THE THIRD LINE OF DEFENCE
The third line of defence is engaged if the first and second lines of defence fail. It incorporates a specific response for each specific pathogen, resulting in adaptive immunity that is mediated by specialist Lymphocytes (cell mediated immunity) or antibodies (humoral immunity). Cell mediated immunity and humoral immunity involve the recognition of foreign matter in the body. Cells of the body are known as “self” and foreign cells are known as “non-self”. Self cells are distinguished from non-self cells by the proteins on the cell membrane. These proteins are called MHC class markers (Major histocompatibility complex) and are coded for by genes and act as cell antigens. The two classes of MHC markers that exist are MHC class I found on all cells but red blood cells and MHC class II markers found only on T and B cells and certain macrophages. These antigens are molecules, often proteins that trigger immune responses which are only initiated when they are detected by T and B cells.
CELL MEDIATED IMMUNITY
Cell mediated immunity involves the action of T cells. T cells are a group of lymphocyte which originate in the bone marrow but mature and differentiate in the thymus gland, attacking pathogens that have invaded the cells of the body. T cells contain T cell receptors which bind to antigens (specific). The four types of T cells that exist are T cells involved are helper T cells (TH), cytotoxic T cells (TC), suppressor T cells (TS) and memory T cells (TM). T cells have receptors which foreign antigen matter bind to and initiate further response from other cells.
When a phagocyte, often a macrophage engulfs a pathogen, it presents some of the pathogen’s antigens on its MHC class II markers. They are transported to the lymph nodes where there is a higher concentration of lymphocytes, especially T cells The macrophage releases a cytokine called interleukin-1 to arouse and attract specific T helper cells. The T cell receptors on the T helper cell bind to the foreign antigen and amplify the signal. Once the T helper cells have identified the pathogen, it releases another cytokine called interleukin-2 to attract B cells, cytotoxic T cells and other T helper cells.
A cytokine is a cell signalling molecule, influencing the behaviour of other cells
Cytotoxic T cells kill pathogen infected body cells. They use their T cell receptors to recognise the class I MHC marker-antigen complex on the membrane of the infected cell. The cytotoxic T cell binds to the class I MHC marker of the infected cell using their T cell receptors. It then secretes perforin proteins that create perforations in the membrane of the infected cell, killing it.
After the pathogen infected cells have been killed and further spread of the disease is inhibited, suppressor T cells inhibit the specific T and B cells for that disease. Suppressor T cells can do this by directly killing immune cells, inhibiting the secretions of immune cells or secreting proteins that alter immune cell functions.
Helper T cells (TH)
Helper T cells are the most important of all the white blood cells. They coordinate immune response from B and T cells. Once activated by interleukin 1 secreted by macrophages, they will secrete interlukin 2 to attract more T and B cells to the particular infection. They also release interferon. They can divide into T memory cells.
- When a pathogen invades the body, it is engulfed by wandering macrophages which present the antigenic fragments on its surface
- This macrophage becomes an antigen-presenting cell, and presents the antigen to helper T cells (TH cells)
- The TH cells bind to the antigen and become activated, and in turn activate the B cell with the specific antibody for the antigen
- This B cell clones and differentiates into plasma cells that produce antibodies and memory cells that form a memory of the pathogen
Suppressor T cells (TS)
Suppressor T cells regulate immune response and stops the activity of the immune system once the invader has been defeated to save resources by the secretion of proteins and enzymes
Cytotoxic T cells (TC)
Cytotoxic T cells recognise and destroy infected, cancer and foreign eukaryotic cells, releasing perforin to lyse the cells and toxins to destroy the cell and its contents. The releases of other cytokines further stimulates macrophages to undergo phagocytosis. TC cells also release interferon.
Memory T cells (TM)
Have the ability to quickly recognise foreign antigens so that a rapid response occurs with subsequent invasions
HUMORAL IMMUNITY
Humoral immunity involves the resistance against diseases involving the production of specific antibodies to bind to specific antigens by. Antibodies are proteins that are produced by B cells (a type of lymphocyte/white blood cell that originate in the bone marrow but them migrates to the lymph nodes, capable of producing antibodies) designed only to attach to a specific antigen. Different B cells must produce different antibodies for different invading pathogens.
An antibody has four chains, 2 light and 2 heavy chains
Two antigen binding sites are present on each antibody, one at the end of each light-heavy chain region so therefore each antibody can bind to two antigens. The only variable regions of an antibody are its antigen binding sites
B cells can usually have antibodies on their cell membranes. Millions of B cells exist hence why millions of antibodies can exist.
When the antibody is stimulated/primed upon the recognition of a particular antigen, mitosis (clonal expansion) occurs, resulting in the many clones. Replication is also stimulated from the release of cytokines by helper t cells. Upon replication, specialisation may occur. These cells may form plasma cells which produce specific antibodies and some memory cells.
Antibodies that have been produced to fight infection remain in the body for long periods of time and attach to memory cells which form a memory of the pathogen and increase the response time of the immune system upon re-exposure to the pathogen.
Antibodies can bind to antigens to immobilze them to enhance phagocytic responses, neutralize the toxins produced by thee pathogens, form antibody-antigen complexes when they bind with the antigen and form agglutination (clumping) allowing phagocytes to engulf it. Complement proteins can also be stimulated to lyse the pathogen's cell membrane.