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Antibodies and their types with functions
Antibodies, also known as immunoglobulins, are Y-shaped glycoproteins produced by plasma cells that recognize and bind to specific antigens. They have a variable region that binds to antigens and a constant region that interacts with other immune system components. The five main classes of antibodies are IgG, IgM, IgA, IgD, and IgE, which differ in structure and function. Antibodies play a key role in humoral immunity by neutralizing pathogens, agglutinating foreign cells, and activating the complement system and effector cells of the immune system.
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Antibodies and their types with functions
- 1. Antibody Structure, Types andFunctions B.ASHOK KUMAR ASSISTANT PROFESSOR KRK GOVT DEGREE COLLEGE ADDANKI-523201 [email protected]
- 2. Antibody • Immunoglobulin • 20%of total plasma proteins-Humoral immunity • These are Glycoproteins belong to Immunoglobulin’s super family • They constitute most of the gamma globulins of blood proteins. • Rodney Porter and Gerald Edleman revealed the structure and got noble prize in 1972. • Large “Y” or “T” shaped protein produced by plasma cells to neutralize pathogens • Antibody recognises a unique antigen via Fab’s (Fragment of Antigen Binding ) variable region • Each tip of “Y” of an antibody contains a paratope which is specific to an epitope of Antigen
- 4. Structure of Immunoglobulins •Antibody ( immunoglobulin) - glycoproteins composed of one or more units, • each containing four polypeptide chains • Two identical heavy chains (H) & two identical light chains (L). • The amino terminal ends of the polypeptide chains show considerable variation in amino acid composition • Each L chain consists of one variable domain, VL, and one constant domain, CL. (220 Aminoacids) • The H chains consist of a variable domain, VH, and three constant domains CH1, CH2 and CH3. (440-550 Aminoacids) • Each heavy chain has about twice the number of amino acids and molecular weight (~50,000) as each light chain (~25,000), resulting in a total immunoglobulin monomer molecular weight of approximately 150,000Dts.
- 6. • Heavy andlight chains are held together by a combination of non-covalent interactions and covalent inter-chain disulfide bonds, forming a bilaterally symmetric structure. • The V regions of H and L chains comprise the antigen- binding sites of the immunoglobulin (Ig) molecules. • Each Ig monomer contains two antigen-binding sites and is said to be bivalent. • The hinge region is the area of the H chains between the first and second Constant region domains and is held together by disulfide bonds. • This flexible hinge (found in IgG, IgA and IgD, but not IgM or IgE) region allows the distance between the two antigen-binding sites to vary.
- 8. Hyper variable regions/Hotspots • Present in both heavy and light chains variable regions • The Light chain variable domain include three hypervariable regions present in between 23-34,50-56 and 89-97 amino acid moieties • In heavy chains four hot spots present in between 1- 23,35-49, 57-88 and 98-107 amino acid moieties • These are brought together to form Paratopes • Paratopes are very specific to Epitopes because of these • For Eg. IgG produced in response to different antigens show variation in these hot spots only.
- 9. Hinge region • Itis an extend peptide sequence between Ch1 and CH2 domains of heavy chain • Rich in cysteine and proline AAs , extremely variable in amino acid sequence • It provides flexibility to antigen binding part • Because of proline content, hinge is highly vulnerable to lytic enzymes viz. Papain, pepsin • Cysteine helps in disulphide bond with opposite heavy chain • Hinge is absent in IgM and IgE • Instead they have an additional constant domain which acts like hinge
- 10. Disulphide bond • Singlecovalent bond • Between thiol groups of cysteine residues • Also known as “S-S bond” or “ Disulphide bridge” • Play an important role in the folding and stability of some proteins secreted to EC medium • Total number of disulphide bonds depend upon the number of domains in the polypeptide chains of Ig molecule.
- 11. Carbohydrate Moiety • Significantamount of carbohydrate in CH2 region • It is an oligosaccharide with variable monosaccharides • May include mannose as in IgM or N-acetyl lactosamine as in IgG • No glycosylation in Fab region • Function is yet to know • May help in passage through biological membranes
- 12. Classes of Immunoglobulins •The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD and IgE. • These are distinguished by the type of heavy chain found in the molecule. • IgGs have gamma-chains • IgMs have mu-chains • IgAs have alpha-chains • IgEs have epsilon-chains and • IgDs have delta-chains.
