Transcript Defense against infectious disease

Defense against
infectious disease
Topics 6.3 and 11.1
Assessment Statements
• 6.3.1 Define pathogen.
• 6.3.2 Explain why antibiotics are effective against bacteria but
not against viruses.
• 6.3.3 Outline the role of skin and mucous membranes in
defence against pathogens.
• 6.3.4 Outline how phagocytic leucocytes ingest pathogens in
the blood and in body tissues.
• 6.3.5 Distinguish between antigens and antibodies.
• 6.3.6 Explain antibody production.
• 6.3.7 Outline the effects of HIV on the immune system.
• 6.3.8 Discuss the cause, transmission and social implications
of AIDS.
Pathogen
• Any living organism or virus that is capable of
causing a disease
• Include:
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Viruses
Bacteria
Protozoa
Fungi
Worms
• Exposure to vast majority does not result in
disease
• Why not?
The “big three” diseases
Disease
Cause
Pathogen
Tuberculosis
Bacterial infection
Mycobacterium
tuberculosis
AIDS
Viral infection
Human
immunodeficiency
virus (HIV)
Malaria
Protozoan
infection
Plasmodium sp.
“neglected” diseases
Disease
Pathogen
Protozoan infections
 African trypanosomiasis
 Kala-azar (visceral leishmaniasis)
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Trypanosoma gamviense, T. rhodiense
Leishmania donovani
Helminth (worm) infections
 Ascariasis
 Trichuriasis
 Hookworm infection
 Urinary schistosomiasis
 Hematobiliary schistosomiasis
 Lymphatic filariasis
 Onchocerciasis
 Dracunculiasis
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Ascaris lumbricoides
Trichuris trichiura
Necator americanus
Schistosoma haematobium
Schistosoma mansoni
Wuchereria bancrofti
Onchocerca volvulus
Dracunculus medinensis
Bacterial infections
 Trachoma
 Leprosy
 Buruli ulcer
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Chlamydia trachomitis
Mycobacterium leprae
Mycobacterium ulcerans
Antibiotics
• Both fungi and bacteria act as
decomposers and sometimes compete
with one another for food
• Some microorganisms produce chemicals
called antibiotics to inhibit growth of their
competitors
• Antibiotics interfere with bacterial
metabolic processes such as DNA
replication, transcription, translation,
ribosome function, and cell wall formation
Why are antibiotics effective against bacteria but
not against viruses?
• Bacteria background
– Prokaryotic
– Different kind of protein synthesis
– Cell wall
• Antibiotics are chemicals which take advantage of
differences between prokaryotic and eukaryotic cells
• Categories:
– Selectively blocks protein synthesis
– Inhibits the production of a new cell wall, thus blocking their
ability to grow and divide
• Virus background
– Make use of our body cells’ metabolism
– Any chemical that could inhibit this would also damage our
cells
Non-specific immunity
• The ability to resist infection by a disease
is termed immunity
• Non-specific immunity allows the body to
resist infection by a wide range of
pathogens
Role of skin
• Barrier to infection
• Two layers
– Dermis (sweat glands, capillaries,
sensory receptors and dermal cells
which give structure and strength to
the skin)
– Sebaceous glands secrete sebum
with maintains skin moisture and
slightly lowers pH which inhibit the
growth of bacteria and fungi
– Epidermis (constantly being replaced
as underlying dermal cells dies and
are moved upwards)
• As long as are skin stays intact,
we are protected from most
pathogens entering living tissue
Role of stomach acid
• Kills most of ingested particles
Role of mucus membranes – secrete mucus
that has the anti-bacterial enzyme lysozyme
Area with
mucous
membrane
What it is and does
Trachea
Tube which carries air to and from the lungs; pathogens
and harmful particles are trapped and expelled or
swallowed
Nasal passages Tubes which allow air to enter the nose and then the
trachea; pathogens and harmful particles are trapped and
expelled or swallowed
Urethra
Tube which carries urine from bladder to the outside;
pathogens and harmful particles are trapped and expelled
Vagina
Reproductive tract leading from uterus to the outside;
pathogens and harmful particles are trapped and expelled
Role of phagocytic leukocytes
• If microorganisms get past the physical
barriers and enter the body, phagocytic
cells engulf them by endocytosis
• A.k.a. white blood cells
• Found in bloodstream
• Macrophage
– Type which gets involved early in the process of
fighting off a pathogen
– Large wbcs that are able to change their
cellular shape to surround an invader and take
it through the process of phagocytosis
– Often referred to as amoeboid motion
– Can squeeze in and out of small blood vessels
When a macrophage meets a cell
• Recognizes ‘self’ cells from ‘not-self’
• Recognition based on the protein molecules
that make up part of the surface of all cells
and viruses
• If the proteins are ‘self’, then the cell is left
alone
• If the proteins are ‘not-self’, the macrophage
engulfs the invader by phagocytosis
• Lysosomes within the macrophage chemically
digest whatever has been engulfed
• Type of response is non-specific b/c the
identity of the pathogen has not been
determined at this point
Specific Immunity
• If microorganisms get past the physical
barriers, proteins and other molecules on
the surface of pathogens are recognized
as foreign by the body and they stimulate
