Micro Lecture: Active and Passive Immunity PDF

PHARMACEUTICAL MICROBIOLOGY IMMUNOLOGY. Active and passive immunity DR. KASHIF MAROOF  Active immunity Artificiall Naturally ACTIVE IMMUNITY y acquired...

PHARMACEUTICAL MICROBIOLOGY IMMUNOLOGY. Active and passive immunity DR. KASHIF MAROOF  Active immunity Artificiall Naturally ACTIVE IMMUNITY y acquired acquired Active immunity occurs when antigens enter the body and the individual’s immune system actively responds by producing antibodies and specific lymphocytes. This exposure to antigens may be unintentional, as when one becomes ill with a disease, or intentional, when one is purposely exposed to an antigen.  NATURALLY ACQUIRED ACTIVE IMMUNITY  Before vaccines were fully developed, the only way to become immune to a disease was by suffering the disease and recovering. Thus, such naturally acquired active immunity follows a bout of illness and occurs in the “natural” scheme of events.  However, this is not always the case, because subclinical diseases also may bring on the immunity. For example, many people have acquired immunity from subclinical cases of mumps or from subclinical fungal diseases. So, this active production of antibodies represents the primary antibody response.  Memory cells are responsible for the production of antibodies in a secondary antibody response. The cells remain active for many years and produce IgG almost immediately upon a subsequent exposure to the same antigen or pathogen that triggered the primary antibody response.  ARTIFICIALLY ACQUIRED ACTIVE IMMUNITY  Artificially acquired active immunity is less risky and represents an easier way to become immune to an infectious disease. This form of active immunity develops after the immune system produces antibodies following an intentional exposure to antigens; that is, through vaccination. Because the antigens usually are contained in an immunizing agent, such as an inactivated or toxoid vaccine, the exposure is called “artificial.”  VACCINES  Vaccines are composed of treated microorganisms , chemically altered toxins, or chemical parts of microorganisms. Such vaccines work by mimicking a “natural” infection. By exploiting the immune system’s ability to recognize antigens and respond with antibodies and lymphocytes, a vaccine triggers a primary antibody response. However, because the vaccine has been altered in some way, the pathogen or toxin usually does not trigger the disease and the person vaccinated does not become ill. Importantly, memory cells are formed, which now establish active immunity. If the vaccinated person is exposed to the same antigen at some later time, the immune system acts swiftly and produces a secondary antibody response, stopping the infection before it can make the individual sick. Therefore, the person stays healthy. Vaccines may be administered by injection, oral consumption, or, as is used for some TYPES OF VACCINES  ATTENUATED VACCINES.  Some microbes can be weakened in the lab such that they should not cause disease. They are still able to grow or replicate, but attenuated means they will multiply only at low rates in the body and fail to cause symptoms of disease. Because the attenuated microbes multiply or replicate for a period of time within the body, they increase the dose of antigen to which the immune system will respond. Such vaccines are the closest to the natural pathogens and, therefore, they generate the strongest immune response. Often, the person vaccinated will have lifelong immunity. Also, attenuated organisms can be spread to other people and reimmunize them, or immunize them for the first time. ATTENUATED VACCINES.  ATTENUATED VACCINES.  Today, there are many viral vaccines that consist of attenuated viruses. The Sabin oral polio vaccine, as well as the measles, mumps, and chickenpox vaccines, contain attenuated viruses.  To avoid multiple injections of immunizing agents, it is sometimes advantageous to combine vaccines into a single-dose vaccine. The measles-mumps- rubella (MMR) vaccine is one example. In 2005, the U.S. Food and Drug Administration (FDA) approved a combination vaccine (Proquad) for children 12 months to 12 years old. This single- dose vaccine protects against chickenpox, measles, mumps, and rubella. Making a vaccine with attenuated bacterial cells is more difficult.  DOWNSIDE OF ATTENUATED VACCINES . The downside of attenuated vaccines results from their continued multiplication. Because the vaccines contain dividing or replicating bacteria or viruses, there is a remote chance one of them could mutate and revert back to a virulent form capable of causing disease. Usually a healthy person with a fully functioning immune system (immunocompetent) clears the infection without serious consequence. However, individuals with a compromised immune system, such as patients with AIDS, should not be given attenuated vaccines, if possible.  On a global scale, attenuated vaccines may not be the vaccine strategy of choice. These vaccines require refrigeration to retain their effectiveness, which could present a problem in many developing nations lacking widespread refrigeration facilities  INACTIVATED VACCINES.  Another strategy for preparing vaccines is to “kill” the pathogen. These vaccines are relatively easy to produce because the pathogen is killed by simply using certain chemicals, heat, or radiation. However, the inactivation process alters the antigen so it produces a weaker immune response. The Salk polio vaccine and the hepatitis A vaccine typify such preparations of inactivated whole viruses. For protection from diseases like hepatitis A, booster shots are required to maintain immunity (memory cells) for long periods of time.  INACTIVATED VACCINES. Compared to attenuated vaccines, inactivated vaccines are safer as they cannot mutate and therefore cannot cause the disease in a vaccinated individual. The vaccines can be stored in a freeze- dried form at room temperature, making them a vaccine of choice in developing nations. However, the need for booster shots can be a drawback when people do not keep up their booster schedule. INACTIVATED VACCINES.  TOXOID VACCINES.  For some bacterial diseases, such as diphtheria and tetanus, a bacterial toxin is the main cause of illness. So, a third immunization strategy is to inactivate these toxins and use them as a vaccine. Such toxins can be inactivated with formalin, and the resulting inactivated toxin is called a toxoid. Immunity induced by a toxoid vaccine allows the body to generate antibodies and memory cells to recognize the natural toxin, should the individual again come in contact with it.  