IMMUNITY (MB 315)

DEFINITION

Immunity Latin immunis, free of burden] refers to the resistance exhibited by the host
towards injury caused by microorganisms and their products.
The complex reaction a host animal undergoes after contact with microorganisms can
be grouped under the broadly defined heading of resistance. Protection against
infectious diseases is only one of the consequences of the immune system, which in its
entirety is concerned with the reaction of the body against any foreign antigen.

CLASSIFICATION

Immunity against infectious diseases is of different types. The discrimination between

self and nonself, and the subsequent destruction and removal of foreign material, is
accomplished by two arms of immune system, the innate (or “natural”) immune system,
and the adaptive (or “acquired”), specific immune system

I. INNATE OR NATURAL IMMUNITY

The body’s first line of defense against invasion by microorganisms is the innate
immunity or “natural” immune system, which is essential for the health of an organism.
It is the resistance to infections which an individual possesses by virtue of his genetic
or constitutional make up. Repeated exposure to a pathogen does not enhance the
innate immune system.

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a. Nonspecific and Specific Immunity
It may be nonspecific, when it indicates a degree of resistance to infections in general,
or specific where resistance to a particular pathogen is concerned. Innate immunity
may be considered at the level of species,race or individual.

i. Species Immunity
Resistance or susceptibility (lack of resistance) to infections can vary from one species
of animal to other. It refers to the total or relative refractoriness to a pathogen, shown
by all members of a species.

Examples
i. Mice are extremely susceptible to infection by Streptococcus pneumoniae. Humans,
on the other hand, are relatively resistant to Streptococcus pneumonia infection.
ii. The rat is strikingly resistant to diphtheria whilst the guinea pig and humans are
highly susceptible.
iii. All human beings are totally unsusceptible to plant pathogens and to many animal
pathogens such as rinderplast or distemper.

Mechanisms of Species Immunity

Physiological and biochemical differences: The mechanisms of species immunity are
not clearly understood, but may be due to physiological and biochemical dif¬ferences
between the tissues of the different host spe¬cies, which determine whether or not a
pathogen can multiply in them.

2. Racial Immunity
Within a species, different races may show differences in susceptibility to infections.
This is known as racial immunity. Such racial differences are known to be genetic in
origin, and by selection and inbreeding.

Examples
i. High resistance of Algerian sheep to anthrax: It is the classic example.
ii. Susceptibility to tuberculosis: The people of Negroid origin in the USA are more

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 susceptible than the Caucasians to tuberculosis. But such comparisons are vitiated
by external influences such as differences in socioeconomic levels.
iii. Genetic resistance to Plasmodium falciparum malaria: It is seen in some parts of
Africa and the Mediterranean coast and is attributed to the hereditary abnormality of
the red blood cells (sickling ) prevalent in the area. These red blood cells cannot be
parasitized by malarial parasite. It confers immunity to infection by the malarial
parasite and may have evolved from the survival advantage conferred by it in a
malarial environment.

3. Individual Immunity
The differences in innate immunity exhibited by different individuals in a race is known
as individual immunity. The role of heredity in determining resistance to infection is well
illustrated by studies on tuberculosis in twins. If one homozygous twin develops
tuberculosis, the other twin has a 3 to 1 chance of developing the disease compared
with a 1 in 3 chance if twins are heterozygous.

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Factors Influencing the Level of Immunity

1. Age

i. Fetus in Utero
The two extreme of life carry higher susceptibility to infectious diseases as compared
with adults. The fetus in utero is protected from maternal infection by the placental
barrier. But some pathogens cross this barrier causing overwhelming infection leading
to fetal death, while others such as Toxoplasma gondii, rubella, herpes,
cytomegaloviruses lead to congenital malformations. The higher susceptibility of the
young appears to associate with immaturity of immune system.

ii. Newborn Animals

Newborn animals are more susceptible to experimental infection than adult animals,
e.g. coxsackievirus causes fatal infection in suckling mice but not in adult mice. Some
infections like measles, mumps, poliomyelitis and chickenpox tend to be more severe in
adults than in young children. This may be due to more active immune response
producing greater tissue damage.

iii. In the Elderly

It besides a general waning of the activities of the immune system, physical

abnormalities (e.g. prostatic enlargement leading to stasis of urine) or long-term
exposure to environmental factors (e.g. smoking) are common causes of increased
susceptibility to infection.

