Introduction to immunology

Pathogenic microorganisms are endowed with special properties that enable them to cause
disease, if given the right opportunity

In some instances, the body does not allow the organisms to enter. In others, even if they
enter, are eliminated by different mechanisms. In still others, even if they remain inside, the
defenses combat with them. Our ability to ward off disease in general is called resistance
(immunity). Vulnerability or lack of resistance is susceptibility

Immunity is defined as the resistance exhibited by the host towards injury caused by the
microorganisms and their products.

Immunity involves the defensive response, when a host is invaded by foreign organisms or
other foreign substances (pollen, insect venom, transplanted tissue). Body cells that become
cancerous are also recognized as foreign and may be eliminated.

TYPES OF IMMUNITY

Immunity to infectious agents can result from innate immunity, acquired immunity or both
INNATE IMMUNITY

Innate immunity is an invariable, hereditary response—an inborn defense.

It is independent of previous exposure to disease causing agents and foreign substances.

The innate immunity depends on the non-specific mechanisms, molecular defenses and the
activity of the phagocytic cells.

Innate immunity may be non-specific, when it indicates a degree of resistance to infection in

general or specific, when resistance to particular pathogen is concerned.

Innate immunity may be considered at the level of species, race and individual.

In species immunity, all individuals of a species are born with resistance to an infectious agent
that causes disease in another species.

For example, humans are immune to most infectious agents that causes disease in pets and
other domesticated animals.

The mechanisms of species immunity are not clearly understood, but may be due to
physiological and biochemical differences between the tissues of the different host species that
determine, whether or not a pathogen can multiply in them.

Within a species, different races show difference in susceptibility to infections. This is known as
racial immunity. The classical example of racial immunity is the resistance to anthrax by
Algerian sheep, where as sheep in general are susceptible to anthrax.

Individuals in a race exhibit difference in innate immunity.

The genetic basis of individual immunity is evident from studies on the incidence of infectious
disease in twins.

Homozygous twins exhibit similar degree of resistance or susceptibility to lepromatous leprosy

and tuberculosis.

An individual’s resistance to disease also depends on age, nutritional status, stress, hormone
influence and general health

Age: Two extremes of life carry higher susceptibility to infections in comparison to adults.
The heightened susceptibility of the fetus to infection is related to the immaturity of the
immune system.

In neonates, the antibodies, immune competent cells and also the complement level remain
suboptimal

Hormonal influence: Diabetes, hypothyroidism and adrenal dysfunctions are associated with
enhanced susceptibility to infections.

Corticosteroids depress host resistance by anti-inflammatory and antiphagocytic effects and

also by suppressing antibody formation.

Nutrition: The interaction between malnutrition and immunity is very complex.

But in general, malnutrition depresses both cell mediated immunity (CMI) and antibody
mediated immunity (AMI). CMI and AMI responses to T cell-dependent antigens are primarily
reduced in malnutrition.

Stress: Whether psychological or physical, stress adversely affects the immune response.

Mechanism of Innate Immunity

First line of defense

Physical barriers:

 Skin and mucous membrane form an important line of defense.

Intact skin is impenetrable to most of the bacteria.

 Its low pH and presence of fatty acid makes the environment inhospitable for bacteria
other than commensals

 The continual shedding of the squamous epithelium also reduces bacterial load. If the
continuity of the skin is compromised, the skin may be secondarily infected.

The mucous membranes form a less formidable barrier.

 The mucus with entrapped bacteria is swept away by cilia of the ciliated respiratory
mucosa or the villi in the intestine particles are swallowed and coughed out by cough
reflex.

 The flushing effect of the body secretions reduces the microbial flora.

 Any slowing of urinary flow increases the chance of ascending infection.

  Saliva teeming with oral bacteria flows to the back of throat and is swallowed; gastric
acidity destroys most swallowed bacteria.

 Commensal flora in the intestine prevents the colonization by pathogenic bacteria

Chemical factors (Antimicrobial substances):

The barrier defense of skin and mucous membrane are reinforced by the presence of
antibacterial substances.

 Lysozyme, a hydrolytic enzyme, found in the mucus secretions and in tears, is able to
cleave the peptidoglycan of the bacterial cell wall.

 Saliva contains antibacterial hydrogen peroxide (H2O2).

 The low pH of stomach and vagina is inimical to most bacteria.

Several substances, possessing antimicrobial property, have been described in blood and
tissue. These include:

 Beta-lysine active against anthrax and related bacilli.

 Basic polypeptides (leukin from leukocytes and plakin from platelets).

 Lactic acid found in the muscle tissue and in the inflammatory zone.

 Lactoperoxidase in the milk.

 Virus inhibiting substances (antiviral substances) inhibit viral hemagglutinin.

