Types of Immunity
The main function of the immune system is to prevent or limit infections by pathogenic microorganisms, such as bacteria, viruses, parasites, and fungi. The recognition of microorganisms and for-eign substances is the first event in immune responses of a host. The body’s defense mechanisms can be divided into: (a) innate (natural) immunity and (b) acquired (adaptive) immunity.
Innate immunity is the resistance that an individual possesses by birth. Innate immunity may be classified as (a) individual immunity, (b) racial immunity, and (c) species immunity.
Individual immunity: Individual immunity denotes resis-tance to infection, which varies within different individuals in the same race and species and is genetically determined. For example, if one homozygous twin develops tuberculosis, there is a very high possibility that the other twin will also develop tuberculosis. But in heterozygous twins, there is a very low possibility of the other twin suffering from tuberculosis.
Racial immunity: Racial immunity denotes a difference insusceptibility or resistance to infection among different races within a same species. For example, races with sickle cell ane-mia prevalent in Mediterranean coast are immune to infection caused by malaria parasite Plasmodium falciparum. This is due to a genetic abnormality of erythrocytes, resulting in sickle-shaped erythrocytes that prevent parasitization by P. falciparum. Similarly, individuals with a hereditary deficiency of glucose-6-phosphatase dehydrogenase are also less susceptible to infection by P. falciparum.
Species immunity: Species immunity denotes a total or relativeresistance to a pathogen shown by all members of a particular spe-cies. For example, chickens are resistant to Bacillus anthracis, rats are resistant to Corynebacterium diphtheriae, whereas humans are susceptible to these bacteria. The exact reason for such type of immunity is not known.
◗ Factors influencing innate immunity
The factors that may influence innate immunity of the host include age and nutritional status of the host.
Age: Extremes of age make an individual highly susceptible tovarious infections. This is explained in part by the immature immune system in very young children and waning immunity in older individuals. The fetus-in-utero is usually protected from maternal infections by the placental barrier. However, human immunodeficiency virus (HIV), rubella virus, cytomeg-alovirus, and Toxoplasma gondii cross the placental barrier and cause congenital infections.
Very old people are susceptible to suffer more than young people from a disease (e.g., pneumonia) and have high mortal-ity. Measles, mumps, poliomyelitis, and chicken pox are few examples of the diseases that cause more severe clinical illness in adults than in young children. This may be due to more active immune response in an adult causing greater tissue damage.
Nutritional status: Nutritional status of the host plays animportant role in innate immunity. Both humoral and cell-mediated immunities are lowered in malnutrition. Examples are:
· Neutrophil activity is reduced, interferon response is decreased, and C3 and factor B of the complement are decreased in protein–calorie malnutrition.
· Deficiency of vitamin A, vitamin C, and folic acid makes an individual highly susceptible to infection by many microbial pathogens.
Hormonal levels: Individuals with certain hormonal disordersbecome increasingly susceptible to infection. For example, indi-viduals suffering from diabetes mellitus, hypothyroidism, and adrenal dysfunction are increasingly susceptible to staphylococ-cal infection, streptococcal infection, candidiasis, aspergillosis, zygomycosis and many other microbial infections. Similarly, pregnant women are more susceptible to many infections due to higher level of steroid during pregnancy.
◗ Mechanisms of innate immunity
Innate immunity of the host performs two most impor-tant functions: it kills invading microbes and it activates acquired (adaptive) immune processes. Innate immunity unlike adaptive immunity, however, does not have any memory and does not improve after re-exposure to the same microorganism. The innate immunity is primarily dependent on four types of defensive barriers: (a) anatomic barriers, (b) physiologic barriers, (c) phagocytosis, and (d) inflammatory responses.
Anatomic barriers: Anatomic barriers include skin andmucous membrane. They are the most important components of innate immunity. They act as mechanical barriers and prevent entry of microorganisms into the body. The intact skin prevents entry of microorganisms. For example, breaks in the skin due to scratches, wounds, or abrasion cause infection. Bites of insects harboring pathogenic organisms (e.g., mosquitoes, mites, ticks, fleas, and sandflies), introduce the pathogens into the body and transmit the infection. Skin secretes sebum, which prevents growth of many microorganisms. The sebum consists of lactic acid and fatty acids that maintain the pH of skin between 3 and 5, and this pH inhibits the growth of most microorganisms.
Mucous membranes form a large part of outer cover-ing of gastrointestinal, respiratory, genitourinary, and many other tracts of human host. A number of nonspecific defense mechanisms act to prevent entry of microorganisms through mucous membrane.
· Saliva, tears, and mucous secretions tend to wash away potential invading microorganisms, thereby preventing their attachment to the initial site of infections. These secre-tions also contain antibacterial or antiviral substances that kill these pathogens.
· Mucus is a viscous fluid secreted by the epithelial cells of mucous membranes that entraps invading microorganisms.
