Vomiting can also be a defence mechanism in trying to rid the body of irritants and toxins however this is not foolproof. The effects of hydrochloric acid can also be reduced by milk and proteins so organisms entering the body along with these foodstuffs can have more potential to do harm, The small and large intestine reply greatly on the stomachs bactericidal action. However, they contain normal flora such as escherchia coli which contribute to protection . When these are removed by the administration of broad-spectrum antibiotics or the indiscriminate use of laxatives these areas can then be open to colonistation by pathogenic bacteria. The intestines are also liberally supplied with lymphatic tissue which are involved in the bodies non-specfic and acquired immune defence systems. Diaorrhoea, like vomiting can also be regarded as a defence although it often occurs to late in the cause of an infection to be of much benefit.
The respiratory tract is initially protected by the ciliated nasal mucosa which secretes a backward flow of mucous which traps small particles and has bactericidal and virucidal properities. Lysozyme present in salvia is also present in nasal secretions. The nose also prevents the entry of insects and large particles because of the presence of hairs and sneezing is a protective reflex that expels irritants. The epithelium of the upper respiratory tract is thin so is more prone to infections by rhinoviruses and adenoviruses which are not killed by nasal secretions. We have all experienced these at somepoint, i.e, the common cold.
The trachea and bronchi are lined with a ciliated mucous membrane that helps to trap any orgranisms in debris that escapes through the upper respiratory tract. The cilia in these beat upwards moving a stream of mucous away from the lungs and to the pharynx to be swallowed. Organisms which reach the alveoli are phagocytosed by the alveolar macrophages.The helium of the lungs is also well supplied with lymph nodes which act as a filter. Coughing is a defensive reflex that removes particles or excess mucous, however as we age, or if ill, this reflex can be reduced so recreating a risk of infection. Also swallowing may be impaired leading to an increased risk of pneumonia. We can also put ourselves at risk through smoking as this damages the delicate cilia. Diseases of the respiratory system such as chronic obstructive airway disease weaken the lungs so reducing their ability to fight infection.
In our genitourinary tract the constant downward flow of urine through the ureter and bladder helps against ascending infections. Micturition (passing urine) irrigates the urethra but is less effective in females so provides a greater opportunity for entry of pathogens to invade the bladder. Sexual activity in females may lead to the occurrence of cystitis most commonly caused by coliform bacillis from the perineal area. Also catheterisation creates the opportunity for invasive as it breaks the body’s natural defences and poor aseptic techniques increases this risk. Urinary tract infections is one of the most common hospital acquired infection.
The resident flora of the vagina helps to maintain an acid environment so creating a defence to infection however the use of vaginal deodorants can disturb this PH balance resulting in infection most commonly by candida albicans which causes thrush. Age also affects the production of acid in the vagina so lowering the body’s defence to infection.
The eye also offers a defence as it is constantly irrigated with tears produced by the lachrymal glands; Tears contain high levels of lysozyme. If the body is lacking in Vitamin A these levels reduce which can develop into an eye infection. Blinking is also a defence reflex that expels irritants and ensures an even distribution of tears. In some conditions such as facial paralysis or stroke this reflex is lost and the eye may become dry and this may lead to infection.
The ear has glands which produce cerumen or ear wax which provides a sticky barrier to pathogens. Sometimes the ear produces too much and the ear can become blocked which can lead to a temporary loss of hearing.
Inflammation:
This is seen as a local non-specific defensive response to tissue damage. Its function is to eliminate the cause of the damage, remove the dead cells and restore the constancy of the internal environment and is closely assiociated with wound healing. Inflamation occurs immediately after a physical, chemical or microbiological injury. One example of inflammation is a boil, which exhibits the five characteristics in the imflammatory response, which are redness over the area, swelling, heat, pain and loss of function.
Wound healing or tissue repair:
This is the substitution of viable cells for dead cells and can occurs by regeneration or replacement. In regeneration the new cells are the same type as those that were destroyed and normal function is usually restored. In replacement a new type of tissue develops that eventually causes scar production and the loss of some tissue function. The dominant process depends on the tissues involved and the nature of the wound.
Cells can be classified into three groups; labile, stable and permanent according to their regenerative ability. Labile cells, for example, the skin, mucous membrane and hemopocetic and lymphoid tissues continue to divide throughout life. Damage to these cells can be repaired by regeneration. Stable cells, for example, in connective tissue and glands including the liver, pancreas and endocrine glands do not activity replicate after growth ceases, but they do retain the ability to divide if necessary and are capable of regeneration.
