The Immune System

Submitted To: DR. Sabeen

Submitted By: Imran Haider,

Mubeen Akram &

Muhammad Ikram

University of Okara

Microbes & Pathogenicity

BANO RAI
MPhil
[Type the Biochemistry
company name]
[Pick the date]
 CONTENTS:
 Overview/Key Objective
 The Immune System
 Components of Immune System
 The Innate Vs. Adaptive Response
 Inflammation
 Adaptive Immunity – Humoral and Cellular Immunity
 Adaptive vs. Anergic Immune Functionality
 Antibody
 Conclusion
 References

Module Overview:

Immuno-oncology is an evolving field of study on the role of the immune system in cancer
initiation and growth. This introductory module describes the purpose of the human immune
system, components of the immune system, and innate and adaptive immune responses.

Module Objectives:

Upon completion of this module, we should be able to:

 Describe the purpose of the immune system

 Identify the components of the immune system

 Differentiate between the innate and adaptive immune response

 List the goals of inflammation

 Differentiate between the humoral and cellular mechanisms of adaptive immunity

The Immune System:

The immune system is the body’s biological defense system. The main purpose of the
immune system is to identify self from non-self. The immune system identifies and defends
the body from non-self-proteins, viruses, bacteria, fungi, parasites and other pathogens.
Occasionally, the immune system can make a mistake and attack itself, resulting in
autoimmune disorders. The immune system comprises many different cells, organs, and
tissues that work together to combat infection, cellular damage and disease. Cells of the
immune system include white blood cells, such as macrophages, as well as T and B
lymphocytes. The main lymphoid tissues of the immune system are the thymus and the bone
marrow.

Components of the Immune System:

Organs and Tissues:

The immune system consists of many parts that work together to defend the body against
invaders. The primary parts of the immune system include the bone marrow and thymus. The
bone marrow is extremely important to the immune system because all the body’s blood cells
(including T and B lymphocytes) originate in the bone marrow. B lymphocytes remain in the
marrow to mature, while T lymphocytes travel to the thymus.

Figure1. Parts of the Immune System.

The thymus is a bi-lobed gland located above the heart, behind the sternum and between the
lungs. The thymus is only active through puberty, and then it slowly shrinks and is replaced
by fat and connective tissue. The thymus is responsible for producing the hormone thymosin,
which in turn aids in the production of T cells. While in the thymus, T cells multiply, acquire
different antigen receptors, and differentiate into helper T cells and cytotoxic T cells. Various
proteins (e.g., CD4, CD8) are expressed on the T cell surface. The thymus will have produced
all the T cells an individual needs by puberty

After the T and B lymphocytes have matured in the thymus and bone marrow, they then
travel to the lymph nodes and spleen where they remain until the immune system is activated.
Lymph nodes are located throughout the body. The spleen is located in the upper left area of
the abdomen, behind the stomach, and under the diaphragm. The main function of the spleen
is to filter the blood. Healthy red blood cells easily pass through the spleen; however,
damaged red blood cells are broken down by macrophages (large white blood cells
specialized in engulfing and digesting cellular debris, pathogens and other foreign substances
in the body) in the spleen. The spleen serves as a storage unit for platelets and white blood
cells. The spleen aids the immune system by identifying microorganisms that may cause
infection.

In addition to the lymph nodes and spleen, mucosal associated lymphoid tissues (MALTs)
and gut associated lymphoid tissues (GALTs) play a vital role in the immune system,
although they are considered to be part of the lymphatic system. MALTs are lymphoid tissues
found in parts of the body where mucosa is present, such as the intestines, eyes, nose, skin
and mouth. They contain lymphocytes and macrophages that defend against pathogens
attempting to enter from outside the body. GALTs are lymphoid tissues found in the mucosa
and sub mucosa of the gastrointestinal tract, tonsils, appendix and Peyer’s patches in the
small intestine.

Immune Cells:

Many cells work together as part of the innate (non-specific) and adaptive (specific) immune
system. Immune cells are sometimes called white blood cells or leukocytes.

Granulocytes are a type of leukocyte that contains granules in their cytoplasm containing
enzymes. Neutrophils, basophils and eosinophils are types of granulocytes. Neutrophils are
considered the first responders of the innate immune system. Neutrophils and macrophages
circulate though the blood and reside in tissues watching for potential problems. Both cells
can “eat” bacteria, as well as communicate with other immune cells if an issue arises.

Figure2. Blood Cells

Cells of the adaptive immune system (also called immune effector cells) carry out an immune
function in response to a stimulus. Natural killer T lymphocytes and B lymphocytes are
examples of effector cells. For example, activated T lymphocytes destroy pathogens via cell-
mediated response. Activated B cells secrete antibodies that aid in mounting an immune
response. Effector cells are involved in the destruction of cancer.

