Know Your Immunity Genes : HLA
Immunity is the most complex and life-saving mechanism in humans. One of the primary functions of the immune system is to defend against infection and disease-causing agents (like bacteria, virus etc.) by distinguishing between self and non-self (foreign) agents. For foreign agents, the immune system responds differently. There are different cells and chemicals (proteins) which work together in a specific order to kill and completely remove foreign invaders from the body. A small variation or delay of any of the responses can cause severe illness.
The important cells (immunological cells/leukocytes) and chemicals involved in the immune response include lymphocytes (T cells, B cells and NK cells), neutrophils and macrophages ( these are all types of white blood cells). Other chemicals/proteins include cytokines (predominantly signalling proteins), antibodies and complement proteins.
How does the immune system fight viruses such as coronavirus?
There are different mechanisms that happen simultaneously to kill and remove the virus. The only way a virus survives in the body is by entering into a healthy cell and replicating. After entering, the virus starts producing different proteins and genetic material. All the protein molecules and genetic material come and join together to form more viruses.
All the nucleated cells have MHC class I proteins on the surface of the cells. MHC class II proteins are present on antigen-presenting cells (dendritic cells, macrophages and B cells). These proteins play a crucial role in signalling and initiating the immune system.
When the infected cell starts producing the proteins of the virus, a small part of the viral protein gets attached to MHC class I. The cytotoxic T cells will recognise MHC class I protein along with attached viral protein and release cytotoxic factors which will kill the infected cell. Simultaneously the infected cells release the chemicals called interferons which indicates other neighboring cells about the infection.
A few viruses can outsmart this protective strategy and they continue to spread the infection. The infected cell will not show the viral protein on the MHC class I receptor and show less number of MHC class I proteins than usual. Natural killer cells recognise this and release a few chemicals which kill the cell and activate more T cells and B cells.
On the other hand, when the foreign invader enters the body, the antigen-presenting cells engulf the virus through the process called phagocytosis and break them into small fragments. The cells load these small fragments into the surface receptors (MHC class II) and showcase them to all the other immune cells. The T helper cells (one type of the immune cells) will interact with the antigen-presenting cells and release chemicals which in turn activates more T cells, B cells and antigen-presenting cells and kill the infected cell.
The bond between Human Leukocyte Antigen (HLA) and immunity
A lot of scientific studies have proved that there is a strong association between genetic factors and susceptibility or resistance to viral infection. Chronic viral infection like HIV or HCV imposes major selective pressure on the host’s immune system and was found out to be associated with the host’s genetic factors. Following this discovery, it was found that Human Leukocyte Antigen appeared to be a leading genetic candidate for infectious disease susceptibility.
The Human Leukocyte Antigen is a gene complex which encodes the major histocompatibility complex (proteins) in humans. The HLA gene complex is located on a 3 Mbp stretch within chromosome 6. It is one of the most polymorphic genes in the human body with several thousand alleles encoding for functional polypeptides (proteins). These proteins are also known as antigens and were discovered in the process of organ transplantation. For a successful transplant, the MHC complexes should match each other.
With this high level of polymorphism, the human immune system has a selective advantage against the diversity of microorganisms and antigens the host encounters.
The MHC molecules are broadly classified into two categories
- Class I MHC molecules (HLA-A, -B, -C, – E, -F,- G, -H)
- Class II MHC molecules (HLA-DR, -DQ, -DM, and -DP)
Each molecule has different functions and attracts different immune cells during an immune response.
What happens when the immune system is not regulated?
Immune responses need to be well regulated. Variations and mutations in the MHC increase the chance of autoimmune diseases. Almost all the known autoimmune diseases have been studied and found to be associated with genetic variation in the HLA gene complex.
Type 1 diabetes, one of the most widely studied complex genetic disorders, is an autoimmune disease in which insulin is functionally absent because of the destruction of the β cells in the pancreas by the immune system. The polymorphisms of class II HLA genes encoding DQ and DR are the major determinants of this disease. However, triggers for the autoimmune attack are not fully understood, but it is now widely accepted that both environmental and genetic factors contribute to it.
A lot of studies also proved that there is a strong association between the HLA region and other autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Graves’ disease, ankylosing spondylitis and systemic lupus erythematosus.
Thus the MHC molecules play a crucial role in the regulation of human immune response -they act as presenters of self/foreign – antigens/ peptides to T cell receptors for initiation of tolerance and cytotoxic T cell or helper T cell response.
When the immune system goes into overdrive, or a hyper response, a ‘cytokine storm’ can occur.
Genomepatri Immunity – DNA Based Personalised Immunity Assessment
As part of our initiative in fighting COVID-19, our genome mappers have created Genomepatri ImmunityTM which is a DNA-based immunity report, for better prevention and health. The test analyses known genetic variations associated with immune response and autoimmune diseases. This report also analyses genetic risk for severe infection, including COVID-19.