2. Hormonal Influences and Sex

i. Endocrine Disorders
There is an increased susceptibility to infection in endocrine disorders such as diabetes
mellitus, hypothyroidism and adrenal dysfunction (increased corticoids secretion). The
reason for this disease have not yet been clarified but may be related to enzyme or
hormone activities.
Glucocorticoids are anti-inflammatory agents, decreasing the ability of phagocytes to
ingest material. They also have beneficial effect by interfering in some way with toxic

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effects of bacterial products such as endotoxin. In diabetics, staphylococcal,
streptococcal and certain fungal infections such as candidiasis, aspergillosis and
mucormycosis occur more frequently. Pregnant women are more susceptible to
microbial infection due to increased steroid levels during pregnancy.

ii. Sex
There is no marked difference in susceptibility to infec¬tions between the sexes. In
general, incidence and death rate from infectious diseases are greater in males than in
females. However, infectious hepatitis and whooping cough have a higher morbidity and
mortality in females.

3. Nutrition

In general, both humoral and cell mediated immune processes are reduced in
malnutrition although the adverse effects of poor nutrition on susceptibil¬ity to certain
infectious agents are not now seriously questioned. Protein calorie malnutrition lowers
C3 and factor B of the complement system, decreases the interferon response, and
inhibits neutrophil activity.
Experimental evidence in animals has shown that inadequate diet may be correlated
with increased susceptibility of a variety of bacterial diseases, associ¬ated with
decreased phagocytic activity and leucope¬nia. Viruses are intracellular parasites and
malnutrition might have an effect on virus production, but the usual outcome is
enhanced disease due to impaired immune responses, especially the cytotoxic
response.

4. Stress

A growing body of evidence has demonstrated an inverse relation between stress and
immune function. The end result is an increased susceptibility to infection.

Mechanisms of innate immunity

1. Mechanical Barriers and Surface Secretions
The first defenses are the external and internal body surfaces that are in relatively direct
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contact with the external environment and as are the body areas with which
microorganisms will initially associate. These surfaces include:
A. Skin (including conjuctival epithelium covering the eye)
B. Mucous membranes that line the mouth or oral cavity, the respiratory tract, and the
genitourinary tract.

A). Skin
The intact skin and the mucous membranes provide mechanical barriers that prevent
the entrance of most microbial species. In conditions where the skin is damaged, such
as in burns patients and after traumatic injury or surgery, infections can be a serious
problem.
Even though the structure of the skin itself undoubtedly gives a great deal of protection,
considerably more important are the fatty acids secreted by the sebaceous glands and
the propionic acid by the normal flora of the skin. Secretions from the sebaceous
glands contain both saturated and unsaturated fatty acids that kill many bacteria and
fungi. A striking example of this type of infection is seen in the case of the fungi causing
ringworm of the scalp (species of Microsporum and Trichophyton). This infection is
difficult to cure in children, but after puberty it disappears without treatment,
presumably as a result of a change in the amount and kinds of fatty acids secreted by
the sebaceous glands.
The bactericidal activity of skin secretions is illustrat¬ed by the frequent mycotic and
pyogenic infections seen in persons who immerse their hands in soapy water for long
periods occupationally.

B). Mucous Membrane

General protective mechanisms: A major protective component of mucous membranes
is the mucus itself. This substance serves to trap bacteria before they can reach the
outer surface of the cells, lubricates the cells to prevent damage that may promote
microbial invasion, and contain numerous specific (i.e. antibodies) and nonspecific
antibacterial substances. In addition to mucous activity and flow mediated by cilia
action, rapid cellular shedding and tight intercellular connections provide effective
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barriers. As is the case with skin, specific cell clusters, known as mucosa-associated
lymphoid tissue, exist below the outer cell layer and mediate specific protective
mechanisms against microbial invasion.
Specific protective characteristics: Besides the general protective properties of
mucosal cells, the lining of the different body tracts has other characteristics specific to
each anatomic site.

i. Mouth or Oral Cavity

The mouth or oral cavity is protected by the flow of saliva that physically carries
microorganisms away from the cell surfaces and also contains the lysozyme, which
destroys bacterial cell walls, and antibodies. Harmful agents also heavily colonize the
mouth with microorganisms that contribute to protection by producing substances that
hinder successful invasion. Particles deposited in the mouth are swallowed and
subjected to the action of the digestive juices.

