9.

8 Cancer Biology
Cancer is a disease that involves heritable defects in cellular
control mechanisms that result in the o
of invasive trumors capable of releasing cells that can spread
the disease to ormation
distant sites in the bodton
body. Cancer
has four important characteristics:

1. Uncontrolled cell growth

2. Loss of cell differentiation (specialization)
3. Invasion of normal tissues
4. Metastasis (spread to multiple sites).
The common symptoms of cancer are:

1. Change in bowel or bladder functions

2. A sore throat does not heal
3. Unusual bleeding or
4. Thickening or
discharge
lump in any tissue
5. Indigestion (chronic) or
dificulty
6. Obvious change in a wart or mole
in swallowing

7. Nagging hoarseness or
cough
Types of Cancers
Based on the origin, cancer can be of following types:
1. Carcinoma: If it originates from epithelial cells, it is called
cinomas. For example, squamous cell carcinoma carcinoma. 85% of total cancers are car-
(cancer of the epithelial sheets covering the
channel) or adeno-carcinomas (cancer of an cavity or
2. Sarcoma: It is the epithelium that
originates in glandular tissue).
malignant tumors of connective tissue. They constitute about 2% of the total
cancers. For
example, fibrosarcoma (hbroblasts), liposarcoma
(osteoblasts). (adipocytes) and osteosarcoma
3. Leukaemia: It is the
malignant tumor of stem cells of haemopoietic tissues. They are also called
tumors as they affect the blood cells. They constirute about 4% of liquud
4. Lymphoma: It is thetotal cancers.
malignant tumor of
a
Forexample, Burkitt lymphoma. 4% of secondary lymphoid organs such as spleen and lymph nodcs.
the reported cancers are
5. Myeolma: It is rype of cancerous tumor. It is also known
a lymphomas.
as multiple
Cancerous growth of plasma cells, myeloma or Hodgkin's diseasc
antibodies. type of white blood cell
a
made in the bone marrow that
produce
 n heredity, they can be familial (hereditary) and others are
sporadic (non-hereditary.
Causes of Cancer
h e
arious agents that cause cancer include
v a r i o u s .
chemicals, radiations and a
variety of DNA- and RNA con-
aining viruses. These agents act by altering the genome. These are discussed below in detail.

Chemicals: Carcinogenic chemicals, such as those present in soot or cigarette smoke, are
mutagenic or are converted to mutagenic compounds by cellular enzymes and are main either directly
causes of lung
cancer.

Radiation: Both ionizing X-rays and non-ionizing ultraviolet (UV) radiation (leading cause ofskin
cancer, cause DNA damage.
2Oncogenic viruses: They are cancer causing viruses and are broadly divided into two large groups
depending on the type of nucleic acid found within the mature virus particle:

(a) DNA viruses: DNA viruses have DNA in the mature virus
tumor
particle. Some
polyoma virus, simian virus 40 (SV40), adenovirus and herpes-like viruses. examples are
(b) RNA viruses or retroviruses: RNA viruses have RNA in the
tumor
virus
similar in structure to HIV.
mature particle. They are
4. Genes: The genes present in the normal cells may get triggered under some conditions and cause
cancer. This is because the products of these genes are involved in control of the cell cycle, intercellular
adhesion and DNA repair. They are divided into two broad categories:
(a) Tumor-suppressor genes: They encode proteins that restrain cell growth and prevent cells from
becoming malignant. In human cancer, the product of tumor suppressor gene may be able to sup-
press cancer formation by several different mechanisms.
(b) Oncogenes: They encode proreins that promote the loss of growth control and the conversion of a
cell to a malignant state. Cancer is caused by mutant copies (alleles) of these genes, whose products
may not be regulated.