a specific immune response
• Any chemical that can stimulate an
immune response is referred to as an
antigen
• A protein called an antibody binds to
antigens
• Our bodies can produce a vast array of
different antibodies, each one specific to a
certain antigen
Antibodies
• Protein molecules that we produce in
response to a specific type of pathogen
• Each type of antibody is different
• Each pathogen is made up of either cells
with cell membranes or, in the case of a
virus, a protein coat
• Cellular invaders have proteins called
antigens that are embedded into their
outer surface
• Most pathogens have several different
antigens on their surface and therefore
may trigger the production of many
different types of antibodies
• Each antibody is a protein that is Y shaped
• At the end of each of the forks of the Y is a
binding site
• The binding site is where the antibody
attaches itself to an antigen
• b/c the antigen is a protein on the surface of
a pathogen, the antibody thus becomes
attached to the pathogen
Outcomes of the binding of
antibodies to antigens
• Making the pathogen more recognizable to
phagocytes so that they are more readily
engulfed
• Preventing viruses from docking to host
cells so that they cannot be taken up by
host cells
• Causing sticking together or
“agglutination” of pathogens so that they
are prevented from entering cells and are
easer for phagocytes to ingest
Lymphocytes
• WBCs responsible for the production of
antibodies
• B lymphocytes – differentiate in the bone
marrow
• T lymphocytes – differentiate
Antibody production (Specific
Immune Response)
• The bloodstream contains many different
types of B lymphocytes or B cells
• Each type is capable of synthesizing and
secreting a specific antibody which binds
to a specific antigen
• Problem: there isn’t enough room to have
enough of each type of B cell for the
amount of antibody secretion that may be
needed at various times
• Leukocytes represent roughly 1% of all the
cells in your bloodstream
• Cellular communication methods lead the
cloning of the appropriate B cell type for
antibody synthesis when needed
1. Macrophage encounters a foreign antigen
and engulfs the possible pathogen by
phagocytosis
2. Antigens of the invader are displayed on
the cell membrane of the macrophage –
this is known as antigen presentation
3. Leukocytes known as helper-T cells
chemically recognize the antigen being
presented and become activated
4. Helper-T cells chemically communicate
with the specific B cell type (which has
also come in contact with the antigens)
that is able to produce the antibody
needed
5. animation
Cell cloning
• When a helper-T cell activates a specific B
cell, the activated B cell type begins a
series of cell division known as cell cloning
• Types
– Antibody-secreting plasma cells – secrete
antibodies immediately and help to fight off the
primary infection
– Memory cells – do no secrete antibodies during
the primary infection, but are long-lived cells
which remain circulating in the bloodstream
waiting for a subsequent infection
How HIV damages the immune
system
• Human immunodeficiency virus (HIV) is
the virus that eventually results in the set
of symptoms collectively called acquired
immune deficiency syndrome (AIDS)
• All viruses must find a type of cell in the
body that matches their own proteins in a
complementary way
• Helper-T cell is a communicator cell that
HIV infects
• HIV has a latency period that may be
several years long
• Helper-T cells communicate which cells
need to undergo cloning process and
begin antibody production
• When the helper-T cells begin to die, the
communication ceases and antibodies do
not get produced
• At this stage, the individual no longer fights
off pathogens as they did before and the
symptoms of AIDS start to appear
Issues related to AIDS
• Hard to find a vaccine or cure b/c it ‘hides
away’ for years
• It is waiting for some chemical signal to
become active
• It also mutates very quickly
• The body’s immune responses or vaccines
may not even recognize HIV after it has
mutated several times
• Initially it was difficult to get funding due to
the association of HIV with sexual activity
and drug abuse
• Enzyme-linked immunosorbent assays
(ELISA) are often used to detect the
presence or absence of a particular protein
– Newly infected people will initially produce
antibodies against HIV
– ELISA detects them
• HIV is transmitted person to person by
body fluids
• Blood is now routinely tested for the
presence of blood-borne diseases and
immediately destroyed if pathogens are
found
• Originally labeled as a disease affecting
homosexuals and drug abusers
• Now know that it is rapidly spreading by
heterosexual encounters
• Those diagnosed may be discriminated
• The Ray Brothers
• Until a cure is found, we continue to
lengthen the life-span of those infected
and to educate people on how to decrease
their risk of exposure to HIV
• Vaccine trial
Defence against
infectious disease
Topic 11.1
Assessment Statements
• 11.1.1 Describe the process of blood
clotting.
• 11.1.2 Outline the principle of challenge
and response, clonal selection and
memory cells as the basis of immunity.
• 11.1.3 Define active and passive immunity.
• 11.1.4 Explain antibody production.
• 11.1.5 Describe the production of
monoclonal antibodies and their use in
diagnosis and in treatment.