- 14. • Differences inheavy chain polypeptides allow these immunoglobulins to function in different types of immune responses and at particular stages of the immune response. • The polypeptide protein sequences responsible for these differences are found primarily in the Fc fragment. • While there are five different types of heavy chains, there are only two main types of light chains: kappa (κ) and lambda (λ).
- 16. • Antibody classesdiffer in valency as a result of different numbers of Y-like units (monomers) that join to form the complete protein. • For example, in humans, functioning IgM antibodies have five Y-shaped units (pentamer) containing a total of 10 light chains, 10 heavy chains and 10 antigen-binding sites. • IgA is a Dimer with four antigen binding sites • IgG , IgD and IgE are monomers with two antigen binding sites
- 18. IgG • IgG, amonomer, is the predominant Ig class present in human serum. • Produced as part of the secondary immune response to an antigen, • this class of immunoglobulin constitutes approximately 75% of total serum Ig. • IgG is the only class of Ig that can cross the placenta in humans, and • it is largely responsible for protection of the newborn during the first months of life. • Because of its relative abundance and excellent specificity toward antigens, IgG is the principle antibody used in immunological research and clinical diagnostics.
- 19. The role ofIgG in the immune response • IgG is the major immunoglobulin in blood, lymph fluid, cerebrospinal fluid and peritoneal fluid and • A key player in the humoral immune response. • Serum IgG in healthy humans presents approximately 15% of total blood proteins • The Fc portion of IgG, but not F(ab´)2 or Fab fragments, can cross the placenta of a mother and enter fetal circulation, providing the fetus with postpartum protection. • IgG molecules are able to react with Fcγ receptors that are present on the surface of macrophages, neutrophils and natural killer cells, and can activate the complement system.
- 20. • The bindingof the Fc portion of IgG to the receptor present on a phagocyte is a critical step in the opsonization. • Phagocytosis of particles coated with IgG antibodies is a vital mechanism that cells use to cope with microorganisms. • IgG is produced in a delayed response to an infection and can be retained in the body for a long time. • The longevity in serum makes IgG most useful for passive immunization by transfer of this antibody. • Detection of IgG usually indicates a prior infection or vaccination.
- 21. IgG subclasses • Thereare four IgG subclasses • The subclasses differ in the number of disulfide bonds and the length and flexibility of the hinge region. • Except for their variable regions, all immunoglobulins within one class share about 90% homology, but only 60% among classes. • Determination of IgG subclasses can be a valuable tool in indicating a potential antibody deficiency. • Selective IgG subclass deficiencies are associated with disease. • In cases with prolonged or severe infections, determination of IgG levels can provide additional insight into the manifestation of disease. • It is important to interpret IgG subclass concentrations in correlation to the donor's age since the immune system matures during childhood. • Because of its relative abundance and excellent specificity toward antigens, IgG is the principle antibody used in immunological research and clinical diagnostics.
- 22. IgG class • Propertiesof IgG: • Molecular weight: 150,000 • H-chain type (MW): gamma (53,000) • Serum concentration: 10 to 16 mg/mL • Percent of total immunoglobulin: 75% • Glycosylation (by weight): 3% • Distribution: intra- and extravascular • Function: secondary response
- 23. IgG1 • IgG1 comprises60 to 65% of the total IgG • Predominantly responsible for the thymus- mediated immune response against proteins and polypeptide antigens. • IgG1 binds to phagocytic cells and can activate the complement cascade. • IgG1 immune response can already be measured in newborns and reaches its typical concentration in infancy. • A deficiency in IgG1 isotype is typically a sign of a hypogammaglobulinemia.
- 24. IgG2 • IgG2, thesecond largest of IgG isotypes, • Comprises 20 to 25% of the main subclass • The prevalent immune response against carbohydrate/polysaccharide antigens. • “Adult” concentrations are usually reached by 6 or 7 years old. • Among all IgG isotype deficiencies, a deficiency in IgG2 is the most common and is associated with recurring airway/respiratory infections in infants.
