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Hyper IgM syndrome




Immune system

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Hyper IgM syndrome


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High Yield Notes
10 pages

Hyper IgM syndrome

6 flashcards

USMLE® Step 1 style questions USMLE

1 questions

USMLE® Step 2 style questions USMLE

1 questions

A 3-year-old child comes to the office because of dyspnea, severe cough, and a fever for 4 days. Examination shows tachypnea and bibasal crackles on pulmonary auscultation. Chest X-ray and laboratory tests lead to a diagnosis of Pneumocystis jirovecii pneumonia. Further laboratory tests show abnormally low levels of the IgG, IgA, and IgE immunoglobulins. However, levels of IgM are far above normal. Which of the follow cell surface molecules is most likely defective?

External References

Hyper IgM syndrome is a problem where B cells are unable to undergo antibody class-switching, meaning that they can produce IgM antibodies, or immunoglobulins, but struggle to produce other types of antibodies, and that leaves individuals at risk for certain infections.

Let’s take a look at how B cells end up secreting different types of antibodies.

Each B cell is born in the bone marrow from a stem cell and develops its own B cell receptor, which sits on the cell surface.

The B cell receptor consists of two parts - a protein called CD79 that communicates with the rest of the cell and a membrane bound IgM or IgD antibody that can bind to an antigen.

An antigen is any substance recognized by that particular antibody.

Each antibody has two identical light chains and two identical heavy chains that combine into a Y shape.

So this Y-shaped antibody’s got two arms with identical tips, which is called the variable region.

This variable region contains an antigen binding domain that’s unique to that antibody.

Below the variable region, or toward the point where the arms meet, is the constant region where every member of an antibody class is identical – so all IgM antibodies have the same constant region,

but IgM and IgA constant regions are different.

And there are five classes of antibodies in total: IgM, IgG, IgA, IgE, and IgD class antibodies.

Each antibody class has a slightly different job

For example, IgMs are part of B cell receptors, and are the first free-floating antibodies produced in an immune response.

They’re secreted as a pentamer, meaning there are five antibodies connected together, which provides many binding sites for grabbing antigens and taking them out of the blood.

Each antibody has complement protein binding sites on the heavy chains, so these IgM pentamers are also great at activating complement proteins, which help destroy and remove pathogens.

IgG antibodies stick to the surface of bacteria and viruses – and that prevents them from adhering to and infecting cells.

IgG also allows macrophages and neutrophils to grab and destroy the microbes.

IgA antibodies line mucosal tissues like the gastrointestinal and respiratory tracts and stop microbes from invading in the first place.

IgE antibodies work with eosinophils to destroy parasites.

As for IgD antibodies, they’re also used in some B cell receptors, just like IgMs are, but their function as free-floating antibodies is still unclear.

Each B cell has over 100,000 B cell receptors spread across its surface, all of which bind the same unique antigen.

When a B cell comes in contact with an antigen it recognizes, the B cell presents internalizes that antigen and presents a piece of it on a major histocompatibility complex class II molecule, or MHC-class II for short.

Then, at some point, along comes a CD4+ helper T cell that binds to the presented antigen and when that happens, it expresses a protein called CD40 ligand on its surface.

Hyper IgM syndrome is an X-linked recessive defect in a Th2 cell protein (CD40 ligand) that causes a defect in class switching, resulting in severe infections early in life and susceptibility to opportunistic infections. 
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