Download Defenses Against Disease

Defenses Against Disease
Chapter 36
Defending Against Pathogens
• The world is teeming with microscopic
organisms (microbes)
– Some are parasites, live in or on the bodies
of other living organisms, sometimes doing
harm
– When microbes cause disease they are
called pathogens
Basic Mechanisms of Defense
• There are three basic lines of defense
against disease
• Vertebrate have all three lines of defense
• The first line of defense: nonspecific
external barriers
– Prevent microbes from entering the body
– Examples: skin and mucous membranes
Skin and Mucous Membranes
• The skin is important in blocking microbe
entry and suppressing microbe growth
– Skin is a barrier to microbes
– Skin is continually shed, removing microbes
that gain a foothold on skin
– Many skin secretions contain natural
antibiotics
Skin and Mucous Membranes
• Mucous membranes have effective
microbe defense mechanisms
– Mucous membrane secretions contain
antibacterial enzymes (example: lysozymes)
– Mucus traps microbes entering the nose or
mouth
– Respiratory tract cilia sweep mucus and
microbes away from lungs
Basic Mechanisms of Defense
• The second line of defense: nonspecific
internal barriers
– Occurs when microbes breach nonspecific
external barriers
– Broad internal responses to microbe infection
– Examples: phagocytic white blood cells,
inflammation, fever
Nonspecific Internal Defenses
• Broad defenses that attack microbes that
penetrate the skin
• Three major categories of nonspecific
internal defenses
– Phagocytic cells and natural killer cells
– The inflammatory response
– Fever
Phagocytic cells
• Macrophages and neutrophils
– White blood cells that ingest dead cells,
cellular debris, and microbes by phagocytosis
Natural Killer Cells
• A type of white blood cell
• Attack body cells that are cancerous or
infected with virus
– Secrete enzymes that poke holes in the cell
membrane of virally-infected or cancerous
cells
The Inflammatory Response
• Causes tissues to become warm, red,
swollen, and painful
• Functions
– Attracts phagocytes to infected or injured
tissue
– Promotes clotting
– Initiates protective behavior
The Inflammatory Response
• Tissue is damaged and bacteria enter
body
• Damaged cells produce chemicals that
stimulate mast cells to release histamine
– Capillary walls become "leaky"
– Blood flow increases
– Tissues become swollen, red, and painful to
touch
The Inflammatory Response
• Macrophages are attracted to histamine
– Consume bacteria and release cytokines
that attract more white blood cells
– Pus may be produced
• Blood clots promote healing by isolating
the site
Fever
• Helps combat large-scale infection by elevating
body temperature
• Some cells release cytokines in response to
infection
– Antibacterial cytokines
• Macrophages release endogenous pyrogens: elevate body
temperature
• Other cytokines: decrease iron in the blood
• Both act to slow bacterial reproduction
– Antiviral cytokines: Interferon, which helps cells resist
viral attack
Basic Mechanisms of Defense
• The third line of defense: specific immune
response
– Immune cells selectively destroy specific
invading microbes and toxins
– Invaders are “remembered,” allowing for a
rapid future response to invasion
Immune Response
• 2 types:
• Active Immunity – actively making
antibodies in response to an antigen
• Passive Immunity – receive antibodies
and/or immune cells from someone else.
– Short term immunity. Eventually “new “ cells
are recognized as foreign & destroyed
Immune Response
• The immune response involves
specialized white blood cells called
lymphocytes
• The immune system: lymphocytes, the
chemicals they produce, and the organs
that they live in
Immune Response
• Two major types of lymphocytes
– B cells: formed and differentiate in the bone
marrow
– T cells: formed in the bone marrow;
differentiate in the thymus
Key Characteristics
• An immune response has three steps
– First: the immune system must recognize an
invader
– Second: the immune system must launch an
attack
– Third: the immune system must remember
specific invaders to ward off future infections
Detection of Invaders
• Foreign invaders exhibit characteristic
antigens
– Foreign molecules that are particular to an
invading microbe or toxin
– Immune cells respond to the presence of
antigens
Antibodies and T-cell Receptors
• Antibodies and T-cell receptors recognize and
bind to foreign antigens
• Antibodies are proteins that can be attached to
B cells or free-floating in the blood
• Antibodies
– Y-shaped molecules made of light peptide chains and
heavy peptide chains
– Both chains have constant and variable regions
that form highly specific antigen binding sites
– Each type of antibody is unique to the B cell that
makes them
Antibodies
• There are five different classes of
antibodies(IgA, IgD, IgE, IgG, IgM), which
perform various functions
– Inactivate their antigens by binding them and
causing them to clump together
– Assist white blood cells to engulf microbes
– Activate natural killer cells
– Bind to blood proteins of the complement
system…
Antibodies
– Some classes of antibodies can cross the
placenta and provide immunity to a
developing child (IgG)
– Another class is secreted in breast milk
– Both help the newborn, whose immune
system is not fully developed
T-cell Receptors
• T-cell receptors are attached to T cells
• Consist of 2 polypeptide chains
– Specific binding sites protrude from the T cell
• Bind to antigen, which triggers a T-cell response
• Response is triggered only when they encounter
antigens
– On the membranes of cancerous or infected cells
– Presented on the membranes of macrophages that
have ingested the invading microbes
T-cell Receptors
• Do not directly inactivate pathogens
• Alter the activity of the T cell to which they
are attached
Millions of Antigens Recognized
• The immune system can recognize
millions of different antigens and responds
by producing specific antibodies and Tcell receptors for each antigen
• How does the immune system make so
many specific antibodies and T-cell
receptors?