· In lower respiratory tract, mucous membrane is covered by cilia, the hair-like protrusions of the epithelial cell mem-branes. The synchronous movement of cilia propels mucus-entrapped microorganisms from these tracts.
· In addition, nonpathogenic organisms tend to colonize the epithelial cells of mucosal surfaces. These normal flora generally compete with pathogens for attachment sites on the epithelial cell surface and for necessary nutrients.
Physiologic barriers: The physiologic barriers that contributeto innate immunity include the following:
· Gastric acidity is an innate physiologic barrier to infection because very few ingested microorganisms can survive the low pH of stomach contents.
· Lysozyme, interferon, and complement are some of the soluble mediators of innate immunity. Lysozyme has anti-bacterial effect due to its action on the bacterial cell wall. Interferons are secreted by cells in response to products of viral infected cells. These substances have a general antiviral effect by preventing the synthesis of viral structural proteins. Complement is a group of serum-soluble substances that when activated damage the cell membrane.
· There are certain types of molecules that are unique to microbes and are never found in multicellular organisms. The ability of the host to immediately recognize and com-bat invaders displaying such molecules is a strong feature of innate immunity.
Phagocytosis: Phagocytosis is another important defensemechanism of the innate immunity. Phagocytosis is a process of ingestion of extracellular particulate material by certain specialized cells, such as blood monocytes, neutrophils, and tis-sue macrophages. It is a type of endocytosis in which invading microorganisms present in the environment are ingested by the phagocytic cells. In this process, plasma membrane of the cell expands around the particulate material, which may include whole pathogenic microorganisms to form large vesicles called phagosomes.
Inflammatory responses: Tissue damage caused by a woundor by an invading pathogenic microorganism induces a com-plex sequence of events, collectively known as the inflamma-tory responses. The end result of inflammation may be the activation of a specific immune response to the invasion or clearance of the invader by components of the innate immune system. The four cardinal features of inflammatory responses are rubor (redness), calor (rise in temperature), dolor (pain), and tumor (swelling).
Mediators of inflammatory reactions: Histamine, kinins, acute-phase proteins, and defensin are the important mediators of inflammatory reactions.
· Histamine: It is a chemical substance produced by a varietyof cells in response to tissue injury. It is one of the principal mediators of the inflammatory response. It binds to recep-tors on nearby capillaries and venules, causing vasodilata-tion and increased permeability.
· Kinins: These are other important mediators of inflamma-tory response. They are normally present in blood plasma in an inactive form. Tissue injury activates these small peptides, which then cause vasodilatation and increased permeability of capillaries. Bradykinin also stimulates pain receptors in the skin. This effect probably serves a protective role because pain normally causes an individual to protect the injured area.
· Acute-phase proteins: These include C-reactive pro-teins and mannose-binding proteins that form part of the innate immunity. These proteins are produced at an increased concentration in plasma during acute-phase reaction, as a nonspecific response to microorganisms and other forms of tissue injury. They are synthesized in the liver in response to cytokines called proinflammatorycytokines, namely, interleukin-1 (IL-1), interleukin-6 (IL-6), and tissue necrosis factor (TNF). They are called pro-inflammatory cytokines because they enhance the inflam-matory responses.
· Defensins: They are another important component of theinnate immunity. They are cationic peptides that produce pores in membrane of the bacteria and thereby kill them. These are present mainly in the lower respiratory tract and gastrointestinal tract. The respiratory tract contains b-defensins, whereas the gastrointestinal tract contains a-defensins. The a-defensins also exhibit antiviral activ-ity. They bind to the CXCR4 receptors and block entry of HIV virus into the cell. How these defensins differentiate microbes from some cells is not known.
Adaptive immunity is also called acquired immunity, since the potency of immune response is acquired by experience only. Differences between innate and acquired immunity are summarized in Table 11-1.
◗ Types of acquired immunity
Acquired immunity against a microbe may be induced by the host’s response to the microbe or by transfer of antibodies or lymphocytes specific for the microbes. It is of two types: activeimmunity and passive immunity.
The immunity induced by exposure to a foreign antigen is called active immunity. Active immunity is the resistance devel-oped by an individual after contact with foreign antigens, e.g., microorganisms. This contact may be in the form of:
· clinical or subclinical infection,
· immunization with live or killed infectious agents or their antigens, or
· exposure to microbial products, such as toxins and toxoids.
In all these circumstances, the immune system of the host is stimulated to elicit an immune response consisting of antibod-ies and activated helper T (TH) cells and cytotoxic T lympho-cytes/cells (CTLs).
Active immunity develops after a latent period, during which immunity of the host is geared up to act against the microorganism. Hence it is slow in onset, especially during this primary response. However, once the active immunity develops, it is long-lasting and this is the major advantage of the active immunity. The active immunity is of two types: natural active immunity and artificial active immunity.
· Natural active immunity:It is acquired by natural clinicalor subclinical infections. Such natural immunity is long-lasting. For example, individuals suffering from smallpox become immune to second attack of the disease.
