Immunity
Questions Received:
Why does blood of a particular blood group often contain antibodies against other blood groups?
What are prostaglandins? How are they involved in inflammation?
What is a specific response? What is a non-specific response?
What are the actions of T cells and B cells in an immune system?
Responses:
23rd March 1999
Immunoglobulin A is one of five classes of
antibodies that are able to recognise antigens (molecular markers carried by
cells) that do not belong to the body. They do this by matching the shape of the
antigen molecules exactly. Each antibody is specialised to recognise only one
type of antigen.
IgA makes up 15-20% of the immunoglobulins in the
serum. It is also the main immunoglobulin in a variety
of secretions such as
saliva, milk, and the mucus lining the airways and digestive tract. IgA
antibodies increase in amount during mucosal infections.
Secretory IgA molecules are joined in pairs and complexed with a secretory component which helps in the transport of the antibodies through cells and protects the antibodies after release should they come into contact with protein-dissolving enzymes. The IgA antibodies bind to micro-organisms such as bacteria and protect us against infection by preventing them from attaching to the epithelial surface to gain entry.
20th April 1999
What is the difference between vaccination and immunity?
Vaccination is the introduction of antigenic material - usually derived from an infectious agent such as a bacterium or virus - into someone’s body so that their immune system can prepare defences against it. Then, if the person comes into contact with the infectious agent at a later time, their immune system reacts quickly and strongly against the agent and either prevents the infection from gaining hold or limits it to a relatively mild form. Vaccination was originally given its name from the process of inoculating people with the discharge from cowpox pustules (vacca is the Latin for cow) to protect them from the much more serious disease, smallpox.
Immunity is the ability of the body to resist particular infections. It exists at different levels:
Innate Immunity: the body maintains barriers against infection and in addition tissues are able to eliminate any foreign materials and organisms that penetrate the barriers - phagocytic cells patrol the tissues and mop up materials that should not be there
Acquired Immunity: specialised cells of the immune system recognise and respond to specific foreign antigens, either by direct contact (T lymphocytes) or by the production of antibodies (B lymphocytes)
So vaccination is a process to induce immunity to particular diseases, while immunity is the ability of the body to resist infection.
What is the importance of vaccinations?
Vaccination is a way of reducing the occurrence of infectious diseases in populations and in some cases eliminating them entirely. For example, smallpox has been eliminated by the implementation of vaccination programmes world-wide. Vaccination can also be used to protect more vulnerable people such as babies and young children from infection.
What are some kinds of immune disorders?
The immune system can become weakened to the point where it can no longer fight off infections that would otherwise be relatively harmless. An example is the disease AIDS which is generally considered to be caused by the effects of the Human Immunodeficiency Virus. Sometimes the immune system can turn against normal cells in the body, damaging or killing them. Type 1 diabetes is caused by the autoimmune destruction of beta cells in the child’s pancreas, with the result that no insulin is produced and the control of blood sugar levels is compromised. Multiple sclerosis is another example of an autoimmune disease.
What happens during an allergic response?
An allergic reaction occurs when exposure to a relatively harmless antigen such as pollen or a food material such as peanut triggers off an inappropriate response from the immune system. These antigenic triggers of allergy are called allergens. Antibodies of the IgE family are generated against the allergen by the immune system and released into the blood stream. Cells known as mast cells and basophils mop up some of the antibodies and attach them to their surface, making them highly sensitive to future exposure to the allergen. If the allergen is encountered again, the mast cells and basophils release large quantities of powerful signalling molecules such as histamine, leucotrienes, heparin, and platelet activating factors. These substances cause dilation of local blood vessels, damage to local tissues, loss of fluid from capillaries into the tissues, and contraction of local smooth muscle. A variety of allergic reactions may be produced:
Anaphylaxis - a widespread allergic reaction throughout the vascular system and associated tissues. Histamine released into the circulation causes peripheral vasodilation and loss of plasma into the tissues. People experiencing this reaction may die of circulatory shock within minutes unless noradrenaline is given to counteract the effects of the histamine.