• There are no genes for entire antibody or
receptor molecules
Millions of Antigens Recognized
• Antibodies and T-cell receptors are
proteins encoded by a small number of
genes that specify different versions of
antibody regions
• The different versions can be pieced
together in millions of combinations
Millions of Antigens Recognized
• As each individual B cell develops, it
retains only a few randomly selected
genes
• Thus, each B cell produces only a single
type of antibody, specified by the chance
recombination of antibody genes
Millions of Antigens Recognized
• NOTE: millions of different antibodies and
T cell receptors are produced prior to
infection
– An invading antigen binds to a compatible
antibody or T cell receptor by chance
– The immune system does not design
compatible antibodies and T cell receptors to
bind to an invading antigen
“Self” from “Non-self”
• The immune system
– Distinguishes “self” from “non-self”
– Does not attack normal body cells
• Due to major histocompatibility
complexes (MHC) on body cells
– Large protein and polysaccharide complexes
– ID cells as being “of self”
– Immune cells ignore these cells
– Unique for everyone (except identical twins)
Immune Cells Launch an Attack
• Once an invading antigen has been
detected, two forms of attack occur
– Humoral immunity
– Cell-mediated immunity
Humoral Immunity
• Provided by B cells and circulating
antibodies
• Attack antigens circulating in the
bloodstream and lymph
• Each B cell has a unique antibody
attached to its surface that will only bind
with properly shaped antigens
Humoral Immunity
•
The mechanism of humoral immunity
occurs in the following series of steps
•
Attached B cell antibodies bind to an invading
antigen in the blood
Bound B cell divides rapidly forming many
identical copies (clonal selection)
B cell clones differentiate to form memory B
cells and plasma cells
•
•
Humoral Immunity
• Memory B cells: saved to fight future
infection
• Plasma cells: mass-produce the specific
antibody into the blood
Humoral Immunity
• Antibody binding interactions promote
destruction of the invader by
– Neutralizing toxins
– Promoting phagocytosis
– Causing agglutination, which promotes
phagocytosis
– Activating of complement reactions, which
promote phagocytosis
Cell-Mediated Immunity
• Provided by T cells, which attack cancer
cells and cells that have been invaded by
viruses
• Three types of T cells are involved
– Helper T cells
– Cytotoxic T cells
– Memory T cells
Cell-Mediated Immunity
• Helper T cells
– Bind to antigens “presented” by a
macrophage that consumed them
• Helper T cells
– Produce cytokines that stimulate T cell
division and differentiation
• Will form memory T cells and cytotoxic T
cells
• Will also stimulate division of B cells that
are bound to an antigen
Cell-Mediated Immunity
• Cytotoxic T cells
– Bind directly to cancerous or virally-infected
cells
– Release proteins that poke holes in
cancer/infected cell membrane, killing the cell
• Memory T cells
– Dormant helper T cells that fight future
infection by the antigen that produced it
Memory
• The immune system remembers past victories
• Memory B and T cells remain long after the
infection
• Upon subsequent infection
– Memory B cells form active plasma cells that quickly
make many antibodies
– Memory T cells form active cytotoxic T cells
– The response is so rapid and strong that the repeat
invader never gets a foothold
Basic Mechanisms of Defense
• Invertebrates lack immune defenses
• Rely on non-specific defenses
– External skeletons
– Slimy secretions
– Internal white blood cells that attack
pathogens and secrete proteins to neutralize
invaders and toxins
– Proteins identified in horseshoe crabs are
similar to those found in vertebrates
Vaccinations
• Vaccination involves the injection of
weakened/killed microbes to confer
immunity
• Vaccination
– Inactive antigens stimulate humoral and cellmediated immunity so memory cells form
– Long term immunity results without having to
be exposed to the disease
– Examples: small pox, tetanus, mumps
Antibiotics
• Antibiotics may be administered if the
infection is massive or unusually toxic
• Effective on bacteria, fungi, and protists
– Viruses are unaffected
• Slow microbial reproduction
• Give enough time for natural immunity to
mobilize and remove invading microbes
Allergies
• Allergies are immune responses to
antigens that are not harmful
– Common “allergens” such as pollen, mold
spores, dust, animal dander, and bee stings
– Trigger an inflammatory response that
produces allergy symptoms
– An antigen enters the body and is recognized
by a B cell with complementary antibody
receptors
The Allergic Reaction
• “Allergy” plasma cells secrete “allergy
antibodies” against the antigen
• “Allergy antibodies” bind to mast cells
– Mast cells become sensitized to the presence
of the antigen
• If re-exposed to the allergy-causing