ii. Gastrointestinal Tract

i. Stomach: In the gastrointestinal tract, several sys¬tems function to inactivate
bacteria. The low pH and proteolytic enzymes of the stomach help keep the
numbers of microorganisms low. The high acid¬ity of the stomach destroys most
microorganisms. The pH becomes progressively alkaline from the duodenum to the
ileum.
ii. Small intestine: In the small intestine, protection is provided by the presence of
bile salts that disrupt bacterial membranes and the fast flow of the intestinal
contents that hinders microbial attachment to mucosal cells.
iii. Ileum: The ileum contains a rich and varied flora and in the large intestine, the
bulk of the contents is composed of bacteria. Abundant resident microflora in the
large bowel also contributes significantly to protection.

iii. Upper Respiratory Tract

a). Architecture of the nose: In the upper respiratory tract, nasal hairs keep out large
airborne particles that may contain microorganisms. The very archi¬tecture of the

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 nose prevents entry of microorgan¬isms to a large extent, the inhaled particles
being arrested at or near the nasal orifices. Those that pass beyond are held by the
mucus lining the epitheli¬um, and are swept back to the pharynx where they tend to
be swallowed or coughed out.
b). Sticky mucus: The sticky mucus covering the respiratory tract acts as a trapping
mechanism for inhaled particles.
c). Ciliary motion: Ciliary motion transports the trapped organisms back up the
respiratory tract to the external openings.
d). Cough reflex: Cough reflex is an important defence mechanism of the
respiratory tract and propels the organisms away from the lungs.
e). Mucopolysaccharide: Nasal and respiratory secre¬tions contain
mucopolysaccharide capable of combining with influenza and certain other virus¬es.
When organisms enter the body via mucus membrane, they tend to be taken up by
phagocytes and are transported into regional lymphatic chan¬nels that carry them to
the lymph nodes. Particles that manage to reach the pulmonary alveoli are ingested by
the phagocytic cells present there.

iv). Genitourinary Tract

a). Normal flow of urine: The normal flow of urine flushes the urinary system, carrying
microorganisms away from the body.
b). Spermine and zinc: Spermine and zinc present in the semen carry out antibacterial
activity. Because of short urethra, bladder infection is more common in females.
c). Acidity of the adult vagina: The low pH (acidity) of the adult vagina, due to
fermentation of glycogen in the epithelial cells by the resident aciduric bacilli,
provides an inhospitable environment for colonization by pathogens. A thick mucus
plug in the cervical opening is a substantial barrier.

v). Conjunctiva
i. Lachrymal fluid: Conjunctiva is continually being assaulted by microbe-laden dust and
is kept moist by the continuous flushing action of tears (lachrymal fluid). The eyes

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 become susceptible to infection when lachrymal secretions are absent. Tears
contain large amounts of lysozyme, lactoferrin, and sIgA and thus provide
mechanical as well as physical protection.
ii. Lysozyme: Tears contain the antibacterial substance lysozyme, first described by
Fleming (1922). It is a basic protein of low molecular weight which acts as a
muraminidase. Lysozyme is present in tissue fluids and in nearly all secretions
except cerebro¬spinal fluid, sweat and urine. It acts by splitting certain
polysaccharide components of the cell walls of susceptible bacteria. In the
concentrations seen in tears and other secretions, lysozyme is active only against
some nonpathogenic gram-positive bacteria. However, it occurs in phagocytic cells
in concentra¬tions high enough to be lethal to many pathogens.

C). Interferon
The production of interferon is a method of defense against viral infections. These are a
family of antiviral agents produced by live or killed viruses and certain other inducers.
Interferon has been shown to be more important than specific antibodies in protection
against and recovery from certain acute viral infections. Tissues and body secretions
contain other antiviral substances.

2. Antibacterial Substances in Blood and Tissues

Many microbial substances are present in the tissue and body fluids. These are
nonspecific. These molecules all show the characteristics of innate immunity—there is
no specific recognition of the microorganisms and the response is not enhanced on re-
exposure to the same antigen.

a. Complement System

The complement system possesses bactericidal activity and plays an important role in
the destruction of pathogenic bacteria that invade the blood and tissues.

b. Other Substances

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Several substances possessing antibacterial properties have been described in blood
and tissues. These substances possess antibacterial properties demonstrable
experimentally but their relevance in the natural context is not clearly understood.
These include:
1. Beta lysine: A relatively thermostable substance active against anthrax and related
bacilli.

