Introduction

Definition 

Antisera is defined as a serum present in our blood that contains monoclonal or polyclonal antibodies that provide passive immunization to our body. 

Importance in medicine

Antibodies have many applications in diagnosis therapy and research. All antibodies were produced by inoculating antigens into the animals and taking serum. 

Role of antibodies in the immune system

• Monoclonal antibodies are useful because they are uniform, can be highly specific, and can be readily produced in large quantities for an indefinite period. 
• The core structure of antibodies consists of two identical heavy chains and two identical light chains, forming a disulfide-linked complex.

Cell-mediated immunity

• Humoral immunity, involving B cells, Th2 cells, and antibodies is efficient in removing pathogens and foreign substances from the body fluid.
• In intracellular pathogens, antibodies are ineffective, because they are inaccessible to the antigen.
• The cell-mediated immune response is a specific type of immune response that does not involve antibodies.

Function of Cell-mediated Immunity

• Immunity against obligate intracellular bacteria (Mycobacterium tuberculosis, protozoa (Leishmania), and malaria species) and viruses (smallpox, measles, mumps, etc.).
• T cell-mediated immune response is responsible for the rejection of transplants.
• Immunological surveillance and immunity against cancer.
• Pathogenesis of certain autoimmune diseases (e.g. thyroiditis, encephalitis, etc.).

Antisera as blood serum

Antisera can be defined as the serum present in our blood that contains antibodies produced by the body in response to an antigen like bacteria or viruses. 

They are used for diagnostic purposes and also to cure diseases. Due to advancements in medical technologies, the use of antisera in treatment has increased significantly in the past years. 

The process involves :

• Collection of donor blood who are exposed to a particular antigen.
• Isolation of specific antibodies from the blood specimen.
• Purification and conversion into a concentrated serum, known as antiserum. 
• This process is highly effective, yet expensive.
• Antisera are key tools to diagnose the disease-causing agents and find out the zone of infection. 
• Administration is generally done intravenously and intramuscularly depending upon the diagnosis.

Generation of antisera through immunization or production 

• Antisera is made either through immunization or production.
• The aim of immunization in an individual is to prevent diseases. The purpose of the immunization program is to combat infectious diseases like smallpox (caused by the variola virus ), poliomyelitis (poliovirus), tetanus (caused by the bacterium Clostridium tetani ), diphtheria (Corynebacterium diphtheriae), etc.
• Immunity against infections is achieved by active and passive immunization. Active immunization is achieved naturally, clinically from the disease, or by artificial means, like vaccines.
• In passive immunization, immunity is obtained naturally from mother to fetus by transfer of antibodies through milk or artificial injections.
• The antibodies developed inside the body are then extracted from the serum of these animals and are used as Antisera. These serums are highly used in diagnostics or therapeutic treatment.
• They are also produced by the insertion of DNA to target-specific antibodies into the mammalian cells. 

Methods of immunizing animals

• The ancient technology for the generation of polyclonal and monoclonal antibodies involves the immunization of an animal.
• The selection of the best animal species and targeting their immune system to receive antibody responses are important in obtaining higher-quality antibodies and the construction of hybridomas.
• Hybridomas are obtained by the process of fusion of myeloma cells and spleen B cells.
• A subtle amount of opportunities are available for the researchers to intervene and manipulate the response concerning a particular antigen. The suitable choice of animal and the adjuvants are necessary to extract the desired antigen dose.

Ethical considerations

Several ethical considerations need to be taken care of while conducting antisera research. 

Factors include

1. Antisera is made by injecting the experimental animal with an antigen and then harvesting its antibodies. It can lead to pain or distress to the animal. 

2. Potential risks are based on antisera research. Human subjects can experience multiple reactions after being injected with antigens. So, it is important to ensure that any risks are minimized before proceeding with human experiments.

3. Proper consent should be taken directly or indirectly before experimentation during the research.

What is polyclonal antisera?

They are antibodies that are produced by multiple clones of B-cells.

Advantages

1. It can recognize more than one epitope on an antigen, thus allowing it to become more effective at binding. They also can neutralize the side effects of pathogens.

2. They are used for both diagnostic and therapeutic purposes. On the contrary, monoclonal antibodies are only used for therapeutic purposes. 

3. Polyclonal antisera are less expensive as compared to monoclonal antibody production. It can produce large amounts of antibodies at a very low cost.

Limitations

However, it possesses a lot of limitations:

1. Low specificity
2. Cross-reactivity proteins may lead to false results. 
3. Productivity is time-consuming and cost-effective. 
4. Variations in the final product. 

What is monoclonal antisera?

• Monoclonal antisera ( also called MAbs ) act like proteins made in laboratories that act like proteins called antibodies in our bodies.
• They seek out antigens i.e., foreign materials and stick to them in order to destroy them.
• Laboratories-made monoclonal antibodies help to protect our own immune system.