Because toxoid vaccines are inactivated products, booster shots are necessary. Single-dose vaccines include diphtheria- pertussis- tetanus vaccine (DPT) and the newer diphtheria-tetanus-acellular pertussis (DTaP) vaccine. For other vaccines, however, a combination single-dose vaccine may not be useful because the antibody response may be lower for the combination than for each TOXOID VACCINES.  SECOND GENERATION OF VACCINES  To minimize the risks of vaccination, second- generation vaccines have been developed that contain only a fragment of the bacterium or virus. These subunit and conjugate vaccines generate acquired immunity that lacks a cytotoxic T-cell response.  SUBUNIT VACCINE  Unlike the whole agent attenuated or inactivated vaccines, the strategy for a subunit vaccine is to have the vaccine contain only those parts or subunits of the antigen that stimulate a strong immune response. These subunits may be epitopes. For example, the subunit vaccine for pneumococcal pneumonia contains 23 different polysaccharides from the capsules of 23 strains of Streptococcus pneumoniae.  Adverse reactions to such subunit vaccines are very rare because only the important subunits of the antigen are included in the vaccine. These subunits cannot produce disease in the person vaccinated.  CONJUGATE VACCINES  Conjugate vaccines have a polysaccharide component, but that sugar is stuck to a protein or some other carrier so your immune system will respond to the sugar on the bacteria better.  Haemophilus influenzae b (Hib), which is responsible for a form of child- hood meningitis, produces an external glycocalyx coat called a capsule. Since the capsular polysaccharides by themselves are not strongly immunogenic, the strategy here is to conjugate (attach) capsular polysaccharides to a carrier which will stimulate a strong immune response. The result is the Hib vaccine.  RNA VACCINE  When an mRNA vaccine is delivered, the RNA material teaches our body how to make a specific type of protein that is unique to the virus, but does not make the person sick. The protein triggers an immune response, which includes the generation of antibodies that recognize the protein. That way, if a person is ever exposed to that virus in the future, the body would like have the tools (antibodies) to fight against it.  Pfizer-BioNTech and Moderna COVID-19 vaccines which are mRNA vaccines.  PASSIVE IMMUNITY  Passive immunity develops when antibodies enter the body from an outside source (in contrast to active immunity, in which individuals synthesize their own antibodies).  Again, the source of antibodies may be unintentional, such as a fetus receiving antibodies from the mother, or intentional, such as the transfer of antibodies from one individual to another.  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. The process occurs in the “natural” scheme of events. The maternal IgG antibodies remain with the child for approximately three to six months after birth and play an important role during these months of life in providing additional resistance. Certain antibodies, such as measles antibodies, remain for 12 to 15 months. 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 antibodyalthough IgG and IgM also have been found in the milk.  ARTIFICIALLY ACQUIRED PASSIVE IMMUNITY  Artificially acquired passive immunity arises from the intentional injection of antibody- rich serum into the patient’s circulation. The exposure to antibodies is thus “artificial.” In the decades before the development of antibiotics, such an injection was an important therapeutic tool for the treatment of disease. The practice still is used for viral diseases such as Lassa fever and arthropodborne encephalitis, and for bac- terial diseases in which a toxin is involved. For example, established cases of botulism, diphtheria, and tetanus are treated with serum containing their respective antitoxins.  SERUM RENDERING ARTIFICIALLY ACQUIRED PASSIVE IMMUNITY.  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 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, and when 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 serum in which most antibodies are found. Gamma globulin usually consists of a pool of sera from different human donors, and thus contains a mixture of antibodies (usually IgG), including those for the disease to be treated.  HERD IMMUNITY  A population without a vaccination program is vulnerable to disease epidemics. Many people will suffer from the disease; some may die, while others could be left with a permanent disability. Even with a vaccination program, if insufficient numbers of citizens get the vaccination, the pathogen still can infect those who are not protected. Vaccinations are never meant to reach 100% of the population. This shortfall is partly due to some people simply not being vaccinated or because some individuals simply respond poorly to a vaccine; all such individuals remain susceptible and unprotected. Still, the lack of 100% vaccination is not seen as a problem as long as most of the population is immune to an infectious disease. This makes it unlikely a susceptible person will come in contact with an infected individual. This phenomenon, called herd (community) immunity, implies that if enough people in a population are immunized against certain diseases, then it is very difficult for those diseases to spread.  HERD IMMUNITY  Microbiologists and epidemiologists believe that when greater than 85% of the population is vaccinated (herd immunity threshold), the spread of the disease is effectively stopped. The rest of the “herd” or population remains susceptible, which is allowable because it then becomes very hard for pathogens “to find someone” who isn’t vaccinated. Susceptible individuals are protected from catching the disease, and if one of these individuals should catch the disease, there are so many vaccinated people in the “herd” that it is unlikely the person could easily spread it. Herd immunity can be affected by several factors. One is the environment. People living in crowded cities are more likely to catch a disease if they are not vaccinated than non-vaccinated people living in rural areas because of the constant close contact with other people in the city. Another factor is the strength of an indi- vidual’s immune system. People whose immune systems are compromised, either because they currently have a disease or because of medical treatment (anticancer or antirejection drugs), may not be able to be immunized. They are at a greater risk of catching the disease to which others are immunized.