Question

IMMUNOLOGY CLINICAL SCENERIO QUESTIONS: theres no more information but whats provide below

During convalescence, the patient is in isolation at home, his symptoms resolved completely by day 13, and he returned to his clinician’s office for a check-up at day 20, when he was feeling well, with progressive increases in plasma SARS-CoV-2-binding IgM and IgG antibodies from day 7 until day 20.

Now that the patient is convalescing, explain these questions:

1.What cellular events are necessary to shift from plasma IgM to IgG production? Explain class switching.

2.What are the major roles of IgM and IgG found in plasma during this type of infection?

3.What types of antibodies would you find within the respiratory tract environment? Explain how these antibodies are produced and secreted, and what their major functions are in the respiratory tract.

4. What happens to the large numbers of B cells at the end of the primary response (convalescence)? Explain how those may diminish during convalescence and address memory.

Answer 1

1.What cellular events are necessary to shift from plasma IgM to IgG production? Explain class switching.

Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG. During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same (the terms variable and constant refer to changes or lack thereof between antibodies that target different epitopes). Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.

Class switching occurs after activation of a mature B cell via its membrane-bound antibody molecule (or B cell receptor) to generate the different classes of antibody, all with the same variable domains as the original antibody generated in the immature B cell during the process of V(D)J recombination, but possessing distinct constant domains in their heavy chains.

Naïve mature B cells produce both IgM and IgD, which are the first two heavy chain segments in the immunoglobulin locus. After activation by antigen, these B cells proliferate. If these activated B cells encounter specific signaling molecules via their CD40 and cytokine receptors (both modulated by T helper cells), they undergo antibody class switching to produce IgG, IgA or IgE antibodies. During class switching, the constant region of the immunoglobulin heavy chain changes but the variable regions, and therefore antigenic specificity, stay the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1, IgG2 etc.).

The order of the heavy chain exons are as follows:

1. μ - IgM
2. δ - IgD
3. γ3 - IgG3
4. γ1 - IgG1
5. α1 - IgA1
6. γ2 - IgG2
7. γ4 - IgG4
8. ε - IgE
9. α2 - IgA2

Class switching occurs by a mechanism called class switch recombination (CSR) binding. Class switch recombination is a biological mechanism that allows the class of antibody produced by an activated B cell to change during a process known as isotype or class switching. During CSR, portions of the antibody heavy chain locus are removed from the chromosome, and the gene segments surrounding the deleted portion are rejoined to retain a functional antibody gene that produces antibody of a different isotype. Double-stranded breaks are generated in DNA at conserved nucleotide motifs, called switch (S) regions, which are upstream from gene segments that encode the constant regions of antibody heavy chains; these occur adjacent to all heavy chain constant region genes with the exception of the δ-chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes, including activation-induced (cytidine) deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases.The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing unwanted μ or δ heavy chain constant region exons and allowing substitution of a γ, α or ε constant region gene segment. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the antibody heavy chain. In the absence of non-homologous end joining, free ends of DNA may be rejoined by an alternative pathway biased toward microhomology joins. With the exception of the μ and δ genes, only one antibody class is expressed by a B cell at any point in time. While class switch recombination is mostly a deletional process, rearranging a chromosome in "cis", it can also occur (in 10 to 20% of cases, depending upon the Ig class) as an inter-chromosomal translocation mixing immunoglobulin heavy chain genes from both alleles.

2.What are the major roles of IgM and IgG found in plasma during this type of infection?

It's in blood and other body fluids, and protects against bacterial and viral infections. IgG can take time to form after an infection or immunization. Immunoglobulin M (IgM): Found mainly in blood and lymph fluid, this is the first antibody the body makes when it fights a new infection.

Antibodies are major components of humoral immunity. IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. By binding many kinds of pathogens such as viruses, bacteria, and fungi, IgG protects the body from infection.

The IgM antibodies are the first antibodies to be produced in the body in response to an infection. IgM antibodies are larger than IgG antibodies and when present in high numbers, may indicate a recent or new active infection. In short, a positive IgM may be a sign of a current, or very recent, infection.