Immune System

Chapter 12

Immune System

• Definition: the body's defense against infectious organisms and other invaders.

• Through a series of steps called the immune response, the immune system attacks organisms and substances that invade body systems and cause disease

Antibiotics• Antibiotics are substances or compounds that kill or inhibit the

growth of bacteria by targeting the metabolic pathways of prokaryotes

• Specific prokaryotic features that may be targeted by antibiotics include key enzymes, certain ribosomes and the bacterial cell wall

• Because eukaryotic cells do not have these features, antibiotics can kill bacterial cells without harming humans (or viruses)

• Virus do not carry out metabolic reactions themselves but instead infect host cells and take over their cellular machinery

• Viruses need to be treated with specific antiviral agents that target features specific to viruses (e.g. reverse transcriptase in retroviruses)

Function of the immune system:

– Fight infection through the production of cells that inactivate foreign substances or cells.

– 2 general categories of defense mechanisms:• Nonspecific defenses

– Like fortress walls of the system• Specific defenses

– Work like security guards

Nonspecific Defenses1st Line of Defense

• Skin– Protects external structures (outer body areas)– A dry, thick and tough region made of predominantly dead

surface cells– Contains biochemical defense agents (sebaceous glands

secrete chemicals which inhibit the growth of some bacteria)

– The skin also releases acidic secretions to lower pH and prevent bacteria from growing

• Mucous Membranes– Protect internal structures (externally accessible cavities

and tubes, such as trachea, vagina and urethra)– A thin region containing living surface cells that release

fluids to wash away pathogens (mucus, tears, saliva, etc.)– Contains biochemical defense agents (secretions contain

lysozyme, which can destroy cell walls and cause cell lysis)– Mucous membranes may be ciliated to aid in the removal

of pathogens (along with physical actions such as coughing or sneezing)

Nonspecific Defenses1st Line of Defense

Nonspecific Defense2nd line of defense

• Inflammatory response- a nonspecific defense reaction to tissue damage caused by injury or infection

• White blood cells multiply; blood vessels expand; phagocytes (WBC) engulf and destroy bacteria

• Fever- elevated body temperature– Important because many pathogens can survive only within a narrow

temperature range

• Interferon- proteins that help other cells resist viral infections

• Function: inhibit the synthesis of viral proteins in infected cells and help block viral replication

Phagocytic Leucocytes• Phagocytic leucocytes circulate in the blood but may move into body

tissue in response to infection– White blood cells, specifically neutrophils and macrophages

• They concentrate at sites of infection due to the release of chemicals (such as histamine) from damaged body cells

• Pathogens are engulfed when cellular extensions (pseudopodia) surround the pathogen and then fuse, sequestering it in an internal vesicle

• The vesicle may then fuse with the lysosome to digest the pathogen• Some of the pathogens antigenic fragments may be presented on the

surface of the macrophage, in order to help stimulate antibody production

• This mechanism of endocytosis is called phagocytosis ('cell-eating')

Antigens vs. Antibodies• Antigen: A substance that the body recognizes as foreign and that

can evoke an immune response• Antibody: A protein produced by certain white blood cells (B

lymphocytes, plasma cells) in response to an antigen

• Antibodies are made up of 4 polypeptide chains joined together by disulphide bonds to form a Y-shaped molecule

• The ends of the arms are where the antigens bind and these areas are called the variable regions, as these will differ between antibodies

• Each type of antibody will recognize a unique antigenic fragment, making this interaction specific (like enzyme-substrate interactions)

Specific Defenses• Used if a pathogen gets past the nonspecific defenses– Immune response- series of specific defenses that attack

the particular disease-causing agent– Cells that recognize specific antigens

• B lymphocytes (B cells)- provide immunity against antigens and pathogens in the body fluids; called humoral immunity

• T lymphocytes (T cells)- provide defense against abnormal cells and pathogens inside living cells; called cell-mediated immunity

Humoral Immunity• Antigens of pathogens are recognized by B cells• B cells grow and divide producing plasma cells and memory B

cells• Plasma cells release antibodies- proteins that recognize and

bind to antigens• Antibodies attack the pathogen in the bloodstream• Memory B cells remain capable of producing antibodies

specific to that pathogen• Secondary response is much faster and greatly reduces that

chance that the disease would develop a second time• Antibody structure has specific binding sites for antigens;

adults can produce about 100 million different types of antibodies

Cell-Mediated Immunity• T cells divide and differentiate into killer T cells (cytotoxic T-

cells), helper T cells, suppressor T cells, and memory T cells• Killer T cells track down and destroy the bacteria, fungi,

protozoan, or foreign tissue that contains the antigen• Helper T cells produce memory T cells• Memory T cells will cause a secondary response if the same

antigen enters the body again• Suppressor T cells release substances that shut down the

killer T cells• Rejection is a process in which an organ is recognized as a

foreign object and is attacked by the immune system

Antibody Production• B lymphocytes (B cells) are antibody-producing cells that develop

in the bone marrow to produce a highly specific antibody that recognizes one type of antigen

• When wandering macrophages encounter a pathogen, they digest it and present the antigenic fragments on their surface to helper T lymphocytes (T cells)

• These cells activate the appropriate B cell which divides and differentiates into short-lived plasma cells that produce massive quantities of antibody (~2,000 molecules per second for ~4 - 5 days)

