Two general types of immunity are recognized – natural immunity and acquired immunity.
The word “immune” is derived from the Latin stem immuno, meaning safe, or free from. In its most general sense, the term implies a condition under which an individual is protected from disease. This does not mean, however, that one is immune to all diseases, but rather to a specific disease or group of diseases.
Immunity or disease resistance is the ability of an organism to resist the development of a disease. The study of immunity is called immunology, while the infected person with no disease is known as immune. Immune system forms the third line of defence. The most peculiar characteristic of immune system is that it can differentiate between ‘self (body’s own cells) and ‘non-self (foreign microbes).
Type # 1. Natural Immunity:
Natural immunity is an inborn capacity for resisting disease. It begins at birth and depends on genetic factors expressed as physiological, anatomical, and biochemical differences among living things. Examples of natural immunity are the lysozyme found in tears, saliva, and other body secretion, acidic pH of the gastrointestinal and vaginal tracts, and interferon produced by body cells to protect against viruses.
A race or species may inherit a resistance to a certain infectious disease. This resistance is spoken of as natural immunity.
Many of the organisms that attack humans do not attack animals. Typhoid-fever infections do not occur in animals except after massive experimental inoculations with the specific organisms. Human leprosy has never been transmitted to animals successfully. Meningitis does not occur spontaneously in animals but may be produced experimentally. Many of the animal diseases do not occur spontaneously in man.
It is not known why differences in species susceptibility exist. It may be because of differences in temperature, metabolism, diet, etc. Diseases of warm-blooded animals cannot ordinarily be transmitted to cold-blooded animals, and vice versa.
The various races probably exhibit differences in their resistance to disease, although in many cases this may be due to differences in living conditions, to immunity acquired from mild infections in childhood, or to other causes. Negroes and American Indians are said to be more susceptible to tuberculosis than the white race. On the other hand, Negroes exhibit more immunity to yellow fever and malaria than the white race.
Laboratory animals of the same species, kept under identical environmental conditions, exhibit only slight differences in their resistance or susceptibility to experimental disease. On the other hand, humans show wide differences in susceptibility to disease.
For example, during an epidemic of influenza there are always some individuals who do not contract the disease even though in close contact with the virus. These individuals exhibit a higher degree of resistance than do the majority of people.
Type # 2. Acquired Immunity:
Acquired immunity, by contrast, begins after birth. It depends on the presence of antibodies and other factors originating from the immune system.
Although the emphasis will be on antibodies and antibody-mediated immunity it should be remembered that cellular immunity is also an important consideration in the total spectrum of resistance. An individual of a susceptible species may acquire a resistance to an infectious disease either accidentally or artificially. This resistance is spoken of as an acquired immunity.
Many of the infectious diseases, such as typhoid fever, scarlet fever, and measles, usually occur only once in the same individual. The resistance of the host to the disease is increased so that another exposure to the same specific organism usually produces no effect. This resistance or immunity may last for a limited time or for life.
Immunity may be acquired artificially by means of vaccines or by the use of immune serums. If the immunity is acquired by means of vaccines, it is spoken of as active immunity; if it is acquired by the use of immune serums, it is spoken of as passive immunity.
Four types of acquired resistance are generally recognized:
i. Naturally Acquired Active Immunity:
Active immunity develops after antigens enter the body and the individual’s immune system responds with antibodies. The exposure to antigens may be unintentional or intentional. When it is unintentional, the immunity that develops is called naturally acquired active immunity.
Naturally acquired active immunity usually follows about of illness and occurs in the “natural” scheme of events. However, this need not always be the case because subclinical diseases may also bring on the immunity. For example, many individuals have acquired immunity from subclinical cases of mumps or from subclinical fungal diseases such as cryptococcosis.
Memory cells residing in the lymphoid tissues are responsible for the production of antibodies that yield naturally acquired active immunity. The cells remain active for many years and produce IgG immediately upon later entry of the parasite to the host. Such an antibody response is sometimes called the secondary anamnestic response, from the Greek anamnesis, for recollection.
ii. Artificially Acquired Active Immunity:
Artificially acquired active immunity develops after the immune system produces antibodies following an intentional exposure to antigens. The antigens are usually contained in an immunizing agent such as vaccine or toxoid and the exposure to antigens is “artificial”.
Viral vaccines consist of either inactivated viruses incapable of multiplying in the body or attenuated viruses, which multiply at low rates in the body but fail to cause symptoms of disease. The Salk polio vaccine typifies the former while the Sabin oral polio vaccine represents the latter.
