Principles of Immunology

Immunology is the branch of biology that deals with the study of the immune system, types,
components, its biological processes, physiological functioning, and its disorders. The immune
system generally functions by recognizing and destroying foreign antigens such as, disease causing
microorganisms. The immune system acts as the body’s defense system by protecting cells, tissues
and organs from invading infections. This is achieved through various lines of defense. Immunity,
therefore, is the ability of the body to resist infections that can damage the tissues and organs.
The term immunity is derived from the Latin word “immunis” (exempt), which originally referred
to the protection from legal prosecution offered to the Roman senators during their tenures in office.
This term was adopted subsequently to designate the naturally acquired protection against diseases,
such as measles or smallpox. It indicated that an individual can develop lifelong resistance to a certain
disease after having contracted it only once.
The cells and molecules responsible for immunity constitute the immune system, and their collec
tive and coordinated response to foreign substances is called the immune response. A fully functional
immune system can distinguish healthy tissue from unwanted substances. If it detects an unwanted
substance, it will mount an immune response, which is a complex attack to protect the body from
invaders like bacteria, viruses, and parasites. It also recognizes and removes dead and faulty cells.
However, sometimes when the immune system is weak or compromised, the host becomes
susceptible to infections such as; flu, fever or other serious conditions. This implies that the immune
system does not always get it right, hence Sometimes, it is unable to fight effectively e.g. due to a
person’s health conditions, which can affect how the system works.

Antigens

Antigens are substances that trigger an immune response in a host. They induce the immune system
to produce protection against them. Thus, antigens are substances that the body’s immune system
does not recognize, and therefore tries to attack them. Antigens can come from outside or inside the
body. Antigens that enter the body from outside through ingestion, inhalation or injection are known
as exogenous antigens, and they include; pathogens (Any portion of microorganisms, such as, surface
protein, capsule, toxins, cell wall can serve as antigens), chemicals, toxins, allergens, pollens e.t.c.
while endogenous are found inside the body, where cells and tissues, such as cancer cells, can express

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antigens that are recognized by the immune system. (This is so because although cancer cells are
derived from normal body cells, they undergo genetic and epigenetic changes that can lead to the
expression of new antigens or altered self-antigens, which are recognized by the immune system
leading to mounting of immune response against such cells).

It is pertinent to understand that naturally, antigens are present on normal body cells, these are
histocompatibility antigens, which are referred to as self-antigens or autoantigens, which help the
immune system to distinguish between self and non-self cells. However, there is a subtle distinction
between the autoantigens and self-antigens. Autoantigen refers to specific self-antigens that are
targeted by the immune system and mistakenly attacked, leading to autoimmune diseases, such as,
rheumatoid arthritis, lupus, type I diabetes e.t.c. Thus, in this case, the immune system mistakenly
identifies the autoantigens as foreign and mounts an immune response against them.

Hence, while all autoantigens are self-antigens, not all self-antigens are autoantigens.

Antigens, therefore serve as markers that the immune system recognizes. Generally, antigens are
made up of proteins, peptides, polysaccharides or other biomolecular substances. However, a
combination of lipid or nucleic acid with proteins or polysaccharides can form more complex
antigens. An example is lipopolysaccharides which are vital components of endotoxins produced by
gram-negative bacteria.

Generally, each antigen has its own unique shape that the immune system uses to identify it. An
antigen possesses distinct sites/specific region on its surface, termed an epitope or antigenic
determinant, which are recognized by antibodies. While paratopes are regions on an antibody that
recognize and bind to specific epitopes on an antigen. Antibodies produced against a specific antigen,
recognizes and interacts with the specific epitopes through antigen-binding sites, called paratopes to
trigger immune responses.

Haptens

Haptens are small foreign substances which are non-protein molecules, that require a carrier
molecule to induce an immune response. That means they cannot trigger immune response on their
own, but can only become antigenic when bonded to a larger carrier molecule. Examples of haptens
include; naturally occurring lactose, substances like, benzene arsonate or trinitrophenol. Also, many
drugs that cause allergic reactions e.g. penicillin, also act as haptens.