2. Basic polypeptides such as leukins extracted from leukocytes and plakins from
platelets.
3. Acidic substances, such as lactic acid found in muscle tissue and in the
inflammatory zones; and
4. lactoperoxidase in milk.

3. Microbial Antagonisms
The skin and mucous surfaces have resident bacterial flora which prevent colonization
by pathogens. Invasion by extraneous microbes may be due to alteration of normal
resident flora, causing serious diseases such as staphylococcal or clostridial
enterocolitis or candidiasis following oral antibiotics. The extreme susceptibility of
germ free animals of all types of infections is an example of the importance of normal
bacterial flora in native immunity.

4. Cellular Factors in Innate Immunity

Natural defense against the invasion of blood and tissues by microorganisms and other
foreign particles is mediated to a large extent by phagocytic cells which ingest and
destroy them. Phagocytic cells, originally discovered by Metchnikoff (1883), were
classified by him into microphages (polymorphonuclear leukocytes) and macrophages.

Macrophages

Macrophages consist of histiocytes which are the wandering ameboid cells seen in
tissues, fixed reticulo-endothelial cells and monocytes of blood. Monocytes enter the

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blood, and differentiate after they reach the capillaries of a particular tissue. In
connective tissue they are known as histiocytes, in kidneys as mesangial cells, in bones
as osteoclast, in brain as microglial cells, in lungs as alveolar macrophages, in liver as
Kupffer cells, and in spleen, lymph nodes and thymus as sinus lining macrophages.
Phagocytic cells reach the sites of inflammation in large numbers, attracted by
chemotactic substances, and ingest particulate materials. Capsulated bacteria, such as
pneumococci, are not readily phagocytosed except in the presence of opsonins. They
are more readily phago¬cytosed when trapped against a firm surface such as the
alveolar wall than when they are free in tissue fluids.

Phagocytosis

Phagocytosis is part of the innate immune response, during which microorganisms,

foreign particles, and cellular debris are engulfed by phagocytic cells such
as neutrophils and monocytes in the circulation, and macrophages and neutrophils in
interstitial spaces.

Stages of Phagocytosis

Phagocytosis consists of three stages:

1. Attachment of the microorganisms or foreign material to the phagocytic cell.
2. Ingestion by the cell and drawn into the cell by endocytosis. Once internalized, the
bacteria are trapped within phagocytic vacuoles (phagosomes) in the cytoplasm.
3. Degradation of the foreign material or microorgan¬ism within the phagocytic cells.
The phagosome containing the material to be destroyed fuses with a granule-containing
lysosome, generating a phagolysosome. The bacteria are subjected to the action of the
lytic enzymes in the phagolysosome and are destroyed.
Some bacteria, such as mycobacteria and brucellae, resist intracellular digestion and
may actively multiply inside the phagocytic cells. Phagocytosis in such instances may
actually help to disseminate infection to different parts of the body. The importance of
phagocytosis in protection against infection is evidenced by the enhanced susceptibility
to infection seen either when the phagocytic cells are depleted, as in agranulocytosis, or
when they are functionally deficient, as in chronic granulomatous disease.
In nonspecific defence against viral infections and tumors a class of lymphocytes called

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natural killer (NK) cells are important. They selectively kill virus infected cells and tumor
cells. NK cells are activated by interferons.

5. Inflammation

If the surface chemical and physiologic defences of the body are breached by a
pathogen, inflammation can result, which is an important, nonspecific defence
mechanism. Sequences of events in acute inflammation in response to an injury will be:
1. Vasodilation.
2. Increased vascular permeability.
3. Emigration of leukocytes.
4. Chemotaxis.
5. Phagocytosis.

Vasodilation
The inflammatory response causes the normally tight junctions between endothelial
cells lining the capillaries, and between epithelial cells of the mucosal surface, to
reversibly separate. Increased blood flow to injured area provides increased delivery of
plasma proteins, neutrophils, and phagocytes (vasodilation).

Increased Vascular Permeability

Protein-rich exudates containing immunoglobulins and complement moves into injured
area (increased permeability). Neutrophils and macrophages adhere to endothelial cells
of capillaries.

