biology

Mendelian susceptibility to mycobacterial disease

Mendelian susceptibility to mycobacterial disease is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Mendelian susceptibility to mycobacterial disease rather than just read about it. In short: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disease. It is a primary immunodeficiency featured by molecular defects in IL12/IFNγ dependent signalling pathway, leading to increased susceptibility to local or disseminated infections by environmental mycobacteria, Mycobacterium bovis Bacille Calmette-Guerin strain, nontyphoidal and typhoidal Salmonella serotypes.

Key takeaways

Mendelian susceptibility to mycobacterial disease belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Mendelian susceptibility to mycobacterial disease to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Mendelian susceptibility to mycobacterial disease from memory before moving on to harder problems.

Reference excerpt

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disease. It is a primary immunodeficiency featured by molecular defects in IL12/IFNγ dependent signalling pathway, leading to increased susceptibility to local or disseminated infections by environmental mycobacteria, Mycobacterium bovis Bacille Calmette-Guerin strain, nontyphoidal and typhoidal Salmonella serotypes.

Symptoms and signs Normally patients who suffer from this disease are young children under 3 years which have also lack of response to IFN-γ cytokine replacement therapy. This disease is very rare and have high index of mortality. Following symptoms and signs are:

recurrent wheezing dyspnea asthma-like symptoms recurring fever productive cough endobronchial mycobacterial infection low hemoglobin Patients with IFNγR1 deficiency can also suffer of disorders of the lung, parenchymal lung diseases caused by mycobacterial infections, hylar lymphadenopathy, or endobronchial disease. If these patients have nontubercular mycobacterial infection there should be suspicion for immunodeficiency. Transplantation of hematopoietic stem cell is the only one curative therapy for these patients. Children with partial MSMD usually have milder clinical phenotype, later onset, less severe infections, better response for IFNγ and antibiotic therapy, better survival rates and normally they don't need hematopoietic stem cell transplant.

Pathophysiology Phagocytes are important components of the innate immune system for the body defence against infections by mycobacteria and other intracellular pathogens. The professional phagocytes include neutrophils, dendritic cells, macrophages and monocytes. These cells engulf the pathogens by phagocytosis and activate the adaptive immune system to facilitate the elimination of the infection. Cytokine signalling is the key for the interplay between the innate and adaptive limbs of the immune system, the most important of which is the IL12-dependent, IFNγ-mediated pathway. The phagocytes recognize mycobacteria and other pathogens by their pattern recognition receptors (PRR), which include Toll-like receptors (TLR) and NOD2. Once the pathogen is phagocytosed, the macrophages secrete IL12, which is a heterodimer formed by IL12p40 and IL12p35. IL12 receptors, composed of IL12Rβ1 and IL12Rβ2 subunits, are expressed on T lymphocytes and NK cells. It is associated with the signalling cascade formed by TYK and JAK2 kinases, eventually leading to STAT4 phosphorylation and nuclear translocation. The final response to IL12 stimulation is IFNγ production and secretion. The IFNγ receptor is expressed on the macrophages and other cells and consists of IFNγR1 and IFNγR2 subunits. It is associated with the signalling pathway of JAK1 and JAK2, leading to the homodimerization of STAT1 molecule. It is the common pathway for enhancing expression of a variety of IFNγ-inducible genes, accounting for the confinement and killing of intracellular pathogens. Genetic defects impairing the IL12/IFNγ pathway increase the susceptibility to mycobacterial infections by impeding either the production or the response to IFNγ. Since the discovery of MSMD in 1996, multiple autosomal and two X-linked genes are identified in MSMD phenotypes, classified under the category of defects in intrinsic and innate immunity in the 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies. IFNγR1 deficiency was the first identified genetic disorder described as MSMD. Mutation in genes encoding IFNγR1 can be dominant or recessive and it can lead to partial or complete deficiency of this receptor. IFNγR1 gene is located in to chromosome 6q23.3 and it is formed of 22 868 base pairs which are composed in 7 exons.

Diagnosis Mendelian susceptibility to mycobacterial disease may be suspected in people with disseminated infections caused by environmental mycobacteria or BCG. Children with a complete deficiency in the interferon-gamma receptor have significant elevations in plasma concentrations of interferon-gamma, which can be measured by ELISA.

References

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Worked examples

Example 1 — a first encounter with Mendelian susceptibility to mycobacterial disease

Start with the simplest possible case. Write down what Mendelian susceptibility to mycobacterial disease claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Mendelian susceptibility to mycobacterial disease before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Mendelian susceptibility to mycobacterial disease ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Mendelian susceptibility to mycobacterial disease

In research: Mendelian susceptibility to mycobacterial disease appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Mendelian susceptibility to mycobacterial disease in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Mendelian susceptibility to mycobacterial disease is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genetic diseases and disorders, Immune system disorders, Rare diseases, so understanding it makes those chapters shorter.
In everyday life: Look for Mendelian susceptibility to mycobacterial disease outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Mendelian susceptibility to mycobacterial disease in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Mendelian susceptibility to mycobacterial disease means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Mendelian susceptibility to mycobacterial disease out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Mendelian susceptibility to mycobacterial disease in simple terms?

Why does Mendelian susceptibility to mycobacterial disease matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Mendelian susceptibility to mycobacterial disease?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Mendelian susceptibility to mycobacterial disease.