Cancer Detection and Diagnosis

Timely detection and diagnosis can prevent cancer dissemination from the origin. The majority of cancer
deaths are due to the dissemination oftumor cels from the primary rumor and their growth at distal organs,
that is, treatment unlikely to succeed once a local benign lesion metastasizes.
Cancer detection is based on:
1. In biopsy, a piece of the suspected tissue cut into thin sections and isstained with haematoxylin and
cosin (H&E) and examined under microscope (histopathological evaluation) to see rapidly dividing
cancer cells by a pathologist.
. Blood and bone marrow tests are done for leukaemias.
P'SA and colonoscopy are done for breast, cervical, prostrate and
colon
3. Mammography, Pap smear test,
cancers, respectively.
such as Her-2/neu, EGFR, BRCAI and BRACA2 generally
4. Antibodies against cancer specific antigens
cancers of different types.
are used for detection of
uses magnetic held and non-ionizing radia
resonance imaging (MRI)
5. Non-invasive in vivo magnetic
tions to study the changes
in living tissue.
tomography (SPECT) generates a 3D image of the organ.
6. Single photon emission computed
identihcation of genes that may cause cancer can be
Molecular biology techniques involving
employed.
9.7 Immunology and Immunity
the capacity to recognize and defend ao
immunology is the study of immunity, which refers
to
against infec
tious agents and other foreign substances.
iS innate when it acts against anu i
Susceptibility is vulnerability to infectious agents. Immunity
agent and adaptive when it acts against a particular
infectious agent. Immunology is the study ious
of fecious
immuniy. The immune system is the body system
that provides the host with specific immuni.
to
specihc
lar infectious agents. particu-
Types of Immunity
Innate Immunity
Innate immunity provides non-specific, hereditary detense and protection against many pathogene.
thout
prior exposure. It is present at the time of birth. It is accomplished by:
1. Physical barriers: Skin on our body is the main barrier which prevents entry of the microoroan:c
Mucus coating of the epithelium lining the respiratory, gastrointestinal and urogenital tracts also i
in
trapping microbes entering our body.
2. Physiological barriers: Acid in the stomach, saliva in the mouth, tears trom eyes-al prevent micr
bial growth.

Adaptive Immunity
Acquired adaptive immunity provides specific, non-hereditary defense and protection after exposure to
specific pathogen. It is gained after birth and is due to virtue of lymphocytes. It can be of two types
1. In active immunity, an individual's own immune system makes antibodies.
2. In passive immunity, ready-made antibodies are introduced into the body through vaccination.
 OGY AND IMMUNITY
1/A1UN
.167
Tissues ofthe Immune System
C e l l sa n d T i s s

em cell,
oictic stem cell can give rise to two ditterent
Ahematopor progenitor cells (Figure 9):
eloid progenitor cell: It can
enitor cell:, differentiate into most of the
nd neutrophils), macrophages, or dendritic cells. various blood cells (c.g,, red blood cells,
ophi ogenitor cell: It can difterentiate into of the any
2. Lymphoic
various types of
or B
cels). lymphocytes (NK cells,
Tcells,
Stem Cell

Lymphoid Myeloid
Stem Cell
Progenitor

T Cell Natural Killer

B Cell
Progenitor Cell Granulocytes
Progenitor

THelper Cel Neutrophil Eosinophil Basophil Mast Cell Monocyte

PlasmaCell
L
T Cytotoxic
Memory Cell Cell
Dendritic Cell

Macrophages

Figure 9 Differentiation of a hematopoietic stem cell of the

bone marrow.

Their
Leucocytes are defensive cells that are important to both innate and acquired immune responses.
functions have been discussed in Table 1.
Table 1 Functions of Leucocytes
Functions
Cell Types
Bcell specialized to recognize a specific foreign antigen.
Precursor of plasma cell,
to the production of
antibodies directed against a spe-
Biochemical factory devoted
Plasma cell
ciic antigen. in the lym-
stimulation by the immune system and remains
Memory cel Remembers the original
phoid tissue. achieve
the immune system to
in
Helper T cell Assists the immune process by helping other cells
an efhicient immune response
cells.
kills infected body cells recruited by helper T
ytotoxic T cell Detects and
membrane receptors for IgG, so they show antibody depen-
Natural killer Natural killer cells have neutralize virus
Natural to attack and
(ADCC). They help
oell (NK) dent cell mediated cytotoxicity
infected and tumor cells.
and membranes against infection
and guard blood, skin
mucus

Neutrophil Phagocytic (Continued

 168 CHAPTER MICROBIOLOGY
AND TS INDUSTR A As..
CATIONS
Table 1 Continued
Cll Types Functions

Help in detoxifying foreign substanoces and help in turning off intiammatore.

