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5/7/2022

12.1 Immune system


12.2 Development of Immunity
12.3 Concept of self and non-self
12.4 Immune Disorder

12.1 Immune system

• Describe human lymphatic system and


explain its function in relation to immunity.
• Describe antibody (structure and function),
antigen, epitope and the development of B
and T cells
• Describe the roles of macrophages, B
cells and T cells.

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LYMPHATIC SYSTEM

 One of its functions is to help defend the body against pathogens


 The system consists of lymph (lymphatic fluid), lymphatic vessels and various organs that
are important in body’s defense system
 Lymphatic organs include the lymph nodes, tonsils, spleen, bone marrow and thymus
 Bone marrow and thymus are sites for the development of lymphocytes (important in
immunity)
 Lymphocytes (like all blood cells) originate from the bone marrow
 Lymphocytes that continue their maturation in the bone marrow, develop into B cells
 Lymphocytes that continue their maturation in the thymus, develop into T cells
 The lymph moves in the lymphatic vessels towards the right lymphatic duct or thoracic
duct
 Along the way, lymph must pass through lymph nodes
 There, any pathogens present in lymph will encounter macrophages (phagocytic action)
and lymphoctyes (immunity mechanism)

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LYMPHATIC SYSTEM

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Function of Lymphatic System in Immunity

 The lymphatic system aids the immune system in removing and destroying waste debris,
dead blood cells, pathogens, toxin and cancer cells.

 Lymph nodes act as filters or traps for foreign particles and are important in the proper
functioning of the immune system.

 Lymph nodes are packed tighly with lymphocytes and macrophages.

 The lymphatic system returned the remainder of the body fluid to the blood circulatory
system.

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ANTIBODY (IMMUNOGLOBULIN)
 A specific protein molecule known as immunoglobulin produced by plasma cells that
recognizes and bind to specific antigens.

 Have unique ability to attach themselves to the foreign substances/ bodies known as
antigen.

 By attaching themselves to the antigen, they act as markers that send signal to other parts
of the immune system.

 There are five classes of antibody such as IgM, IgG, IgA, IgD and IgE; each interacts with
specific type of antigen only

 A typical antibody molecule is Y-shaped

 It consists of 4 polypeptide chains (2 heavy chains and 2 light chains) joined by disulphide
bridges

 Each chain consists of a variable region and a constant region

 Functions of antibodies
 fight infections and diseases caused by pathogens
 Recognize and bind to the antigens

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Variable
region

heavy chain

light chain
light chain

Disulphide
bridge Constant
region

ANTIBODY

Antibody binds to a small, specific portion of an antigen to form an antigen-antibody complex


Antigen-antibody interaction occurs

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CLASSES OF ANTIBODIES

The polypeptide chains making


up the light and heavy chains are
here drawn as cylinders. The
antigen binding site is at the
amino ends of the L and H
chains. Papain digestion of IgG
splits the molecule into Fab, Fc,
and Fd fragments.
Immunoglobulin classes

Structure of immunoglobulin G

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CLASSES OF ANTIBODIES
Based on differences in structure of constant regions on heavy chains, antibody can be
divided into 5 classes :

a) IgG

(i) Most abundant (80% - 85% of total serum) – largely responsible for immunity
(ii) are monomer
(iii) Occurs primarily in plasma
(iv) Smallest – crossing the placenta -> temporary protection to newborn
(v) Provide naturally – acquired passive immunity
(vi) Neutralize bacterial toxins
(vii) Participate in complement fixation
(viii) Enhance phagocytosis.

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CLASSES OF ANTIBODIES
b) IgM

(i) Largest antibody – consists of 5 basic Y molecules (monomers) held together by a


joining or J-chain and disulphide bonds (pentameric structure)
(ii) 5% - 10% of total serum
(iii) First to appear in an infection (primary response)
(iv) Involved in agglutination and complement fixation.

c) IgA

(i) 10% - 15% of total serum – are dimer


(ii) Secretory antibody – primarily occurs in secretions ( mucus, saliva,
gastrointestinal tract, human milk)
(iii) Protects mucosal surfaces (membranes) ; protect newborns, from invasion by
pathogens
(iv) Consists of 2 basic Y molecules with 4 combining sites.
(v) Promotes neutralization and agglutination of antigens on mucous membranes.

