Lec5
T or F: Fab have composed only of constant region
F, variable & constant
In humans there are........classes of heavy chains designated by........
Five, gamma (ɣ),alpha (α), mu (μ), delta (δ), and epsilon (ε).
Antibody idiotypeis determined by :
Gene rearrangement ,Junctional diversity ,Somatic hyper-mutations
Immunoglobulins are ......
Glycoprotein molecules that are produced by plasma cells in response to an immunogen (antigen).
properties of these heavy chains determine the five immunoglobulin.
IgG, IgA, IgM, IgD, and IgE
The subclass of IgG
IgG1, IgG2, IgG3, and IgG4.
Immunoglobulin allotype is
Its the allele of the antibody chains found in the individual.
The secretory piece function.....
help the IgA to be transported across mucosa and also protects it from degradation in the secretions.
Especially large number ofpolymorphismswere discovered in IgG antibody subclasses which used in
forensic medicine and in paternity testing,
IgA increases in:
1) Most cases of Cirrhosis of the liver. 2) Certain stages of collagen & other autoimmune disorders such as rheumatoid arthritis & lupus erythematosus. 3) Chronic infections not based on immunologic deficiencies.
IgM increases (in newborns) :
1)- rubella virus. 2)- cytomegalovirus. 3)- syphilis. 4)- toxoplasmosis.
IgG increase in .......
1)Chronic granulomatous infections. 2) Rheumatoid arthritis. 3) Hyperimmunization. 4) Liver disease. 5) Severe Malnutrition.
What is the Immunoglobulin Basic Structure?
1-Heavy and Light Chains. 2-Disulfide bonds.
How is this diversity generated?
(1) Rearrangement of antibody gene segments, called combinatorial joining. (2) Generation of different codons during antibody gene splicing. (3) Somatic mutations.
Properties of IgM
-3rd most common serum Ig. -the first Ig to be made by the fetus& by virgin B-cells when it is stimulated by Ag. -IgM is a good complement fixing Ig. -good agglutinating. -IgM binds to some cells via Fc receptors. - B-cell surface.
What are Functions of Immunoglobulins ?
-Antigen binding (primary function) -Effector Functions (Usually require Ag binding)
How Do B Ce lls Produce Antibodies?
-B cells from stem cells in the bone marrow of adults (liver of fetuses). -After maturation B cells migrate to lymphoid organs (lymph node or spleen). -when they encounter Ag it recognizes it stimulated & divides to many clonal = plasma cells which secret antibodies.
Effector Functions of the immunoglobulin?
-Fixation of complement ->Leading to lysis of cells, release of biologically active molecules -Binding to various cell types-> cells that have Fc receptors for immunoglobulins and the binding can activate the cells to perform some function .
IgA properties
-IgA is the 2nd most common serum Ig. -IgA is the major class of Ig in secretions -> tears, saliva, colostrum & mucus -Normally IgA does not fix complement, unless aggregated. -IgA can bind to some cells.
IgD properties:
-IgD is found in low levels in serum -IgD is primarily found on B-cell surfaces where it functions as a receptor for Ag. -IgD does not bind complement.
IgE properties:
-IgE is the least common serum. -involve allergic reactions. -plays a role in helminthic parasitic diseases. -binding of eosinophils to IgE-coated helminths results in killing of the parasite. -IgE does not fix complement.
Disulfide bonds in immunoglobulin structure contains ....
-Inter-chain bonds: heavy and light chains and the two heavy chains are held together. -Intra-chain bonds: Within each of the polypeptide chains.
Binding the Fc for immunoglobulin and cells activate function like.....
-Opsonization -antibody-dependent cell-mediated cytotoxicity. (ADDC) -Activation of the classical complement system -immunoglobulins bind to receptors on placental trophoblasts leading to its transfer across the placenta.
Properties of IgG
-major in serums 75% -major Ig in extra vascular spaces. -only class of Ig that crosses the placenta. -Fixes complement -Binding to cells .
Describe the AgG structure?
-monomers.