Eosinophil tions by releasing histamine-degrading enzymes trom their granules reac
Release histamine. a chemical that helps in initiating the inttammatory response
Basophil nse.
Mast cell Initiator of the intammatory response which aids the arrival of leucocytes at a
infection, secretes histamine and is important in allergic response.
site of

Monocyte They are involved in innate immunity.

Dendritic cells They have long membrane extensions that resemble the dendrites of nerve celk
(DC) hence their name. These cels are phagocytic and are involvod in initiating the
acquired immunity.
Macrophage The body's first cellular line of detense; also serves as antigen presenting cell to B
and
nd
T cells and engulfs antibody-covered cells.

Dual Nature of the Immune System

The dual roles of the immune system consist of humoral immunity, which is carried out mainly bv B Grll
and plasma cels, and cell-mediated immunity, which is carried out mainly by certain T cels.

Humoral Immune Response or Antibody Mediated Immune System (AMIS)

These immune responses is mediated by B cells (B lymphocytes), which on activation
differentiate into
plasma cells secrete antibodies. It is also known as antibody-mediated immune system or
esponse. It
depends on rwo main factors:
1. The ability of B cells to recognize specihc
antigens.
2. Their ability to initiate responses that the
protect body against foreign agents. The most common
response is the production of antibodies that will inactivate an antigen and lead to destruction of infec
tious organisms.

Antigens and Antibodies

1. An antigen is a foreign substance that can elicit a specihc immune response. Most antigens are pro-
teins, but some are polysaccharides, nucleoproteins, or glycoproteins.
2. Each antigen has several epitopes, or antigenic determinants.
3. An antibody, or immunoglobulin, is a
prorein produced in response to the presence of an antigen.
Antibodies bind to epitopes on the antigen to destroy it.
They are Y-shaped protein molecule called a monomer. Each monomer is made up of four
polypeptide
chains-two identical light (L) chains and wo identical heavy (H) chains (Figure 10). The chains are held
together by disulphide bonds. The chains have constant and variable regions. The variable regions of each
chain have a particular shape and charge that enable the molecule to bind a
binding site (ABS). particular antigen called antigen

Cell Mediated Immunity or Cell-Mediated Immune

System (CMIS)
It is mediated by T lymphocytes which once activated themselves reaches to site of infection and acts
antigens. Helper T lymphocytes activate B cells and killer T cells. Killer T cells kills the antigens. Memory
on
cells are also present which retain the memory of antigen which has entered in our body, so that in turure,
 Heavy ehaina, Antigen
binding ste

Light chain

Fab fragment
Oo
Carbohydrate
Disulphide bond
Complement
binding site

Constantregions
Site of bonding- Fc fragment
of lightand
h e a v yc h a i n s
to macrophages
Ability to croSs
placenta

Figure 10 Structure of antibody.

antibod-
recognizes it and acts on it. There are specific
enters, our immune system quickly
he same antigen antigen.
T cells fora particular
iesand specihic
Vaccination a n d Immunization
to enable the body's
administration of an antigenic material (called vaccine)
immunization is
refers to the On the other hand,
against 1 puticular pathogen.
Vacination Hence, the rwo
to develop immunity fortified against an agent.
mune system becomes is a
individual's immune system whereas immunization
which an vaccine,
the process by reters to administration
only
of a
m a n n e r and

are
vaccination
ditterent -

be achieved by
active or passive
processes Immunization can
antibodies.
process by which body produces
torm of
immunization.

vaccination is an active
Immunization
disecase.
Active Immunization as the one that occurs during a
induces the same response cells.
I. Active
immunization
defenses and memory
develop specific be made from live,
attenu-
to
immune system toxoids. Vaccines can
challenges the vaccines and inactivating
is conferred by Toxoids are made by
. Active immunization or a toxoid.
parts of organisms,
ated organisms, dead
organisms, the haz.
tOxins. diseases nearly always outweigh the
against life-threatening
inc.
is lower than
immunization
their incidence
.The benefts of active serious side ettects,
but
can cause
Reactions to vaccines
ards. themselves.
dences of the diseases

Passive Immunization mechanism as natural passive

transter of ant1bodies.
asive
immunization occurs by the same
 170 CHAPTER 9/MICROBIOLOGY AND ITS INDUSTRIA
A

2. Passive is conferred by antisera such immune globul

APPLI C AT
oulin (gamma glob ACATIONS
immuniy as serum

immune or convalescent sera, and antitoxins.