Emigration of Leukocytes
Leukocytes squeeze through gaps created by contrac¬tion of endothelial cells
(emigration of leukocytes).

Chemotaxis
Neutrophils and macrophages move to site of injury in response to gradient of
chemotactic mediators released by injured tissue (chemotaxis).

Phagocytosis

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Phagocyte attaches to the microorganisms and engulfs it by endocytosis and
microorganisms are degraded by oxygen radicals and digestive enzymes
(phagocytosis), whereas others (natural killer cells) limit the infection by releasing the
compounds toxic to microorganisms. Inflammation is also accompanied by an
increased concentration of serum proteins called acutephase proteins.

6. Fever

Following infection a rise of temperature is a natural defense mechanism. It not merely

helps to accelerate the physiological processes but may, in some cases, actually
destroy the infecting pathogens. For example, antibody production and T cell
proliferation are more efficient at higher body temperature than at normal levels. Before
penicillin era, therapeutic induction of fever was employed for the destruction of
Treponema pallidum in patients suffering from syphilis. Fever aids recovery from viral
infections by stimulating the production of interferon.

7. Acute Phase Proteins

A sudden increase in the plasma concentration of certain proteins, collectively termed

‘acute phase proteins’ occurs as a result of infection or tissue injury. These include C
reactive protein (CRP), mannose binding protein, alpha-1-acid glycoprotein, serum
amyloid P component and many others. The alternative pathway of complement is
activate by CRP and some other acute phase proteins. They are believed to enhance
host resistance, prevent tissue injury and promote repair of inflammatory lesions.

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II. ACQUIRED IMMUNITY
Acquired immunity refers to the resistance that an individual acquires during his lifetime.
Acquired immunity can be obtained by natural or artificial means and actively or
passively. Acquired immunity is of two types: active immunity and passive immunity.
(Fig. 1 ).

a. Active Immunity

Active immunity is induced after contact with foreign antigens. It is also known as
adaptive immunity as it represents an adaptive response of the host to a specific
pathogen or other antigen. This involves the active functioning of the host’s immune
apparatus leading to the synthesis of antibodies and/or the production of
immunologically active cells.

Immune Response

a. Primary Response
Active immunity sets in only after a latent period which is required for the
immunological machinery to be set in motion. There is often a negative phase during
the development of active immunity during which the level of measurable immunity may
actually be lower than it was before the antigenic stimulus. This is because the antigen
combines with any pre-existing antibody and lowers its level in circulation. Once
developed, the active immunity is long lasting.

b. Secondary Response
If an individual who has been actively immunized against an antigen, experiences the
same antigen subsequently, the immune response occurs more quickly and abundantly
than during the first encounter. This is known as secondary response. This implies that
the immune system is able to retain for long periods the memory of a prior antigenic
exposure and to produce a secondary type of response when it encounters the same
antigen again. This is known as immunological memory. Active immunization is more
effective and confers better protection than passive immunization.

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Types of Active Immunity

1. Natural active immunity

2. Artificial active immunity

1. Natural Active Immunity

Natural active immunity results from either a clinical or an inapparent infection by a

microbe. The immune system responds by producing antibodies and activated
lymphocytes that inactivate or destroy the antigen. Such immunity is usually long
lasting but the duration varies with the type of pathogen. The immunity is life-long
following many viral diseases such as chickenpox or measles. A large majority of adults
in the developing countries possess natural active immunity to poliomyelitis due to
repeated inapparent infections with the polioviruses during childhood.
The immunity appears to be short-lived in some viral diseases, such as influenza or
common cold. In
case of influenza, short-lived immunity is due to the ability of the virus to undergo
antigenic variation, so that immunity following first infection is not effective against
second infection due to an antigenically different virus. In common cold, the apparent
lack of immunity is because the same clinical picture can be caused by infection with a
large number of different viruses. In general, the immunity following bacterial infection
is generally less permanent than that following viral infections. Some, such as typhoid
fever, induce durable protection.
In some infections like syphilis and malaria, the immunity to reinfection lasts only as
long as the original infection remains active. Once the disease is cured, the patient
becomes susceptible to the infection again. This special type of immunity known as
‘premunition’ or infection-immunity. In chancroid, another venereal disease, caused by
Haemophilus ducreyi, there does not appear to be any effective immunity as the patient
may develop lesions following reinfection even while the original infection is active.