Permanent cells cannot replicate and if killed they are replaced by a different type of cell. Neurons are put into this category although they have some ability to recover from damage if the cell body of the neuron is not destroyed if this is destroyed it cannot regenerate. Muscle cells also have little ability to regenerate although they can repair themselves.
Repair of the skin is a good example of wound repair. If the edges of the wound are close together the wound heals by a process called primary union. If the edges are not close together or if there has been a large loss of tissue a process called secondary union occurs.
In primary union the wound fills with blood and a clot forms which bond the edges of the wound together and the surface of the clot dries to form a scab, which seals the wound to help prevent infection. An inflammatory response also includes vaso-dilation increasing blood cells and other substances to the area, Blood vessels permeability increases resulting in odema, also fibrin and blood cells move into the wounded tissues because of this. The fibrin acts to isolate and wall off micro-organisms and other foreign matter. Some of these cells are phagocytic cells called neutrophils which ingest bacteria helping to fight infection they also ingest tissue debris clearing the area for repair. Neutrophils are killed in this process and may accumulate as a mixture of dead cells and fluid called pus.
As phagocytosis proceeds, the epithelium at the edge of the wound undergoes regeneration and migrates under the scab. After a few days the epithelium cells from the edges meet forming a single layer of cells over the wound, The single layer proliferates and differentiates restoring the original epithelium. The scab sloughs after the epithelium is repaired. As the new epithelium forms a second type of phagocytic cell a macrophage, removes the dead neutrophils and cellular debris. Fibroblasts from surrounding connective tissue migrate into the clot producing collagen and other extracellular matrix components. Capillaries grow from the blood vessels at the edge of the wound and resvasularise the area and fibrin in the clot is decomposed and removed. This results in the replacement of the clot by a delicate connective tissue i.e. granulation tissue which consists of fibroblasts, collagen and capillaries. A large amount of granulation tissue sometimes persists, as a scar which at first is bright red due to vascularisation of the tissue. Later the scar will blanch and become white as collagen accumulates and vascular channels are compressed.
Repair by secondary union proceeds in a similar way but there are differences because the wound edges are further apart and the clot may not completely close the gap and it will take longer for regeneration to occur. The increased tissue damage creates a greater inflammatory response so there are more cell debris for the phagocytes to remove creating a greater risk of infection. Much more granulation tissue forms and wound contraction occurs as a result of the contraction of fibroblasts in this tissue,this reduces the size of the wound so it can heal by primary rather than secondary union.
The rate a wound heals varies depending on our general health, the location of the wound, the degree of damage and the treatment applied. Factors which may delay wound healing include disease e.g. diabetes, poor nutritional status and infection.
Chemicals involved in protection
There are a variety of chemicals involved in our non-specific immunity. I have discussed the surface chemicals such as lysozyme other chemicals are histamine, complement prostaglandins .Luekotrienes promote inflammation by causing vasodilation, increasing vascular permeability abtracting leukocytes and stimulating phagocytosis. In addition the protein interferon protects cells against viral infections and perhaps some forms of cancer and genetically manufactured interferon is now part of the treatment used for particular cancers.
In task one I talked about the specific immune system, which involves the ability to recognise, respond to and remember a particular substance. Substances stimulating specific immune responses are antigens. Antigens can be divided into 2 groups, foreign antigens and self-antigens. Foreign antigens are not produced by the body but are introduced from outside it. Components of bacteria, virus and other microorganisms are examples that can cause disease. Pollen, animal hairs, foods, drugs are also foreign antigens and can trigger an overreaction of the immune system and cause allergies. Transplanted tissues and organs that contain foreign antigens can result in a rejection of the transplant. Self antigens are molecules produced by the body that stimulate a specific immune response, the response to self antigens can be beneficial or harmful, for example recognition of tumour antigens can result in tumour destruction whereas autoimmune disease can result when self antigens stimulate unwanted tissue destruction.
Specific immunity was historically divided into 2 parts, humoral and cell-medicated immunity. Early investigations of the immune system found that when plasma from an immune animal was injected into the blood of a non-immune animal the animal became immune. As this process involved body fluids (humors) it was called humoral immunity, it was also discovered that blood cells alone could be responsible for immunity this process was called cell-medicated immunity. Both types of immunity result from the activities of lymphocytes called B cells and T cells, B cells produce proteins called antibodies, which are found in plasma and are responsible for humoral immunity or can be known as antibody-medicated immunity. 3 kinds of T cells are responsible for cell medicated immunity T effecter, T helper and T suppressors. The cell-medicated response is produced by the T effecter cells and the T helper cells increase and the T suppressor cells decrease the activity of the T effecter cells. T helper and T suppressor regulate cell-mediated immunity they also affect B cells in a similar way and therefore also regulate humoral immunity.