IgM structure
-pentamer or monomer. -has an extra domain on the μ chain (CH4) -J chain-> This chain functions in polymerization of the molecule into a pentamer.
IgE increase in:
1) Atopic skin diseases such as eczema. 2) Hay fever. 3) Asthma. 4) Anaphylactic shock.
IgM increases (in adults) in:
1) Malaria. 2) Infectious mononucleosis. 3) Lupus erythematosus. 4) Rheumatoid arthritis
Domains are
3 D images of the immunoglobuline molecule shows that it is not straight. But, it is folded into globular regions each contains an intra- chain disulfide bond.
How many chain structure in Immunoglobulin?
4
T or F: Not all subclasses bind equally well; IgG1 & IgG4 do not bind to Fc receptors.
F, IgG2
T or F: Some of allotypic determinants may be present at places that are well exposed and therefore can be hardly serologically discriminated.
F, not exposed
T or F: Fc are composed constant & variable regions
F, only constant.
T or F: Each B cell produces antibodies that will recognize more than one epitope.
F, only one.
VL and VH together they form......
Antigen binding sites.
Oligosaccharides in immunoglobulin structure are
Carbohydrates are attached to the CH2
region of heavy and light chain are ....
Constant (C) regions (CL and CH) > a.a is the same in all classes variable (V) regions (VL and VH) > a.a different sequences.
CDRs , means that there is.......
Differences in amino acid sequence more frequently than the rest of the variable domain. These determine antigen specificity.
................can be present on immunoglobulin ...................on both heavy and light chains, differing between individuals or ethnic groups and in some cases may pose as.......
Polymorphic epitopes, constant regions,immunogenic determinants.
IgA structure
Serum = Monomer Secretions = Dimer, J chain, secretory component
T or F: Antigen -antibody binding usually does not cause destruction of the antigen.
T
T or F: Both heavy and light chains contain two different regions.
T
T or F: Each human can synthesize antibodies that can bind to more than 10 (10 trillion) different epitopes.
T
T or F: Exposure of individuals to a non-self allotype might elicit an anti-allotype response and became cause of problems.
T
T or F: Individuals with immuno-deficiencies may lack one or more isotypes.
T
T or F: The amino acid sequence of the (CH) domains determines the classes of heavy chains.
T
T or F: humans, all κchains are identical. However, λchains show four slightly different subtypes.
T
Heavy Chain Domains contain.....
VH, CH1, CH2, CH3 (or CH4 in IgM,IgE)
Immunoglobulins Idiotypes are
antigenic determinants of immunoglobulin molecules that are located in the variable region of the antibodies.
Immunoglobulin Isotypes are
are antigenic determinants that characterize classes ( μ, δ, ɣ, α, and ε) and subclasses of heavy chains and types and subtypes of light chains kappa (κ) and lambda (λ).
IgD increase in ......
chronic infections
Hypervariable region also known as.....
complementarity determining regions (CDRs)
The stalk of the Y is termed........
crystallizable fragment (Fc)
In light chain production one V segment is randomly joined with one J- C region by........ and The remaining J segments are ........ from the .........during.........
deletion of the intervening DNA, eliminated, the RNA transcript, RNA processing.
opsoninis is
describe substances that enhance phagocytosis.
If the level of IgM above 20 mg/dl is an indication of......
in utero stimulation of the immune system & stimulation
What are the type of light chain ?
kappa (κ) and lambda (λ),
IgE structure
monomer& has an extra domain in the constant region.
IgD structure
monomer,tail piece
Immunoglobulins bind specifically to one or more antigenic determinant and can result in.......
protection of the host.
Hinge Region is ....
region at which the arms of the antibody molecule forms a Y is called the hinge region because there is some flexibility in the molecule at this point.
The four chains are arranged in......
the form of a flexible "Y" with a hinge region.
Examples of anti-allotype response......
transfusion of blood or in a pregnant woman.
The top of the Y consists of......
two antigen-binding fragments (Fab)
Chains in immunoglobulins composed of .....
two identical light chains and two identical heavy chains.