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                                                                                           Notes
                 IMMUNOBIOLOGY : AN
                    INTRODUCTION
We all get infections, but some of us fall sick more frequently than others. This is
related to the immune system. Proper functioning of immune system protects us
from the infections. On the other hand its malfunctioning provides opportunity to
infectious agents for causing diseases. Besides protection from infection, immune
system also performs a number of other functions. It is about all this that you will
learn in this lesson.
         OBJECTIVES
After completing this lesson, you will be able to :
z   define the term immunity;
z   explain the concept of “self” and “non-self”;
z   describe the types of defence mechanisms in the body;
z   describe the types of immunity;
z   list and describe various cells of the immune system;
z   differentiate between cellular and humoral immunity; innate and acquired
    immunity;
z   describe various components of the immune system;
z   explain the concept of immunization (vaccination) and list various types of
    vaccines.
 31.1 IMMUNITY
Immunity is broadly defined as “the capacity of the body to recognize materials as
foreign to itself and to neutralize, eliminate or metabolize them with or without injury
to its own tissues”.
    Immunobiology is the study of organization and functioning of immune
    system. Immune system provides ‘immunity’ (protection against
    diseases).
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                                         Jenner, the father of immunology
                       Edward Jenner (1749-1823) is considered to be the father of modern
                       immunobiology. He demonstrated that inoculation of cowpox crusts afforded
                       protection to humans against smallpox. He observed that milkmaids who
                       recovered from cowpox never contracted the disease smallpox. Hence the
                       name vaccination from the Latin word “Vacca” for cow came into beng.
           Notes       The milkmaids and the vaccinated individuals were protected from smallpox
                       virus. Such protection gave them what is called `immunity’ to smallpox,
                       although Jenner neither knew the actual causative agent of this disease nor
                       the actual mechanism of protection.
                   Concept of “Self” and “Non-Self”
                   The basis of the above mentioned protection was the ability of the immune system
                   of the milkmaid and vaccinated individuals to distinguish between ‘self (their own
                   tissues) and ‘non-self’ components of the outsiders i.e. the smallpox virus) in this
                   context.
                   An individual induces a physiological response (immune response) to substances that
                   are different from self components. For example, an immune response is induced
                   against pathogens (bacteria, virus, fungi and parasites) attacking the body of the
                   host.
                   Let us now learn about the different ways by which the body defends itself from
                   pathogens and other harmful substances.
                    31.2 DEFENCE MECHANISMS IN THE BODY
                   There are four defence mechanisms in our body :
                   1. Immunity to defend the body from infections.
                   2. Metabolic defence to metabolize and detoxify foreign chemicals.
                   3. Stoppage of bleeding (Haeostasis) to prevent to blood loss.
                   4. Resistance to stress mainly through release of hormone.
                   Immunological defence is the most important defence mechanism. It provides
                   protection against various infective agents e.g. virus, bacteria, fungi and parasites
                   and also against the development of a tumour.
                   Thus immunological defence serves three main functions :
                   1. Defence against microorganisms.
                   2. Recognition and destruction of mutant cells (Surveillance).
                   3. Removal of damaged or non functional cells to maintain normal state
                      (Homeostasis).
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           INTEXT QUESTIONS 31.1
1. Who is considered as the father of immunobiology?
    ............................................................................................................................
2. What are the three main functions of immunological defence?
                                                                                                                                   Notes
     (i)     ..................................................................................................................
    (ii)      ..................................................................................................................
   (iii)      ..................................................................................................................
3. Define immunology.
    ............................................................................................................................
 31.3 IMMUNE SYSTEM
By now, you are aware that immunity to infection is one of the most important
factors facilitating survival of an individual. Immunity is mainly provided by a
complex network of cells, tissues and soluble factors. This network is collectively
referred to as the ‘immune system’. Cells participating in the immune response are
organized into discrete ‘lymphoid tissues and organs’.
1. Tissues and Organs involved in the Immune System
Lymphoid organs are divided into two groups :
(i) Central lymphoid organs or primary lymphoid tissue. Example : Thymus and
    bone marrow.
                               Fig. 31.1 Major lymphoid organs and tissues.