Hybridoma technology for production

• The industrial production of monoclonal antisera starts in the laboratories by inserting an antigen (a molecule that can trigger an immune response) into a mouse.
• The mouse starts producing ‘B lymphocytes’ ( antibody molecule ) to defend itself against the antigen.
• These cells have a very short life span and fuse with immortal tumor cells, which are usually called myeloma cells, producing so-called hybridomas. Hybridomas are immortal cells that have the ability to produce antibodies.
• Various ‘B lymphocyte clones’ against the antigen are withdrawn from the mouse. So, hybridomas will produce various antibodies against the antigen. This mixture of antibodies is known as “polyclonal antibodies”.

Advantages of monoclonal antisera 

• Anti-idiotype monoclonal antibodies have been used with some success in treating human B cell lymphoma and T cell leukemia. 
• A monoclonal antibody can be engineered to insert human sequences that has proved helpful in treatment of B cell lymphoma. 

Limitations

• Highly expensive in terms of large batch cultures. 
• Less effective in the case of certain diseases.
• Specificity is low. 
• The possibility of allergic reactions is high. 
• They may bind with other molecules, resulting in high toxicity levels.

Application of antisera

• They are extensively used in viral diagnostics. 
• Antisera can be used as an antivenom. 
• They are widely used in blood group typing i.e., determination of blood groups. 
• Antisera has proved as an active immunization with respect to certain diseases. 
• From ancient times, serum therapy has been proven to treat influenza. 
• Antiserums are highly effective towards the pathogen and have the ability to intervene in an initial stage. 
• Snake venom is used as an antiserum in snake bites. 

Challenges focusing on the production 

High-quality production of antisera requires a high-cost investment that is highly challenging. This production of antiserums requires a specialized team of high expertise that can be time-consuming. The availability of raw materials is limited such as enzymes and antibodies required. Also, the risk of contamination in such production is extremely high if safety issues are not considered effectively. 

Current ongoing research 

• Vaccination against infectious diseases by the application of monoclonal and polyclonal antiserums (1).
• Detection of oncogene by using synthetic peptides in screening urine samples. This ongoing research can prevent further malignancies in pregnant women (2).
• Immunological advancements in Prostate Cancer by the use of antiserums (3).
• Antigenic interaction between flavivirus and polyclonal antisera involving cross-reactivity (4).

Antisera vs Antibodies 

Q&A

1. What is the difference between an antibody and an antisera?

Antisera is a form of serum that contains antibodies. On the other hand, antibodies are proteins that are naturally produced by our bodies when we encounter foreign particles like bacteria or viruses.  

2. What is antisera in blood?

Antisera are present in the form of antibodies in the blood. They are initiated by the body’s immune system to fight off foreign matter including bacteria and viruses. Antisera are generally used in the diagnosis of diseases and identification of individuals, exposed to pathogens. 

3. Is antisera an antigen?

No, Antisera is not an antigen.

4. What is an example of an antisera?

• Monoclonal Antibodies (mAbs)
• Polyclonal antibodies
• Recombinant antibodies that are produced from rDNA technology

Summary

• Antisera are present in the form of antibodies in the blood.
• They are initiated by the body’s immune system to fight off foreign matter including bacteria and viruses.
• It contains monoclonal or polyclonal antibodies that provide passive immunization to our body.
• They are used for diagnostic purposes and also to cure diseases.
• Due to advancements in medical technologies, the use of antisera in treatment has increased significantly in the past years.
• Antisera are key tools to diagnose the disease-causing agents and find out the zone of infection.
• The administration is generally done intravenously and intramuscularly depending upon the diagnosis.
• Antibodies developed inside the body are then extracted from the serum of these animals and are used as Antisera.
• Monoclonal antisera ( also called MAbs ) act like proteins made in laboratories that act like proteins called antibodies in our bodies.
• They seek out antigens i.e., foreign materials and stick to them in order to destroy them.
• Laboratories-made monoclonal antibodies help to protect our own immune system.
• Polyclonal antibodies are produced by multiple clones of B-cells.
• It has the ability to recognize more than one epitope on an antigen, thus allowing it to become more effective at binding.
• They also have the capability to neutralize the side effects of pathogens.
• A monoclonal antibody can be engineered to insert human sequences that have proved helpful in the treatment of B cell lymphoma.

References

• https://www.mdpi.com/1422-0067/23/3/1703
• https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/0471142301.ns0505s48
• https://www.tandfonline.com/doi/abs/10.1080/03079459308418936
• https://journals.asm.org/doi/abs/10.1128/jcm.32.3.608-612.1994
• https://journals.asm.org/doi/abs/10.1128/jvi.61.12.3688-3693.1987

Written By: Sushmita Mukhopadhyay