffective
Agglutination, in which antibodies "glue together" foreign cells into clumps that are attractive targets for phagocytosis
Precipitation, in which antibodies "glue together" serum-soluble antigens, forcing them to precipitate out of solution in clumps that are attractive targets for phagocytosis
Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it with a membrane attack complex.
-
-
-
-
-
ISOTOPES
IgA: A dimer secreted into mucosal surfaces, such as the gut, respiratory tract, and urogenital tract, that prevents mucosal invasion into the body by pathogens. It is resistant to the proteolytic enzymes found in the gastrointestinal mucosae.
IgD: Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It has been shown to activate basophils and mast cells to produce antimicrobial factors.
IgE: Found in circulation and binds to allergens, triggering histamine release from mast cells and basophils. Also protects against parasitic worms.
IgG: Has four different forms and provides the majority of antibody-based immunity against invading pathogens as the best opsonin of any type of antibody. This is because it expresses a tail for Fc receptors on phagocytes to bind to, which activates phagocytosis. It is the only antibody capable of crossing the placenta to give passive immunity to fetus, and can activate the classical complement system.
IgM: Expressed on the surface of B cells (monomer) and in a secreted pentamer with very high avidity. Eliminates pathogens in the early stages of B cell-mediated (humoral) immunity before there is sufficient IgG. Like IgG, it can also activate the classical complement system.
STRUCTURE
Antibodies are heavy (~150 kDa) globular plasma proteins. The size of an antibody molecule is about 10 nm.They have sugar chains (glycans) added to conserved amino acid residues. In other words, antibodies are glycoproteins
Immunoglobulin domains
The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.
Heavy chain
There are five types of mammalian Ig heavy chain denoted by the Greek letters: α, δ, ε, γ, and μ
Light chain
In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ)
CDRs, Fv, Fab and Fc regions
IMMUNOGLOBIN DIVERSITY
Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens
-
-
-
-
-
-
-
REGULATION
Production and testing
The demonstration that the process is able to produce in good quality (the process should be validated)
-
The characterization of purified antibody (physicochemical characterization, immunological properties, biological activities, contaminants, ...)
-
Preclinical studies
Testing cross-reactivity of antibody: to highlight unwanted interactions (toxicity) of antibodies with previously characterized tissues. This study can be performed in vitro (Reactivity of the antibody or immunoconjugate should be determined with a quick-frozen adult tissues) or in vivo (with appropriates animal models).
Preclinical pharmacology and toxicity testing: preclinical safety testing of antibody is designed to identify possible toxicity in humans, to estimate the likelihood and severity of potential adverse events in humans, and to identify a safe starting dose and dose escalation, when possible.
Animal toxicity studies: Acute toxicity testing, Repeat-dose toxicity testing, Long-term toxicity testing
Pharmacokinetics and pharmacodynamics testing: Use for determinate clinical dosages, antibody activities, evaluation of the potential clinical effects
Before clinical trials
Product safety testing: Sterility (bacteria and fungi), In vitro and in vivo testing for adventitious viruses, Murine retrovirus testing. Product safety data needed before the initiation of feasibility trials in serious or immediately life-threatening conditions, it serves to evaluate dangerous potential of the product.
Feasibility testing: These are pilot studies whose objectives include, among others, early characterization of safety and initial proof of concept in a small specific patient population (in vitro or in vivo testing).
-