Third Line of Defence

• Aims:

• Must be able to state the substances involved in the third line of immunity.

• Should be able to describe the production and differentiation of B and T cells.

• Could be able to outline the role of B and T cells.

The Third Line of Defense

• Specific resistance is a third line of defense.

• Forms the immune response and targets specific pathogens.

• Specialized cells of the immune system, called lymphocytes are:

– B-cells: produce specific proteins called antibodies, which are produced against specific antigens.

– T-cells: target pathogens directly.

B cell:Antibody production

T cell:Cell-mediated immunity

Lymphocytes

The 2nd line of defense

The 3rd line of defense

2

Third Line of Defense

• There are two main components of the vertebrate immune system:

• The humoral immune system involves the action of B-cells, which produce antibodies. The humoral system is associated with serum, the non-cellular part of the blood.

• The cell-mediated immune system is associated with the production of specialized lymphocytes called T-cells.

• The humoral and cell-mediated systems work separately and together to protect us from disease.

Cells of the Third Line of Defense

• Two main groups of lymphocytes are involved in specific immunity.

• All lymphocytes are produced in the bone marrow.

1. Mature in the bone marrow - B lymphocytes or B cells.

2. Mature in thymus gland - T lymphocytes or T cells.

• There are different kinds of B and T cells…

phagocytes

Mast Cell

- Secretes hisatmines

Distinguishing Self • Achieved through the Major Histocompatibility Complex (MHC).

• The MHC = cluster of tightly linked genes on chromosome 6 in humans.

• Genes code for protein molecules (MHC antigens) attached to the surface of body cells.

• The MHC antigens are used by the immune system to recognise its own and foreign material.

• Class I MHC antigens located on surface of all human cells.

• Class II MHC antigens restricted to macrophages and B-cells.

Antigens• Antigens = foreign substances that cause formation of antibodies.

• Antigens include:

– Potentially damaging microbes and their toxins.

– Substances such as pollen and flea and dust mite feces.

– Blood cell surface proteins.

– The surface proteins of transplanted tissues and organs.

B–Cells• B-cells (B-lymphocytes) originate and mature in the bone marrow of

the long bones (e.g. the femur).

• Migrate from the bone marrow to the lymphatic organs.

• B-cells defend against:– Bacteria and viruses outside the cell

– Toxins produced by bacteria (free antigens)

• Each B-cell can produce antibodies against only one specific antigen.

• A mature B-cell may carry up to 100 000 antibody molecules embedded in its surface membrane.

B-Cells

• Each B-Cell only has one type of antibody…

• The body needs to defend itself against millions of antigens.

• Only a small number of each corresponding antibody.

• The type of antibody is genetically predetermined.

• Having a small number of each antibody type means, more chance of ‘recognising’ the antigen.

Humoral Immunity

The humoral response begins when a foreign protein (antigen) activates a particular B-cell.

Other B-cells recognize different antigens

Surface antigen

Recognition

B-cell

PathogenThe particular B-cells multiply, to form many plasma cells.

Plasma cells make antibodies specifically designed to attack and kill the identified pathogen.

Plasma cells

OriginalB-cell

Antibodies

Second Exposure

Some B-cells differentiate into long lived memory cells.

These memory cells will rapidly produce antibodies if the same pathogen enters the body again.

• B-cells differentiate into two kinds of cells:

• Memory cells:When these encounter the same antigen again (even years or decades after the initial infection), they rapidly differentiate into antibody-producing plasma cells.

• Plasma cells:These secrete antibodies against antigens. Each plasma cell lives for only a few days, but can produce about 2000 antibody molecules per second.

Memory cell

Plasma cell

B–Cell Differentiation

Antibody

After the Antigen has Attached to an Immunoglobulin…

• The selected B-Cell then needs to reproduce rapidly so that

there is a large number of identical cells that can respond to

the antigen.

• This is called clonal expansion.

• Cells cloned in this way have exactly the same genetic

material and immunoglobulins.

• Most of these cells will then differentiate into plasma cells…

• Antibodies (immunoglobulins) are proteins made in response to antigens.

– Antibodies recognize and bind to antigens.

– Antibodies are highly specific and can help destroy antigens.

– Each antibody has at least two sites that can bind to an antigen.

Antigens and Antibodies

Antibody

Antigen

One of the two binding sites on the antibody

Molecular model

Symbolic

model

Antibody Structure

16

Immunoglobulins

• Although there are over 10 million different types of immunoglobulins in our bodies, they exist in several classes:

• IgM antibodies are usually the first to be secreted – cause an agglutination of antigens (makes easier for phagocytes).

• IgG activate complement proteins,neutralise toxins directly.

• IgA neutralise pathogens in the digestive, respiratory and reproductive tracts.

• IgE help initiate inflammation after infection.17

Inactivation of AntigensClumping

particulate antigens

Solid antigens such as bacteria are stuck together in clumps.

Bacterial cell

Neutralization

Antibodies bind to viral binding sites and coat bacterial toxins.

VirusToxin

Antibody

Enhances Phagocytosis

MacrophageBacteria

Soluble antigens are stuck together to form precipitates.

Precipitation of soluble antigens

Soluble antigens

Antibodies

Inactivation of Antigens Activation of complement

Tags foreign cells for destruction by phagocytes.

Bacterial cell

Complement

Enhances inflammation

Blood vessel

Macrophage Bacteria

Leads to rupture of cell

Lesion

Bacterial cell

Enhances phagocytosis

Macrophage Bacteria

Activity

• Complete the activities on pages 155 and 156 in Biozone book.

T-Cells• T-cells originate from stem cells and mature after

passing through the thymus gland.

• They respond only to antigenic fragments that have been processed and presented bound to the MHC by infected cells or macrophages (phagocytic cells).

• T-cells defend against:– Intracellular bacteria and viruses.– Protozoa, fungi, flatworms, and roundworms.– Cancerous cells and transplanted foreign

tissue.

• T-cells can differentiate into four specialized types of cell:– Helper T-cell

•Activates cytotoxic T cells andother helper T cells.

•Necessary for B-cell activation.

– Suppressor T-cell

•Regulates immune response by turning it off when no more antigen is present.

– T-cell for delayed hypersensitivity

•Causes inflammation in allergic reactions and rejection of tissue transplants.

– Cytotoxic (Killer) T-cell

•Destroys target cells on contact.

T-Cell Differentiation

The killer T-cells attach to and destroy the abnormal cell. Killer T-cells remain as memory cells to quickly attack any abnormal cells that reappear.

With the assistance of helper T-cells the killer T-cells begin to multiply.

Helper T-cell

Cell Mediated Immunity

Note: HIV (the AIDS virus) disrupts the cellular immune

system by destroying helper T-cells.

Antigens, such as those produced by abnormal cells, are identified by and activate specific killer T-cells.

Killer T-cells Antigen produced by abnormal cell

Recognition

Activity

• Complete the activities on pages 153 in Biozone book.