I just read this review about immunity and I found it very helpful. So, why don’t I share it? I only rewrite it from the book (Immunology for Medical Students, Mosby 2002) with little addition (when necessary).
Ok, the review is about vaccines and clinical problems involving the immune system. The book illustrates the kinds of problem the immune system can cause by following the life of a physician born in 1942.
(1). Infancy
At the age of seven, our patient developed a widespread blotchy rash and high fever. Her family recognized the characteristics rash of measles. However she deteriorates over the next 2 days and develops signs of pneumonia. Luckily, she gradually improves without specific treatment. Measles pneumonia is an unusual complication of this viral infection. Measles also cause brain inflammation (encephalitis) from time to time. A vaccine for measles has been in routine use in the developed worldsince 1970s and has largely prevented these infrequent, but potentially life-threatening, complications. In the developing world, measles remain a major cause of death of young children.
At the age of seven, our patient developed a widespread blotchy rash and high fever. Her family recognized the characteristics rash of measles. However she deteriorates over the next 2 days and develops signs of pneumonia. Luckily, she gradually improves without specific treatment. Measles pneumonia is an unusual complication of this viral infection. Measles also cause brain inflammation (encephalitis) from time to time. A vaccine for measles has been in routine use in the developed worldsince 1970s and has largely prevented these infrequent, but potentially life-threatening, complications. In the developing world, measles remain a major cause of death of young children.
(2). Childhood
As an 11-year-old, our subject goes on a family picnic. A few minutes after eating a peanut butter sandwich, she develops swelling of the face and breathlessness. Luckily her symptoms improve spontaneously. Relatively little was known about peanut-induced anaphylaxis in the 1950s and skin prick and specific IgE testing were not widely available. The experience put her off peanuts for life, and she never had the same experience again. It is also possible she “grew out of” her allergy. This case illustrates how it is possible to have anaphylaxis to specific allergens without any background of allergy.
As an 11-year-old, our subject goes on a family picnic. A few minutes after eating a peanut butter sandwich, she develops swelling of the face and breathlessness. Luckily her symptoms improve spontaneously. Relatively little was known about peanut-induced anaphylaxis in the 1950s and skin prick and specific IgE testing were not widely available. The experience put her off peanuts for life, and she never had the same experience again. It is also possible she “grew out of” her allergy. This case illustrates how it is possible to have anaphylaxis to specific allergens without any background of allergy.
(3). Adolescence
Our subject has now progressed to high school, but her family begins to notice weight loss and irritability. At first her family thinks she is simply studying too hard in her efforts to get a place at medical school. Her condition deteriorates and eventually she goes to see a physician. He finds she has hyperthyroidism and a diagnosis of Grave’s disease is made. She responds very well to drug treatment.
Our subject has now progressed to high school, but her family begins to notice weight loss and irritability. At first her family thinks she is simply studying too hard in her efforts to get a place at medical school. Her condition deteriorates and eventually she goes to see a physician. He finds she has hyperthyroidism and a diagnosis of Grave’s disease is made. She responds very well to drug treatment.
(4). Life as a Student
Our subject is successful in getting into medical school. At the age of 24 while training she is infected with hepatitis B virus. Effective vaccines were not available in the 1960s. She becomes jaundiced and she is also found to have kidney disease. Glomerulonephritis sometimes complicates hepatitis B infection; this is caused by circulating immune complexes of viral antigens and antibodies. Once again she is very lucky and her condition improves gradually. A year later her kidney and liver function is normal and she is thought to have successfully eradicated the hepatitis virus.
Our subject is successful in getting into medical school. At the age of 24 while training she is infected with hepatitis B virus. Effective vaccines were not available in the 1960s. She becomes jaundiced and she is also found to have kidney disease. Glomerulonephritis sometimes complicates hepatitis B infection; this is caused by circulating immune complexes of viral antigens and antibodies. Once again she is very lucky and her condition improves gradually. A year later her kidney and liver function is normal and she is thought to have successfully eradicated the hepatitis virus.
(5). The Family
Our subject’s younger sister has been unwell with fatigue for several weeks. On a visit home, our subject decides her sister may have diabetes, remembering that organ-specific autoimmune disease tends to run in families. The sister’s blood sugar is high, confirming the diagnosis.
Our subject’s younger sister has been unwell with fatigue for several weeks. On a visit home, our subject decides her sister may have diabetes, remembering that organ-specific autoimmune disease tends to run in families. The sister’s blood sugar is high, confirming the diagnosis.
(6). The Family
After a further 15 years, our subject’s sister has developed chronic renal failure as a result of the diabetes. Our subject is unable to act as a donor because of the history of viral hepatitis. One of her siblings is found to be an exact HLA match and donates his kidney. The transplant goes ahead without any signs of rejection. This is lucky, because even in the arlyy 1980s, many of the potent anti-rejection drugs, for example ciclosporin, were not available.
(7). Retirement
Our subject is now 55 and planning her retirement. Unfortunately, she has had two very painful bouts of shingles, caused by reactivation of the chickenpox virus, herpes varicella zoster. She has also suffered from a series of chest and sinus infections. An immunodeficiency state is considered and her T cell, IgG and IgA levels are found to be low. Her blood also contains a monoclonal IgM protein. A sample of bone marrow is taken and shows multiple myeloma. A diagnosis of immunodeficiency secondary to myeloma is made.
