Transcript Pathogens, Disease and Defense Against Disease

Pathogens, Disease and Defense Against Disease
Pathogen – an organism that causes a disease
Examples of organisms that cause disease:
• viruses – influenza, chicken pox, AIDS, measles,
common cold, polio
• bacteria – cholera, diphtheria, pneumonia,
meningitis, tuberculosis, tetanus, salmonellosis
• fungi – athlete’s foot, ringworm, candidiasis,
farmer’s lung, asparagillosis
• protozoa – malaria, amoebiasis, trypansomiasis
(sleeping sickness)
• roundworms – elephantiasis, Ascaris, hookworms
• flatworms – pork and beef tapeworms, liver fluke,
schistosomiasis (bilharzias)
Pathogens gain entry to the body using one of the
following methods:
• from the air (droplets) – diseases of the human
respiratory system can be transmitted when an
infected person coughs or sneezes out droplets
containing pathogens, which are breathed in by an
uninfected person (common colds, flu, diphtheria)
• direct contact – physical contact with an infected
person carries the disease to an uninfected person
through natural body openings (many diseases)
• food/water – pathogens in contaminated food or
water enter the body through the digestive system
(amoebiasis, tapeworm, salmonella poisoning)
• cuts in the skin – allows pathogen to gain entry to
body (tetanus)
• using infected needles – needle may contain
pathogens in tiny drop of infected person’s blood
left on needle – common mode of transmission in
drug addicts (AIDS, blood carried diseases)
• blood transfusions – only occurs if blood supply is
contaminated with a disease such as AIDS
• sexual intercourse – sexually transmitted diseases
gain entry through the soft mucous membranes of
the penis and vagina during sexual intercourse
• insects – blood-sucking insects inject their
mouthparts though the skin and can transmit
pathogens that they sucked out of an infected
person (malaria)
The human body has three lines of defense
against microbial attack:
External barriers – skin and mucous
membranes
1.intact skin acts as a barrier to entry and is
inhospitable to microbial growth
– dry, dead skin does not contain moisture
necessary for microbial growth and most will be
ejected when skin cells are constantly soughed
off
– skin is protected by secretions from sweat and
sebaceous glands that contain natural
antibiotics (lactic acid) that inhibit microbial
growth
2.membranes (in respiratory and digestive
tracts) secrete mucus that contains
antibacterial enzymes (destroy bacterial
cell walls)
– the mucus also physically traps
microbes that enter body through nose
or mouth
– cilia on the membranes sweep up the
mucus with microbes to be swallowed,
coughed or sneezed out
Nonspecific internal defenses – effective against a
wide range of pathogens – three categories:
1. Phagocytic cells and natural killer cells
– the body contains several types of amoeboid white
blood cells that can engulf and digest microbes:
• macrophages (most important) - white blood
cells that crawl around in the extracellular fluid
ingesting microbes by phagocytosis, also act as
“antigen presenting” cells (present parts of
microbe to other cells of immune system)
• natural killer cells – another class of white blood
cells, do not directly attack microbes, act by
destroying the body’s own cells that have been
invaded by viruses, also recognize and destroy
cancerous cells
2.Inflammatory response (localized injury) – results
from injury and large-scale breaches of the skin
such as a cut – inflammation occurs, phagocytes
and killer cells are recruited, injured area is walled
off to isolate infected tissue
– damaged cells release histamine into wounded
area – makes capillary walls leaky and relaxes
smooth muscle surrounding arterioles, wound
becomes red, swollen, and warm
– chemicals are released to initiate blood clotting
(helps to seal off wound and limit entry of more
microbes)
– other chemicals (released by wounded cells and
microbes themselves) attract macrophages to eat
up microbes, dirt, and damaged cells
3.Fever – results when population of microbes
is sufficiently large enough to establish a
major infection
– fever increases the activity of the
phagocytic white blood cells
– fever slows down the reproduction of
microbes
– fever also helps fight viral infections by
increasing the production of interferon
(increases resistance of surrounding cells
to viral attack)
When non-specific defenses fail, the body
launches an Immune Response (specific