Urticaria - when antigen enters specific skin areas it causes the local release of histamine and swellings called hives. Antihistamines provide a suitable treatment.
Hay Fever - this allergic reaction occurs in the nose. Histamine released in response to exposure to the allergen causes fluid leakage into the tissues and produces a runny nose, runny eyes, and sneezing.
Asthma - this allergic reaction occurs in the bronchioles of the lungs. The substances released from the mast cells cause spasm of the smooth muscle surrounding the bronchioles, and breathing through the constricted airways becomes very difficult.
What is an antigen reaction?
Antigens are generally proteins and other large organic molecules. Because of
their size and complexity, each macromolecule has a highly specific shape. Cells
of the immune system are able to recognise these differently shaped antigenic
molecules, and if they encounter antigens that are foreign to the body’s own
repertoire they will mount an immune response.
Recommended Reading
Staines, N.A., Brostoff,J., and James, K. (1993) Introducing immunology (2nd edition). St Louis: Mosby-Year Book Europe Limited.
What is a specific response? What is a non-specific response?
20th April 1999
A specific response occurs when the immune system recognises an antigen that does not belong in the body and then prepares a specific reaction to it. For example, if influenza viruses enter the tissues, cells of the immune system will recognise that the surface antigens of the viruses are different from the normal antigens of the body’s cells and prepare a response. One element of the response is the production by B-cells of large numbers of specific antibodies (proteins) that will be carried via the blood stream to the location of the viruses. Here the antibodies will lock onto the viral antigens. Another element of the specific response is the arrival of specifically sensitised T-cells which can tackle the viruses directly and remove them.
On the other hand, non-specific responses are protective actions carried out by relatively non-specialised cells found throughout the body rather than by the highly-specialised T-cells and B-cells of the immune system. For example, phagocytes (phago- means to eat and -cytes means cells) move around within the tissues and if they encounter anything out of the ordinary they will attempt to dispose of it. Thus, bacteria and debris will be mopped up by the phagocytes. However, although the non-specific responses provide a first line of defence against harmful factors that enter the body tissues, they are less powerful than specific responses.
What are the actions of T cells and B cells in an immune system?
20th April 1999
T-cells and B-cells are specialised lymphocytes (white blood cells).
T-cells are involved in immune responses, particularly the aspect known as cell-mediated immunity. This means that they migrate to the site of the problem and deal with it directly. Thus an infectious organism or a body cell that is transforming into a cancer cell will be tackled by specially equipped T-cells. The population of T-cells has several subpopulations, including helper cells, cytotoxic cells, and suppressor cells, which play a central role in both creating an immune response and then just as importantly calming it down again when the work is done. Some T-cells are known as memory cells, and they retain a memory of an earlier infection so that if the same infection comes along later, the immune system can make a much more rapid and effective response.
B-cells are also involved in immune responses but their role when activated is to generate enormous numbers of antibodies that are specific to non-self antigens. Antibodies are proteins that can latch onto non-self antigens, and since they arrive at the scene of the infection via the blood stream they constitute humoural immunity. The attached antibodies may in some cases be able to disrupt the activities of the infectious organism, but alternatively their presence will facilitate the protective actions of phagocytes and T-cells.
4th May 2004
Thank you for your questions. The main body systems involved in immunity are the immune system, lymphatic system, and cardiovascular system, but I think it would be fair to say that most if not all body systems have some link with immunity, particularly non-specific immunity. So for example, the skin provides a protective barrier against infection, as does the mucosa of the digestive tract. The urinary system and reproductive system also have ways of reducing the risk of infection.
Here are some ideas about the physiological processes happening during an inflammatory response. You may find it helpful to compare the events occurring during inflammation with what happens in a human context when there is a major accident or disaster – the roles of the emergency services, the need to clear away debris, and the reconstruction phase, all requiring communication between those involved.
Inflammation presents as redness, swelling and warmth, and is often associated with pain. The inflammatory phase is an essential component of the tissue repair process following trauma, mechanical irritation, thermal or chemical insult, and a wide variety of immune responses. The inflammatory phase has a rapid onset in the first few hours and reaches its maximum in 2 to 3 days before gradually resolving – usually - over the next 2 or so weeks. Many cytokine signals are produced by cells locally to initiate and control the inflammatory response. Failure to resolve the inflammation can lead to chronic non-healing wounds, whereas uncontrolled matrix accumulation, often involving aberrant cytokine pathways, leads to excess scarring.