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   in Biology      (ii) Peripheral lymphoid organs or secondary lymphoid tissue. Examples spleen,
                        Peyer’s patches, tonsils, lymph nodes and mucosa-associated lymphoid tissue
                        (MALT), which is associated with the respiratory system, urogenital and
                        alimentary canal (Fig. 31.1).
                   2. Cells of Immune System
           Notes (i) Lymphocytes (Lymphoid cells)
                     All these are initially derived from the hemopoietic (blood cell producing) stem
                     cells of bone narrow. Stem cells mean undifferentiated cells which can undergo
                     unlimited division and can give rise to one or several different cell types. Apart
                     from producing lymphocytes bone marrow stem cells also differentiate to
                     produce erythrocytes (red blood cells), thrombocytes (blood platelets),
                     granulocytes and monocytes (white blood cells).
                   (ii) The macrophage
                       These are derived from monocytes.
                       Lymphocytes are the major cell types responsible for performing immune
                       functions. About 1012 lymphocytes constitute the mature lymphoid system in
                       humans. Functionally, lymphocytes are divied into two sub-classes:
                       (i) B-cells or B-lymphocytes
                       (ii) T-cells or T-lymphocytes
                       Morphologically, these cells cannot be differentiated, but functionally these are
                       distinct. Cells of immune system are differentiated on the basis of presence or
                       absence of specific cell surface markers.
                       (a) B-Cells (B-lymphocytes)
                             Main functions of B-cells
                               1. Initiate antibody-mediated immune response.
                               2. Transform into plasma cells which secrete antibodies.
                   Origin of B-Cells
                   “B” stands for Bursa. Studies in birds showed that the bursa of Fabricius, a hind-
                   gut lymphoid organ was the site of antibody-producing cells. These cells are
                   therefore termed as ‘B-cells’ (‘B’ derived from bursa of Fabricius). B-cells mature
                   in the bone marrow and then are carried by the blood to the peripheral lymphoid
                   organs. In mammals, B-cells lineage begins in foetal (embryonic) liver. This process
                   begins during the 8th week of human gestation (pregnancy). The foetal liver
                   continues to be the major site for production of the B-cells, until well into second
                   trimester (4-6 months of pregnancy). Stem cells then populate the bone marrow and
                   thereafter the B-cells are continuously produced in the bone marrow throughout
                   life (Fig. 31.2).
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                                                                                        Notes
                            Fig. 31.2 Origin of B and T Cells
Characteristics of B-cells
(i) B-cells display immunoglobulin as an integral protein of their cell membranes.
(ii) This surface immunoglobulin (antibody) acts as the receptor for antigen specific
      to it.
(iii) B-cells are responsible for the production of antibodies. Activated B-cells
      transform into plasma cells (Fig. 31.3). You will learn about ‘antigen’ and
      ‘antibody’ in the next section of this lesson.
                 Fig. 31.3 B-cell differentiation and antibody production.
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   in Biology          Plasma cells produce thousands of antibody molecules per second
                       before they die in a day or so.
                   Some of the B-cells progeny do not differentiate into plasma cells but rather become
                   ‘memory cells’ which produce antibodies in the event of the antigen re-appearing
                   again in future.
           Notes (b) T-Cells (T-lymphocytes)
                 In contrast to B-cells, other lymphocytes leave bone marrow in an immature state
                 during foetal and early stages of life. These are carried to the ‘thymus’, mature in
                 thymus, and then they migrate to the peripheral lymphoid organ. These cells
                 constitute the second major class of lymphocytes, the T-lymphocyte or T-cells. ‘T’
                 derived from thymus. Production of T-cells is completed early in life, but like
                 B-cells, they also undergo mitosis in peripheral lymphoid organs, the daughter cells
                 being identical to the original T-cells.
                   Main functions of T-cells
                   (i) Regulate immune response.
                   (ii) Mediate cell-mediated immune (CMI) response.
                   (iii) Induce B-cells to produce antibody.
                   T-cells are functionally classified into three categories (TH, TC, TS)
                   1. Helper T-cells (TH)
                        Promote response of B-cells resulting in antibody production (activate other T-
                        cells).
                   2. Cytotoxic T-cells (TC)
                        Kill virus-infected cells and tumour cells.