defense response to a particular
microorganism)
• immune system consists of about 2 trillion
lymphocytes (special type of white blood
cell) distributed throughout body but
clustered in thymus, lymph nodes, and
spleen
• immune response results from interactions
among the various types of lymphocytes
and the molecules that they produce
A successful immune response involves
1) recognizing an invader,
2) launching a successful attack to overcome the
invader, and
3) retaining a memory of the invader to ward off
future infections
• two key lymphocyte cells are involved in the
immune response: B cells and T cells
• arise from precursor cells in bone marrow
• some of these cells are released into
bloodstream and travel to the thymus and
differentiate into T cells (for thymus)
• B cells differentiate in the bone marrow
Step 1: Recognition of the invasion of microbes
• antigens – markers on cells or materials in blood
that are recognized by the immune system
– can be proteins on the cell surface of pathogens or toxins
released by pathogens dissolved in blood (usually large
proteins, polysaccharides, and glycoproteins)
– antigens on our own cells are recognized as “self” and do
not stimulate an immune response
• the surfaces of the body’s own cells bear large
proteins and polysaccharides just like microbes do
• these proteins are collectively called the major
histocompatibility complex (MHC)
• MHCs are unique to each individual – one person’s
MHCs would be recognized as foreign antigens in
another person’s body (which is why tissue/organ
transplants may be rejected)
• any foreign material entering the body can
act as an antigen and stimulate an
immune response
• antigen – “anti” – means antibody, “-gen” –
means generating, so an antigen is an
antibody-generating agent
Antibodies
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large proteins that are either attached to the surfaces of
B cells or dissolved in the blood plasma (these are
called immunoglobins, abbreviated Ig) – recognize and
attach to foreign antigens
Y – shaped molecules made of 4 polypeptides (2
“heavy” chains and two “light” chains)
antibodies have two sites that stick out and constantly
look for antigens (and attach to antigens) and one site
that sticks to the surface of its lymphocyte
antibodies act in two ways: 1) act as receptors and bind
to antigens triggering a response, and 2) act as
effectors and circulate in bloodstream neutralizing
poisonous antigens and destroying microbes bearing
antigens
tips of antibodies form highly specific binding sites for
antigens – each site has a specific shape and binds
only to a specific type of antigen
• there are five classes of antibodies (each
with a different function:
T-cell receptors – T-cells also have receptors
on their surfaces
• also have highly specific binding sites for
particular antigens
• act only as receptors to trigger an immune
response in T-cell (as compared to
antibodies that act as receptors to trigger a
response AND function in destroying foreign
antigens)
Step 2: Overcoming the microbial invasion –
the immune system mounts two types of
attack:
1) humoral immunity is provided by B cells
and circulating antibodies; invaders are
attacked before they can enter body
cells, and
2) cell- mediated immunity is produced by T
cells which attack invaders that have
made their way into body cells
Humoral immunity
• produced by antibodies in the blood – because
antibodies circulate in the bloodstream, humoral
immunity can only defend against invaders in blood
and extracellular fluid
• B cells with specific antibodies on their surfaces
bind to antigens on the invader
• binding causes B cells to divide rapidly – clonal
selection (resulting population of cells are genetic
clones of original parent B cell “selected” by
binding to particular antigen)
• daughter cells differentiate into two cells types:
memory cells and plasma cells
• memory cells do not release antibodies
but play an important role in future
immunity
• plasma cells become enlarged and make
huge quantities of their own specific
antibodies that are released into
bloodstream
antibodies destroy microbes in four ways:
1.neutralization – antibody may combine with
or cover up the binding site of a toxic
antigen such as a bacterial toxin, thereby
preventing the toxin from harming the body
2.promotion of phagocytosis – antibody may
coat surface of microbe and identify it as a
target for circulating phagocytic white blood