• A small proportion of B cell clones develop into memory cells, which may survive for years providing long-term immunity

Blood Clotting

• Clotting (haemostasis) is a mechanism that prevents the loss of blood from broken vessels

• Damaged cells and platelets release chemical signals called clotting factors which trigger a coagulation cascade:

• Clotting factors also cause platelets to become sticky, which then adhere to the damaged region to form a solid plug called a clot

• The clot prevents further blood loss and blocks entry to foreign pathogens

Challenge and Response• When the body is challenged by a foreign pathogen it will

respond with both a non-specific and specific immune reaction

• The body is capable of recognizing invaders as they do not possess the molecular markers that designated all body cells as 'self'

• Non-specific immune cells (macrophages) present the foreign antigens to lymphocytes as examples of 'non-self'

• These lymphocytes can then respond with the production of antibodies to destroy the foreign invaders

Clonal Selection• Each B lymphocyte has a specific antibody on its surface

that is capable of recognizing a specific antigen• When antigens are presented to B cells (and T cells) by

macrophages, only the B cell with the appropriate antibody will become activated and clone

• The majority of B cell clones will differentiate into antibody-producing plasma cells, a minority will become memory B cells (BM cells)

• Because pathogens may contain several antigenic determinants, several B cell clones may become activated

Memory Cells• Because the adaptive immune response is dependent on clonal

expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies

• When a B cell does divide and differentiate into antibody-secreting plasma cells, a small proportion of clones will differentiate into memory cells

• Memory cells remain in the body for years (or even a lifetime)• If a second infection with the same antigen occurs, the memory cells

react faster and more vigorously than the initial immune response, such that the symptoms of the infection do not normally appear

• Because the individual no longer presents with the symptoms of infection upon exposure, the individual is thus said to be immune

Antibody Production• Antigens stimulate an immune response via the production of antibodies• When a pathogen invades the body, it is engulfed by wandering

macrophages which present the antigenic fragments on its surface• This macrophage becomes an antigen-presenting cell, and presents the

antigen to helper T cells (TH cells)• The TH cells bind to the antigen and become activated, and in turn

activate the B cell with the specific antibody for the antigen• This B cell clones and differentiates into plasma cells and memory cells• The plasma cells produce high quantities of specific antibody to the

antigen, whereas memory cells survive in the bloodstream for years• Upon re-exposure to the antigen, memory cells initiate a faster and

stronger response and thus confer long-term immunity

Monoclonal Antibodies

• Monoclonal antibodies (mAb) are antibodies derived from a single B cell clone

• An animal (typically a mouse) is injected with an antigen and produces specific plasma cells

• The plasma cells are removed and fused (hybridised) with tumor cells capable of endless divisions (immortal cell line)

• The resulting hybridoma is capable of synthesising large quantities of specific antigen, for use in diagnosis and treatment

Diagnostic Use• Monoclonal antibodies can be used to test for pregnancy

via the presence of human chorionic gonadotrophin (hCG) • An antibody specific to hCG is made and is tagged to an

indicator molecule (e.g. chromatophore or pigment molecule)

• When hCG is present in the urine it binds to the anti-hCG monoclonal antibody and this complex will move with the fluid until it reaches a second group of fixed antibodies

• When the complex binds to the fixed antibodies, they will appear as a blue line (positive result) due to the presence of the indicator molecule

Treatment Use

• Monoclonal antibodies can be used for the emergency treatment of rabies

• Because the rabies virus is potentially fatal in non-vaccinated individuals, injecting purified quantities of antibody is an effective emergency treatment for a very serious viral infection

Acquired Immunity• Edward Jenner made observations of cowpox and smallpox

infections; infected a boy with cowpox; watched the reaction take place; infected him with smallpox; no development of disease

• Active immunity- type of immunity produced by the body’s reaction to a vaccine– More than 20 serious diseases can be prevented through vaccinations

• Passive Immunity- short-term immunity caused when antibodies produced by other animals for a pathogen are injected into the body– Natural immunity example- mother to fetus– Deliberate exposure example- travelers to other countries or rabies

Vaccination• Vaccinations induce artificial active immunity by stimulating the

production of memory cells • A vaccine contains weakened or attenuated forms of the pathogen

and is (usually) injected into the bloodstream• Because a modified form of the pathogen is injected, the individual

should not develop disease symptoms• The body responds to the vaccine by initiating a primary immune

response, resulting in the production of memory cells• When exposed to the actual pathogen, the memory cells trigger a

secondary immune response that is much faster and stronger• Vaccines confer long-term immunity, however because memory

cells may not survive a life time, booster shots may be required

Benefits of Vaccinations• Vaccination results in active immunity• It can limit the spread of infectious diseases (pandemics /

epidemics)• Diseases may be eradicated entirely (e.g. smallpox)• Vaccination programs may reduce the mortality rate of a

disease as well as protect vulnerable groups (e.g. youth, elderly)

• Vaccinations will decrease the crippling effects of certain diseases (e.g. polio)

• It will decrease health care costs associated with treating disease conditions

Risks of Vaccinations

• Vaccinated individuals may produce (mild) symptoms of the disease

• There may be human error in the preparation, storage or administration of the vaccine

• Individuals may react badly to vaccines (e.g. hypersensitive / allergic reactions)

• Immunity may not be life long - booster shots may be required

• There may be possible toxic effects of mercury-based preservatives used in vaccines