                   3. Suppressor T-cells (TS)
                        Suppress helper T-cells and may also B-cells to limit/regulate activity of the
                        latter.
                     Thus we see that T-cells mediate two general type of immunological functions
                     : effector and regulatory.
                   Structurally, T-cells are differentiated on the basis of presence or absence of some
                   specific surface molecules (T-cell receptors). But both B-cells and T-cells work in
                   cooperation.
                              INTEXT QUESTIONS 31.2
                   1. Name the two categories of immune cells.
                        (i)    ..................................................................................................................
                       (ii)    ..................................................................................................................
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2. Name the organ found in birds where B-cells are produced.                                                                           in Biology
    ............................................................................................................................
3. Write the two main functions of B-cells.
     (i)     ..................................................................................................................
    (ii)      ..................................................................................................................
4. Name the cells responsible for synthesis of antibodies.                                                                         Notes
    ............................................................................................................................
5. What is the function of T-helper cells?
    ............................................................................................................................
 31.4 ANTIGEN AND ANTIBODY
While discussing about ‘self’ and ‘non-self, we got a broad idea of antigen. Let
us learn more about it.
31.4.1. Definition and Properties of an antigen
  An antigen is any foreign molecule that can trigger a specific immune
  response.
Most antigens are either proteins or very large polysaccharides. Another term
‘immunogen’ is also used for antigen. However, there is a slight difference between
the two. Immunogen describes a molecule that provokes an immune response while
antigen describes a molecule which reacts with the antibody produced.
Paratopes and Epitopes : The part of antibody molecule which makes contact with
the antigen is termed the paratope. The part of antigen molecule that makes contact
with paratope is called the epitope. There may be a series of epitopes on an antigen.
Such epitope clusters are called ‘antigenic determinant’.
Requirements for becoming an antigen :
l. Substance should be foreign to the host.
2. Molecular weight of molecule should be 10,000 Dalton or more.
3. It should possess chemical complexity.
31.4.2 Antibody : Definition and properties
  Antibody is a protein molecule produced in animals in response to an antigen.
Antibodies belong to the category of proteins called immunoglobulin. Each antibody
molecule is composed of four interlinked polypeptide chains. The two long chains
are called heavy chains, and the two short chains are called light chains. An
antibody has a “stem” called “Fc” portion which comprises the lower half of the
two heavy chains, and two “prongs’ (the amino acid sequences that bind antigen).
  The amino acid sequences of Fc portion are identical (constant) for all
  antibodies of same class. In contrast, amino acid sequences for antigen binding
  sites vary from antibody to antibody in a given class (Fig. 31.4)
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                                                                           One "prong"
                                                        Specific antigen
                                                         binding sites
           Notes
                                      Light chain
                                          Heavy chain                  F ("stem")
                                                Fig. 31.4 Antibody structure
                   31.4.3 Type of immunoglobulins
                   z There are five major classes of antibodies (or immunoglobulins) distinguished
                       by the amino acid sequences in the heavy chains. These classes are designated
                       as Ig, IgD, IgA, IgE, IgG and IgM (1g = Immunoglobulin)
                   z They also differ in their molecular weights and functions.
                   z IgG is found in highest concentration (almost 75% of the total immunogloblulins
                       in humans).
                   z Antibodies are produced by plasma cells which are differentiated B-cells. Each
                     B-cell type produces antibodies which react with a particular epitope of antigen.
                   z Secreted antibodies travel all over the body through blood and reach antigens
                     of the kind that stimulate the immune response, combine with antigens (Fig.
                     31.5) and then direct an attack (by phagocytic cells which eat up foreign
                     material) and eliminate the antigen or the cells bearing them.
                                                    Antigen
                                                              Antigenic determinant
                                                              Antigen binding site
                                                                  Antibody
                                             Fig. 31.5 Antigen-antibody binding
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 31.5 TYPES OF IMMUNE RESPONSES                                                         in Biology
Broadly, immune responses can be classified into two categories : Non-specific
immune responses and specific immune responses.
1. Non-specific immune responses are those which non-selectively protect
   against foreign substances or cells without having to recognize their specific
   identities. Phagocytosis (engulfing, of particulate matter) by macrophages and
   extracellular killing by proteins known as ‘complement’. There are two non- Notes
   specific types of immune responses.