cells to engulf
3. agglutination – antibodies have multiple binding
sites and may bind to antigens on two different
microbes holding them together
– more and more antibodies link up with antigens on
different microbes clumping them together
– this enhances phagocytosis
4. complement reactions – the antibody-antigen
complex on the surface of an invading cell may
trigger a series of reactions with blood proteins
called the complement system
– these complement proteins bind to antibodies and
attract phagocytic cells or may directly destroy invaders
by creating holes in their plasma membranes (similar to
natural killer cells)
Monoclonal antibodies
• antibodies of the same type produced by cloning
in the laboratory – antibodies are useful for many
medical and scientific purposes
• antigen is injected into animal and resulting
plasma cells (antibody factories) are extracted
and merged with a myeloma (cancer) cell to form
a hybridoma (plasma cells will not divide outside
the body but cancer cells will)
• hybridomas divide under laboratory conditions
and produce the desired antibodies – monoclonal
antibodies
• because they are specific for a particular antigen,
can be used for a number of purposes in
diagnosis and treatment of disease
Example of monoclonal antibody use for diagnosis:
• pregnancy tests - use an antibody that binds to a
hormone released by embryo (HCG) – urine
containing potential hormone is exposed to
antibodies, if hormone (antigen) is present,
antibodies will bind and change color
• diagnosis of HIV (ELISA test)
Example of use in treatment:
• used to target cancer cells (monoclonal
antibodies are made with drugs attached to them)
• emergency treatment of rabies or cancer
• may be used for tissue typing to test for
transplant compatibility
Cell-mediated immunity
• produced by T cells, primary defense
against body’s own cells when they have
become cancerous or have been infected
by viruses
• also important in overcoming infection by
fungi or protists
• three types of T cells contribute to cellmediated immunity:
1. Cytotoxic T-Cells
2. Helper T-Cells
3. Suppressor T-Cells
Cytotoxic T cells
• release proteins that disrupt the infected
cell’s membrane
• this attack is activated when receptors on the
cytotoxic T cell’s membrane bind to antigens
on surface of infected cell – create giant
holes in target cell’s membrane
Helper T cells
• when receptors of these cells bind to
antigen, the cells release chemicals
(hormone-like) that assist other immune
cells in their defense of the body
• chemicals stimulate cell division and
differentiation in both B cells and cytotoxic T
cells
• very little immune response (cell-mediated
or humoral) can occur without the boost
provided by helper T cells (reason why
AIDS is so deadly)
Suppressor T cells
• act after an infection has been conquered
– help to shut off the immune response in
both B cells and cytotoxic T cells
• after infection is over, some suppressor T
cells and helper T cells remain and
function as memory T cells to help protect
the body against future exposure to the
same antigen
Step 3: “Remembering” the antigen for protection
against future exposure to the same
pathogen/antigen
• memory cells allow us to retain immunity to
antigens
• B and T memory cells survive for many years
• if body is exposed to antigens to which the immune
system as previously mounted a response, the
appropriate memory cells recognize the invaders –
they begin to multiply rapidly and produce a second
immune response by generating huge populations
of plasma cells and cytotoxic T cells
• second immune response is very rapid – invasion is
overcome so fast, there may be no noticeable
symptoms of infection
Secondary Immune Response
Summary of Humoral and CellMediated Immune Responses
Immunity and vaccinations
• Natural active immunity – immunity provided by
memory cells after body has been exposed to an
antigen – antibodies can be produced much more
quickly in a secondary response (ex. Chicken pox
– usually only get it once)
• vaccinations produce an artificial active immunity
• vaccinations contain dead or weakened versions
of bacteria or virus
• vaccination is injected and body launches an
immune response
• memory cells are left behind to provide natural
active immunity
Vaccinations are beneficial but may pose some
dangers
Benefits:
• vaccinations have almost eradicated many diseases
from the world – ex. Small pox
• deaths due to disease can be prevented – ex.
