1. Immune System
Chapter 12

2. 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

3. 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)

4. 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

5. Nonspecific Defenses 1st 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

6. Nonspecific Defenses 1st Line of Defense
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)

7. Nonspecific Defense 2nd 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

8. 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')

9. 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) 

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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