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CLASSES OF ANTIBODIES
d) IgD

(i) Single Y molecule (monomer) – less than 1%


(ii) Binds to surface of B lymphocytes (antigen receptor on B cells)
(iii) Believe to function as immune receptors – react with antigen determinants which
then initiates development humoral immunity
(iv) No known function in serum.

e) IgE

(i) ~0.002% of total serum


(ii) Y molecules with 2 sites (monomer)
(iii) Involved in allergic reactions resulting in the release of histamine and other
chemical.

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Five Classes of immunoglobulins

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ANTIGEN

 Any foreign or non-self substance such as protein, RNA, DNA and carbohydrate present on
bacteria, virus or fungi.

 An antigen is any substance that causes the immune system to produce antibodies against
it.

 An antigen may be a foreign substance from the environment such as chemicals, bacteria,
viruses or pollen.

 An antigen may also be formed within the body, as with bacterial toxins or tissue cells.

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Antigen

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EPITOPE
 Epitopes are antigenic determinants, present on the surface of every antigen.
 The specific shape of part of the antigen molecule that can be recognized by an antibody or
T cell receptor.
 Has the shape which is specific to certain antibody.
 Antibody binds to an antigen at its epitope.

Epitopes

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THE DEVELOPMENT OF T CELL AND B CELL

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 Stem cells in the bone marrow produce immature lymphocytes during fetal stage.

 Some migrate to the thymus gland, stay there until mature then develop into T cell.

 T cell differentiate into Cytotoxic T cell, Helper T cell and Suppressor T cell.

 Some of the lymphocyte mature in the bone marrow, develop into B cell.

 The T cells and B cells reside in separate regions of the spleen, lymph nodes and other
lymph tissues.

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ROLES OF MACROPHAGES, B CELLS AND T CELLS

Role of Macrophages

 Engulf virus, bacteria and foreign particle (antigens) and bring the fragments
of antigen to its surface so that it can be recognized by Helper T cell (becomes
Antigen Presenting Cell).
 Release interleukin 1 when stimulated by Helper T cell upon binding with the
Antigen Presenting Cell.

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ROLES OF DEFENCE CELLS (MACROPHAGES, B CELLS AND T


CELLS)

• Macrophage

Antigen Presenting Cell (APC)

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Role of T cells

 In general, T cell involved in cell mediated immune response.


 Specific function of each type of T cell
i) Cytotoxic (Killer) T cell – destroy antigen directly causing it to burst or
undergo lysis.
ii) Helper T cell – Stimulate B cells to proliferate and activate the action of
other T cells such as cytotoxic T cells.
iii) Suppressor T cell - Cause both B cells and T cells to become less active

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• T cells

There are 2 main types of T cells:


i. cytotoxic T cells (TC)
- act to destroy cancer cells and cells infected
by pathogens
ii. helper T cells (TH or T4)
- act to help activating/stimulating TC and B
cells in immunity responses

T cells have a cell receptors and surface protein


CD4 or CD8 which recognize and bind to antigens
found on infected cells or on any antigen-
presenting cells (can be a macrophage)

Major histocompatibility complex (MHC) of body


cells will present/display fragments of antigens to
be identified by the T cells

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(Surface protein)

/ T8 cell (Cytotoxic T cell) / T4 cell (Helper T cell)


(T cell receptor)

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Role of TH in immunity
Usually, a macrophage performs phagocytosis on pathogens, and there will be antigen
fragments in the macrophage

Receptor of TH recognizes and binds the antigen fragment presented by MHC of the
macrophage

The macrophage secretes interleukin-1 (a type of cytokine ~ that activates lymphocytes)

This activates TH to divide, producing clones of TH (all with receptors for that specific antigen)

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 Activated TH will also secrete interleukin-2 that activates TC (to perform cell-mediated
immune response) and B cells (to perform humoral immune response)

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Role of B cells

 Carry out humoral immune response.


 Proliferate to form plasma cells that produce antibodies and memory cells
when they are stimulated by Helper T cell.

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• B-Cell / B-Lymphocyte

B cells have antigen receptors which recognize


and bind to specific free antigens

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B-lymphocyte

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12.2 Development of immunity

• Explain cell-mediated and humoral


immune responses.
• Outline the antigen-antibody reactions
(precipitation, agglutination, neutralization,
complement fixation )

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DEVELOPMENT OF IMMUNITY

 The immune system exhibits two types of responses to antigen which


are
 Humoral immune response
 Cell-mediated immune response
 Humoral immune response involves antibodies produced by B
lymphocyte cells in response to a specific antigen.
 Cell-mediated immune response is active against bacteria and viruses
within infected body cells or against cancerous cell.