measles are a major cause of death of small
children in some parts of the world
• long-term disabilities due to disease can be
prevented – ex. if a pregnant woman becomes
infected with Rubella during pregnancy, the baby
can be born deaf, blind, and heart and brain
damage – mumps can cause infertility in men
Dangers:
• excessive amounts of vaccination may reduce the
ability of the immune system to respond to new
diseases – ex. it has been suggested that having too
many vaccinations in a short time harmed soldiers
fighting in the Gulf War
• immunity provided by vaccination may not be as
effective as immunity provided by actually catching a
disease – vaccination of children might make them
vulnerable to more severe infection as adults (ex. as
with measles)
• there can be danger of side effects from some
vaccines – ex. whooping cough vaccination
sometimes causes brain damage, and MMR vaccine
(measles, mumps, rubella) may increase the chance
of autism
Passive immunity
• immunity provided by antibodies formed by another
organism
• natural passive immunity – antibodies from mother
are passed to fetus through the placenta or passed
to baby through colostrum (first breast milk
produced) after birth
• artificial passive immunity – a person is given
ready-made antibodies (ex. Anti-serum for a
poisonous snake bite
• passive immunity is only temporary, antibodies are
eventually broken down and no immunological
memory is provided since the person did not make
the antibodies themselves
AIDS – Acquired Immune Deficiency Syndrome
• caused by two viruses – human
immunodeficiency viruses 1 and 2 (HIV-1
and HIV-2)
• viruses undermine the immune system by
infecting and destroying helper T cells
(responsible for stimulating both cellmediated and humoral immune responses
• AIDS does not directly kill its victims, they
become increasingly susceptible to
opportunistic diseases as the helper T cell
population declines – these other diseases
finally kill them
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HIV is a retrovirus – contains RNA as its genetic
material
– reproduce by transcribing RNA to DNA (using
reverse transcriptase) and then inserting the
DNA into the chromosome of a host cell
– eventually the infected cell begins transcribing
and translating the viral DNA and more viruses
are produced that enter into the bloodstream
– proliferating viruses eventually kill the host
helper T cell
– as the number of helper T cells decline, the
lymphocytes are no longer signaled to act
during an invasion and the victim no longer
produces sufficient antibodies to fight diseases
HIV infected Helper T cell
people become infected with HIV in several ways:
1. sexual intercourse – virus is present in semen and
vaginal secretions
2. in traces of blood on a hypodermic needle that is
shared by IV drug abusers
3. across the placenta from a mother to a baby, or
through cuts during childbirth or in milk during
breast-feeding
4. in transfused blood or with blood products such as
Factor VIII used to treat hemophiliacs
5. accidents causing blood contamination – the
disease can be transmitted between a patient and a
surgeon during operations, and between a patient
and a dentist through cuts in the skin
6. tattoos and ear piercing with infected needles
Social implications of AIDS:
• due to ignorance about the methods of
transmission, some people feel
uncomfortable in the company of HIV
positive people
• HIV positive people may have difficulty
obtaining health insurance, finding jobs,
having friends and building normal social
relations
• sexual life styles have changed due to the
awareness of and education about AIDS –
use of condoms has become prevalent
Blood Clotting
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can be considered as a body defense against
disease – stops the loss of blood, seals off the
wound, and prevents entry of pathogens
platelets – small cell fragments that circulate in
blood – play and important role
clotting begins with release of clotting factors
from damaged tissue cells or from the blood
plasma
clotting factors set off a series of reactions in
which the product of each reaction is the
catalyst of the next reaction
• this system helps ensure that clotting only
happens when it is needed and makes it a
very rapid process
• in the last reaction fibrinogen, a soluble
plasma protein, is altered to form long
protein fibers called fibrin
• fibrin forms a mesh of fibers across the
wound
• blood cells are caught in the mesh and soon
form a semi-solid blood clot
• vitamin K and calcium are needed in the
process