Non-effector cells are antigen-presenting cells (APCs), such as dendritic cells, regulatory T
cells, tumor-associated macrophages and myeloid-derived suppressor cells. Non-effector cells
cannot cause tumor death on their own. Non-effector cells prevent the immune action of the
effector cells. In cancer, non-effector cells allow tumors to grow.
 Figure3. Cytotoxic T cell

Glossary of Immune System Components:

 Antigen any substance that is able to cause an immune response in the body.
Examples include bacteria, chemicals, toxins, viruses and pollen.
 Antigen presenting cell (APC) Cells, such as macrophages, dendritic cells
and B cells that can process protein antigens into peptides.
 Antibody (Ab) Special proteins created by white blood cells that can kill or
weaken infection-causing organisms. Antibodies travel through the blood stream
looking for specific pathogens.
 Basophil A basophil is a type of phagocytic immune cell that has granules.
Inflammation causes basophils to release histamine during allergic reactions.
 B lymphocyte A B lymphocyte is a type of white blood cell that develops in the
bone marrow and makes antibodies.
 Memory B cell B cells that are long lived and remember past antigen exposure.
 Plasma B cell Activated B cells that produce antibodies. Only one type of
antibody is produced per plasma B cell.
 Cytokine A type of protein that impacts the immune system by either ramping it up
or slowing it down.
 Dendritic cell dendritic cells are antigen-presenting cells (APCs). Antigen is
combined with major histocompatibility complex and presented on a dendritic cell to
active T and B lymphocytes.
 Eosinophil An eosinophil is a type of immune cell (leukocyte, or white blood cell).
They help fight infection or cause inflammation.
 Granulocyte Granulocytes (including eosinophils, neutrophils and basophils)
are a type of white blood cell that releases toxic materials, such as antimicrobial
agents, enzymes, nitrogen oxides and other proteins, during an attack from a
pathogen.
 Human leukocyte antigens Human version of the major histocompatibility
complex (MHC).
 Natural killer (NK) cell the primary effector cell of innate immunity; the first
responders of the immune system. They interact with signals from other cells
(activating and inhibitory).
 T lymphocyte (also called T cell) Cytotoxic T cells are the primary effector
cells of adaptive immunity.
 Memory T cell Derived from activated cytotoxic T cells, memory T cells are
long-lived and antigen-experienced. One memory T cell can produce multiple
cytotoxic T cells.
 Helper T cell Helper T cells secrete cytokines that help B cells differentiate into
plasma cells. These cells also help to activate cytotoxic T cells and macrophages.
 Regulatory T cell Regulatory T cells (or Tregs) help to suppress the immune
system.
 Lymphocyte Lymphocytes are immune cells found in the blood and lymph tissue.
T and B lymphocytes are the two main types.
 Macrophage Macrophages are large white blood cells that reside in tissues that
specialize in engulfing and digesting cellular debris, pathogens and other foreign
substances in the body.
 Mast cell Mast cells release histamine and help to get rid of allergens.
 Monocyte Large white blood cells that reside in the blood stream that specialize in
engulfing and digesting cellular debris, pathogens and other foreign substances in the
body. Monocytes become macrophages.
  Neutrophil A type of white blood cell, granulocyte, and phagocyte that aids in
fighting infection. Neutrophils kill pathogens by ingesting them.
 Phagocytes It eats up pathogens by attaching to and wrapping around the
pathogen to engulf it. Once the pathogen is trapped inside the phagocyte, it is in a
compartment called a phagosome. The phagosome will then merge with a lysosome
or granule to form a phagolysosome, where the pathogen is killed by toxic materials,
such as antimicrobial agents, enzymes, nitrogen oxides or other proteins.

The Innate vs. Adaptive Immune Response

The first line of defense against non-self-pathogens is the innate, or non-specific, immune
response. The innate immune response consists of physical, chemical and cellular defenses
against pathogens. The main purpose of the innate immune response is to immediately
prevent the spread and movement of foreign pathogens throughout the body. Examples are
skin, hair and cough mucous membrane

The second line of defense against non-self-pathogens is called adaptive immune response.
Adaptive immunity is also referred to as acquired immunity or specific immunity and is only
found in vertebrates. The adaptive immune response is specific to the pathogen presented.
The adaptive immune response is meant to attack non-self-pathogens but can sometimes
make errors and attack itself. When this happens, autoimmune diseases can develop (e.g.,
lupus, rheumatoid arthritis). E.g. Pus, swelling and redness

The hallmark of the adaptive immune system is clonal expansion of lymphocytes. Clonal
expansion is the rapid increase of T and B lymphocytes from one or a few cells to millions.
Each clone that originates from the original T or B lymphocyte has the same antigen receptor
as the original and fights the same pathogen.

While the innate immune response is immediate, the adaptive immune response is not.
However, the effect of the adaptive immune response is long-lasting, highly specific, and is
sustained long-term by memory T cells.

