3.2.4: Cell recognition and the immune system (B lymphocytes, humoral immunity, and antibodies)

Humoral immunity is called humoral immunity because it involves antibodies and antibodies are soluble in blood and tissue fluid (humour).

There are many different types of B lymphocyte, each produces andifferent antibody in response to a specific antigen. Here's how:

• An antigen (on the surface of a pathogen/foreign cell/toxin, for example) enters the blood/tissue fluid, there will be a B cell that has a complimentary antibody on it's surface
• The antibody attaches to this antigen
• The antigen enters the B cell (by endocytosis)
• The B cell presents the antigien on it's surface (this is also known as 'processing')
• T helper cells (a type of T lymphocyte) binds to the processed antigens and stimulated the B cells to divide by mitosis (clonal selection) to form a clone of identical B cells which all produce the antibody that is specific to the foreign antigen.

Often, some pathogens have many different antigens so many different B cells make clones at the same time. As each clone produces one specific antibody, the antibodies are referred to as monoclonal antibodies. Each clone develops into either:

• Plasma cells: these secrete antibodies (usually) into blood plasma. They survive for only a few days but can make around 2000 antibodies per second (that's quick). These antibodies lead to the destruction of the antigen therefore plasma cells are responsible for the immediate defence of the body against infection. 
• Memory cells: these are responsible for the secondary immune response. They live considerable longer than plasma cells but do not produce antibodies. Instead, they divide rapidly into plasma cells and more memory cells when they encounter the same pathogen once again (e.g a new infection but of the same infection......did that make sense?????not sure lol). The plasma cells they produce in turn produce antibodies to fight the new infection and the new memory cells circulate in the blood and tissue fluid (humour). Because of this, memory cells provide long-term immunity against the original infection. An increased quantity of antibodies is secreted faster the second time round ensuring that the infection sis destroyed before it can cause any/much harm.

NOTE: The production of antibodies and memory cells is known as the primary response.

To summarise, the overall response of B cells:

• Surface antigens of invading pathogen are taken up by a B cell
• The B cell processes the antigens and presents them on its surface
• helper T cells attached to the processed antigens, activating the B cells
• The B cells are stimulated to divide (by mitosis) forming clones of the B cell with the complimentary antibody
• These clones either form plasma or memory cells
• The cloned plasma cels secrete antibodies to attach to and destroy the pathogen
• The cloned memory cells can respond to future infections by dividing rapidly and developing into plasma cells which produce complimentary antibodies (the secondary immune response)

So, what actually are antibodies?

Antibodies are proteins with specific binding sites synthesised by plasma B cells when the body is infected by non-self material. The antibody reacts with a complimentary antigen by binding to it. Each antibody has two specific and identical binding sites. They are made of proteins which leads to a massive variety of antibodies.

They are made up of four polypeptide chains. Two are long (heavy chains) and two are shorter (light chains). As mentioned above, each antibody has a specific binding site that fits very precisely onto a specific antigen forming an antigen-antibody complex. This binding site is different on different antibodies and is therefore known as the variable region (the rest of the antibody is the constant region - this binds to receptors on cells such as B cells).

Antibodies do not directly destroy the antigen, they just prepare it for destruction. If the pathogen is a bacterial cell, the antigen can prepare it in one of two ways:

• Cause agglutination (clumps of the bacterial cell form, making it easier for the phagocytes to locate them as they are less spread out)
• Act as markers that stimulate phagocytes to engulf the bacterial cell to which they are attached (phagocytosis)

It is of medical value if we can produce a single type of antibody outside of the cell, these are known as monoclonal antibodies. Some uses of monoclonal antibodies are:

• Direct/indirect monoclonal antibody therapy.
• Monoclonal antibodies are produced that are specific to cancer cells (for example)
• These antibodies are administered to a patient and attach themselves to the receptors on the cancer cells
• They block the chemical signals that stimulate the uncontrolled growth of the cancer cells.
• The advantages of this is that, since antibodies are highly specific and not toxic, they lead to fewer side effects than other forms of therapy (e.g chemo/radiotherapy)
• Indirect monoclonal antibody therapy involves attaching a cytotoxic/radioactive drug to the antibody, therefore the cell that the antibody attaches to dies
• They can be used in small doses which is cheaper and less invasive and reduces the side effects of other drugs that may be used alternatively
• Medical diagnosis
• They are used for the diagnosis of hepatitis/chlamydia/influenza infections as they produce a much more rapid result than conventional methods of diagnosis
• One example is prostate cancer: men with prostate cancer often produce higher numbers of PSA (prostate specific antigen). By using a monoclonal antibody that reacts with this antigen is is possible to obtain a measure of the amount of PSA in a mans blood. Whilst this does not diagnose the disease it gives a good indication/early warning that the cancer may be present
• Pregnancy testing
• Placenta produces a hormone known as hCG (human chorionic gonadatrophin). This is present in mamas urine
• Monoclonal antibodies linked to coloured particles are present on home pregnancy tests
• If hCG is present it binds to these antibodies and the hCG-antibody complex moves along the strip creating a coloured line

Monoclonal antibody ethical issues:

• Monoclonal antibody production involves inducing mice with cancer to create tumour cells
• There have been some deaths associated with the use of monoclonal antibodies and multiple sclerosis treatment
• in March 2006 six healthy volunteers trialed a new monoclonal antibody and within minutes suffered multiple organ failures, although all survived.
• Monoclonal antibodies have been used successfully to treat a number of diseases