Just a quick preface: I am NOT a licensed physician. I am a high school student who enjoys researching interesting medical phenomena. I just enjoy writing about medicine and science!
Agammaglobulinemia is a group of inherited immune diseases, characterized by the lack of antibodies in the blood and lymph due to the lack of specific lymphocytes. Let's start with what lymphocytes are; lymphocytes are a type of white blood cell. They come in two types T cells and B cells. The job of B cells are to make antibodies that are used to attack invading bacteria, viruses, and toxins. The job of T cells are to destroy the body’s own cells that have been taken over by viruses or have become cancerous. To get a better understanding of how the immune response works let’s look at how a virus infects the body. It starts with exposure to the virus, this can occur in a variety of ways exposure almost always occurs at the site of an opening to the body like the mouth, nose, or even a cut or splinter. Once the virus has entered into our body’s it will look for a host cell, as without a host cell a virus is just a dormant particle. The infection truly begins with the attachment of virus proteins to surface receptors of a host cell. The virus is then brought into the cell via receptor mediated endocytosis. When the virus enters the cell it becomes encapsulated in a membrane bound capture vesicle. The vesicle is then transferred by microtubules by host proteins called kinesins. During the transport, the viral membrane and the capture vesicle membrane fuses. It is then where the capsid or the outermost layer of the virus begins to encode the viral core RNA or DNA into proteins. Then the viral proteins are released into the cytoplasm where they are directed by host proteins to the host cell nucleus. At the nuclear membrane the viral core utilizes host protein channels to enter. Inside the nucleus the already existing host cell machinery is hijacked by the virus to replicate the viral genome and make MRNA or messenger RNA. This MRNA is sent to ribosomes in order to direct the synthesis of the viral proteins which are then sent back to the nucleus to associate with RNA and make encapsulated nucleoproteins. The encapsulated nucleoproteins then leave the nucleus again and are sent to the surface of the cell. Viral surface proteins are made in the cytoplasm and are also sent to the surface of the cell to combine with the encapsulated nucleoproteins to make progeny viruses which leave the cell by budding. These progeny viruses are then sent to repeat the same process to other cells. It's at this point where the immune response would kick in, this is because when the virus is inside the cell the immune system cannot identify the virus easily. Cells to combat this use molecules called class I major histocompatibility complex proteins or MHC class I this is because these molecules display pieces of protein from inside the cell on the cell surface. Therefore, if the cell has been hijacked by a virus pieces of the viral proteins will be presented on the surface of the cell. A great way to think of B cells are as a form of preventative care because antibodies focus on preventing a viral infection. Antibodies can prevent a viral infection in many different ways. Antibodies can neutralise the virus by binding to them. Antibodies can also work together to get viral particles to stick together in a process called agglutination, these agglutinated viruses make it easier for immune cells to target the virus as opposed to singular viral particles. Antibodies can also activate phagocytes by binding to Fc receptors on the surface of phagocytic cells and as a result trigger phagocytosis, a process in which the phagocyte engulfs and destroys the virus. Similar to activating phagocytes, antibodies can also activate the complement system which promotes the phagocytosis of viruses. In terms of the immune response of T cells I think of them as damage control as they focus on destroying the cells that the virus has already infected. T cells circulate looking for already existing infections, and they use TCRs or T cell receptors to identify viral peptides so the T cell can release cytotoxic factors to kill the infected cell. In terms of Agammaglobulinemia, the group of immune disorders consists of three variants: X-linked agammaglobulinemia (XLA), X-linked agammaglobulinemia with growth hormone deficiency, and Autosomal recessive agammaglobulinemia (ARA). All the different types of agammaglobulinemia consist of the same main issue, that there is a deficiency in the number of mature B cells. This means that patients with Agammaglobulinemia essentially lose an entire layer of their protection against infection. With a lack of antibodies patients don't have any defense to prevent the infection in the first place but only are able to attack cells that have
already been infected. This is why one of the trademark symptoms of Agammaglobulinemia is serial bacterial and viral infections. These infections most commonly occur as ear infections, sinusitis, pneumonia, diarrhea due to parasites. Symptoms don't start to manifest themselves until months after birth as maternal IgG lasts for several months by when they have to start producing their own antibodies. Infections can range in severity and often most of the risk is in the earlier years of development before diagnosis as Immunoglobulin replacement therapy is a lifelong and life saving treatment for agammaglobulinemia. Now let's look at the differences between the different types of Agammaglobulinemia. The main differences lie in the way that a patient contracts the condition. X-linked agammaglobulinemia (XLA) and X-linked agammaglobulinemia with growth hormone deficiency are both contracted through a mutation carried on the X sex chromosome specifically on the BTK gene. While Autosomal recessive agammaglobulinemia is contracted in the autosomal recessive pattern with a mutation on a non sex chromosome specifically on the IGHM gene. There have only been about 10 documented cases of X-linked agammaglobulinemia with growth hormone deficiency but it can be just as easily treated as the rest with, in addition to the immunoglobulin replacement, growth hormone supplementation. The incidence for agammaglobulinemia is about 1 in 250,000 males in the US for X-linked and 1 in 2,000,000 births for Autosomal recessive agammaglobulinemia.
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