2. Artificial Active Immunity

Artificial active immunity is the resistance induced by vaccines. Vaccines are

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preparations of live or killed microorganisms or their products used for immuniza¬tion.
Vaccines are made with either: 1. Live, attenuated microorganisms, 2. Killed
microorganisms, 3. Microbial extract, 4. Vaccine conjugates, 5. Inactivated toxoids

Table 1: Comparison of active and passive immunity

Active immunity Passive immunity
. Produced actively by host’s immune system . Received passively.
No active host participation
. Induced by infection or by immunogens . Readymade antibody transferred
. Durable effective protection . Transient, less effective
. Immunity effective only after lag period, i.e. . Immediate immunity
time required for generation of antibodies
and immunocompetent cells.
. Immunological memory present . No memory
. Booster effect on subsequent dose . Subsequent dose less effective
. ‛Negative phase’ may occur . No negative phase
. Not applicable in the immunodeficient . Applicable in immunodeficient

Both bacterial and viral pathogens are targeted by these diverse means.

Examples of Vaccines

Bacterial vaccines

a. Live (BCG vaccine for tuberculosis)

b. Killed (Cholera vaccine)
c. Subunit (Typhoid Vi-antigen)
d. Bacterial products (Tetanus toxoid)

Viral Vaccines
a. Live
• Oral polio vaccine—Sabin
• 17D vaccine for yellow fever

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• MMR vaccine for measles, mumps, rubella.
b. Killed
• Injectable polio vaccine—Salk
• Neural and non-neural vaccines for rabies
• Hepatitis B vaccine
c. Subunit—Hepatitis B vaccine

Live Vaccines
Live vaccines initiate an infection without causing any injury or disease. The immunity
following live vaccine administration, therefore, parallels that following natural infection.
However, it may be of a lower order than induced by infection. In, general, live vaccines
are more potent immunizing agents than killed vaccines The immunity lasts for several
years but booster doses may be necessary. Live vaccines may be administered orally
(as with the Sabin vaccine for poliomyelitis) or parenterally (as with the measles
vaccine).

Killed Vaccines
Killed vaccines are usually safe and generally less immunogenic than live vaccines, and
protection lasts only for a short period. They have, therefore, to be administered
repeatedly, generally at least two doses being required for the production of immunity.
The first is known as the primary dose and the subsequent doses as booster doses.
Killed vaccines are usually administered by subcutaneous or intramuscular route.
Parenteral administration provides humoral antibody response. Antibody response to
killed vaccines is improved by the addition of ‘adjuvants’, for example, aluminum
phosphate adjuvant vaccine for cholera.

b. Passive Immunity

The immunity that is transferred to a recipient in a ‘readymade’ form is known as

passive immunity. Here the recipient’s immune system plays no active role. There is no
lag or latent period in passive immunity, protection being effective immediately after
passive immunization. There is no negative phase. The immunity is transient, usually
lasting for days or weeks, only till the passively transmitted antibodies are metabolized

17
and eliminated. There is no secondary type response in passive immunity. Rather,
subsequent administration of antibodies is less effective due to immune elimination.
When a foreign
antibody is administered a second time, it is eliminated more rapidly than initially.
Following the first injection of an antibody (such as horse serum), its elimination is only
by metabolic breakdown but during subsequent injections its elimination is much
quicker because it combines with antibodies to horse serum that would have been
produced following its initial injection. The usefulness of repeated passive
immunization is limited by this factor of immune elimination. This happens when
foreign (horse) serum is used and when human serum is used immune elimination is
not a problem.

Main Advantage of Passive Immunity

i. The prompt availability of large amount of anti¬body.
ii. It is employed where instant immunity is required as in case of diphtheria,
tetanus, botulism, rabies, hepatitis A and B following exposure because of its
immediate action

