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Transcript
Pathogen
and Defense
8.2 Structure
of DNAAgainst Disease (Topic 6.3 &11.1)
Fighting the
Enemy Within!
8.2
of DNA
6.3.1Structure
Define pathogen
• A pathogen is a disease-causing agent
• Example:
6.3.2
Explain why
are effective against bacteria
8.2 Structure
of antibiotics
DNA
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)
6.3.2
Explain why
are effective against bacteria
8.2 Structure
of antibiotics
DNA
but not against 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 transcriptase
in retroviruses)
http://www.youtube.com/watch?v=Rpj0emEGShQ (How a virus attacks your body)
http://www.sumanasinc.com/scienceinfocus/sif_antibiotics.html (The Rise in Antibiotic Resistance)
6.3.2
Explain why
are effective against bacteria
8.2 Structure
of antibiotics
DNA
but not against viruses
6.3.3
Outline the
of skin and mucous membranes in
8.2 Structure
ofrole
DNA
defense against pathogens
First Line of Defense
• The first line of defense against infection are the surface
barriers that prevent the entry of pathogenic substances
• Examples: skin and mucous membranes
6.3.3
Outline the
of skin and mucous membranes in
8.2 Structure
ofrole
DNA
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
6.3.3
Outline the
of skin and mucous membranes in
8.2 Structure
ofrole
DNA
defense against pathogens
•
•
•
•
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)
6.3.4
Outline how
leukocytes ingest pathogens in
8.2 Structure
of phagocytic
DNA
the blood and in body tissue
Second Line of Defense
•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
6.3.4
Outline how
leukocytes ingest pathogens in
8.2 Structure
of phagocytic
DNA
the blood and in body tissue
Phagocytic leukocytes (macrophages) circulate in the blood
but may move into body tissue in response to infection
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html Phagocytosis
6.3.4
Outline how
leukocytes ingest pathogens in
8.2 Structure
of phagocytic
DNA
the blood and in body tissue
•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')
8.2
ofbetween
DNA antigens and antibodies
6.3.5Structure
Distinguish
Third Line of Defense
• 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 micro-organism and have memory (can respond
more effectively upon reinfection)
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
8.2
ofbetween
DNA antigens and antibodies
6.3.5Structure
Distinguish
• Antibodies are made up of 4 polypeptide chains (2 light and
2 heavy 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 enzymesubstrate interactions)
8.2
ofbetween
DNA antigens and antibodies
6.3.5Structure
Distinguish
8.2
ofbetween
DNA antigens and antibodies
6.3.5Structure
Distinguish
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
Challenge and Response
Challenge:
Response:
pathogen enters blood
- Pathogen engulfed by macrophage
- Macrophage takes on the antigen (or
epitope - cell surface protein)
- Macrophage presents epitope to T cells
- Complementary helper T cells are activated
- Helper T cell stimulates appropriate B cell
- B-cell produces clones
- Clones become either plasma cells or
memory cells
- Plasma cells produce antibodies
- Memory cells remain as immunity to the
pathogen
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
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
(THcells)
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
Clonal Selection
•When antigens are presented to B cells (and TH 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 antibodyproducing plasma cells, a minority will become memory
B cells (BM cells)
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
http://www.youtube.com/watch?v=HUSDvSknIgI Fighting infection by clonal selection
http://www.sumanasinc.com/webcontent/animations/content/monoclonalantibodies.html Monoclonal antibodies
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
• Because pathogens may contain several antigenic
determinants, several B cell clones may become activated
(polyclonal activation)
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
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
6.3.6
/ 11.1.4 Explain
antibody production
8.2 Structure
of DNA
11.1.2 Outline the principle of challenge and response, clonal
selection and memory cells as the basis of immunity
• 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
8.2
ofeffect
DNAof HIV on the immune system
6.3.7Structure
Outline the
• The human immunodeficiency virus (HIV) is a retrovirus
that infects helper T lymphcytes (TH cells)
• Reverse transcriptase allows viral DNA to be produced
from its RNA code, which is integrated into the host cells
genome
8.2
ofeffect
DNAof HIV on the immune system
6.3.7Structure
Outline the
• After a number of years of inactivity (during which
infected TH cells have continually reproduced), the virus
becomes active and begins to spread, destroying
the TH 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
8.2
ofeffect
DNAof HIV on the immune system
6.3.7Structure
Outline the
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html
6.3.8
Discuss the
8.2 Structure
of cause,
DNA transmission and social
implications of AIDS
Cause
• Acquired Immunodeficieny Syndrome (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
6.3.8 Discuss the cause, transmission and social
8.2
Structure
of DNA
implications
of AIDS
Transmission
• HIV is transmitted through the exchange of bodily fluids
(including unprotected sex, blood transfusions, breast
feeding, child birth, etc.)
• The risk of exposure to HIV through sexual contact can
be reduced by using latex protection (condoms)
• 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)
6.3.8
Discuss the
8.2 Structure
of cause,
DNA transmission and social
implications of AIDS
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, 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
8.2
Structure
11.1.1
Describeof
theDNA
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:
8.2
Structure
11.1.1
Describeof
theDNA
process of blood clotting
• 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
8.2
Structure
11.1.1
Describeof
theDNA
process of blood clotting
• 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
8.2
Structure
of DNA
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. ex: placenta, colostrum
or by injection (e.g. blood transfusions)
8.2
Structure
of DNA
11.1.3
Define active
and passive immunity
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
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
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
•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
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
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
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
Pregnancy Test
• An antibody specific to hCG is made and is tagged to an
indicator molecule (e.g. chromatophore or pigment
molecule)
http://www.sumanasinc.com/webcontent/animations/content/pregtest.html Pregnancy Test
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
• 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
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
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.
11.1.5
Describeof
theDNA
production of monoclonal antibodies and
8.2 Structure
their use in diagnosis and treatment
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
8.2
Structure
of principle
DNA
11.1.6
Explain the
of 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
8.2
Structure
of principle
DNA
11.1.6
Explain the
of vaccination
• 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
8.2
Structure
of DNA
11.1.7
Discuss the
benefits and dangers of vaccination
Benefits:
• 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
8.2
Structure
of DNA
11.1.7
Discuss the
benefits and dangers of vaccination
Risks:
• 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