antigens, they bind to antibodies on the
mast cells
– The mast cell becomes stimulated
The Allergic Reaction
• The stimulated mast cells release
histamine, which causes leaky capillaries
and local inflammatory effects
The Allergic Reaction
• Respiratory allergy effects
– Excess mucus production
– Runny nose
– Sneezing
– Congestion
• Food allergy effects
– Nausea
– Diarrhea
Autoimmune Diseases
• A condition where antibodies mistakenly
attack the body’s own cells
• Examples
– Many cases of juvenile-onset diabetes
– Multiple sclerosis
– Rheumatoid arthritis
• Treatments
– Replacement therapy (example: transfusions)
– Immune suppression (drugs)
Immune Deficiency Diseases
• The inability to mount an effective immune
response to infection
• Example: severe combined immune
deficiency (SCID)
– Genetic disorder resulting in few or no
immune cells
– Minor infections can be fatal
– Can be treated by viral gene therapy
AIDS
• Acquired Immune Deficiency
Syndrome (AIDS) is a devastating
immune deficiency disease
• Caused by human immunodeficiency
viruses 1 and 2 (HIV-1 and HIV-2)
– Infect and destroy helper T cells
• AIDS does not kill directly
– Results in an increased susceptibility to
disease as helper T cells decline
HIV
• Human Immunodeficiency Virus (HIV) is a
retrovirus that infects and destroys
helper T cells
• HIV binds to a helper T cell and enters it
• Then it hijacks the cell’s metabolic
machinery, forcing it to make more HIV
particles
• The HIV particles emerge, taking an outer
coating of T-cell membrane with them
HIV
• If untreated, helper T cell levels eventually
diminish
• Immune responses are weakened, and
the person is diagnosed with AIDS
• A person infected with AIDS is highly
susceptible to other infections
• The life expectancy for untreated AIDS
victims is about 1 to 2 years.
HIV
• HIV does not survive long out of the body
• Methods of transmission
– Direct contact of broken skin or mucous
membranes with virus-laden body fluids
– Examples
•
•
•
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Blood
Semen
Vaginal secretions
Breast milk
Treatments of AIDS
• Combinations of drugs targeting viral
replication can disable HIV and slow the
progress of AIDS, dramatically increasing
life expectancy
• However
– HIV can mutate into forms resistant to the
drugs
– In some patients the drugs have severe side
effects
Treatments of AIDS
• Development of a vaccine has not been
successful
– HIV disables the immune response that a
vaccine depends on
– HIV mutates rapidly
Cancer
• Cancer is a disease characterized by the
unchecked growth of malignant tumor
cells
• Tumors are populations of cells that grow
at abnormal rates
• Two types of tumors
– Benign: remain confined to one area
– Malignant: grow uncontrollably and
spread to other areas
Cancer
• Cancer cells form every day
• Natural killer and cytotoxic T cells weed out
most cells
– Detect slight differences in cell membrane proteins
as “non-self” antigens
– Not all cancers are detected
– Some lack “non-self” antigens
– Some tumors grow too quickly for the immune
system to handle
• Some tumors attack the immune system,
suppressing the immune response
Medical Treatments for Cancer
• Three main cancer treatments
– Surgery
– Radiation
– Chemotherapy
Medical Treatments for Cancer
• Surgery
– Actively removing tumors when located
– Not all patches of cancer cells are detectable
or removable by surgery
– Remaining cancer cells can grow and spread
Medical Treatments for Cancer
• Radiation
– Can be used to destroy microscopic clusters
of cancer cells
– Not useful for systemic cancers due to
widespread tissue damage that would result
Medical Treatments for Cancer
• Chemotherapy (drug treatment)
– Supplements surgery and radiation treatment
– Attacks the machinery of cell division,
suppressing cancer growth
– Unfortunately, healthy cells divide too and are
affected
Monoclonal Antibodies
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Process by which large quantities of antibodies (targeted against a
particular antigen X) can be produced.
A mouse is immunized by injection of an antigen X to stimulate the
production of antibodies targeted against X. The antibody forming
cells are isolated from the mouse's spleen.
Monoclonal antibodies are produced by fusing single antibodyforming cells to tumor cells grown in culture. The resulting cell is
called a hybridoma.
Each hybridoma produces relatively large quantities of identical
antibody molecules. By allowing the hybridoma to multiply in culture,
it is possible to produce a population of cells, each of which
produces identical antibody molecules. These antibodies are called
"monoclonal antibodies" because they are produced by the
identical offspring of a single, cloned antibody producing cell.
Once a monoclonal antibody is made, it can be used as a
specific probe to track down and purify the specific protein that
induced its formation