Immunology Genetics

What is Immunity? 

The modern word "immunity" in the medical literature derives from the Latin immunis, which was used by the Ancient Romans as a meaning exemption from military service, tax payments or other public services.

It is newly used in the field of medicine and immunity is that a person who has previously had and recovered from a contagious disease and being able to resist to this disease.

How does the immune mechanism work in the body?

Immune organs are found throughout the body, including in the bone marrow, tonsils and all lymph nodes, spleen, thymus gland, and intestines.

In immunity, some of the cells that made in the bone marrow are called "lymphocytes". These cells go to the Thymus gland and trained here and become "T Lymphocytes" which are responsible for cellular defence, these are like trained commando soldiers with blue berets. Some other lymphocytes are trained in the intestine and are defined as "B lymphocytes". They are like commando soldiers with Burgundy berets and are responsible for humoral defence by producing antibodies. Humoral immunity is a defence system made using antibodies against pathogens/microorganisms found outside the cell. In addition, Natural killer cells (NK) produced in the bone marrow are large granular lymphocytes and are the soldiers who use their lethal weapon directly against these pathogens/microorganisms and are the most important cells of natural immunity.

What are the types of Immunity?

There are two types of immunity, Innate (natural) immunity and adaptive (acquired) immunity. Natural immunity is the first line of defence that the body employs against invading pathogens, such as bacteria, viruses, and fungi. It is a non-specific defence mechanism that is present from birth and provides immediate protection against a wide range of pathogens. Natural immunity includes physical and chemical barriers, such as the skin, mucous membranes, and digestive enzymes, that prevent pathogens from entering the body. It also includes immune cells, such as macrophages and natural killer cells, that can recognize and destroy invading pathogens.

Acquired immunity, also known as adaptive immunity, is a specific and targeted immune response that develops after exposure to a particular pathogen. It is tailored to a specific pathogen and provides long-lasting protection against future infections. Acquired immunity is mediated by immune cells called lymphocytes, which can recognize and respond to specific pathogens.

Acquired immunity can develop in several ways, including through natural infection, vaccination, or passive transfer of antibodies from another individual. Once acquired, immunity can provide long-lasting protection against future infections with the same pathogen.

Acquired immunity is an important component of the immune system and plays a critical role in protecting the body against infectious diseases. However, it is important to note that acquired immunity can be weakened or compromised in certain individuals, such as those with immunodeficiency disorders or those taking immunosuppressive medications.

What are Immune Diseases?

Inadequate barriers in the body, which means that frequent recurrence of wounds in the mouth or body, insufficient cilia in the nose, leukoplakia in the tongue and insufficiency of tonsils and adenoids, cause recurrent infections.

Primary Immunodeficiency; covers diseases that increase the susceptibility to infections caused by the deficiency of one or more cells, cell ligands, proteins, cytokines and cytokine receptors, and proteins necessary for intracellular warning systems of the immune system.

Since Bruton's definition of X-linked agammaglobulinemia (XLA), more than 120 primary immune deficiencies have been defined with the developments in technology; In approximately 75% of cases, the underlying molecular disorder could be identified.

Humoral immune system disorders account for 50-60% of primary immune deficiencies, T-cell defects 10-15%, combined immune deficiencies 15-29%, phagocytic system 10-15% and 1-3%. causes complement system disorders.

On the other hand, Secondary immune (acquired) diseases, occur not congenitally but later on due to the damages caused by various chemicals and by the environment factors that effects the immune system. Common causes of these diseases include malnutrition, stress, burns, certain autoimmune diseases and viruses.

What tests are done to measure immunity?

Considering the history and physical examination findings and immune deficiency, the first step laboratory examination is complete blood count and peripheral smear. In the complete blood count, attention should be paid to the absolute lymphocyte and neutrophil count, and the platelet level. If the lymphocyte value is normal for age, severe T cell deficiency is excluded. If the neutrophil count is consistently high in the absence of infection, leukocyte adhesion defect should be considered. The presence of thrombocytopenia and a small platelet volume are typical for Wiskott-Aldrich disease.

If antibody deficiency is thought to be in the foreground, serum immunoglobulin values should be requested, and the results should be interpreted by comparing them with normal values for age.

If the immunoglobulin levels are normal, the patient has a history of frequent infections and if they are >4 years old, IgG subgroups should be checked. Finally, genetic tests should be done to look at the genetic factors that affect the immunity of people.

What is Immunogenetics?

Immunogenetics is a branch of genetics that studies the genetic basis of the immune system and its response to various pathogens and other foreign substances. This field examines the genes and genetic variations that affect the immune system's ability to recognize and respond to antigens, as well as the role of these genes in the development of immune-related diseases.

Immunogenetics seeks to identify genetic variations that affect immune function and the development of immune-related diseases such as autoimmune disorders, allergies, and immune deficiencies. An important area of study in immunogenetics is the major histocompatibility complex (MHC), a gene region on chromosome 6 that is responsible for regulating immune responses to foreign substances. Genetic variations in MHC can affect an individual's ability to mount an effective immune response and are associated with an increased risk of autoimmune diseases and certain infections.

Immunogenetics also plays an important role in the development of personalized medicine, particularly in the field of cancer immunotherapy. By analyzing a patient's genetic profile, researchers can identify potential targets for immune-based therapies and develop personalized treatment plans tailored to the patient's individual immune response.

Which genetic tests are done to check immunity?

Especially if congenital Leukopenia or Neutropenia is considered in the patient, genetic testing or panel testings are recommended which will analyzed the specific genes like ELANE, HAX1, WAS, G6PC3, GFI1, JAGN1, CSFR3.

If general immunodeficiency is considered, an immunodeficiency panel is recommended.

Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome are several examples of the syndromes and comprehensive gene panels. Bone marrow failure panel or whole exome analysis (WES) or whole genome analysis (WGS) can be also performed as the latest Next Generation Sequencing methods.

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References:

1. Şefik Alkan: 50 Soruda Bağışıklık. February 2022

2. Aydomuş Ç, Şiraneci R. İmmün Yetersizlikte Tanısal Yaklaşım. JOPP Derg 2(2):52-54, 2010