Inflammation:
Inflammatory response plays a critical role in immunity. When tissues are damaged, the
inflammatory response is initiated, and the immune system becomes mobilized. The immune
cells of the innate immune system (i.e., neutrophils and eosinophils) are the first recruited to
the site of tissue injury or damage via blood vessels and lymphatic system, followed by
macrophages.

If the damage occurs near the surface of the skin, redness and swelling may be visible. Pain
and warmth are also symptoms of inflammation.

The goals of the inflammatory response are to:

1. Prevent initial establishment of infection or remove damaged tissue.

2. Prevent the spread of infection or repair damaged tissue.
3. Recruit effector cells if the immune cells of the innate immune system cannot control
infection or repair damaged tissue.
4. Mobilize effector cells (T and B lymphocytes).

Adaptive Immunity – Humoral and Cellular Immunity:

There are two main mechanisms of immunity within the adaptive immune system – humoral and cellular.

Humoral immunity is also called antibody-mediated immunity. With assistance from helper T cells, B cells
will differentiate into plasma B cells that can produce antibodies against a specific antigen. The humoral
immune system deals with antigens from pathogens that are freely circulating, or outside the infected cells.
Antibodies produced by the B cells will bind to antigens, neutralizing them, or causing lysis (dissolution or
destruction of cells by a lysin) or phagocytosis.

Cellular immunity occurs inside infected cells and is mediated by T lymphocytes. The pathogen's antigens
are expressed on the cell surface or on an antigen-presenting cell. Helper T cells release cytokines that help
activated T cells bind to the infected cells’ MHC-antigen complex and differentiate the T cell into a
cytotoxic T cell. The infected cell then undergoes lysis.

Activated vs. Anergic Immune Functionality:

The activated immune system is one in which the white blood cells are actively mounting a
response to an antigen or pathogen.
Anergy, or immune intolerance, occurs when the there is a failure to mount a complete
immune response to an antigen. Anergy can occur in both T and B lymphocytes.

Antibody:
An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced
mainly by plasma cells that is used by the immune system to neutralize pathogens such as
pathogenic bacteria and viruses. 

Figure4; Antibody

Structure:

1. Fab

2. Fc
 3. Heavy chain

4. Light chain

5. Antigen binding site

6. Hinge region

Fab Antigen binding filament is recombinantly produced cysteine protease that digests in
the hinge region of antibodies. FC The fragment crystallizable region (Fc region) is the tail
region of an antibody that interacts with cell surface receptors called Fc receptors and
some proteins of the complement system. This property allows antibodies to activate
the immune system

There are two types; Paratope and Epitope

A paratope, also called an antigen-binding site, is a part of an antibody which recognizes

and binds to an antigen. It is a small region (of 5 to 10 amino acids of the antibody's Fc
region, part of the fragment antigen-binding (Fab region), and contains parts of the
antibody's heavy and light chains. Each arm of the Y shape of an antibody monomer is tipped
with a paratope, which is a set of 6 complementarity-determining regions (CDR loops) - 3 of
each light and heavy chain extending from the fold of antiparallel beta sheets.

The part of the antigen to which the paratope binds is called an epitope. This can be
mimicked by a mimotope. The figure given on the right hand side depicts the antibody
commonly found on a B leukocyte. The engraved inner portions of idiotype (encircled region
no.5 in the above diagram) are the paratope where the epitope of the antigen binds.

B Cells:
B cells of the adaptive immune system, Antibodies can occur in two physical forms,

1. A soluble form in the blood plasma. 2. A membrane bound form - as the B-cell

receptor (BCR).

The BCR help- differentiation into either antibody factories called plasma cells or memory B
cells. Soluble antibodies are released into the blood and tissue fluids, as well as
many secretions to continue to survey for invading microorganisms.
Classes/Isotypes
 The five different types of Fc regions allow antibodies to be grouped into
five Isotypes.

o IgG

o IgM

o IgA

o IgE

o IgD

 The different suffixes of the antibody isotypes denote the different types of heavy
chains the antibody contains, with each heavy chain class named alphabetically: α
(alpha), γ (gamma), δ (delta), ε (epsilon), and μ (mu). This gives rise to IgA, IgG,
IgD, IgE, and IgM, respectively.

Figure6;Multiple Antigen Molecule

Some antibodies form complexes that bind to multiple antigen molecules. Antibody isotypes

not found in mammals
  IgY- Found in birds and reptiles
 IgW- Found in sharks and skates

Conclusion:
Immunity works in a co-ordinated fashion to respond to numerous threats from the
environment. It is essential to good health, from the moment of conception, when the
mother’s immune system starts protecting the growing baby, until old age. As medicine has
progressed, physicians have slowly learned how to apply an understanding of the
fundamentals of immunology to reinforce and repurpose the immune response, providing
greater protection against infection or targeting cancers. Immunotherapy has been improving
human health since Edward Jenner coined the term vaccination and it will have much more to
contribute in the future.

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