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Antibodies

Antibodies, also called immunoglobulins (Ig) are large Y-shaped glycoproteins produced by plasma
B-cells of the body’s immune system to identify and neutralize foreign substances. They are of
various types: IgG, IgA, IgM, IgE IgD. When an antigen comes in contact with a B cell, it causes the
B cell to divide and clone. These cloned B cells release millions of antibodies into the blood stream
and lymphoid system.

Components of the Immune System

The immune system refers to a collection of cells, chemicals and processes that function to protect
the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes
(organisms such as bacteria, fungi, and parasites), viruses, cancer cells, and toxins. The immune
system consist of different types of cells and organs that confer protection on the body against foreign
agents/antigens. The immune system consists of a range of components, which are classified as: cells,
organs and messenger molecules. All the cells and molecules of the immune system are distributed
in all the tissues of the body as well as lymphoid organs, which help to eliminate microbial infections,
decrease the growth of tumours and start the repairing process of damaged tissues.

1. Immune Cells (White blood cells/leukocytes) : The cells of the immune system are primarily
white blood cells (WBCs), and also known as leukocytes that circulate through the blood stream and
tissues to locate the site of infections and respond to injury or illness by attacking foreign substances
in the body. Once the white blood cells arrive, they produce antibodies which attach to the invader,
thus fighting it. her to protect against infections and disesases. White blood cells are constantly
looking for pathogens, and when they find one by locating the site of infection, they begin to send
signals to other white blood cells about their location, thereby multiplying, once sufficient, they attack
the invader by producing antibody proteins to attach to the antigen and destroy it. White blood cells
are formed in the soft tissue inside the bones (bone marrow).
They are of various types as follows:

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Fig 1: Classification of White Blood Cells

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There are two main types of leukocytes, or white blood cells: Granulocytes and agranulocytes,
however, the agranulocytes comprise of two types; lymphocytes and monocytes.
Granulocytes
Granulocytes are the most common type of WBCs and they include; neutrophils, eosinophils and
basophils. They are a type of WBCs that contain large granules in their cytoplasm as well as a
nucleus. There is a unique nuclear morphology in granulocytes and as a result of their varying nuclei
shape, they are known as polymorphonuclear leukocytes, because their nuclei are divided into
multiple lobes/sections. They are produced in the bone marrow. Granulocytes are phagocytes which
are capable of ingesting foreign substances. The granules of enzymes which they possess enables
them to digest microbes, hence they do not release antibodies like the lymphocytes. Approximately
60% of the white blood cells are granulocytes. They are critical to the body’s antimicrobial and
inflammatory responses. Granulocytes are involved in innate immunity and play a role in
phagocytosis, release of granules that contain antimicrobial peptides and enzymes, as well as
producing effector molecules such as; cytokines, histamine, chemokines, and other factors. The
diameter of these cells is close to 12-16 micrometers, which is larger than red blood cells.
Neutrophils: These are the most abundant granulocytes out of the immune cells constituting about
60% to 70 % of all white blood cells. Neutrophils normally do not leave the bone marrow, where
they are produced until they are mature. Once neutrophils receive suitable signals, they leave the
blood to arrive at the site of infection, however, they do not revert to blood but turn into pus cells
and die. They migrate early to the site of infection /inflammation. They are phagocytic, meaning
they can ingest and destroy microbes. They also release antimicrobial proteins from their granules
to combat infections. They kill pathogens but also die as a result. They play a crucial role in immune
response and tissue repair.

Eusinophils: These account for close to 1% of the circulating WBCs. They possess a kidney shaped
nucleus that is lobed. Their granules contain a unique protein which is crucial for killing pathogens.

Basophils: These account for close to 0.5% of the circulating WBCs and the least common type of
granulocyte. Their nucleus is lobed into 2 lobes.

Mast cells: These are also a type of granulocyte found in tissues wherein the granules are richly
supplied with histamine and heparin.

