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2). Your friend is interning in a research lab at CERN in Switzerland. The lab t

ID: 199518 • Letter: 2

Question

2). Your friend is interning in a research lab at CERN in Switzerland. The lab they are working in is studying a family of mice named the Quarks. The family consists of parents named Up and Down, monozygotic twins Charm and Strange, and their third child Bottom. In other words, Bottom is Charm and Strange's little brother (and all three mice are the offspring of Up and Down). At the immunoglobulin heavy chain locus Up is homozygous for 3a and Down is heterozygous, having both 3a and 3"(note: in mice the different alleles are named with letter superscripts) a). Charm has come down with a disease caused by Micrococcus blackholeu and she is unable to launch an effective antibody response against the bacteria. However, the rest of the Quarks have all encountered the pathogen and produced high levels of lgG antibodies against the bacteria. Your friend wants to transfer immunoglobulin to Charm from a family member to confer passive immunity. Which family member, if any, would be least likely to in induce anti-allotype. antibodies in Charm? (1 point) ii. Which family member, if any, would be likely to induce anti-isotype antibodies in Charm? (1 point) b). Would injecting serum lgG from Up into Down induce anti-allotypic antibodies? Why or why not? (1 point) c). Bottom suffers from Higgs Syndrome, a condition characterized by extreme weight gain due to the presence of an anti-leptin lgG3 auto-antibody. Should your friend be able to guess which of the other family members will also develop this syndrome (i.e have the same anti-leptin lgG3 antibody)? Explain your reasoning. (1 point) d). Bottom has just discovered his long-lost evil twin Top. Top has a component in his serum called W particles. The W particles appear to be immunolglobulins and have been found to bind to lgG3 antibodies from Down. Using this information determine Top's genotype for 3. (1 point)

Explanation / Answer

a) IgG antibody is the main serum immunoglobulin, consisting of about 80% ofthe total. Itc an be considered as a general purpose antibody, where it performs functions like protection against infectious agents active in blood and tissues.

i) Allotypic determinants refer to multiple alleles that exist for some genes and which lead to subtle amino acid differences in some members of a species. Generally, antibodies to allotypic determinants are produced when injected from one member of a species into another member of the same species which has different allotypic determinants. In this case, Charm has a monozygotic twin Strange. Generally identical twins have the same allotype, hence Strange will least likely be able to induce an anti-allotype antibody.

ii) Isotypic determinants refer to the genetic variations or differences in the constant region of the heavy chain of the IgG classes and subclasses within a species. generally, within a species, all members carry the same constant region genes. Different species will have different constant region genes, and will express different isotypes. So if we inject antibodies from one species into other, only then will it produce anti-isotypic antibodies. In this case there is no other species involved, hence would not result into anti-isotype antibody production.

b) It is given in the information that Up and Down have different set of gamma globulins in the heavy chain locus. In each individual, there are multiple alleles which code for different amino acids. Hence, injecting antibodies from one person to another, except for identical twins, may result in the production of anti-allotypic antibody. Hence in this case anti-allotypic antibodies may be produced.

c) Generally, any autoimmune disorder can develop due to inheritance from parents. It can be autosomal recessive, where both parents are carriers, or autosomal dominant where one parent has a dominant mutation or X-linked inheritance. In this case it is possible that one or both of the parents have a mutation which is inherited in Bottom, and hence shows Higgs syndrome. The other offsprings may also develop this disease, if it is inherited from the parents. It will depend on the type of inheritance. Recessive mutations will have a 1/4 chance of inheritance in the offsprings. If Bottom has a twin, he/she has a chance of developing the disease.

d) Generally, IgG has four sub-classes : IgG1, IgG2, IgG3, IgG4. The W particles maybe the anti-IgG3 antibodies, as they are binding to IgG3 antibodies from Down. Bottom may be homozygous for gamma 3a.

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