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Immunology Part 2

CAPE Biology
R.Wint

Objectives
1. Define antigen and epitope
2. Define immune response
3. Describe the origin and differentiation of T-cells, CD8 and AIDS
4. Describe the origin and differentiation of B-cells
5. Explain the process of antigen presentation initiating an immune response
6. State the types of antibodies G.A.M.E.D
7. Label and annotate the structure of antibody
8. Outline the mechanism of humoral mediated response
9. Outline the mechanism of cell-mediated response
10.Explain the role of memory cells in conferring long-term immunity
11.Explain the types of active and passive immunity
12.Define vaccine
13.Explain how vaccine confer immunity
14.Define monoclonal antibody
15.Describe the applications of monoclonal antibodies in cancer drug
MabThera, pregnancy testing, AIDS Test

Immune System
The immune system of animals serves to
protect the organism from invading cells/
foreign substances.
It is an elaborate and coordinated system that
to generate an enormous variety of cells and
molecules capable of specifically recognizing
and eliminating an apparently limitless variety
of foreign invaders.
Animal Immune system is defined for its ability
of recognition , effector response and
memory

Lymphatic System

Immunity
Immunity is our ability to ward off
diseases caused by pathogens or their
products and to protect against
environmental agents.
There are two general types of immunity:
Innate Immunity: refers to defences that
are present at birth, does not elicit a
specific recognition of pathogen, nor does
it have a memory response
Adaptive Immunity: a specific response
to a specific microbe (slower) and it has a
memory component

Immunity Map (By


R.WINT)
Immunity
Adaptive

Cell
Mediate
d

Phagocyt
osis

Humoral
(Antibody
)

Active

Natural

Innate

Inflammati
on

Passive
Artificial

Natural

Artificial

Anatomi
c
Complem
ent

Cell-Mediated and Humoral Mediated Immunity

ADAPTIVE IMMUNITY

Adaptive Immunity
Adaptive immunity effects a highly specific
response against an antigen, and it is
characterised by its memory component.
Antigen: a molecule that elicits antibody
formation and an immune response. Found on
microbes/ foreign agents
Antigen specificity is possible because the
adaptive immune system can generate
tremendous diversity of cells to recognise the
billions of unique antigens
Immunolgic Memory: the second encounter
with the same antigen induces a faster and more
intense immune response

Branches of Adaptive
Immunity
1. Humoral Immunity: effects an immune
response by inactivating antigen using
antibodies produced by B-lymphocytes
2. Cell-mediated is coordinated by Tlymphocytes that proliferate and effect
an immune response among themselves
and stimulate other immune cells
B-cells and T-cells become activated upon
exposure of an antigen

Overview

B-Cell Maturation/Differentiation
Recall that all blood cells originate from stem cells in the
red bone marrow in a process known as haemopoeisis.

Outline
1. B-lymphocytes mature in the bone marrow into a nave
B-cell expressing a unique antigen binding receptor
(antibody) on its membrane.
2. Activation: When the nave B-cell encounters and binds
a complementary antigen for the first time, this induces
the B-cell to rapidly divide.
3. Clonal Expansion: The B-cell progeny proliferates and
differentiates into memory B-cell, and the effectors
plasma cells
4. Fate:

memory B-cell express the same unique antibody as parent Bcell on their surface
Plasma cells instead secrete antibody that are major effectors
in humoral immunity

B-cell Differentiation

T-lymphocyte
Differentiation
T-lymphocytes differentiate in the red bone
marrow, but it matures in the thymus gland

Outline
1. T-cell matures in thymus, expressing T-cell
receptors TCR on cell membrane.
2. Nave T-cell via its TCR bind to antigen-MHC
complex expressed on antigen presenting cell
3. Activation/Clonal expansion: T-cell
proliferates and differentiates into memory T
cells and effector T cells

Classes of Effector T cell


Two main classes of effector T-cells that can
be distinguished by the presence of special
surface membrane molecules CD4 and CD8
1. T-helper cells: binds MHC-II secrete
chemicals that stimulate activation of B
cells, Tc cells, other immune cells. Express
CD4
2. T-cytotoxic cells, Tc: binds MHC-I,
secretes chemicals that are toxic to
pathogens. Expresses CD8

MHC- Major Histocompatibility


Complex
MHC are glycoproteins that are
responsible for antigen presentation.
For T-cells to be activated, the antigen
must be bound to an MHC recpetor
2 classes of MHC
1. MHC-1 : found on all cells in organism;
bind and present endogenous antigens
2. MHC-II: found on cell surface of antigen
presenting cells.

Cell-Mediated in Action
Viruses infect cells by
inserting their own RNA
or DNA into the host cell.
1. Infected host cells will
express a MHCI/antigen complex that
is recognised by Tc cells
. TC Cells will bind, via Tcell receptors to the
MHC-I/antigen complex
and infected cell and
destroy the infected cell

HIV and T-cells


Once HIV has entered the body, the
immune system initiates anti-HIV
antibody and cytotoxic T cell
production.
However, it can take one to six
months for an individual exposed to
HIV to produce measurable
quantities of antibody.
The immune response is
weakened as memory T cells

HIV/ CD4T-cell
Infection
HIV causes illness by
infecting and depleting
CD4 T cell population.
By doing that the
immune system
becomes severely
weakened.
HIV infects and
programs CD4 T cells
to produce a large
number of more HIV
virus, and in doing so
the CD4 T cells is
destroyed.

