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 foreign 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
• 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 resistance 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 in susceptibility or resistance to
infection among different races within a same species.
For example, races with sickle cell anemia 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
sickleshaped erythrocytes that prevent parasitization by P. falciparum.
Similarly, individuals with a hereditary deficiency of glucose6-
phosphatase dehydrogenase are also less susceptible to infection by P.
falciparum
Species immunity
Species immunity denotes a total or relative resistance to a pathogen
shown by all members of a particular species.
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 to various 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,
cytomegalovirus, 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 mortality. 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 an important role in innate
immunity. Both humoral and cellmediated 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 disorders become increasingly
susceptible to infection.
For example, individuals suffering from diabetes mellitus,
hypothyroidism, and adrenal dysfunction are increasingly susceptible to
staphylococcal 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 important 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 and mucous 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 covering 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 secrections 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 membranes. 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
• 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 antibacterial 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 combat invaders displaying such molecules is a strong feature of innate
immunity.
Phagocytosis
• Phagocytosis is another important defense mechanism of the innate
immunity.
• is a process of ingestion of extracellular particulate material by
certain specialized cells, such as blood monocytes, neutrophils, and
tissue 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 wound or by an invading pathogenic
microorganism induces a complex sequence of events, collectively known
as the inflammatory 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 reaction
Histamine,
kinins,
acutephase proteins, and
defensin are the important mediators of inflammatory reactions
inflammatory reactions
• Histamine: It is a chemical substance produced by a variety of cells in
response to tissue injury.
• It is one of the principal mediators of the inflammatory response.
• It binds to receptors on nearby capillaries and venules, causing
vasodilatation and increased permeability
• Kinins:
• These are other important mediators of inflammatory response.
• They are normally present in blood plasma in an inactive form.
• Tissue injury activates these small peptides, which then cause
vasodilatation and increase 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 proteins 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
proinflammatory cytokines, namely, interleukin-1 (IL-1), interleukin-6 (IL6),
and tissue necrosis factor (TNF).
• They are called proinflammatory cytokines because they enhance the
inflammatory responses.
• Defensins:
• They are another important component of the innate 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 -defensins, whereas the gastrointestinal
tract contains -defensins.
• defensins also exhibit antiviral activity. They bind to the CXCR4
receptors and block entry of HIV virus into the cell.
Adaptive (Acquired) Immunity
• Adaptive immunity is also called acquired immunity, since the
potency of immune response is acquired by experience only
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: active immunity and passive immunity
Active immunity
• The immunity induced by exposure to a foreign antigen is called
active immunity.
• Active immunity is the resistance developed 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.
• 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 clinical or 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 by vaccines.
vaccines.
• There is a wide range of vaccines available against many microbial
pathogens.
• These may be live vaccines, killed vaccines, or vaccines containing
bacterial products
Mediators of active immunity
Active immunity is mediated by 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 the blood and
mucosal secretions called antibodies.
• The antibodies 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 elimination by various effector mechanisms.
• Humoral immunity is the principal defense mechanism against
extracellular microbes.
• Cell-mediated immunity:
• It is mediated by both activated TH 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 bacterial and protozoal pathogens.
• CTLs play an important role in killing virus-infected cells and tumor
cells. They act by killing altered self-cells
• Antigen recognition:
• Antigens, which are generally very large and complex, are not
recognized in their entirety by lymphocytes.
• 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 complex antigen
• 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 mechanisms.
• This diversification helps in conferring the specificity, one of the
cardinal characteristics of the immune system
Major histocompatibility complex (MHC):
It is a large genetic 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 conversion of proteins into MHC-associated peptide fragments is
called antigen processing and presentation.
Passive immunity
• When immunity is conferred by transfer of serum or lymphocytes
from a specifically immunized individual, it is known as passive
immunity.
• This is a useful method for conferring resistance rapidly, i.e., without
waiting for the development of an active immune response.
• Passive immunity may be natural or artificial.
• When immunity is conferred by transfer of serum or lymphocytes
from a specifically immunized individual, it is known as passive
immunity.
• This is a useful method for conferring resistance 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 passed from mother to fetus during pregnancy.
• This forms the basis of prevention of neonatal tetanus in neonates by
active immunization 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 antibodies in mother against
tetanus toxin, which are subsequently transmitted from mother to fetus
through placenta.
• The antibodies 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 individual 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 lifespan of these antibodies and the
possibility of hypersensitivity 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 disadvantages of
passive immunity.
Local Immunity
• 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 IgA antibodies 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 community.
Eradication of an infectious disease depends on the development 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.