Bacterial vaccines fall into similar categories: the older whooping cough (pertussis) vaccine consists of dead cells, while the tuberculosis vaccine is composed of attenuated bacteria. Whole microorganism viral and bacterial vaccines are commonly called first-generation vaccines.
One advantage of vaccines made with attenuated organisms is that organisms multiply for a period of time within the body, thus increasing the dose of antigen administered. This higher dose results in a higher level of immune response than that obtained with the single dose of inactivated organisms. Also, attenuated organisms can spread to other individuals and re-immunize them or immunize them for the first time.
However, attenuated organisms may be hazardous to health because of this same ability to continue multiplying. In 1984, for example, a recently immunized soldier spread vaccinia (cowpox) viruses to his daughter. She, in turn, infected seven young friends at slumber party.
With only one notable exception, there are no widely used bacterial vaccines made with whole organisms and used for long-term protection. The exception is the older pertussis vaccine, now in the process of being replaced by the acellular pertussis vaccine composed of Bordetella pertussis extracts. Other bacterial vaccines made with organisms are used for temporary protection.
For instance, when health officials suspect that water contains typhoid bacilli, they may administer a vaccine for typhoid fever. Bubonic plague or cholera vaccines are also available to limit an epidemic. In these cases, the immunity lasts only for several months because the material in the vaccine is weakly antigenic.
Weakly antigenic vaccines are also available for laboratory workers who deal with rickettsial diseases such as Rocky Mountain spotted fever, Q fever, and typhus. The danger in these vaccines is that the residual egg protein in the cultivation medium for rickettsiae may cause allergic reactions in recipients.
Immunizing agents that stimulate immunity to toxins are known as toxoids. These agents are currently available for protection against diphtheria and tetanus, two diseases whose major effects are due to toxins. The toxoids are prepared by incubating toxins with a chemical such as formaldehyde until the toxicity is lost.
To avoid multiple injections of immunizing agents, it is advantageous to combine vaccines into a single dose. Experience has shown this possible for the diphtheria-pertussis-tetanus vaccine (DPT), the newer diphtheria-tetanus-acellular pertussis vaccine (DTaP), the measles-mumps-rubella vaccine (MMR) and the trivalent oral polio vaccine (TOP).
There is even a vaccine that will immunize against four diseases simultaneously – in 1993, the FDA approved a combined vaccine which includes diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and Haemophilus influenzae b (Hib) vaccine. Marketed as Tetramune, the quadruple vaccine is used in children aged 2 months to 5 years to protect against the DPT diseases as well as Haemophilus meningitis.
For other vaccines, however, a combination may not be valuable because the antibody response is lower for the combination than for each vaccine taken separately. Immunologists believe that poor phagocytosis by macrophages is one reason. Activation of suppressor T-lymphocytes may be another reason.
Modern immunologists foresee the day when preparations called subunit vaccines, or second- generation vaccines, will completely replace whole organism vaccines. For example, pili from bacteria may be extracted and purified for use in a vaccine to stimulate antipili antibodies. These would inhibit the attachment of bacteria to tissues and facilitate phagocytosis.
Another example is the vaccine for pneumococcal pneumonia, licensed for use in 1983. The vaccine contains 23 different polysaccharides from the capsules of 23 strains of Streptococcus pneumoniae. Still another example is the vaccine against Haemophilus influenzae b, the agent of Haemophilus meningitis.
Also composed of capsular polysaccharides, the so-called Hib vaccine has been available since 1988 and has been a critical factor in reducing the incidence of Haemophilus meningitis from 18,000 cases annually (1986) to a few dozen cases in current years (1995).
Another form of vaccine is the synthetic vaccine, or third-generation vaccine. This preparation represents a sophisticated and practical application of recombinant DNA technology.
To produce the vaccine, three major technical problems must be solved: the immune-stimulating antigen must be identified: living cells must be reengineered to produce the antigens; and the size of the antigens must be increased to promote phagocytosis and the immune response. Thus far, the process has been successful for a vaccine for foot-and-mouth disease licensed in 1981.
The genetic engineering process has also worked for a synthetic vaccine for hepatitis B. The vaccine is marketed by different companies as Recombivax and Engerix-B. Because the vaccine is not made from blood fragments (as the previous hepatitis B vaccine was), it relieves the fear of contracting human immunodeficiency virus (HIV) from contaminated blood.
Many immunologists believe that the synthetic agents will usher in a Renaissance of vaccines. In 1993, for example, biotechnologists announced the development of a cholera vaccine containing Vibrio cholera whose genes for toxin production were experimentally removed. An AIDS vaccine also looms on the horizon.