There are two essential elements in the inflammatory process - vascular and cellular cascades. These occur in parallel and are significantly interlinked. The chemical mediators that make an active contribution to this process are many. In recent years, the identification of numerous 'growth factors' had led to several important discoveries and potential new treatment lines.
The inflammatory response causes the blood vessels to become leaky releasing plasma and neutrophils into the surrounding tissue. The neutrophils phagocytose debris and micro-organisms and provide the first line of defence against infection. They are aided by local mast cells. As fibrin is broken down as part of this clean-up the degradation products attract the next cell involved. The task of rebuilding is complex and requires cells to direct the process - the macrophages. Macrophages are able to phagocytose bacteria and provide a second line of defence. They also secrete a variety of chemotactic and growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor beta (TGF-â) and interleukin-1 (IL-1).
Vascular Events
In addition to the vascular changes associated with bleeding, there are also marked changes in the state of the intact vessels. There are changes in the calibre of the blood vessels, changes in the vessel wall and in the flow of blood through the vessels. Vasodilation of undamaged vessels in the vicinity of the wound follows an initial but brief vasoconstriction and persists for the duration of the inflammatory response. Flow increases through the main channels and capillary bed. The cause of this dilation is primarily by chemical means (histamine, prostaglandins and complement cascade components C3 and C5) whilst the nervous system exerts an additional influence. The white blood cells marginate, platelets adhere to the vessel walls, and the endothelial cells swell. There is an increase in the permeability of the local vessels (also mediated by numerous of the chemical mediators) and increased movement of exudate into the damaged tissues.
The flow and pressure changes in the vessels allow fluid, smaller solutes, and plasma proteins to pass into the tissue spaces. The chemical mediators responsible for the permeability changes include histamine, serotonin (5-HT), bradykinin and leukotreines and prostaglandins. The effect of the exudate is to dilute any irritant substances in the damaged area and a fibrin clot forms, providing a meshwork in the wound area between the surrounding intact tissues. The meshwork traps particles and debris, and aids the activity of phagocytes. Mast cells in the damaged region release hyaluronic acid and other proteoglycans which convert the exudate into a gel which limits local fluid flow and further traps various particles and debris.
Cellular Events
Within minutes of the wounding, neutrophils actively migrate from the blood vessels into the tissues. These are followed by several other cell types including monocytes, lymphocytes, eosinophils, basophils and some red cells. In the tissue spaces the monocytes become macrophages. The main groups of chemical mediators responsible for chemotaxis are some components of the complement cascade, lymphokines, factors released for the neutrophils and peptides released from the mast cells in the damaged tissue. Numerous chemical mediators have been identified as having a chemotactic role, for example, PDGF (platelet derived growth factor) released from damaged platelets in the area. Components of the complement cascade (C3a and C5a), leukotreines (released from a variety of white cells, macrophages and mast cells) and lymphokines (released from polymorphs) have been identified. Macrophages and neutrophils act as early debriders of the wound. Dead and dying cells, fibrin mesh and clot residue all need to be removed. One of the chemicals released as an end product of phagocytosis is lactic acid, which is one of the stimulants of cellular proliferation.
The effects of acute inflammation are largely beneficial: the fluid exudate dilutes the toxins and escaped blood products include antibodies (and systemic drugs), the fibrinogen forms fibrin clots providing a mechanical barrier to the spread of micro-organisms (if present) and additionally assists phagocytosis, the gel like consistency of the inflammatory exudate prevents the spread of the inflammatory mediators to surrounding intact tissues. Transportation of invading bacteria to the lymphatic system stimulates an immune response whilst the increased blood flow contributes to the increased cell metabolism necessary for the proliferative stage by increasing local oxygen content, supply of necessary nutrients and removal of waste products. The leucocytes provide a mechanism for the phagocytosis of foreign material, bacteria, dead cells, with the neutrophils and monocytes (becoming macrophages) making the greatest contribution.