- 25. IgG3 • IgG3 comprisesaround 5 to 10% of total IgG • plays a major role in the immune responses against protein or polypeptide antigens. • The affinity of IgG3 can be higher than that of IgG1.
- 26. IgG4 • Comprising usuallyless than 4% of total IgG • IgG4 does not bind to polysaccharides. • In the past, testing for IgG4 has been associated with food allergies, and • Elevated serum levels of IgG4 are found in patients suffering from sclerosing pancreatitis, cholangitis and interstitial pneumonia caused by infiltrating IgG4 positive plasma cells. • The precise role of IgG4 is still mostly unknown.
- 27. IgM class • Propertiesof IgM: • Pentamer , Largest antibody • Molecular weight: 900,000 • H-chain type (MW): mu (65,000) • Serum concentration: 0.5 to 2 mg/mL • Percent of total immunoglobulin: 10% • Glycosylation (by weight): 12% • Distribution: mostly intravascular • Function: primary response • Eliminates pathogens in early humoral immunity before sufficient IgG.
- 28. IgA class • Propertiesof IgA: • Dimer , Secretory antibody • Molecular weight: (Alpha)320,000 (secretory) • H-chain type (MW): alpha (55,000) • Serum concentration: 1 to 4 mg/mL • Percent of total immunoglobulin: 15% • Glycosylation (by weight): 10% • Distribution: intravascular and secretions like saliva, tears, breast milk, mucosal area of gut, Respiratory tract, Urinogenital tract • Function: protect mucus membranes and prevents pathogen colonization
- 29. IgD class • Propertiesof IgD: • Monomer • Molecular weight: 185,000Dts • Half life of 2-3 days • H-chain type (MW): delta (70,000) • Serum concentration: 0 to 0.4 mg/mL • Percent of total immunoglobulin: 0.25% • Glycosylation (by weight): 13% • Distribution: lymphocyte surface • Function: 1.an antigen receptor on B-cells which are not exposed to antigens • 2.it activates basophils and mast cells to produce antimicrobial factors
- 30. IgE class • Propertiesof IgE: • Discovered by Teruka and Kimishige Ishizaka in 1966 • Scarce isotype found only in mammals • Molecular weight: 190,000Dts • Half life of 2-3 days • H-chain type (MW): epsilon (73,000) • Serum concentration: 10 to 400 ng/mL • Percent of total immunoglobulin: 0.002% • Glycosylation (by weight): 12% • Distribution: basophils and mast cells in saliva and nasal secretions • Function: protect against parasites and allergy.
- 31. Functions of Antibodies •Neutralization • Agglutination • Precipitation • Opsonization • Complement activation(Fixation) • Activation of Effector Cells • Natural Antibodies
- 32. Neutralization • Neutralizing antibodiesblock parts of the surface of bacterial cell or virion to render its attack ineffective
- 33. Agglutination • “Glue together”foreign cells into clumps • Clumps are attractive targets for phagocytosis
- 34. Precipitation • Glue-together serumsoluble antigens • Forcing them to precipitate out of solution in clumps • Clumps are attractive targets of phagocytosis
- 35. Complement activation • Fixationin which antibodies latched to foreign cell • Encourage complement to attack it with membrane attack complex which leads to – Lysis of the foreign cell – Encouragement of inflammation by chemotactically attracting inflammatory cells
- 36. Activation of Effectorcells • By coating the pathogen antibodies can activate effector functions like – Phagocytosis – Mast cells and neutrophils to degranulate – Natural killer cells will release cytokines and cytotoxic molecules – Ultimately results in destruction of invading microbe
- 37. Natural antibodies • Humansand higher primates • Defined as “antibodies produced without any previous infection, vaccination, other foreign exposure or passive immunization” • Can activate classical complement pathway leads to lysis of enveloped virus particles prior to adaptive immunity • Rejection of Xenotransplanted organs is the result of Natural antibodies