What Comprises the Immune System? 

The collaboration between the cells and proteins that work together as a defense system against infection comprises the immune system.Each of them performs a variety of tasks to recognize and/or react against a foreign body. 

Categories of Immune Responses 

Innate immune response 

It involves the immune cells that respond to infection rapidly and reliably. The cells involved in the innate immune response are natural killer (NK) cells, monocytes, and complement proteins. 

Adaptive immune response 

It involves Tcells and Bcells that are trained such that they do not attack the body’s cells. The advantages of the adaptive response are the long-term memory and the ability of the immune system to adapt to new germs. 

When compared to the adaptive immune system, the innate immune system is largely intact at birth. 

What can go wrong with the Immune System?

An immune system disorder occurs when the immune system doesn’t work the way it should. 

• If a person is born with a weak immune system, it is called primary immunodeficiency. 
• If a person gets a disease that weakens his immune system, it is called acquired immunodeficiency. 
• If a person has an immune system that is too active, he might develop an allergic reaction. 
• If a person has an immune system that turns against his body cells, it is called an autoimmune disease. 

Some of the major disorders of the immune system are: 

• Hypersensitivity 
• Autoimmunity  
• Transplant rejection

What is Hypersensitivity? 

When the immune response to a foreign antigen is more harmful than the antigen itself and wherein the immunological state “over-reacts” to the antigen,the condition is termed hypersensitivity.  

The hypersensitivity involves the adaptive immune response that is the highly specific reactions by the T or B cells before exposure to the antigen. The sensitizing of the individual after the first exposure does not cause a hypersensitive reaction. The reaction is seen only on the secondary exposure. 

Types of Hypersensitivity

Hypersensitivity following secondary exposure to antigen comes in four basic forms:  

1. Type I: It involves allergic reactions (“immediate” hypersensitivity) that are rapid (2-30 minutes) and are mediated by IgE. 
2. Type II: It involves cytotoxic reactions such as the complement activation that damages the cell through the antibodies IgM or IgG. 
3. Type III: It involves immune complex reactions that are the excess antibody/antigen complexes that cause cell damage. 
4. Type IV: It includes delayed cell-mediated reactions. The type IV hypersensitivity is associated with damages to the cell involving T cells & macrophages. 

Apart from type IV, all the others are antibody-mediated. 

What is Autoimmunity?

The generation of an immune response to self-antigens is referred to as autoimmunity. Usually, such reactions are prevented by the body.  

• In the thymus, T cells with receptors that bind self-antigens are rendered anergic or are eliminated.  
• In the bone marrow or the periphery, B cells with antibodies that bind self-antigens are eliminated or rendered anergic. 

In some rare cases T and/or B cells that recognize self-antigens survive & are activated, causing cell destruction. 

Generation of Autoimmunity

Some of the factors that are thought to trigger autoimmunity are as follows: 

• Genetic factors, for example,certain HLA-DRB1(human major histocompatibility complex (MHC) class I) alleles are associated with particular autoimmune disorders. 
• Foreign antigens that copy self-antigens like peptide antigens from certain viral and bacterial pathogens are very similar to specific self-peptides. T and B cells continue to respond to tissues expressing the similar self-peptide, once an immune response is generated to the pathogen. 

Example of some autoimmune diseases and the autoantibodies produced in each case: 

• Systemic lupus erythematosus- antibodies to self-including DNA (deoxyribonucleic acid) and histone proteins. 
• Rheumatoid arthritis- immune responses to self-antigens in synovial membranes of the joints. 
• Type 1 diabetes- immune responses to self-antigens in pancreatic β cells (insulin-producing cells). 
• Multiple sclerosis- immune response to myelin basic protein in the Schwann cells (cells that form myelin sheath of neurons). 

What is Transplant Rejection?

It is referred to as the rejection of organs and tissues due to the presence of non-self MHC class I molecules. There are three HLA(human leukocyte antigen) genes resulting in up to six different HLA proteins per individual. Each person’s HLA is unique and there are many different HLA alleles in the human population. 

How do the Transplanted Cells get Killed?

When the recipient has no tolerance to donor MHC: 

• The recipient’s T cells that bind strongly to the donor MHC molecules with peptides are activated. 
• The MHC representation of foreign donor MHC peptides takes place.  

As a result, the cytotoxic T lymphocytes (CTLs)are activated that attack & kill donor cells. Moreover, the activated B cells produce donor MHC-specific antibodies. This leads to antibody-mediated cytotoxicity toward the donor cells. 

How can a Transplant be Protected?

A transplant can be protected inside the recipient cell with the help ofimmunosuppressants.  

• Drugs such as cyclosporine are given to the recipient to suppress the adaptive immune response. As antibodies to donor MHC molecules are still produced, humoral immunity is not suppressed. The recently developed drugs are capable of repressing both the cellular and humoral immune responses. 
• There is a greater risk of infection as normal, healthy immune surveillance is impaired. 

Examples of How the Immune System Fights Against Pathogens

Bacteria 

The environment as well as the human body harbors several bacteria. The skin and internal mucous membranes act as physical barriers to pathogens. The bacteria enter the body through the broken skin or mucous membranes that appear due to disease, inflammation, or injury. As the bacteria enter the tissues, neutrophils recognize them with the help of complement proteins or antibodies coating the surface of the bacterial cells. The neutrophils then engulf the bacteria and destroy them. 

If the functionality of the antibodies, complement, and neutrophils are all normal, the bacteria is effectively killed and removed from the body. Recurrent bacterial infections can occur when the number of bacteria is overwhelming or there are defects in antibody production, complement fixation, and/or neutrophils. 

Viruses 

The methods by which the human body fights and defends itself against bacteria and viruses are different. Viruses “hide” from the immune system and multiply inside the cells. A virus-infected cell releases cytokines to alert other cells to the infection. As a result, the non-infected cells are prevented from getting infected. However, many viruses can outsmart this protective strategy, and continue to infect healthy cells. 

The circulating T cells and NK cells become alerted to a viral invasion and migrate to the site where they kill the cells that harbor the virus. It is a destructive mechanism of killing viruses because many of the body’s cells can be sacrificed in the process.  

While the T lymphocytes are killing the virus, they are also instructing the B lymphocytes to make antibodies. The antibodies help prevent the infection when the body is exposed to the same virus a second time. At such times, memory T-cells are also produced and rapidly respond to the second infection, which also leads to a milder course of the infection. 

Context and Applications

This topic is significant in the professional exams for both undergraduate and graduate courses.                                                                                                     

• Bachelors in Immunology 
• Bachelors in Biochemistry 
• Bachelors in Microbiology 
• Masters in Immunology  
• Bachelors in Medicine and Bachelor of Surgery