Pathogen and Defense Against Diseases (Topic 6.3 & 11.

1)

6.3.1 Define pathogen
!
A pathogen is a any disease causing .
!
Examples: virus, bacteria, prions, broidsd, fungi, protozoans.

6.3.2 Explain why antibiotics are effective against bacteria but not against viruses
!
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, 70S ribosomes and the bacterial cell
wall
!
Because eukaryotic cells do not have these features, antibiotic can kill bacterial cells without harming humans (or viruses)
!
Viruses 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 transcription in
retroviruses)





First Line of Defense
!
The first line of defense against infection are the skin and mucus that prevent the entry of pathogenic substances
!
Examples: Skin, mucous membranes
6.3.3 Outline the role of skin and mucous membranes in defense against pathogens
Skin
!
Protects external structures (outer body areas)
!
A dry, thick and tough region made of predominantly dead surface cells
!
Contains sebaceous glands - secrete chemicals which inhibit the growth of some bacteria
!
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.)
!
Secretions contain lysozyme, which can destroy cell walls and cause cell lysis
!
May be ciliated to aid in the removal of pathogens (along with physical actions such as coughing or sneezing)


!
The second line of defense against pathogenic invasion are the non-specific defense mechanisms
!
Non-specific mechanisms do not differentiate between types of microorganisms and always invoke the same response
!
Examples: phagocytic leukocytes, inflammation, fever and anti-microbial proteins
o
inflammation: red because of more blood, swelling because of histamines in injured area, more blood rushing to
injured area & more platelets so more white blood cells and clotting

6.3.4 Outline how phagocytic leukocytes ingest pathogens in the blood and in body tissue
!
Phagocytic leukocytes (macrophages) circulate in the blood but may move into body tissue in response to infection


!
They concentrate at sites of infection due to the release of histamine from damaged body cells
!
Pathogens are engulfed when 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 is called phagocytosis ('cell-eating')
Overview of Phagocytosis by a Leukocyte




!
The third line of defense are the specific defenses, coordinated by a type of leukocyte called lymphocytes
!
These can recognize and respond specifically to different types of microorganism and have memory (can respond more
effectively upon reinfection)

6.3.5 Distinguish between antigens and 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 (2 light and 2 heavy chains) joined together by disulfide 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 an unique antigenic fragment, making this interaction specific (like substrate interactions)
Structure of a Generalized Antibody





6.3.6 / 11.1.4 Explain antibody production

11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity

Challenge and Response
!
Challenge: pathogen enters blood
!
Response: - Pathogen engulfed by macrophage
- Macrophage takes on the antigen (or epitome - cell surface protein)
- Macrophage presents epitope to Helper T-Cells
- Complementary helper t cells is activated
- Helper T cell stimulates appropriate B celll
- B-cell produces clones
- Clones become either plasma cells or memory cells
- Plasma cells produce antibodies
- Memory cells remain as immunity to the pathogen


Clonal Selection
!
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
H
cells)
!
When antigens are presented to B cells (and T
H
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
(B
M
cells)


!
Because pathogens may contain several antigenic determinants, several B cell clones may become activated (polyclonal
activation)

!
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


!
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



6.3.7 Outline the effect of HIV on the immune system
!
The human immunodeficiency virus (HIV) is a retrovirus that infects helper t lymphocytes (T
H
Cells)
!
Reverse transcriptase allows viral DNA to be produced from its RNA code, which is integrated into the host cells genome
!
After a number of years of inactivity (during which infected T
H
cells have continually reproduced), the virus becomes active
and begins to spread, destroying the T
H
cells in the process (known as the lysogenic cycle)
!
This results in lower immunity as antibody production is compromised - the individual is now susceptible to opportunistic
infections





normal T
H
: 602




6.3.8 Discuss the cause, transmission and social implications of AIDS
Cause
!
Acquired Immunodeficiency Syndrom (AIDS) is a collection of symptoms and infections caused by the destruction of the
immune system by HIV
!
While HIV infection results in a lowering in immunity over a number of years, AIDS describes the final stages when observable
symptoms develop

Transmission
!
HIV is transmitted through the exchange of bodily fluids (including unprotected sex, blood transfusions, breast feeding, child
birth, etc.)
!
A minority of people are immune to HIV infection (they do not have the CD4+ T cell receptor that HIV needs to infect the
cell)

Social Implications
!
People with HIV may be stigmatized and discriminated against, potentially leading to unemployment and poverty
!
Majority of people who die from AIDS are at a productive age (25-40), which may cripple a country's workforce and
economic growth
!
It can result in an increased number of orphans, taxing a country's welfare resources
!
Poverty may increase transmission of Aids (due to poor education and high cost of treatments), creating a moral obligation
for assistance from wealthier countries


11.1.1 Describe the process of blood clotting

!
Clotting (hemostasis) 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 convert the inactive zymogen, prothrombin, into the activated enzyme, thrombin
!
Thrombin catalyzes the conversion of the soluble plasma protein fibrinogen into an insoluble form (fibrin)
!
Fibrin forms an insoluble mesh of fibers that trap blood cells at the site of damage
!
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
cell immunity-tcells
humoral immunity-B cells

11.1.3 Define active and passive immunity
Active immunity: Immunity due to the production of antibodies by the organism itself after the body's defense mechanisms are
stimulated by antigens
Passive immunity: Immunity due to the acquisition of antibodies from another organism in which active immunity has been
stimulated.
!
This passive acquisition of antibodies can be achieved via the placenta, colostrum or by injection (e.g. blood transfusions)


11.1.5 Describe the production of monoclonal antibodies and their use in diagnosis and treatment
!
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 (hybridized) with tumor cells capable of endless divisions (immortal cell line)
!
The resulting hybridoma is capable of synthesizing large quantities of specific antibodies, for use in diagnosis and treatment



Production of Monoclonal Antibodies


Diagnostic Use:
!
Monoclonal antibodies can be used to test for
1) pregnancy via the presence of human chorionic gonadotrophin (hCG)
2) HIV via Elisa test (if positive, turns yellow)

Pregnancy Test
!
An antibody specific 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 antibdyand 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


Elisa Test
!
A tray is coated with antigens for a pathogen.
!
serum samples are taken from a patient.
!
If samples contain the antibodies, a color change occurs which shows the patient is carrying the pathogen and the body is
trying to fight it.

Elisa Test

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
!


11.1.6 Explain the principle of vaccination
!
Vaccinations induce artificial active immunity by stimulating the production of memory cells
!
A vaccine contains weakend or attenuated forms of the pathogen and is (usually) injected into the bloodstream
!
Because a modified form of the pathogen is injected, the individual (usually) 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 may be required


11.1.7 Discuss the benefits and dangers of vaccination
Benefits:
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Vaccination results in active immunity
!
It can limit the spread of infectious diseases (pandemics / epidemic)
!
Diseases may be eradicated (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:
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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