Although the immune system is divided into 3 i.e. non-specific immunity, humoral immunity and cell-medicated immunity, the immune system responses often involve components of more than one type of immunity for example, the specific immune system has the ability to recognise and remember specific antigens, once recognition has occurred many of the events that lead to the destruction of the antigen are non specific immune system activities such as inflammation and phagocytises.
There are immune system problems of clinical significance; I will explain some of these.
Hypersensivity reactions are an understandable response by the body to particular antigens, which it has encountered before however the initial number of antibodies formed may be small. If an individual is exposed to the same antigen again there may be sufficient antibodies in the circulation to neutralise the antigen but if large amount of the antigen are inhaled, eaten or come in contact with the skin there may not be sufficient circulatory antibodies within the cells. When this antigen – antibody – reaction takes place within the cells an allergic reaction occurs. These reactions can have many features such as, headaches, skin rashes, oedema of the arms and legs, angio-neurotic oedema (swelling of the lips and face), vomiting, diahorrhoea, rhinitis, sinusitis and catarrh.
The most serious allergic reaction is anaphylaxis, cytotoxic reactions and immune complex disease. In anaphylaxis the chemicals released from the mast cells and basophils cause systemic vasodilatation a drop in blood pressure and cardiac failure. In cyototoxic reactions IgG or IgM combines with the antigen on the surface of a cell resulting in the activation of complement and subsequent lysis of the cell. Transfusion reactions caused by incompatiable blood types are an example of this.
Autoimmune diseases occur because the immune system fails to differentiate between self and foreign antigens. In most instances this failure is probably due to a breakdown of tolerance i.e. T suppressor cells no longer prevent an immune system response to self antigens. Although it is not clear how autoimmune diseases begin they operate through the same mechanisms as hypersensitivity reactions except that this is stimulated by self antigens. Thrombocytopenia purpura is an example of an autoimmune disease, this is a cytotoxic reaction were antibodies bind to platelets, complement is activated and the platelets are lysed, this depletion of platelets leads to bleeding in the skin and internal organs. In systematic lupus erythematosus antibodies that form immune complexes with nuclear substances such as DNA are produced and symptoms include a facial rash, fever and progressive kidney failure. Other autoimmune diseases are rheumatoid arthritis and rheumatic fever.
Immunodeficency is not uncommon as it can have many causes, inadequate protein in the diet inhibits protein synthesis and antibody levels will decrease. Stress can depress the immune system, fighting an infection can deplete the lymphocyte and granulocyte reserves making us more susceptible to infection. Diseases that cause proliferation of lymphocytes for example, leukaemia’s and myelomas can result in an abundance of lymphocytes that do not function properly. The immune system may also be suppressed by drugs to prevent graft rejection. Congential immunodeficiency’s may involve inadequate B and T cell formation or both. Severe combined immunodeficiency disease (SCID) involves both B and T cells were they fail to differentiate, unless the sufferer is kept in a sterile environment or is given a bone marrow transplant death from infection occurs. As discussed previously in task 1, transplants can cause problems. There are a cluster of genes in humans called the human lymphocyte antigen (HLA) genes which are responsible for the antigenic labelling of tissues. These genes control the production of HLA’s which are inserted onto the surface of cells. The immune system recognisees self from foreign antigens because self cells are marked with HLA’s, so a rejection of transplanted tissue is caused by the rejection of foreign HLA’s.
To reduce rejection a tissue match is performed and only tissues with similar HLA’s to the recipient have a chance of being accepted to prevent rejection.
Much research is on going into how the immune system responses new knowledge could create therapies to selectively augment or diminish immune responses against particular antigens and may also result in selective desensitisation to treat allergy or asthma or control transplant rejection. There is a promising new approach to treating cancer patients this is trying to generate an immune response to the cancer by vaccinating the sufferer with their own cancer cells. Usually cancer cells are ignored by the immune system because they are seen as ‘self’, however there us now evidence that the tumour may carry antigens that are not present on other cells and if this is the case it may be possible to force the immune system to mount a response. However this research is still in a early stage and requires more in depth work before it is able to cure cancer.
Ross and Wilson – Foundations of Anatomy and Physiology
References:
Anatomy and Physiology – Seely, Stephens and Tate
– the immune system in Health and Disease – (national institution for medical research)
The Royal Marsden,+*///* hospital manual of clinical procedures. (sixth edition)