2. Specific immune responses (adaptive immune response) depend upon the
   immunological recognition of the substances or cells to be attacked. Specific
   immune responses are again of two types :
    (a) Cell mediated immune responses : Mediated by cytotoxic
        T-cells and natural killer cells. These constitute major defence against
        intracellular viruses and cancer cells.
    (b) Antibody-mediated or humoral immune responses : These responses
        are mediated by antibodies secreted by plasma cells, which arise from
        activated B-cells. They constitute major form of protection against
        bacteria and viruses.
The above two differ from each other as shown in Table 31.1
Both cell mediated and antibody mediated immune responses are facilitated by helper
T-cells and inhibited by suppressor T-cells (Fig. 31.6)
                                                      Bone marrow
                                                       stem cells
                           Thymus
                          processing
                                                              Bursa processing
                                                                    B-Lymphocytes
              T-Lymphocytes
                                                                    Antigen
          Antigen                      Co-operation
                     Lymphoblasts
                                                           Plasma cells
                          Cell mediated
                        immune response                Humoral immune response
                                                         (Antibody formation)
                    Fig. 31.6 Cell-mediated and humoral immune responses
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   in Biology                    Table 31.1: Differences between cell-mediated and humoral
                                              (antibody mediated) immune responses
                        Cell-mediated immune response                                          Humoral immune response
                    1. Killing of intracellular organisms.                       1. Antibodies specifically combine
                                                                                    with antigen which stimulate
                                                                                    their production.
           Notes    2. Destruction of tumour cells                               2. The combination of antibody with
                                                                                    antigen may result in clumping of molecules
                                                                                    or particles, their toxicity may be
                                                                                    neutralized, their uptake and digestion
                                                                                    by phagocytes may be facilitated.
                    3. Rejection of graft tissue.                                3. Combination of antigen with antibody
                                                                                    may also cause lysis of cellular antigens
                                                                                    present on the red blood cells or bacteria.
                    4. Delayed type of hypersensitivity
                       reaction after contact with certain
                       antigen.
                              INTEXT QUESTIONS 31.3
                   1. Name the part of antigen which makes contact with antibody.
                       ............................................................................................................................
                   2. How many types of immunoglobulins are known? (Give only the number).
                       ............................................................................................................................
                   3. Name the immunoglobulin found in highest concentration.
                       ............................................................................................................................
                   4. Which type of immune response is responsible for the killing of cancer cells?
                       ............................................................................................................................
                    31.6 TYPES OF IMMUNITY
                   There are two main types of immunity : (i) Natural or innate (i.e. genetic, from birth),
                   and (ii) Acquired (i.e. developed during life time).
                   A. Natural or Innate Immunity
                   A healthy individual is generally immune to potentially harmful microorganisms by
                   a number of very effective mechanisms. These mechanisms are termed innate or
                   natural immunity. Innate defence consists of three main components :
                   (i) Physical barriers (preventing entry of germs)
                   (ii) Phagocytic cells and (Dealing with germs which enter)
                   (iii) Soluble components (complement)
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(i) Physical Barriers                                                                          in Biology
It is the first line of defence. It means preventing the entry of pathogens into the
body. (Fig. 31.7).
Skin : The outer tough layer of skin is formed of keratin and is almost impermeable
to germs. Sebaceous glands in the skin generate an acidic environment by producing
lactic acid which kills many pathogens.
Epithelial lining of various organs : The respiratory tract, the alimentary tract Notes
(the gut) and the urino-genital tract have an exterior epithelial cell layer covered
by a protective mucous lining. In the respiratory tract, cilia covering to the external
surface of the epithelial cells continually beat upwards towards the nasopharynx and
this helps to expel particles and pathogens. Epithelial cells are constantly renewed
and their removal expels pathogens lodged on their surface.
Body secretions : Body secretions such as sweat and secretion from eyes also ward
off pathogens. Other body fluids contain molecules which are bactericidal that is capable
of killing bacteria (e.g., spermine in seminal fluid, hydrochloric acid in gastric juice).
                      Fig. 31.7 Natural physical barriers to infections
If the germs somehow enter the body by evading physical barriers of the body, the
other two main defence mechanisms come into play – phagocytosis and the
bactericidal effect of soluble chemical factors collectively known as complement
system which are described below.