1. Natural Passive Immunity

This is the resistance passively transferred from mother to baby through the placenta.
After birth, immuno¬globulins are passed to the newborn through the breast milk. The
human colostrum, is rich in IgA antibodies which are resistant to intestinal digestion,
gives protec¬tion to the neonate up to three months of age.
The human fetus acquires some ability to synthesize antibodies (lgM) from about the
twentieth week of life but its immunological capacity is still inadequate at birth. It is only
by about the age of three months that the infant acquires a satisfactory level of
immunologi¬cal independence. Until then, maternal antibodies give passive protection
against infectious diseases to the infant.
Transport of antibodies across the placenta is an active process and, therefore, the
concentration of anti¬body in the fetal blood may sometimes be higher than that seen
in the mother. Protection so afforded will ordi¬narily be adequate against all the
common infectious diseases in the locality. Therefore, most pediatric infec¬tions are
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more common after the age of three months when maternal immunoglobulins
disappear than in younger infants.
By active immunization of mothers during pregnancy, it is possible to improve the
quality of passive immunity in the infants because pregnant woman’s antibodies pass
across the placenta to her fetus. Immunization of pregnant women with tetanus toxoid
is recommended for this purpose in countries where neonatal tetanus is common.

2. Artificial Passive Immunity

Artificial passive immunity is the resistance passively transferred to a recipient by the

administration of anti¬bodies. Although this type of immunity is immediate, it is short
lived and lasts only a few weeks to a few months. The agents used for this purpose are
pooled human gamma globulin, hyperimmune sera of animal
or human origin and convalescent sera. These are used for prophylaxis and therapy.

Types of immunoglobulin preparations: Two types of immunoglobulin preparations are

available for passive immunization.

A. Human Immunoglobulins
a. Human normal immunoglobulin
b. Human specific immunoglobulin

a. Human Normal Immunoglobulin

Human normal immunoglobulin (HNIG) is used to provide temporary protection against

hepatitis A infection for travelers to endemic areas and to control institutional and
hosehold outbreaks of hepatits A and to prevent measles in highly susceptible
individuals. HNIG also protects those with agammaglobulinemia.

b. Specific (Hyperimmune) Human Immunoglobulin

These preparations are made from the plasma of patients who have recovered recently
from an infection or are obtained from individuals who have been immunized against a
specific infection. Preparations of specific immunoglobulins are available for passive
immuniza¬tion against tetanus (human tetanus immunoglobulin; HTIG), hepatitis B

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(HBIG), human rabies immunoglob¬ulin (HRIG), varicella-zoster immunoglobulin (ZIG)
and Antivaccinia immunoglobulin (AVIG).
Human immune serum does not lead to any hyper¬sensitivity reaction, therefore, there
is no immune elimi¬nation and its half-life is more than that of animal sera. It has to be
ensured that all preparations from human sera are free from the risk of human
immunodeficiency virus (HIV), hepatitis B, hepatitis C and other viruses.

B. Nonhuman (Antisera)
The term aniserum is applied to materials prepared in animals. Equine hyperimmune
sera such as antitetanus serum (ATS) prepared from hyperimmunized horses used to
be extensively employed. They gave temporary protection but disadvantage is that may
give rise to hypersensitivity and immune elimination. Since human immunoglobulin
prepararations exist only for a small number of diseases, antitoxins prepared from
nonhu¬man sources (against tetanus, diphtheria, botulism, gas gangrene and snake bite)
are still the main stay of passive immunization.

Indications of Passive Immunization

1. To provide immediate protection to a nonimmune host exposed to an infection and
lack active immu¬nity to that pathogen and when there is insufficient time for active
immunization to take effect, e.g. ex¬posure to a toxin or poison.
2. Treatment of some infections.
3. For the suppression of active immunity when it may be injurious, e.g. administration
of anti-Rh (D) IgG to Rh-negative mother, bearing Rh-positive
baby at the time of delivery to prevent isoimmuni¬zation.
4. Immunocompromised or immunodeficient indi¬viduals, e.g. children with
hypogammaglobuline¬mia, individuals with AIDS, patients receiving chemotherapy,
organ transplant recipients receiv¬ing immunosuppressive therapy.

Combined Immunization
Combined immunization is a combination of active and passive methods of
immunization which is sometimes employed. For example, it is often undertaken in
some diseases such as tetanus, diphtheria, rabies. Ideally, whenever passive
immunization is employed for immediate protection, combined immunization is to be
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preferred, as in the protection of a nonimmune individual with a tetanus prone wound.
The person exposed to tetanus may be injected ATS on one arm and tetanus toxoid on
the other arm with separate syringe followed by full course of tetanus toxoid. Similarly,
AIDS and diphtheria toxoid can also be practiced.