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HUMORAL IMMUNE RESPONSE


• Involves B cells activation and production of antibodies that circulate in the blood and
lymph
• This is initiated when B cells are activated by
binding with free antigens or by IL-2 secreted
by activated TH
• Activated B cells form memory B cells and
plasma cells
• Memory B cells are cells that may respond
rapidly upon subsequent exposure to the
same antigen
• Plasma cells are cells that secrete antibody
specific to that antigen

[Memory B cells and plasma cells may


divide to form clones to enhance the
immune response]

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HUMORAL OR ANTIBODY-MEDIATED IMMUNE RESPONSE


 This Immune response may or may not  Then Helper T cell with receptor and
involved Helper T cell (T4 or TH cell). If surface protein CD4 recognize and binds
Helper T cell involved, this cell must to the Class II MHC-antigen complex
activated by macrophages which present as molecules on the surface of B cells.
APC.
 Then Helper T cell secretes Interleukin 2.
 Helper T cell has a receptor and surface
protein CD4 that recognize class II MHC-  Interleukin 2 stimulates the B cells to
antigen complex molecules presented on divide and form a large clone of effector
the surface of APC. B cells (plasma cells) and memory cells.

 Then Helper T cell binds to APC and  The plasma cells produce a large
stimulates the APC to secretes Interleukin I. quantity of antibody with specific
configuration.
 Interleukin I then stimulates the Helper T
cell to secrete Interleukin 2.  The antibodies released then destroyed
antigen including pathogen and parasitic
 Interleukin 2 then stimulates the division of worms,
Helper T cell to produce clones of helper T
cell.

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HUMORAL OR ANTIBODY
MEDIATED IMMUNE
RESPONSE

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Antibody formation in a repeated infection

 When body is exposed to an antigen for the 1st time, primary immune response occurs
 It takes about 10 – 17 days to generate maximum effector cells response
 This is when B cells are activated to produce many memory cells and plasma cells
 While plasma cells are developing, the person may become ill
 Later, the illness disappears as antibodies (secreted by plasma cells) act on the antigens
 Plasma cells are short-lived cells
 Memory cells are long-lived cells, bearing receptors specific for that antigen

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 If that person is exposed to the same antigen some other time, the response is faster (2 – 7
days), of greater magnitude and more prolonged
 This is the secondary immune response
 This is due to the memory cells that respond rapidly by readily generating plasma cells
 Secretion of antibodies is faster and more numerous
 Antigens are destroyed early; no chance to cause any illness

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CELL MEDIATED IMMUNE RESPONSE

 The immunity response which depends on the action of Cytotoxic T cell or TC cells.
 This is initiated when TC is activated by binding to Class I MHC-antigen complex on the
surface of infected cell / cancer cell
 Tc cell has receptor and surface protein CD8 that can recognize class I MHC protein on the
surface of infected cell / cancer cell. Tc cell then bind to infected cell.
 Interleukin 2 (IL-2) secreted by activated TH enhances the activation of TC
 Activated TC may divide, forming more TC cells and memory T cells
 Memory T cells may respond rapidly upon subsequent exposure to the same antigen
 Activated TC cell release protein perforin molecules with the presence of interleukin 2.
 Perforin molecule puncture and create pores in the membrane of the infected cell allowing
water and ions flow into the cell causing the cell swelling and lysis.
 This deprives the antigens of their host cells so that they cannot reproduce.
 Cytotoxic T cells also attack and gradually destroy transplanted organs.
 The activation and killing action of cytotoxic T cell is known as the cell mediated immune
response.

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Helper T cell

Cytotoxic T cell

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CELL MEDIATED IMMUNE RESPONSE

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TYPES OF ANTIGEN- ANTIBODY INTERACTION

i) Neutralization

- antibodies bind to and block activity of the antigen


- antibodies may bind to surface of a pathogen and in a process called opsonization, the
bound antibodies enhance macrophage attachment to the pathogen, which leads to
phagocytosis

ii) Agglutination

- antibody binds to a number of pathogens, thus linking (clumping) the pathogens together
- the large complex will be easily phagocytosed by macrophages

iii) Precipitation

- antibodies bind to a number of soluble antigen molecules, thus linking the molecules to
form immobile precipitates
- this enhances phagocytosis by macrophages

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TYPES OF ANTIGEN- ANTIBODY INTERACTION


iv) Complement fixation

- antibodies attach to surface of pathogen and then, the antibodies combine with
complement proteins
- this activates the complement proteins to form lesions (pores) in the pathogen’s cell
membrane
- this leads to lysis of the pathogenic cell

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TYPES OF ANTIGEN- ANTIBODY INTERACTION

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