The vast majority of infection can be dealt with by innate and adaptive immune systems working in unison. Some infections, for example measles (1), are usually cleared by the immune system and only cause trivial problems in the vast majority of cases. But even measles can be life threatening in some individuals. Other infections (for example hepatitis B) are much harder for the immune system to clear and can cause life-long infection. Either type of infection can be prevented by the use of vaccines.
Vaccines stimulate components of the adaptive immune system to produce immunological memory. Specific antibodies either prevent infection from taking place or bind to toxin produced by pathogens, reducing the severity of the disease.
Vaccines produced from killed pathogens or recombinant proteins are very safe but tend to produce weak responses. Adjuvants are often used to boost the effects of killed or subunit vaccines. Other vaccines use live pathogens that have been attenuated. Live vaccines are often more effective than killed or subunit vaccines, but there is a higher risk of side-effects.
Newer technologies aim to stimulate the immune system in novel ways, for example by inserting the gene for an antigen using DNA vaccines.
Hypersensitivity reactions are important cause of disease and are caused by the immune system reacting to a range of antigens. These antigens can include peptides produced by microbes. It is possible that in some infections (for examples, forms of leprosy) the immune response causes at least as much damage as the pathogen itself.
Atopy is an immediate hypersensitivity reaction to environmental antigens, mediated by IgE (type I hypersensitivity). We use the term allergy synonymously. Allergic diseases are one of the commonest forms of hypersensitivity and are thought to be increasing in prevalence in the developed world. This increase in allergy is occurring although immunity mediated by T helper 2 (TH2) cells, IgE, and mast cells, which was originally developed to fend off worm infestations, is less required as these are now rare in the developed world. There is also a decline in bacterial infections in developed countries; the hygiene hypothesis suggests that this may skew the immune system towards TH2 responses.
The most widely recognized forms of allergy occur immediately after patients have been exposed to allergens and are caused by the effects of mast cell degranulation after IgE crosslinking (2). Allergy can also have a late phase, mediated largely by eosinophils. The late phase accounts for many of the symptoms of disease such as asthma.
Apart from infections and allergens, hypersensitivity can also occur in response to autoantigens. Although a degree of autoimmunity is normal, autoimmune mechanisms can cause disease through three mechanisms: direct effects of antibodies (type II hypersensitivity), immune complexes (type III) or delayed hypersensitivity (type IV). Autoimmunity has complex genetic and environmental origins and reflects the breakdown of normal self tolerance. It is not unusual for these diseases, especially organ-specific autoimmune disease, to run in families.
In type II hypersensitivity, antibodies bind to cells, causing a number of effects. In either instance, hemolytic anemia is the result. Antibodies can also mimic the effects of trophic hormones, as in Grave’s disease (3). Detection of these autoantibodies, using a variety of techniques, is used to help make the diagnosis.
Type III hypersensitivity is caused by immune complexes. These can form in the tissues (for example farmer’s lung) or circulate in the blood. Although circulating immune complexes can be the consequence of autoimmune disease, they can also be the result of exogenous antigens, usually from infections, as in (4). Immune complexes activate the innate immune system and cause inflammation. The kidneys are very often the targets for this process.
Type IV hypersensitivity can also be the result of infection (for example tuberculosis, leprosy) or autoimmunity. In the autoimmune disease insulin-dependent diabetes, rheumatoid arthritis and multiple sclerosis, T cells infiltrate the target organs and cause chronic inflammation (5). The damage in each case is mediated by cytokines. Tumor necrosis factor is probably the most important of these. Each of these autoimmune diseases is associated with specific autoantibodies. Although these may be useful in making the diagnosis, they are not strongly implicated in damaging the target organs.
Transplantation is used to replace diseased organs. In all types of allogeneic transplant, except for corneal transplant, rejection is a major problem. At its most severe, hyperacute rejection takes place when antibodies bind allogeneic HLA antibodies, destroying the transplanted organ within minutes. Acute rejection is caused by T cells responding to allogeneic antigens in the donor organ. These two types of rejection are similar to type II and type IV hypersensitivity, respectively. The fetus resembles a transplanted organ but it is not rejected by the mother because T cells responses are dampened down by systemic factors (estrogens and cytokines), and natural killer cells are inhibited by local factors in the uterus.
Bone marrow transplant is a special case because T cells arising from the donor can attack the recipient, giving rise to graft-versus-host disease. The risks of graft rejection and graft-versus-host disease are minimized by tissue typing techniques (6).
Immunodeficiency can occur as a result of primary defects within the immune system or secondary to external factors. Primary immunodeficiencies usually have genetic components. Severe secondary immunodeficiencies occur in patients infected with HIV, malignancies or after specific drug treatments. Mild secondary immunodeficiencies occur in patients with poor nutrition and during physiological stress.
Immunodeficiencies cause either recurrent infection or opportunist infections with low-virulence organisms. They need to be rcognized because, if left untreated, infections can cause irreversible damage or death. The type of infection often gives important clues to the severity and type of immunodeficiency operating (7).
Cells of the innate immune system quite often form malignancies. This is especially true of B cells because they can be infected with Epstein-Barr virus and because they undergo somatic hypermutation. Much is known about the genetic basis of these lymphoid malignancies.
The immune system also has a role in fighting cancers, although, more often than not, the immune system recognizes oncogenic viruses rather than tumor antigens themselves. Many tumors have developed molecular mechanisms for evading the immune system. Tumor immunotherapy aims to reverse some of these mechanisms.
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