Antigens and the initiation of an immune response

Use this page to revise the following concepts within antigens and the initiation of an immune response:

What are antigens?

Antigen recognition plays a key role in both the innate and adaptive immune systems. Antigens are small molecular components of cells or non-cellular biological materials. Most often, they are parts of membrane or surface proteins of cells and non-cellular pathogens such as viruses. When these proteins are on the surface of our own cells they do not usually initiate an immune response, as they are determined to be self antigens. If the proteins are foreign or non-self antigens they will eventually generate antibodies - hence the name antigen, from “anti(body)-generator”.

Antibodies are small Y shaped proteins that are secreted by B plasma lymphocytes. They destroy or deactivate the pathogen when they bind to the antigens on that pathogen. Antibodies are complementary to a specific antigen (the shape of the antibody binds specifically to the shape of the antigen). You can learn more about antigen presentation and the lymphocytes in the adaptive immune system in the humoural response. Antibodies are produced by the adaptive immune system but they work alongside the innate immune system to assist it.

Graphic representing and explaining the binding of antibodies to antigens. On the top left is a rod-shaped bacterium with a flagellum, that has antigens on its surface, represented as round proteins and labelled “Antigen on the surface of a bacteria”. An antibody, represented as several rectangular sections arranged into a Y-shape, is bound to one of the antigens, by the left-hand tip of its Y-shape. This is labelled “Antibody specific to this bacterial antigen”. On the top right is a virus represented as a round lipid envelope around genetic material represented by a squiggled line, with several proteins embedded in the envelope shown as bars with rounded ends. These are labelled “Antigen on the surface of a virus”. Several antigens are bound to a pair of antibodies, these are labelled “Antibody specific to this viral antigen”. On the bottom left there is three yeast cells, brown oblong shapes, with round structures on their surface labelled ”Antigens on the outer surface of yeast (a type of fungi)” and the bottom right is a complex microorganism, a multicellular larva with sense organs at one end and covered in cilia. It is labelled “Antigens on the outer surface of miracidial form of Schistosoma mansoni (a type of parasite)”. Two more antibodies are pictured between the lower pathogens, with arrows pointing to the pathogens. These antibodies are labelled “Eventually, specific antibodies generated by the adaptive immune system come to bind to the matching specific antigens that generated that antibody's production

An analogy for antigens is that they are biological signposts or QR codes. They give different types of information to all the different cells that read the signs/codes. One cell can have several different signs. Some signs describe “I am part of this plant” and some say “I am a root cell”. In an animal, a cell might have signs giving information that they are an “B type blood cell” or “liver cell”. Immune system cells travel around the body checking cells to see if they are “self” or “non-self” and so recognise non-self antigens as potential pathogens.

graphic analogising an innate immune cell reading antigens on a series of cells to the reading of QR codes. In the top left is a cell of the innate immune system. Lines connect it to several cells and a virus. Two of the cells have QR codes with a tick and “self”, while the other cell and the virus have red QR codes with a red X and “Non-self/foreign.

Antigens can give both general information (“I am a virus”) as well as highly specific information (“I am this specific strain of virus”). Our innate immune system cells will be able to recognise viruses as “non-self” and act to destroy them. However, the innate immune system is not able to distinguish between different viruses and classify them. That is the role of the adaptive immune system, (especially cytotoxic T cells) that can distinguish and target specific pathogens.

A graphic representing the antigens of viruses as QR codes. On the left panel, there are two viruses, each structured as genetic material inside a protein capsid, surrounded by a lipid envelope, with several proteins embedded in its surface labelled antigen. The antigens of each virus are illustrated in different colours and connected to two different QR codes each in the same colour as the corresponding antigen. On the right-hand panel there is a macrophage, with the label “Part of the innate immune system” and a lymphocyte with the label “Part of the adaptive immune system”. The lymphocyte has a large receptor on its surface that is binding to a copy of one of the antigens. Above the macrophage: “This macrophage will attack either/both/any viruses”, above the lymphocyte”This cytotoxic T cell will only attack the virus it is specific to (e.g. the "blue" virus).

Antigen recognition and major histocompatibility complexes

Major histocompatibility complex (MHC) molecules are proteins found on the surface of cells that help the body's immune system recognise and respond to antigens. There are two main types involved in immunity , MHC I and MHC II. In humans, MHC I molecules are also known as human leukocyte antigens (HLA).

MHC I Class proteins

MHC I are found on all cells except red blood cells. The MHC I protein itself gives information, like a QR code, that the cell is part of that body and “self”. MHC I can also display additional antigens from within the cell such as viral antigens if the cell becomes infected.

A human cell showing multiple MHC I receptors on its surface. An inset zooms in on one MHC I, showing it has a ‘tail’ embedded in the cell membrane, and then is formed by several protein subunits that form a rough rectangle with a pocket of space on the extracellular side. Zooming on on the receptor further, an inset shows a QR code.

MHC I are also used to show antigens from pathogens that have entered that cell, e.g. viruses and some bacteria. Immune system cells recognise that antigen as being “non-self” foreign and begin an immune response.