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Agranulocytes
Agranulocytes typically possess larger nuclei than the other types of white blood cells, because they
lack cytoplasmic granules. Their functions are similar to those of the granulocytes in that they
mediate immunological response to foreign substances. However, they release antibodies that
directly attach to invaders instead of releasing granules. They are categorized as: monocytes and
lymphocytes.
Monocytes: They are the largest leukocytes, measuring between 15mm to 22m in diameter, which is
approximately twice the size of red blood cells. They originate in the bone marrow and circulate in
the blood stream comprising of about 5-10 % of white blood cells. They begin their life cycle in the
bone marrow and upon maturity, they enter the blood stream and tissues to defend the body against
foreign invaders. They also do not produce or release antibodies. Monocytes are involved in
phagocytosis, presenting antigens to T cells and producing inflammatory cytokines.

Monocytes differentiate into 2 types of cells: dendritic cells and macrophages. Dendritic cells reside
in superficial tissues, such as tissues just beneath the skin, the linings of the nose, lungs, stomach and
intestine. They are responsible for alerting other cells to help fight infection. When antigens invade
the tissues, dendritic cells locate them and release proteins called, cytokines that notify other white
blood cells to come to the site of the infection and destroy the invader. Macrophages are cells on the
front line. They surround the invader, ingesting and killing it with toxic enzymes. Macrophages also
help to remove dead cells from body tissues and bloodstream. Hence, macrophages help to clean
up after a response by removing pathogens, dead neutrophils and other debris.

Lymphocytes

Lymphocytes are a type of white blood cells that play a central role in the adaptive immune response.
They are responsible for recognizing and responding to specific antigens. They account for about
20-30% of all leukocytes. Lymphocytes are characterized by; small size, large nucleus, minimal
cytoplasm and ability to recognize and respond to specific antigens. Lymphocytes help the body
remember previous invaders and recognize them if they return to attack again. Lymphocytes begin
their life in bone marrow from where they circulate in the blood and lymphatic system, patrolling
for signs of infection or disease. They are a critical component of the immune system, primarily
classified into 3 main types; B lymphocytes (B cells), T lymphocytes (T cells) and natural killer cells

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(NK cells). B lymphocytes are a type of white blood cells which mature in the bone marrow and
produce antibodies that target specific antigens. B cells have receptors that test the antigen to see if
they are fit together, like a lock and key. Once it’s a fit, B cells make chemicals called antibodies that
possess the same shape to recognize the antigen. Upon activation by an antigen, B cells differentiate
into plasma cells which secret large quantities of antibodies and memory B cells which provide long
term immunity by responding quickly to future encounters with the same antigen. T cells originate
in the bone marrow and mature in the thymus, playing key role in identifying and responding to
pathogens and cancer cells. T cells can be classified into; helper T cells, cytotoxic T cells, regulatory
T cells and memory T cells. Natural killer cells comprise about 5 – 20 % of circulating lymphocytes
in humans, playing crucial role in recognition and elimination of virus infected cells and tumour cells
without prior sensitization. They are able to distinguish between healthy and abnormal cells by
detecting the presence or absence of major histocompatibility complex class I molecules. They
release cytotoxic granules once they encounter an antigen. These granules contain perforin and
granzymes, thereby causing apoptosis in the infected or malignant cells.

2. Lymphoid Organs

Lymphoid organs are specialized tissues and organs that play crucial role in the production,
development, maturation and function of immune cells. They are basically classified as: primary
lymphoid organs and secondary lymphoid organs.

Primary lymphoid organs

Bone marrow: the bone marrow is the site of hematopoiesis, where immune cells are produced. It
is the Soft tissue in the center of the bones that produces blood cells.

The thymus: A gland behind the breastbone, near the heart where, where white blood cells known
as T lymphocytes mature, particularly during childhood. It is thus the site of T cell maturation.

Secondary lymphoid organs

Lymph nodes: These are small, bean-shaped glands throughout the body, especially in the neck,
underarms, groin, and abdomen. Lymph nodes trap pathogens and other foreign substances, and

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prevent them from spreading to other parts of the body. Immune cells gather in lymph nodes and
react when antigens are present. This can lead to swelling.They filter lymph fluid carrying white
blood cells and other substances. Lymph nodes activate immune responses by presenting antigens
to T and B cells to coordinate immune response. They also store immune cells which can be quickly
deployed to fight infections.