· Artificial active immunity: It is induced in individuals byvaccines. There is a wide range of vaccines available against many microbial pathogens. These may be live vaccines, killed vaccines, or vaccines containing bacterial products (Table 11-2).
Mediators of active immunity: Active immunity is mediatedby humoral immunity and cell-mediated immunity. These two types of immunities are mediated by different components of the immune system and function in different ways to kill different types of pathogens.
· Humoral immunity: It is mediated by molecules in theblood and mucosal secretions called antibodies. The anti-bodies are secreted by a subset of lymphocytes known as B cells. The antibodies recognize microbial antigens, combine specifically with the antigens, neutralize the infectivity of microbes, and target microbes for elimina-tion by various effector mechanisms. Humoral immunity is the principal defense mechanism against extracellular microbes.
· Cell-mediated immunity: It is mediated by both activatedTH cells and CTLs. Cytokines secreted by TH cells activate various phagocytic cells, enabling them to phagocytose and kill microorganisms. This type of cell-mediated immune response is especially important against a host of bacte-rial and protozoal pathogens. CTLs play an important role in killing virus-infected cells and tumor cells. They act by killing altered self-cells.
Differences between humoral and cell-mediated immunities are summarized in Table 11-2.
Antigen recognition: Antigens, which are generally very largeand complex, are not recognized in their entirety by lympho-cytes. Instead, both B and T lymphocytes recognize discrete sites on the antigens called antigenic determinants, or epitopes. Epitopes are the immunologically active regions on a com-plex antigen, the regions that actually bind to B-cell or T-cell receptors.
B cells and T cells differ in their mechanisms of antigen recognition. While B cells recognize the antigen by interacting with the epitope on their own, T cells recognize the antigen only when the epitope is “presented” by one of the specialized antigen-presenting cells. Once the antigen has been recognized, these cells then go on to diversify by several intricate mecha-nisms. This diversification helps in conferring the specificity, one of the cardinal characteristics of the immune system.
Major histocompatibility complex (MHC): It is a largegenetic complex with multiple loci. The MHC loci encode two major classes of membrane-bound glycoproteins: class I and class II MHC molecules. Class II molecules present antigens to the TH cells, while class I molecules do the same for CTLs. In order for a foreign protein antigen to be recognized by a T cell, it must be degraded into small antigenic peptides that form complexes with class I or class II MHC molecules. This con-version of proteins into MHC-associated peptide fragments is called antigen processing and presentation.
When immunity is conferred by transfer of serum or lympho-cytes from a specifically immunized individual, it is known as passive immunity. This is a useful method for conferring resis-tance rapidly, i.e., without waiting for the development of an active immune response. Passive immunity may be natural or artificial.
Natural passive immunity: It is observed when IgG is passedfrom mother to fetus during pregnancy. This forms the basis of prevention of neonatal tetanus in neonates by active immu-nization of pregnant mothers. It is achieved by administering tetanus toxoid to pregnant mothers during the last trimester of pregnancy. This induces production of high level of antibod-ies in mother against tetanus toxin, which are subsequently transmitted from mother to fetus through placenta. The anti-bodies subsequently protect neonates after birth against the risk of tetanus. Natural passive immunity is also observed by passage of IgA from mother to newborn during breast feeding.
Artificial passive immunity: It is induced in an individ-ual by administration of preformed antibodies, generally in the form of antiserum, raised against an infecting agent. Administration of these antisera makes large amounts of antibodies available in the recipient host to neutralize the action of toxins.
The preformed antibodies against rabies and hepatitis A and B viruses, etc. given during incubation period prevent replication of virus, and hence alter the course of infection. Immediate availability of large amount of antibodies is the main advantage of passive immunity. However, short lifes-pan of these antibodies and the possibility of hypersensitiv-ity reaction, if antibodies prepared in other animal species are given to individuals who are hypersensitive to these animal globulins (e.g., serum sickness), are the two noted disadvan-tages of passive immunity.
Differences between active and passive immunity are summarized in Table 11-3.
Combined passive–active immunity is carried out by giving both preformed antibodies (antiserum) and a vaccine to provide immediate protection and long-term protection, respectively, against a disease. This approach is followed for prevention of certain infectious conditions, namely, tetanus, rabies, and hepatitis B.
The immunity at a particular site, generally at the site of invasion and multiplication of a pathogen, is referred to as local immunity. Local immunity is conferred by secretory IgAantibodies in various body secretions. These antibodies are produced locally by plasma cells present on mucosal surfaces or in secretory glands. Natural infection or attenuated live viral vaccines given orally or intranasally induces local immunity at gut mucosa and nasal mucosa, respectively.
Herd immunity refers to an overall level of immunity in a commu-nity. Eradication of an infectious disease depends on the devel-opment of a high level of herd immunity against the pathogen. Epidemic of a disease is likely to occur when herd immunity against that disease is very low indicating the presence of a larger number of susceptible people in the community.