On the right is a virus, structured as genetic material inside a protein capsid, surrounded by a lipid envelope, with several proteins embedded in its surface labelled antigen. One antigen is connected to a QR code. On the left is a human cell showing multiple MHC I receptors on its surface, and squiggled lines inside the cell and bound to the MHC I receptors, representing viral antigens. An inset zooms in on one MHC I, showing it has a ‘tail’ embedded in the cell membrane, and then is formed by several protein subunits that form a rough rectangle with a pocket of space on the extracellular side. In the pocket is an antigen. Zooming on on the receptor further, an inset shows a QR code.

There is high variability in the gene responsible for encoding MHC I proteins so no two humans are likely to have identical MHC I molecules. This high variability can result in rejection in organ transplantation. Transplanted cells are targeted by natural killer cells patrolling the body looking for foreign or incorrect MHC I proteins. This is also why immunosuppressant drugs are given to transplant patients, to decrease the body’s natural immune reaction.

A graphic of Natural Killer cells interacting with cells. On the left, the natural killer cell has a receptor that binds to a normal MHC I on the surface of a liver cell. There is a green tick labelled ignore. On the right another natural killer cell has its receptor bound to a foreign MHC I on a transplanted liver cell. It has a red cross labelled destroy. A red arrow extends from the natural killer cell to the transplanted liver cell to represent that the NK cell will destroy that cell.

When cells are infected by viruses or have become cancerous, their MHC I molecules may no longer be produced (missing), may be malformed, or may display non-self antigens. When these cells are checked by NK cells the NK will destroy the incorrect cells by causing those cells to begin apoptosis.

A graphic of Natural Killer cells interacting with cells. In the left-hand panel, the natural killer cell has a receptor that binds to a normal MHC I on the surface of a cell labelled “Liver cell”. There is a green tick labelled ignore. In the middle panel, the natural killer cell binds via receptor to a malformed MHC I that is missing a protein subunit, on a cell labelled “Cancerous or infected liver cell”. There is a red cross labelled destroy and a red arrow extending from the natural killer cell to the cancerous or infected liver cell to represent that the NK cell will destroy that cell. On the right-hand panel, Another natural killer cell extends its receptor towards another cell also labelled “Cancerous or infected liver cell”. This one is missing it’s MHC I. Again, there is a red cross, Destroy and the red arrow.

MHC II class proteins

MHC II class proteins are found on all antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells, and are used to present foreign antigens to T cells in the adaptive immune system response. T cells can then create specific cytotoxic T cells that will go and “scan” for that specific antigen being presented by infected cells. They are very good at finding and targeting that specific infection but they will ignore other infections. Meanwhile, the innate immune system will attack any foreign antigens.

graphic representing antigen presentation by a dendritic cell to a T cell, and the resulting action of the cytotoxic T cells. On the left, there is a large dendritic cell with many pseudopodia, and multiple MHC II receptors. Inside the cell is a phagosome containing antigens from a pathogen, and these same antigens are presented on the surface of the MHC II receptors. A T cell extends a receptor to also bind an antigen that is presented on an MHC II. This interaction is labelled “Dendritic cell with antigen presented on MHC II”. On the right are two Cytotoxic T cells, each interacting with an infected cell via their MHC I receptor. The middle panel shows the Cytotoxic T cell binding to a Normal MHC I that is presenting a viral antigen, on a cell labelled “Infected liver cell presenting target viral antigen on MHC” The antigen has the same appearance as those presented by the dendritic cell. There is a red cross labelled destroy and a red arrow extending from the T cell to the infected liver cell to represent that the T cell will destroy that cell. On the right is another Cytotoxic T cell that is bound to a Normal MHC I presenting a different viral antigen, on a cell labelled”Infected liver cell presenting non-target viral antigen on MHC”. Next to the interaction is the label “Ignore”.

The next section covers the process of inflammation which is important for recruiting immune system cells to a wound or pathogen in order to start checking antigens and responding accordingly.

Inflammation

Inflammation is one of the first responses of the innate immune system to a pathogen passing the body’s defensive barriers. It is a natural immune system process that responds to irritation, either from chemical damage, a wound, or a pathogen entering the body’s tissues. Inflammation works to increase the number of responding leukocytes and blood components (such as complement proteins or platelets) and to facilitate their access to the site of the irritation.

The process of inflammation begins with mast cells promoting vasodilation (dilation of the blood vessels) and macrophages recruiting more innate system cells. During inflammation, antigens from the pathogens are transported by dendritic cells to the lymph nodes and presented to lymphocytes in the adaptive immune system.

Click on the hotspots in the image below to explore the steps and cells involved in inflammation in response to a bacterial infection.

Whilst the steps for inflammation generally remain the same there are some other specialised leukocytes that are recruited when the pathogen is a parasite or a virus.

Click on the hotspots in the following image to see more about the roles of eosinophils, basophils, and natural killer cells.

The next section covers how cells infected by a virus can respond by releasing interferons and how the activation of complement proteins assists with inflammation and phagocytosis.