• 11.1.6 Explain the principle of vaccination.
• 11.1.7 Discuss the benefits and dangers of
vaccination.
Why does blood clot?
• When small blood vessels get broken,
blood escapes from the closed circulatory
system
• Our bodies create a clot which ‘seals’ the
damaged blood vessels preventing
excessive blood loss and helping to
prevent pathogens from entering the body
• Prothrombin and fibrinogen are plasma
proteins which circulate in the blood
• Platelets are cell fragments which also
circulate
Blood clotting sequence
• Blood vessel is damaged
•
• Damaged cells release
chemicals which stimulate
platelets to adhere to the
damaged area
• Other platelets begin adhering •
to those platelets
• To strengthen the plug, the
damaged tissue and platelets
•
release chemicals called
clotting factors which convert
prothrombin into thrombin
Thrombin is an active
enzyme which catalyses the
conversion of soluble
fibrinogen into the relatively
insoluble fibrin
Fibrin is a fibrous protein
which forms a mesh-like
network that helps to
stabilize the platelet plug
More cellular debris gets
trapped in the fibrin mesh
and soon a stable clot has
formed preventing both
further blood loss and entry
of pathogens
Hemophilia
• Inherited blood disorder which is sexlinked
• Most are male
• People born with hemophilia have little or
no clotting factor
Principles of true immunity
• Challenge and response
– Immune system challenged by an antigen
during 1st infection in order to develop an
immunity
– Macrophages, helper-T cells, B cells
• Clonal selection
– Identification of plasma B cells
– Multiple cell divisions to build up #s of same cell
• Memory cells
– Provide long-term immunity
Types of immunity
• Active
– Always leads to the production of memory cells
– Provides long-term immunity
• Passive
– When an organism acquires antibodies which
were produced in another organism
– Only the organism which produces the
antibodies has the memory cells
– Mother to fetus through placenta
– From mother’s colostrum
– Injection of antibodies in antisera (antivenoms
produced for treatment of poisonous snake and
spider bites)
Polyclonal antibodies
• Primary immune response
• Pathogen is being recognized as many
antigens and not just one
• Each of the protein types can cause an
immune response and thus several
different kinds of plasma B cells undergo
clonal selection, so several different kinds
of antibodies are produced and several
different kinds of memory cells remain
after the infection
• It is difficult to separate the different kinds
of antibody that have been produced
Monoclonal antibodies
• Researchers have developed a clever and
unique procedure for forming many
antibodies, all of the same type
• Procedure:
– Inject an antigen into a laboratory animal
– Animal is given time to go through a primary
immune response
– Response is polyclonal
– Spleen is harvested to gain access to many
blood cells
– B cells kept alive by fusing them with cancerous
(myeloma) cells
– When B cells and myeloma cells are grown
together a few of the cells fuse together and
become a cell called a hybridoma
– These hybrid cells produce antibodies of a
particular type and they are very long lived (as
are all cancer cells)
– Individual hybridomas transferred and cultured
in separate containers
– Each container is tested for the presence of a
particular antibody by use of the ELISA test
– Enzyme-linked immunosorbent assay test
identifies which containers hold a pure colony of
B cells which are producing the type of antibody
desired
– These cells are cultured for a very long period
of time
– animation
Uses of monoclonal antibodies
• Diagnosis
– Pregnancy testing which detects human
chorionic gonadotrophin (HCG)
– Anti-HCG antibodies are chemically bonded to
an enzyme which catalyses a color change
when the antibody encounters HCG molecules
• Treatment
– Monoclonal antibodies that target the cancercell antigens
– Antibody could be chemically modified to carry
with it a toxin specific for this type of cancer
– Antibody could contain a radioisotope for pinpoint radiation therapy
How does a vaccine result in
immunity?
• One cannot be immune to a pathogen before being
exposed to it at least once
• For many diseases, vaccines have been developed
that act as the first exposure to the pathogen
• Vaccine is developed by weakening a pathogen
and then injecting the pathogen into the body
• Methods:
– Selecting a weak strain
– Heating the pathogen
– Chemical treatment of pathogen
• Infection is not prevented, but the secondary
immune response is quicker and more intense than
the primary response
Benefits and dangers of
vaccination
Benefit
Danger
Possible total elimination of the disease
(ex. Smallpox)
Prior to 1999, many vaccines contained
thimerosal, a mercury-based
preservative. Mercury has been shown to
be a neurotoxin.
Decrease in spread of epidemics and
pandemics
Perception exists that multiple vaccines
given to children in a relatively short
period of time may ‘overload’ their
immune system
Preventative medicine is typically the
most cost-effective approach to
healthcare
Anecdotal evidence suggested that MMR
vaccine may have a link the onset of
autism (no support from clinical studies)
Each vaccinated individual benefits b/c
the full symptoms of the disease do not
have to be experienced in order to gain
immunity
Cases have been reported of vaccines
leading to allergic reactions and
autoimmune responses