(ii) Phagocytic Cells
When the micro-organisms or inert particles such as colloidal carbon enter the tissue
fluid or blood stream, these are very rapidly engulfed and destroyed by phagocytic
cells. Such cells may either be circulating in body fluids or may be fixed in some
tissues. This phenomenon is called phagocytosis (literally meaning ‘eating’ by the
cell). The engulfment and destruction/digestion of microorganisms is assigned to
two major types of cells named as microphages (certain WBC) and macrophages
(in Liver and Spleen).
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   in Biology      Important features of phagocytic cells
                   1. They rapidly engulf the foreign molecular foreign agent oncoming in contact
                      or which they come in contact with.
                   2. They contain digestive enzymes to breakdown engulfed material.
                   3. They are an important link between innate and acquired immunity (described
                      below).
           Notes
                   (iii) Complement System
                   The group of proteins known as ‘complement’ provides another innate immunity
                   mechanism for killing microbes without prior phagocytosis.
                       Complement system is an extremely complex system consisting of at least
                       20 proteins.
                   Some of the complement components are designated by the letter ‘C’ followed by
                   a number. The most pivotal and most abundant component is C3. Complement
                   component may also act as opson in (e.g. C36). Opson is that type of antibody whose
                   binding to antigens on virus or bacterium facilitates their subsequent ingestion by
                   the phagocytic cells. Such antibodies can also cause direct destruction of microbes
                   by making their membrane leaky.
                   B. Acquired Immunity
                   It is the immunity mediated by lymphocytes and characterized by antigen specificity
                   and memory.
                   An acquired immunity may be brought about in an individual in two main ways:
                   1. By infection, so that antibodies are produced against the infective agent and by
                      deliberate artificial immunization. This is termed as actively acquired immunity.
                   2. By transfer from an actively immunized individual through blood, serum
                      component etc. This is called passively acquired immunity.
                   (i) Actively acquired immunity
                   Actively acquired immunity due to infection falls into two general categories.
                   (i) Some infections, such as diphtheria, whooping cough, smallpox and mumps
                       usually induce a lifetime immunity i.e. a patient once recovered does not get
                       the disease subsequently.
                   (ii) Other diseases such as common cold, influenza, bacillary dysentery and
                        pneumococcal pneumonia confer immunity for a shorter period, sometimes only
                        for a few weeks.
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(ii) Passively acquired immunity                                                           in Biology
It may be developed in the following ways :
1. Transfer of antibodies (e.g. IgG) from mother into foetus across the placenta.
2. Breast fed children also receive antibodies from the mother’s milk.
3. Pooled human immunoglobulin is also used as source of antibody in a number
   of cases including measles infection and infectious hepatitis.
                                                                                       Notes
4. Human immunoglobulin is also given to patients with a congenital inability to
   make antibody globulin.
 31.7 ACTIVE IMMUNIZATION (VACCINATION)
People had observed in the past that individuals who recovered from certain diseases
are protected for lifetime from recurrences. This gave rise to the concept of
immunization. Edward Jenner introduced vaccination in 1796 using cowpox to
protect against smallpox.
The objective of vaccination is to introduce the attenuated germs into the body. The
body then generates specific population of memory cells. These memory cells can
rapidly increase in number on the renewed contact with the same antigen and more
antibodies can be produced to provide protection against infection.
31.7.1 Type of Vaccine
Three main types of vaccines are available :
1. Killed organisms as vaccines   : Examples : typhoid, cholera, pertussis
   (whooping cough), rabies and poliomyelitis.
2. Live attenuated (weakened) organisms as vaccines; Examples: BCG, Rubella,
   measles and polio.
   Attenuation mimics the natural behaviour of the organism without causing
   disease. The actively multiplying organism provides a sustained antigen supply.
3. Toxoid vaccines : Examples: diptheria and tetanus.
   Toxoid is a chemically or physically modified toxin that is no longer
   harmful but retains immunogenicity.