Inflammatory Outcomes
Thus, the inflammatory response includes a vascular response, a cellular and fluid exudate, with resulting oedema and phagocytic activation. The complex interaction of the chemical mediators not only stimulates various components of the inflammatory phase, but also stimulates the proliferative phase. The course of the inflammatory response will depend upon the number of cells destroyed, the original cause of the process and the tissue condition at the time of insult.
Resolution is a possible outcome at this stage where the injury has been slight and few cells have been destroyed
Suppuration occurs in the presence of infective micro-organisms when pus forms. Pus consists of dead cell debris, and living, dead and dying polymorphs suspended in the inflammatory exudate. The presence of an infection will delay the healing of a wound.
Chronic inflammation may follow the acute reaction or may develop slowly with no initial acute phase. Chronic supervening on acute usually involves some suppuration whilst gradual onset chronic inflammation can have one of several causes including local irritants, poor circulation, the presence of limited numbers of micro-organisms or immune disturbances. Chronic inflammation usually produces more fibrous material than inflammatory exudate. Frequently there is some tissue destruction, inflammation and attempted healing occurring simultaneously.
Healing by fibrosis occurs when
fibrin deposits from the inflammatory stage are partly removed by macrophages
and gradually replaced by granulation tissue which becomes organised to form
scar tissue. Capillary budding occurs and fibroblasts generate connective
tissue.
With regard to the nurse’s role and responsibility in relation to hospital
acquired infection, you should be able to find some helpful material on the
Nurse Minerva page about Infection
Control.
12th May 2004
This is an interesting question, and the answer that you develop in your project will be influenced by the stage you have reached in your understanding of the body. We don't want to do the project for you, so here are some ideas for you to select from and develop.
The most natural starting point is to remember that the immune system defends the internal environment of the body from invading micro-organisms and viruses, and also looks out for and deals with cells in the body that are beginning to become transformed into cancer cells. These are direct contributions to homeostasis - free of the damaging effects of infection and cancer, the normal processes of homeostasis can take place. So it will be worthwhile for you to review the non-specific and specific immune processes and see how this protective role is achieved.
The immune system is complex and potent, and although usually it works very effectively, it can occasionally cause problems within the body by turning against normal cells within the body - autoimmune disease. So as well as considering the ways in which the immune system contributes to homeostasis, you might also want to look at the ways in which the immune system itself is kept in balance (Van Parijs and Abbas, 1998).
At a more detailed level, people are finding that the immune system contributes to homeostasis in a large number of subtle ways. Recent research is showing that molecules generated by the immune system are involved in nutrient transport, receptor regulation, and other physiological effects. For example, immunoglobulins transport nutrients from the intestinal lumen to body tissues for absorption, and also transport breakdown products of internal metabolism to other tissues where they can be recycled or excreted (Humphrey and Klasing, 2004). Immunoglobulins influence the response of target organs throughout the body to neurotransmitters and hormones - they regulate cell receptors for insulin, thyroid hormones, acetylcholine, parathyroid hormones, serotonin, and dopamine. Bone homeostasis is mainly regulated by the balance between bone formation and resorption, and involves the coordinated action of osteoblasts and osteoclasts. Osteoblasts are bone-forming cells, and osteoclasts resorb bone matrix. Although the activities of these cells are regulated by the local microenvironment, it has recently been shown that bone homeostasis is greatly influenced by components of the immune system (Rho, Takami, and Choi, 2004). So we are developing a better understanding of the wide-ranging effects that the immune system has on homeostasis.
References
Humphrey, B.D., and Klasing, K.C. (2004) Modulation of nutrient metabolism and homeostasis by the immune system. World's Poultry Science Journal, 60(1), 90-100 (March).
Rho, J., Takami, M., and Choi, Y. (2004) Osteoimmunology: interactions of the immune and skeletal systems. Molecules and Cells, 17(1), 1-9 (Feb 29).
Van Parijs, L., and Abbas, A.K. (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science, 280(5361), 243-248 (Apr 10).