 A cysteine-rich peptide called defensins secreted by a variety of cells (epithelial cells,

neutrophils, macrophages) in the skin and mucous membrane.

 Other molecules with microbicidal functions include cathelicidin, deoxyribonuclease

(DNases) and ribonuclease (RNases).

 Acute phase proteins:

In an acute phase of infection, pathogens ingested by macrophages stimulate the synthesis and
secretion of several cytokines. Cytokines such as interleukin-1 (IL-1) and IL-6 travel through the
blood and cause the liver to synthesize and secrete acute phase proteins into the blood.
Interferons (a group of signaling proteins): A method of defense against virus infection is the
production of interferon (IFN) by cells stimulated by live or killed viruses and certain other
inducers. IFN has been shown to be more important than specific antibodies in protection
against and recovery from certain acute viral infections.

Immunoglobulin (also known as antibodies):

All classes of immunoglobulins (Ig) have been detected on mucous membranes, but IgA is the
most important, because it is present in the greatest amount. IgA is a dimer, linked by secretory
piece that not only aids transport, but also renders it resistant to proteolytic enzymes in the
secretions. IgA is not involved in complement -mediated killing (classical pathway), but impedes
adherence, an essential first step in colonization.

Complement system:

The complement is a group of serum proteins that circulate in an inactive state. A variety of
specific and non-specific immunologic mechanisms can convert the inactive form of
complement proteins into an active form leading to lysis of bacteria, cells and viruses;
promotion of phagocytosis (opsonization); triggering of inflammation; secretion of immune-
regulatory molecules and clearance of immune complex from the circulation

Cytokines and chemokines:

 The cytokines are secreted by leukocytes and other cells and are involved in innate
immunity, adaptive immunity and inflammation.
  Cytokines act in an antigen non-specific manner, triggering a wide range of biological
activities from chemotaxis to activation of specific cells.

 Chemokines are subgroups of cytokines of low molecular weight involved in chemotaxis

(chemical-induced migration).

Commensal flora: It prevents colonization by pathogens. Commensals protect the host by

various mechanisms:

 Competition for available food and tissue receptors.

 Production of toxic substances, such as fatty acids or antagonistic substance such as

bacteriocins.

 Stimulation of antibodies (natural antibody that may cross react with pathogens).

 Keeping the immune system primed, so that the monocytes bear class II
histocompatibility antigens needed for immune response.

Second line of defense

When the first line of defense fails, either because of congenital or acquired defects, then the
way to deeper tissue is open to bacteria and the next lines of defense come to play.

Cellular factors in innate immunity:

 Natural defense against the invasion of the blood and tissue is mediated by phagocytic
cells.

 Phagocytosis is the process by which the invading organisms are ingested by phagocytic
cells, ingestion being followed by intracellular killing.

 Many cells are able to ingest the particles, e.g. endothelial cells, but three cells may be
regarded as professional phagocytes. These are neutrophils, macrophages and to a
much lesser degree eosinophils.

 Macrophages consist of histiocytes (wandering ameboid cells found in the tissue), the
fixed reticulo-endothelial cells and blood monocytes.
The innate immune system provides a rapid, initial means of defense against infection using
genetically programmed receptors that recognize these structural features of microbes that are
not found in the host.

 Such receptors are known as pattern recognition receptors (PRRs), which are found on
or in phagocytic cells, which bind to pathogen associated molecular patterns (PAMPs)

 PAMPs are conserved, microbes-specific carbohydrates, proteins, lipids and/or nucleic

acid (e.g. lipopolysaccharide, peptidoglycan, etc.).

 PRRs binding to PAMPs result in phagocytosis and enzymatic degradation of the

infectious organisms

Pattern recognition receptors engagement can lead to activation of the host cell and its
secretion of antimicrobial substances.

PRRs include:

 Toll-like receptors (TLRs), which signals the synthesis and secretion of cytokines to
promote inflammation by recruiting cells.

 Scavenger receptors that are involved in internalization of bacteria and phagocytosis of

host cells that are undergoing apoptosis.

 Opsonins, the molecules (C3a, IgM), which bind to microbes to facilitate their
phagocytosis.
Inflammation:

Tissue injury, initiated by the entry of pathogens leads to inflammation, which is an important
non-specific mechanism of defense. Hence, inflammation acts as a protective phenomenon.

 Blood flow to the particular part is increased.

 There is an outpouring of plasma, which dilutes the toxins and enzymes.

 Chemotactic factors including C5a, histamine, leukotrienes, etc. will attract phagocytic
cells to the site. The increased vascular permeability will allow easier access for
neutrophils and monocytes. Vasodilation means more cells in the vicinity.