31.7.2 Important Vaccines – BCG, DPT and MMR
z BCG = Bacillo Calmette Guerin (Calmette and Guerin were the scientists who
    contributed in the development of tuberculosis vaccine).
z DPT is a triple vaccine (or antigen) for diptheria and tetanus toxoids and for
    pertussis Bordetella pertussis, the whooping cough organism.
z MMR vaccine = Attenuated strain of measles, mumps and Rubella).
Another class of vaccines termed as polysaccharide vaccines are available
comprising vaccines for influenza, meningitis and pneumonia. In these vaccines, the
relevant immunogenic portions of the organism are used.
Vaccines of future : against Malaria, Leprosy, Anthrax, AIDS
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                               INTEXT QUESTIONS 31.4
                   1. Mention two physical barriers of the body.
                       ............................................................................................................................
                   2. Macrophages are found in large numbers in the following organs :
           Notes
                        (i)      ..................................................................................................................
                       (ii)      ..................................................................................................................
                       (iii)     ..................................................................................................................
                   3. Give two examples of each of the following:
                        (i) Killed organism vaccine ...........................................................................
                       (ii) Live attenuated organism vaccine ............................................................
                       (iii) Toxoid vaccine ..........................................................................................
                               WHAT YOU HAVE LEARNT
                   z   There are various types of defence mechanisms in our body. Immunity defends
                       us against infections.
                   z   Immune system is a complex network of cells, tissues and soluble factors
                       working in close co-ordination.
                   z   Thymus and bone marrow are the central or primary lymphoid organs.
                   z   Lymphocytes which are the major cells performing immune functions are of two
                       main types - B-lymphocytes and T-lymphocytes.
                   z   B-cells are transformed into plasma cells which produce antibodies.
                   z   Foreign molecule which triggers an immune response is called antigen.
                   z   Antibodies (immunoglobulins) are of five types, of which 1gG is found in the
                       highest concentration.
                   z   There are two main types of immune responses — specific and non-specific.
                   z   Specific immune responses can be either cell-mediated or antibody (humoral)-
                       mediated.
                   z   There are two types of immunity — natural or innate and acquired.
                   z   Vaccination is a type of actively acquired immunity.
                   z   There are three types of vaccines – (i) killed organisms as vaccines,
                       (ii) live attenuated organisms as vaccines, and (iii) toxoid vaccines.
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        TERMINAL EXERCISES
1. Define the term immunity.
2. What are the main defence mechanisms operating in our body?
3. ‘Immune system is a complex network of cells, tissues and soluble factors’. Notes
   Justify this statement.
4. Describe the process of antibody production.
5. List main functions of T-cells.
6. Draw a schematic diagram of the structure of antibody.
7. What are the main physical barriers of the body?
8. Describe important features of phagocytic cells.
9. Give one main difference between passively acquired immunity and actively
   acquired immunity.
10. Define the process of attenuation.
11. Name two toxoid vaccines.
12. What do the following abbreviations mean?
   (i) BCG          (ii) DPT         (iii) MMR
        ANSWERS TO INTEXT QUESTIONS
31.1   1. Edward Jenner
       2. Broadly immunological defence serves three functions :
          (i)    Defence against microorganisms.
          (ii)   Homeostasis i.e. removal of damaged (non functional) cells to
                 maintain normal state.
          (iii) Surveillance i.e. recognition and destruction of mutant cells.
       3. Study of organisation and function of the immune system.
31.2   1. (i) Central or primary lymphoid organs.
          (ii) Peripheral or secondary lymphoid organs.
       2. Bursa of Fabricius.
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   in Biology             3. Main functions of B-cells:
                             (i) Initiate antibody mediated-immune response.
                             (ii) Transform into plasma cells which secrete antibodies.
                          4. Plasma cells/B-cells
                          5. Promote response by B-cells resulting in antibody production and also
           Notes
                             activate other T-cells.
                   31.3   1. Epitope
                          2. Five
                          3. Immunoglobulin G
                          4. Cell-mediated immune response
                   31.4 1. (i) Skin
                             (ii) Epithelial cell layer of respiratory system.
                          2. (i) Lung
                             (ii) Liver
                             (iii) Spleen
                          3. (i) Typhoid vaccine, Pertussis vaccine.
                             (ii) BCG, Rubella vaccine.
                             (iii) Diphtheria vaccine, Tetanus vaccine.
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