Immune Response

Pathogens are organisms which cause disease. We’re all adapted to prevent these from getting into our bodies in the first place. If a pathogen does manage to sneak it’s way in, our immune system kicks into action, activating various types of white blood cells to manufacture antibodies and kill the pathogen.

Barriers to prevent entry of pathogens

Our bodies have several defensive barriers to prevent us becoming infected by pathogens. For example:

• Our body cavities (e.g. eyes, nose, mouth, genitals) are lined with a mucus membrane which contain an enzyme called lysozyme. Lysozyme kills bacteria by damaging their cell walls, causing them to burst open.

• Our skin acts as a physical barrier to stop pathogens from getting inside of us. If our skin is cut or wounded, our blood quickly clots to minimise the entry of pathogens.

• The trachea (windpipe) contains goblet cells which secrete mucus. Pathogens that we inhale become trapped in the mucus, which is swept towards the stomach by the action of ciliated epithelial cells.

• Our stomach contains gastric juices which are highly acidic - these will denature proteins and kill any pathogens that have been ingested in our food and drinks.

• The insides of our intestines and the surface of our skin are covered in harmless bacteria which will compete with any pathogenic organisms and reduce their ability to grow.

Non-Specific Immune Response

The non-specific immune response is our immediate response to infection and is carried out in exactly the same way regardless of the pathogen (i.e. it is not specific to a particular pathogen). The non-specific immune response involves inflammation, the production of interferons and phagocytosis.

Inflammation - the proteins which are found on the surface of a pathogen (antigens) are detected by our immune system. Immune cells release molecules to stimulate vasodilation (the widening of blood vessels) and to make the blood vessels more permeable. This means that more immune cells can arrive at the site of infection by moving out of the bloodstream and into the infected tissue. The increased blood flow is why an inflamed part of your body looks red and swollen.

Production of interferons - if the pathogen which has infected you is a virus, your body cells that have been invaded by the virus will start to manufacture anti-viral proteins called interferons. They slow down viral replication in three different ways:

1. Stimulate inflammation to bring more immune cells to the site of infection

2. Inhibit the translation of viral proteins to reduce viral replication

3. Activate T killer cells to destroy infected cells

Phagocytosis

Phagocytes are a type of white blood cell which can destroy pathogens - types of phagocyte include macrophages, monocytes and neutrophils. They first detect the presence of the pathogen when receptors on its cell surface bind to antigens on the pathogen. The phagocyte then wraps its cytoplasm around the pathogen and engulfs it. The pathogen is contained within a type of vesicle called a phagosome. Another type of vesicle, called a lysosome, which contains digestive enzymes (lysozymes) will fuse with the phagosome to form a phagolysosome. Lysozymes digest the pathogen and destroy it. The digested pathogen will be removed from the phagocyte by exocytosis but they will keep some antigen molecules to present on the surface of their cells - this serves to alert other cells of the immune system to the presence of a foreign antigen. The phagocyte is now referred to as an antigen-presenting cell (APC).

Specific Immune Response

The specific immune response happens after the non-specific response and is an attack aimed at a particular antigen. It involves the activation of two types of immune cells: T lymphocytes and B lymphocytes.

T lymphocyte response

T lymphocytes are white blood cells which contain receptors on their cell surface. Different T cells have different shaped receptors on their surface (so they will each bind to a different-shaped antigen). When a particular T cell binds to a complementary antigen (e.g. on a antigen-presenting cell or on a pathogen), the T cell will become activated - this is called clonal selection. Once it is activated, the T cell divides by mitosis to produce clones of itself - this is called clonal expansion. There are different types of T cell which play different roles in the immune response:

• T helper cells release chemicals (they release a type of cytokine called interleukins) to activate B lymphocytes.

• T killer cells destroy any cells which have been infected with the pathogen.

• T regulatory cells suppress other immune cells and prevent them from attacking our own (host) cells.

• T memory cells remain in the bloodstream in low levels in case reinfection occurs. If the antigen is detected again at a later date, they will divide into T helper, T killer and T regulatory cells.

B lymphocyte response

B cells are activated when chemicals are released from T helper cells. They are also activated when the antibody molecules on their cell surface bind to a complementary antigen. Different B cells have different shaped antibodies on their surface, so only the B cells with the correct-shaped antibodies will be activated. Once they are activated, the B cells divide by mitosis and differentiate into two kinds of cell - plasma cells and memory cells.

• Plasma cells produce antibodies with a complementary shape to the antigen.

• Memory cells remain in the bloodstream in low levels in case reinfection occurs. If the antigen is detected again at a later date, they will quickly divide into plasma cells.

Antibody structure

Antibodies have a quaternary structure made up of four polypeptide chains (two heavy chains and two light chains) held together by disulfide bridges. They are composed of a variable region (which is different in different antibodies) where the antigen-binding site is located. The antigen-binding site has a complementary shape to the antigen which makes it specific to that particular antigen. There is also the constant region which is the same for all antibodies. The constant region contains another binding site which allows the antibody to bind to immune system cells, such as B cells or phagocytes. In between the variable region and the constant region is the hinge region which provides the antibody with flexibility.

How antibodies work

Antibodies work to destroy pathogens in three different ways.

1. Agglutination - antibodies each contain two antigen-binding sites which means they can bind to two pathogens at the same time. This causes pathogens to become clumped together. Phagocytes can then engulf and digest lots of pathogens at the same time, which makes phagocytosis more efficient.

2. Neutralising toxins - certain pathogens, such as bacteria, make us feel ill by releasing toxins. Antibodies can bind to toxins which renders them harmless (it neutralises them). The antibody-toxin complex can then be destroyed by phagocytes.

3. Blocking access to human cells - pathogens enter host cells when their antigens bind to receptor molecules on host cells (like a key opening a lock). When antibodies bind to antigens, it prevents the antigen from fitting in the receptor which means it can’t get inside the cell.

Membrane-bound and secreted antibodies

Antibodies can either be membrane-bound (e.g. found on the surface of B cells) or secreted by plasma cells and float freely in the bloodstream. The heavy chains of these two types of antibody differ slightly - the heavy chains of membrane-bound antibodies contain an extra region which enables attachment to the cell membrane.

The heavy chains for both antibodies are produced from the same gene. A gene can produce two (or more) different proteins through a process called alternative splicing. Splicing is a process where the non-protein coding parts of a gene (the introns) are snipped out and the protein-coding regions (the exons) are stuck together to form a mature mRNA molecule. Certain genes will splice their exons in different combinations, so that different proteins are produced. Alternative splicing means that multiple proteins can be produced from the same gene and explains why organisms display a huge number of proteins from a relatively small number of genes.

Next Page: Immunity and Vaccination