The spleen: An organ at the upper left of the abdomen where immune cells gather and work. serves
as a filter for the blood, removes old and damaged red blood cells, removes infectious agents and
uses them to activate lymphocytes. It also acts as a reservoir for immune cells.

Tonsils and adenoids: These are located in the throat and they trap pathogens entering through the
mouth and nose and help filter these substances.

Skin: This is the largest organ in the body which acts as a physical barrier and contains immune cells
that respond to infections.

Appendix: This is becoming increasingly recognized as an important organ in the immune system
particularly in relation to gut health. It is a small finger-like lymphoid organ attached to the large
intestine. They contain a high concentration of lymphoid cells which protects the gut from
pathogens.

Fig 2: ANATOMY OF THE IMMUNE SYSTEM

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Fig 3: The Immune System

Types of Immunity

There are basically 2 types of immunity, namely; innate and adaptive immunity. It is made up of
the innate (general) immune system and the adaptive (specialized) immune system. These two
systems work closely together and take on different tasks.

Innate Immunity
Innate immunity is the resistance that an individual possesses by birth. Hence every individual is
born with innate immunity, otherwise known as natural immunity. It is therefore a type of general
protection against foreign substances. Innate immunity is the body’s first line of defense which does
not have to be learned. It is an antigen-independent (non-specific) defense mechanism that is used
by the host immediately or within hours of encountering an antigen. It responds in the same way to
all pathogens and foreign substances, which is why it is referred to as the "non-specific" immune
system. The innate immune response has no immunologic memory and, therefore, it is unable to
recognize or “memorize” the same pathogen should the body be exposed to it in the future. Hence,
the innate immune system can’t always stop germs from spreading in the body.

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Innate immunity may be classified as (a) individual immunity, (b) racial immunity, and (c) species
immunity. Individual immunity denotes resistance to infection, which varies within different
individuals in the same race and species and is genetically determined. Racial immunity denotes a
difference in susceptibility or resistance to infection among different races within same species.
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.
Innate (natural) immunity is the body’s first line of defense against harmful substances/antigens and
it is a natural, nonspecific and immediate response that is present at birth,
Components and processes of the Innate Immune System
The innate immune system utilizes several components/barriers that participate in defense against
invaders with each of these defenses having their own non-specific host-defense mechanisms.

1. Anatomical barriers or defense: All outer and inner surfaces of the human body are a key part of
the innate immune system. The anatomical barrier of innate immunity involves mechanical,
chemical and biological barriers that act as the first line of defense against the pathogen.

Mechanical / physical barriers: Mechanical barriers or physical barriers prevent the entry of pathogens
into the body. These barriers include; skin, mucous membranes and epithelial cells, which all
provide physical barrier against pathogens. The skin is the first mechanical barrier that makes entry
of pathogens difficult owing to the epidermis. The outermost layer of the skin, called the epidermis,
is composed of multiple layers of epithelial cells (keratinocytes, melanocytes e.t.c.) which are tightly
packed and connected together to provide strong adhesion thereby making it difficult for pathogens
to penetrate. These help to maintain the integrity of the skin. Additionally, skin has an acidic pH
ranging from 4.5 to 5.5 owing to several factors, such as sweat, sebum e.t.c.

Chemical barriers: Chemical barriers block entry of pathogens at body openings and inner body
surfaces. Examples of chemical barriers include sweat, breastmilk, mucus, saliva, tears, semen,
vaginal secretion e.t.c. Sweat contains lactic acid, urea and other acidic components that contribute
to the skin’s acidic pH which help to prevent microbial proliferation. Sebum produced by the skin’s
sebaceous glands, contains fatty acids and other acidic compounds that help maintain the skin’s

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acidic pH and prevent pathogens. Natural moisturizing factors (NMF) produced by the skin’s
keratinocytes contain amino acids, lactic acids and other acidic compounds. Semen has zinc which
is intolerable by pathogens. The digestive juices produced in the stomach also kill foreign invaders.

Biological barriers: There are a number of harmless bacteria that live inside our urinary, gastrointestinal
and reproductive tracts that make the environment inhospitable for pathogens or harmful bacteria
to survive in our body.

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