Adoptive Immunity
Injection of immunologically competent lymphocytes is known as adoptive immunity
and does not have general application. Instead of whole lymphocytes, an extract of
immunologically competent lymphocytes, known as the ‘transfer factor’, can be used.
This has attempted in the treatment of certain types of diseases for example,
lepromatous leprosy.

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MEASUREMENT OF IMMUNITY

It is not possible to measure accurately the level of immunity in an individual. Estimates

of immunity are generally made by statistical methods using large numbers of
individuals.

Demonstration of the Specific Antibody

Immunity can be tested by a simple method by relating its level to some convenient
indicator, such as demon¬stration of the specific antibody which is not always reliable
because the immune response to a pathogen consists of the formation of antibodies to
several anti¬gens present in it, as also to the production of cellular immunity.
A variety of techniques can be used to demonstrate antibodies such as agglutination,
precipitation, comple¬ment fixation, hemagglutination inhibition, neutraliza¬tion, ELISA
and others. In the absence of exact infor¬mation as to which antigen of the pathogen
constitutes the ‘protective antigen” serological attempts to measure immunity are at
best only approximations.

LOCAL IMMUNITY

Besredka (1919-24), proposed the concept of local immunity and it has gained
importance in the treatment of infections which are localized or where it is opera¬tive in
combating infection at the site of primary entry of the pathogen. Local immunity is
conferred by secretory immunoglobulin A (secretory IgA ) produced locally by plasma
cells present on mucosal surfaces or in secretory glands. There appears to be a
selective transport of such antibodies between the various mucosal surfaces and
secretory glands.

Examples
1. Poliomyelitis immunization
In poliomyelitis, active immunization provides systemic immunity with the killed vaccine.
The antibodies neutralize the virus when it enters the bloodstream. But it does not
prevent multiplication of the virus at the site of entry, the gut mucosa, and its fecal
shedding. Natural infection or immunization with the live oral vaccine provide local
intestinal immunity.

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2. Influenza immunization
Similarly, in influenza, immunization with the killed vaccine evokes humoral antibody
response and the antibody titer in respiratory secretions is often not high enough to
prevent infection. Natural infection or the live influenza vacicine administered
intranasally provides local immunity.

HERD IMMUNITY

It is the level of resistance of a community or a group of people to a particular disease

and is relevant in the control of epidemic diseases. When a large number of individuals
in a community (herd) are immune to a path¬ogen the herd immunity is said to be
satisfactory. Herd immunity provides a human barrier to the spread of the disease in the
human herd. It can be affected by several factors such as the environment and the
strength of an individual’s immune system.

Low Herd Immunity

Epidemics are likely to occur on the introduction of a suitable pathogen when herd
immunity is low which is due to the presence of large numbers of susceptible
individuals in the community.

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High Level of Herd Immunity

Eradication of communicable diseases depends on the development of a high level of

herd immunity rather than on the development of a high level of immunity in individuals.
For herd immunity to operate well in a community or a country, vaccine uptake rates
must exceed 90 percent.

1. Endo-N-acetyl hexosamines, known as lysozymes.

2. Endopeptidases.
3. Amidases.

Acute Phase Proteins

Certain proteins in the plasma, collectively termed ‘acute phase proteins’, increase in
concentration in response to early ‘alarm’ mediators such as interleukin-1(IL-1), IL-6 and
tumor necrosis factor (TNF), released as a result of infection or tissue injury.

KEY POINTS

• Immunity refers to the resistance exhibited by the host towards injury caused by
microorganisms and their products.
• Innate or natural immunity is the resistance to infections which an individual
possesses by virtue of his genetic or constitutional make up.
• Factors influencing the level of immunity are age, hormonal influences and sex,
nutrition and stress
• Mechanisms of innate immunity
– Mechanical barriers and surface secretions.
– Antibacterial substances in blood and tissues.
– Microbial antagonisms.
– Cellular factors in innate immunity.
– Inflammation.
– Fever.

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 – Acute phase proteins.
• Acquired immunity is of two types: (i) active immu¬nity and (ii) passive immunity
• Natural active immunity results from either a clini¬cal or an inapparent infection by
a microbe.
• Artificial active immunity is the resistance induced by vaccines.
• The immunity that is transferred to a recipient in a ‘readymade’ form is known as
passive immunity.
• Herd immunity is the level of resistance of a com¬munity or a group of people to a
particular disease.

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