T h e benefits of passive immunization are limited to providing only temporary Dro.
bulin), hype
ettects are mainly
allergic
in nature. rotectio the side
Future of Immunization
.Subunit vaccines produce fewerside effects than whole-cell killed vaccines and offer
do attenuated vaccines. offer greater safer
2. Recombinant DNA vaccines contain genes for antigens of pathogens inserted into than
organisms genomes and are very safe.
3. There is
hope for an infuenza vaccine that will protect against all strains offu with one. 0genic
shot.
9.8 Cancer Biology
Cancer is a disease that involves heritable defects in cellular control mechanisms
of
that result in thd
invasive tumors capable of
has four
releasing cells that can spread the disease to distant sites in the tion
important characteristics: ancer
1. Uncontrolled cell
2. Loss of cell differentiation
growth
3. Invasion of normal tissues
(specialization)
4. Metastasis (spread to multiple sites).
The common symptoms of cancer are:
.
Change in bowel or bladder functions
2. A sore throat does not heal
3. Unusual bleeding
4. Thickening or
or
discharge
lump in any tissue
5.
Indigestion (chronic) or difficulty in swallowing
6. Obvious change in a wart or mole
7. Nagging hoarseness or cough
Types of Cancers
Based on the origin, cancer can be of following types:
1. Carcinoma: If it originates from
epithelial cells, it is called carcinoma. 85%% of total cancers are car
cinomas. For example, squamous cell carcinoma
(cancer of the epithelial sheets covering the
channel) or adeno-carcinomas (cancer of an cavity or
2. Sarcoma: It is the epithelium originates glandular tissue).
that in
malignant tumors of connective tissue. They constitute about 2% of the toal
cancers. For
example, hbrosarcoma (hbroblasts), liposarcoma (adipocytes) and osteosarcoma
(osteoblasts).
3. Leukaemia: It is the
malignant tumor of stem cells of haemopoietic tissues.
They are also called liquid
tumors as they affect the blood cells. They constitute about 4% of thetotal cancers.
4. Lymphoma: It is malignant tumor of secondary lymphoid organs such as
a
For example, Burkitt lymphoma. 4% of the reported cancers are spleen and lymph nodes.
5. Myeolma: It a type of cancerous tumor. It is also known as lymphomas. or
is

Cancerous growth of plasma cells, a multiple myeloma Hodgkins discax

type of white blood cell made in the bone marrow that
antibodies. produc
 RIOLOGY

171
thcy
can
can ibe familial (hereditary) and orhers
cduv, are
spnradic (non hereditarv)
C o u i s e sO r C a n c cer

Canat Cause cancer include chemicals, racdiations and

thar

aGents act by altering the genome. These are variety of DNA and RNA con
a
g c n t s

7
ainng 1UsCS 7hese
7he
discused belorw in detail.
1. "arcinogenic chemicals, Such as those present in soot or
C h e m c a l s :C a r o

mutagcnIC or:
are
cigarette
converted to mutagenic compounds by cellular enzymes smoke, are
either directhy
and are main causes of lurng
Radiation: Bor
cancc
ionizing X-rays and
non-ionizing ultraviolet (UV) radiation
cam cause DN ONA damage. (leading cause of skin
ruses: They
Oncogenic viruses: They are cancer
causing viruses and are broadly divided into
the type of nucleic acid
depending on the found within the mature virus
two large groups
particl
viruses: DNA viruses have DNA in the mature virus particle. Some examples are
tumor
viruse;
DNA
(a) polyoma virus,simian virus 40 (SV40), adenovirus and

or retroviruses: RNA viruses have

herpes-like
RNA in the
viruses.
mature virus particle. They are
RNA
viruses
rumor
(b) structure to HIV.
similar in
present in the normal cells may get triggered under some conditions and
present and cause
The genes onditions
4 Genes: This is because the products of these genes are involved controlof
involved in control of the cell cycle, intercelluar
are divided into two broad categories:
and DNA repair. They
cancer.