AIDS develops when


CD4 T cell count falls
below 350 cells/uL -200
cells/uL
Because HIV destroys
CD4 T cells, AIDS is
characterised by
opportunistic infections
like tuberculosis,
pneumonia etc

HIV and T-Cell

Antigen Presentation
Antigen presentation links innate immunity to adaptive
immunity.
Antigen presenting cells, eg. Dendritic cells, express
MHC-II on their membrane.
1. APC phagocytose substance bearing antigen
2. Antigen is processed inside APC and then bind to MHC-II
3. MHC-Antigen complex is transferred from within cell to
the cell surface
4. T-cell with TCR complementary to antigen-MHC-II
complex will bind to it and become activated

Antibody Effectors of
Humoral
Antibody or immunoglobin are globulin
proteins that bind specific antigens
Antibodies released by plasma circulate in
serum
Antibody bind antigen to form an antigenantibody complex
Antibody bind specific regions on the antigen
called the epitope
The binding of an antibody to an antigen
protects the host by tagging foreign cells and
molecules for destruction by phagocytes and
complement.

Antibody Structure
All antibodies are
heterodimers
consists of 4
peptide chains.
2 identical light
chains and 2
identical heavy
chains connected

Antibody Structure
1. Variable region: the
site that bind antigen;
unique for only one
antibody
2. Constant region:
same amino acid
sequence for a class of
antibodies
3. Fc region: Y-shaped
portion; bind to a
complement or
another cell

Classes of Antibody
5 classes of antibodies: IgG, IgA, IgM IgE
IgD
1. IgG: most abundant antibody in serum;
Can cross blood vessels an enter tissue
Natural passive immunity: cross
placenta to protect developing foetus
Complement activation
Enhances phagocytosis by opsonisation
Neutralise virus and microbial toxins

Classes of Antibodies
2. IgM : 10% of serum
First antibody to appear primary
response to an antigen
Effective at agglutination of
antigen (ABO blood transfusion)
Complement activation

Classes of Antibody
Immunoglobulin A -- Ig A
Most abundant in mucus
membranes and body secretions
Helps prevent attachment of
microbial pathogens to mucosal
membranes e..g respiratory tract
and intestines

Ig D and Ig E
Ig D
no defined function

Ig E:
0.0002% of serum, but increases in
allergic response
Mediates allergic (hypersensitivity)
reactions, (eg asthma hay fever) by
stimulating histamine production
Lysis of parasitic worms

Antibody Summary
Ig G

Ig M

Ig A

Ig D

Ig E

Humoral in Action

Antibodies

Role of memory cells


Memory cells possess the specific
recognition apparatus that allows for
a more intense and rapid immune
response

Acquired Immunity
Active: direct exposure to the antigen
that stimulates an immune response
Passive: transfer of antibodies from
one individual to another
Passive immunity lasts only as long as
the antibody is present in serum.
Temporary since antibodies have a short
lifespan

Active Immunity
1. Natural Active Immunity: when the
person is exposed to the antigen in
environment, becomes sick and then
recovers. Immunologic memory
develops.
2. Artificial Active Immunity
(Vaccination/Immunisation): the
administration of the weakened form
of the antigen into the body to induce
an immune response.

Passive Immunity
1. Naturally passive immunity: the
transfer of antibodies from mother
to foetus (IgG) / mother to infant via
breast milk (IgA)
2. Artificial passive immunity: the
transfer of serum antibodies from an
already immune donor to a person.
(normally lasts for 3 weeks)

Applications of
Antibodies
Antibodiesare proteins produced by theB
lymphocytesof the immune system in
response to foreign proteins,
calledantigens.
Each B cell in an organism synthesizes only
one kind of antibody specific for one type
of antigen
Therefore antibodies can be used to
identify the presence of specific antigens/or
substances

Monoclonal Antibodies
(MABS)
To use antibodies as a tests for
detecting antigens, antibodies are
needed in large quantities.
However to be useful as a tool,
substantial amounts of a single
antibody (and that antibody alone)to
avoid mixed results.
E

Monoclonal Antibodies
(MABS)
Monoclonal antibodies

are cultured antibodies


produced from a single
type of hybridoma B
cells.
Hybridoma is a fusion of
a single type of B-cell
with an immortal
cancerous B-cell
(myeloma).
Hybridoma B cells allow
for the unlimited
production of a single
antibody

MABS Production
1. Introduction of antigen
into mouse in order to
activate B-cells specific
for that antigen
2. Isolate the activated B
cells
3. Fuse activated B-cells
with myeloma B cells to
make hybridoma
4. Screen hybridoma for the
ones specific to the
antigen.
5. Culture that single line of
hybridoma and isolate
monoclonal antibody

Application of MABS
Monoclonal antibodies can detect/mark
special proteins of interests
1. Diagnostic pregnancy Test to detect
hcg hormone in urine.
2. Diagnostic test for AIDS- ELISA test
3. Monoclonal antibodies can be used to
classify strains of a single pathogen.
Eg Neisseria gonorrhea has over 80
strains

MAB Pregancy Test

MABtherapy and Cancer


Cancer cells are mutated self-cells that divide
uncontrollably and invade other tissue. Because they
are still self-cells, it is difficult for immune system to
target them.
Cancer therapy: engineered monoclonal antibodies
bind proteins that are only expressed by cancer cells.
MABs can work against cancer in the following ways
1. Tag cancer cells for destruction by the immune
system
2. Deliver anti-cancer drugs specifically to cancer cells
3. Block signals that allow cancer cells to divide
4. Block signals produced by cancer cells that suppress
immune system

MAB therapy