Immunizations may be administered by injection, oral consumption, or nasal spray, as currently used for some respiratory viral diseases. Booster immunizations commonly follow as a way of raising the antibody level by stimulating the memory cells to induce the secondary anamnestic response. This is why a “tetanus booster” is given to anyone who sustains a deep puncture wound by a soil- contaminated object if they have not had a tetanus immunization in the previous ten years.
Substances called adjuvants increase the efficiency of a vaccine or toxoid by increasing the availability of the antigen in the lymphatic system. Common adjuvants include aluminum sulfate (“alum”) and aluminum hydroxide in toxoid preparations, as well as mineral oil or peanut oil in viral vaccines. The particles of adjuvant linked to antigen are taken up by macrophages and presented to lymphocytes more efficiently than dissolved antigens.
Experiments also suggest that adjuvants may stimulate the macrophage to produce a lymphocyte-activating factor and thereby reduce the necessity for helper T-lymphocyte activity. Moreover, adjuvants provide slow release of the antigen from the site of entry and provoke a more sustained immune response. A high priority in the development of synthetic vaccines is the production of suitable adjuvants.
iii. Naturally Acquired Passive Immunity:
Passive immunity develops when antibodies enter the body from an outside source (as compared to active immunity in which individuals synthesize their own antibodies). The infusion of antibodies may be unintentional or intentional, and thus, natural or artificial. When unintentional, the immunity that develops is called naturally acquired passive immunity.
Naturally acquired passive immunity, also called congenital immunity, develops when antibodies pass into the fetal circulation from the mother’s bloodstream via the placenta and umbilical cord. These antibodies, called maternal antibodies, remain with the child for approximately 3 to 6 months after birth and fade as the child’s immune system becomes fully functional. Certain antibodies, such as measles antibodies, remain for 12 to 15 months. The process occurs in the “natural” scheme of events.
Maternal antibodies play an important role during the first few months of life by providing resistance to diseases such as pertussis, staphylococcal infections, and viral respiratory diseases. Because the antibodies are of human origin and are contained in human serum, they will be accepted without problem. The only antibody in the serum is IgG.
Maternal antibodies also pass to the newborn through the first milk, or colostrum, of a nursing mother as well as during future breast feedings. In this instance, IgA is the predominant antibody, although IgG and IgM have also been found in the milk. The antibodies accumulate in the respiratory and gastrointestinal tracts of the child and apparently lend increased resistance to diseases.
iv. Artificially Acquired Passive Immunity:
Artificial acquired passive immunity arises from the intentional injection of antibody-rich serum into the circulation. The exposure to antibodies is thus “artificial.” In the decades before the development of antibiotics, such as injection was an important therapeutic device for the treatment of disease.
The practice is still used for viral diseases such as Lassa fever, hepatitis, and arthropod-borne encephalitis, and for bacterial diseases where a toxin is involved. For example, established cases of botulism, diphtheria, and tetanus are treated with serum containing the respective antitoxins.
Various terms are used for the serum that renders artificially acquired passive immunity. Antiserum is one such term. Another is hyper-immune serum, which indicates that the serum has a higher-than-normal level of a particular antibody. If the serum is used to protect against a disease such as hepatitis A, it is called prophylactic serum.
When the serum is used in the therapy of an established disease, it is called therapeutic serum. Should the serum be taken from the blood of a convalescing patient, physicians refer to it as convalescent serum. Another common term, gamma globulin, takes its name from the fraction of blood protein in which most antibodies are found. Gamma globulin usually consists of a pool of sera from different human donors, and thus it contains a mixture of antibodies including those for the disease to be treated.
Passive immunity must be used with caution because in many individuals, the immune system recognizes foreign serum proteins as antigens and forms antibodies against them in an allergic reaction. When antibodies interact with the proteins, a series of chemical molecules called immune complexes may form, and with the activation of complement, the person develops a disease called serum sickness.
This is often characterized by a hive like rash at the injection site, accompanied by laboured breathing and swollen joints. To avoid the disease, it is imperative that the patient be tested for allergy before serum therapy is instituted. If an allergy exists, minuscule doses should be given to eliminate the allergic state, and then a large therapeutic dose can be administered.
Artificially acquired passive immunity provides substantial and immediate protection to disease, but it is only a temporary measure. The immunity that develops from antibody-rich serum usually wears off within days or weeks. Among the serum preparations currently in use are those for hepatitis A and chickenpox. Both are made from the serum of blood donors routinely screened for hepatitis A and chickenpox.