adhesion

They encode
TnO suppressor genes:human proteins that restrain cell growth and prevent cells from
cancer, the product of rumor suppressor gene may be able to sup
In h
becoming malignant.
Dress cancer
formation by several different mechanisms.
that the loss of growth control and the conversion of a
Oncogenes: They encodeCancer
proteins promote
is caused
malignant state.
mutant
by copies (alleles) of these genes, whose products
cell to a

not be regulated.
may

Detection and Diagnosis of cancer

Cancer can prevent cancer
dissemination from the origin. The majority
Timely detection
and diagnosis at distal organs,
from the primary tumor and their growth
deaths are due
to the
dissemination
of tumor
cells metastasizes.
to succeed once a local benign lesion
chat is, treatment unlikely
is based on:
Cancer detection and
tissue cut into thin sections and is stained with haematoxylin
of the suspected evaluation) to see rapidly dividing
1. In biopsy, piece
a
examined under microscope (histopathological
eosin (H&cE) and
cancer cells by a pathologist.
tests are done tor leukaemias. and colon
Blood and bone marrow
done for breast, cervical, prostrate
test, PSA and colonoscopy are
3. Mammography, Pap
smear

cancers, respectively. Her-2/neu, EGFR, BRCAI and BRACA2 generally

Antibodies against cancer specific antigens such as
4.
of different types. non-ionizing radia-
used for detection of magnetic field and
cancers
are
(MRI) uses

S. Non-invasive in vivo magnetic resonance imaging

tissue.
tions to study the changes in living
(SPECT) generates a 3D image
of the organ.
be
tomography can
Sungle photon emission computed
cancer
that may cause
o. identification of genes
7. Molecular biology techniques involving
employed.
 AND ITS
9/MICROBIOLOGY
INDUST
172
CHAPTER
RIAL APPCA

Treatment of Cancer
or combining
two or more ofthe
thefollo
following
Cancer is currently
treated either singly
removed by surgery. Prelimm:.. processes:
be completely
. Surgery: Benign
tumor can
Kemoval of the breae 802 ofthhe surgery
the tumor, or
the entire
organ. ncert
to r e m o v e either

mastectomy, and
that of prostate
tumor is called prostatectomy. Suro
Surgery tumo is caly'eds
is not
metastasis.
radiation therapy, it
involves the use of ionizine possiossbi le durduriinngg
2. Radiotherapy: Also called
external beam radiotherapy (EBRT)
or internally via brachytherapy to kill cancer radiadon
tion texternally vis
cells andly a
size of the tumors.
with drugs. However,
there may side
anticancer there
3. Chemotherapy: It involves
treatment

effect
4.
to hair loss, etc.
Immunotherapy: In this, the proteins encoded by oncogenes
are inhibited. I.
ted. It
induces the
leading
tumor. a-Interteron can be used to activare th
fight the
own immune system to
immune systepatm. iens
Antiangiogenic strategies are used to prevent a breast, calon
solid tumor (those in
and lune
from inducing the formation ofnew blood vessels that are requircd to supply the tumors e and lung, ctt
and other materials.

9.9 Stem Cells

The stem cells differentiate and generace a population of healthy new blood cellsi
body. New regenerative medicines with the aid of stem cells have power to create living tient's
tissues that can regenerate and repair tissues and organs in the and
nd 6functionad
due to age, disease or congenital defects. Stem cells
body that could have hee l
possess the power to
aged areas and regenerate new cells and tissues by repair ana a renewal go particularly theset dadam.
to

functionality. process, thus restoring their

heir
Stem cell can be of rwo
types:
1. Embryonic stem cels: They are undifferentiated cells extracted from the
potential to tune into a embryo. They have the
variery of specialized cell types. They are also called as hES
Stem Cells). These cells are derived from the inner cel mass of (human Embryonic
renewing and is thus pluripotent. They can turn into 220 developing blastocysts. A hES is sef
body. any different cell types found in the human
2. Adult stem cells:
These are the stem cells that are
organism. These are the ells that remain in an found in different tissues of the developed, adu
give rise to specialized cell rypes. undifferentiated or unspecialized state. These cels an
bone marrow and are They are generally derived from the adult human blood located in te
re-infused back into the same
donor.