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

nor does it have a memory response • Adaptive Immunity: a specific response to a specific microbe (slower) and it has a memory component .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.

WINT) Immunity Adaptive Cell Mediate d Phagocyt osis Humoral (Antibody ) Active Natural Innate Inflammati on” Passive Artificial Natural Artificial Anatomi c Complem ent .Immunity Map (By R.

Cell-Mediated and Humoral Mediated Immunity ADAPTIVE IMMUNITY .

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 .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.

Humoral Immunity: effects an immune response by inactivating antigen using antibodies produced by B-lymphocytes 2.Branches of Adaptive Immunity 1. 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 .

• Outline 1. B-lymphocytes mature in the bone marrow into a naïve B-cell expressing a unique antigen binding receptor (antibody) on its membrane. Activation: When the naïve B-cell encounters and binds a complementary antigen for the first time. 2. 3.B-Cell Maturation/Differentiation • Recall that all blood cells originate from stem cells in the red bone marrow in a process known as haemopoeisis. and the effectors plasma cells 4. this induces the B-cell to rapidly divide. 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 . Clonal Expansion: The B-cell progeny proliferates and differentiates into memory B-cell.

B-cell Differentiation .

T-lymphocyte Differentiation • T-lymphocytes differentiate in the red bone marrow. Activation/Clonal expansion: T-cell proliferates and differentiates into memory T cells and effector T cells . T-cell matures in thymus. but it matures in the thymus gland • Outline 1. 2. expressing T-cell receptors TCR on cell membrane. Naïve T-cell via its TCR bind to antigen-MHC complex expressed on antigen presenting cell 3.

Tc cells. other immune cells. secretes chemicals that are toxic to pathogens. Tc: binds MHC-I.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. Expresses CD8 . Express CD4 2. T-helper cells: binds MHC-II secrete chemicals that stimulate activation of B cells. T-cytotoxic cells.

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

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

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 . • However.HIV and T-cells • Once HIV has entered the body. the immune system initiates anti-HIV antibody and cytotoxic T cell production.

HIV/ CD4T-cell Infection • HIV causes illness by infecting and depleting CD4 T cell population. AIDS is characterised by opportunistic infections like tuberculosis. • AIDS develops when CD4 T cell count falls below 350 cells/uL -200 cells/uL • Because HIV destroys CD4 T cells. pneumonia etc . 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.

HIV and T-Cell .

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

.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 .

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. bind to a complement or another cell . Fc region: Y-shaped portion.Antibody Structure 1.

IgA.Classes of Antibody • 5 classes of antibodies: IgG. 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 . IgM IgE IgD 1.

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 Antibodies 2.

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

Ig D and Ig E • Ig D – no defined function • Ig E: – 0. but increases in allergic response – Mediates allergic (hypersensitivity) reactions.0002% of serum. (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 .

– Temporary since antibodies have a short lifespan .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.

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

(normally lasts for 3 weeks) . 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.Passive Immunity 1.

called antigens. • 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 .Applications of Antibodies • Antibodies are proteins produced by the B lymphocytes of the immune system in response to foreign proteins.

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

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

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

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

MAB Pregancy Test .

Deliver anti-cancer drugs specifically to cancer cells 3. Tag cancer cells for destruction by the immune system 2. Block signals produced by cancer cells that suppress immune system . MABs can work against cancer in the following ways 1.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. Block signals that allow cancer cells to divide 4.

MAB therapy .