 There is formation of fibrin barrier, which limits the inflammation.

 There is activation of complement and also the specific defenses.

Fever:

A rise of temperature following infection, helps in following ways:

1. Mobilization defenses.

2. Accelerate repairs.

3. Inhibits pathogens.

4. Stimulates the production of IFNs and helps in recovery from virus infection.
Acquired Immunity

The resistance an individual acquires during life is called acquired immunity.

Active Immunity (Adaptive Immunity)

 Active immunity or adaptive immunity is capable of recognizing and selectively

eliminating specific foreign microorganisms and molecules, i.e. tumor antigens,
transplanted antigens, etc.
  This involves the active functioning of the individual’s immune apparatus, either in
producing antibody or creating immune-competent cells for cell-mediated immunity
(CMI).

 Active immunity sets in only after a latent period, which the immunological machinery
needs for its functioning. Once developed the active immunity is long lasting.

 When the individual is facing the same antigen subsequently, there is no latent or lag
phase and the immune response is prompt, powerful and prolonged.

 Adaptive immune system has a very large repertoire of specific antigen receptors that

can recognize virtually, any component of the foreign invader.

Adaptive immunity focuses on four important characteristic features:

1. Antigenic specificity: The antigenic specificity of the immune system permits it to

distinguish minor difference among antigens. The antibodies can distinguish between
two protein molecules that differ in only a single amino acid

2. Diversity: The immune system is capable of generating tremendous diversity in its

recognition molecules, permitting to recognize vast arrays of unique structures on
foreign antigens

3. Immunological memory: Once the immune system recognized and responded to an

antigen, it exhibits immunological memory to recognize the same antigen, subsequently
and react in a heightened manner

4. Self/non-self-recognition: the immune system, normally responds to foreign antigens,

indicating that it is capable of distinguishing self from non-self

The adaptive immunity is not independent of innate immunity. They interact constantly

Naturally acquired active immunity:

 This type of immunity is obtained when a person is exposed to antigens in the course of
daily life.
 Once acquired, the immunity lasts for rest of its life such as in measles and chickenpox

Artificially acquired active immunity:

 This type of immunity results from vaccination or immunization.
  Vaccinations may be inactivated bacterial toxins (toxoids), killed microorganisms, live
but attenuated microorganisms or parts of microorganisms such as capsules.
 These substances can no longer cause disease, but can stimulate immune response

Passive Immunity
Passive immunity is resistance exhibited by the host, when ready-made antibodies or defensive
cells are introduced into the body.
This form of protection is passive, because the individuals own immune system does not make
antibodies or defensive cells against the disease producing agents or toxins.

Naturally acquired passive immunity:

This type of immunity involves natural transfer of antibodies from mother to her infant and also
from mother to fetus.
Certain antibodies (IgA) are passed from the mother to her nursing infants in breast milk,
especially in the first secretion called colostrum. The immunity in infants last as long as baby
feeds on breast milk.
During pregnancy, some of the maternal antibodies are also transferred through placenta to
the fetus. If the mother is immune to diphtheria, rubella or polio, the newborn will be
temporarily immune to these diseases as well.

Artificially acquired passive immunity:

 This type of immunity involves the introduction of antibodies into the body.
 These antibodies come from animal or person, who is already immune to the disease.
Examples:
1. Hyperimmune sera of animal or human origin. Common examples are
antitetanus serum (ATS), antidiphtheria serum (ADS), anti-gas-gangrene serum
(AGS), antisnake venom, etc.
2. Convalescent sera from patients very recently recovered from measles,
rubella, etc.

ADOPTIVE IMMUNITY
 Adoptive immunity is a special type of immunization, where the immunocompetent cells
are injected.
 At times, instead of whole lymphocytes, an extract of lymphocytes (transfer factor of
Lawrence) may be introduced as a therapeutic procedure in certain disease, such as
lepromatous leprosy, immunodeficiency diseases such as Wiskott-Aldrich syndrome,
disseminated malignancy, etc.
Local Immunity
 The mucosal immune system is composed of the lymphoid tissues that are associated
with the mucosal surface of the gastrointestinal, respiratory and the urogenital tracts.
These include mucosal-related Igs.

 The primary function of the mucosal immune system is to provide defense to the host at
mucosal surface, locally.

 The concept local immunity has gained importance in the treatment of infections, which
are either localized or where it is operative in combating infection at the site of primary
entry of pathogens

 Influenza (live-attenuated) vaccine is most effective when given in nasal spray.

Herd Immunity
 Herd immunity refers to an overall immunity exhibited by a community, which is
relevant in the control of epidemic diseases.
 When the herd immunity is satisfactory, epidemic does not occur. When it is less, the
prevention of epidemic can be done by mass immunization.