Immune System
Ch 31
Advanced Placement Biology in Brandon High School
2013-2014
Teacher: Mrs. Radjewski; Room 224;
Upstairs next to Mrs. Spezia in Room 222
Diagonal from the Social Studies Office, otherwise known as
the Social Studies Cave with the nasty microwave.
Defense against Pathogens
• Pathogens
– Harmful organisms and viruses that can cause
disease
– Animals have 2 defensive mechanisms against
them to provide immunity
• The ability to avoid disease when invaded by
a pathogen
1. Innate immunity
2. Adaptive immunity
Innate Immunity
• Nonspecific – used against a wide variety of
invasive organisms
• Includes barriers such as the skin, which is a 1st
line of defense for the body
• Also includes phagocytic cells (phagocytes) as a
2nd line of defense for the body
– They ingest foreign cells (phagocytosis)
• These defenses may be presented all the time, or
activated in response from an injury or invasion
by a pathogen (if activated, it is rapid)
• Most animals have innate immunity
Adaptive Immunity
• Specific
• Distinguishes between substances made by
the organism (self) and substances that are
not part of the organism (nonself)
• Involves antibody proteins that recognize,
bind to, and aid in the destruction of specific
viruses and bacteria
• Typically slow to develop, but long lasting
• Only found in vertebrate animals
White Blood Cells (WBC’s)
• Blood contains 5 billion RBC’s and 7 million
WBC’s
• Also called leukocytes
• Play major role in immune system
• Two major kinds
1. Phagocytes – large cells that engulf pathogens
by phagocytosis (involves in innate and adaptive)
•
Example: macrophages
2. Lymphocytes – only involved in adaptive
•
Example: B cells and T cells
4 Major Components of Immune System
1. Antibodies – proteins that bind specifically to
substances identified by immune system as
nonself
– Binding inactivates and destroys microorganisms
and toxins
– Can act as a tag on nonself cells, making them
easier for immune system to attack
– Produced by B cells (type of lymphocyte)
2. Major Histocompatibility Complex
(MHC)
• Proteins that are self-identifying cells
• Play a major role in coordinating interactions
between lymphocytes and macrophages (type
of phagocyte)
• Two classes
– MHCI – found on surface on most mammalian
cells
– MHCII – found on most immune system cells
3. T Cell Receptors
• Integral membrane proteins on the surfaces of
T cells (type of lymphocyte)
• Recognize and bind to nonself substances
4. Cytokines
• Soluble signaling proteins released by many
cells
• Bind to cell surface receptors and alter the
behavior of their target cells
• They can
– Activate and inactivate B cells
– Activate and inactivate macrophages
– Activate and inactivate T cells
31.2 Innate Defenses are Nonspecific
Suppose a bacteria lands on human
skin….challenges the bacteria faces:
• Physical barrier
of the skin
– Bacteria can
rarely
penetrate
intact skin
– Broken skin
increases the
risk of
infection
More challenges…
• Saltiness of skin
– Bacteria will have a hard time growing
• Presence of normal flora
– Competition for space and nutrients
Pathogen lands on inside nose or
another internal organ….defenses it
will encounter are:
• Mucus
– Slippery secretion produced by mucous
membranes, which lines various body cavities
– Traps microorganisms and will be removed by cilia
• Lysozyme
– Enzyme made by mucous membranes, that cleave
the cell wall of bacteria causing them to burst
open
More defenses inside nose….
• Defensins
– Made by mucous membranes
– Peptides of amino acids containing hydrophobic
portions that are toxic to bacteria and other
pathogens
– Insert themselves in plasma membranes of these
organisms and make membranes freely permeable
to water and all solutes, thus killing the invaders
If Bacteria gets into body, 2nd line of
defense will begin…
• Phagocytes
– Recognizes
pathogenic cells
and then ingest
them by
phagocytosis
2nd Line of Defense continued…
• Natural Killer Cells
– Lymphocytes
– Can distinguish between healthy cells and those
who are infected by viruses or are cancerous
– Can initiate apoptosis (programmed cell death) in
the target cells
2nd Line of Defense continued…
• Complement Proteins
– 20 different proteins
– Once activated, a cascade occurs
1. One complement protein binds to components on the
surface of the invading cell. This binding helps
phagocytes recognize and destroy the invading cell
2. Another protein activates the inflammation response
and attracts phagocytes to the site of infection
3. Finally, other proteins lyse the invading cell
2nd Line of Defense continued…
• Interferons
– Signalling proteins (cytokines)
– Help increase the resistance of neighboring cells
to infection
– Can bind to receptors on the plasma membrane of
uninfected cells, stimulating a signaling pathway
that inhibits viral reproduction if the cell near it
are infected
Inflammation
• Response when tissue is damaged because of
infection or injury
• Redness, swelling, and heat near damaged site
• Can be painful
• Is important
– It isolates the area to stop the spread of the damage
– It recruits cells to the location to kill any pathogens
– It promotes healing
Response to Inflammation
• Mast Cells
– Adhere to the skin and linings of organs and
release numerous chemical signals
• Tumor necrosis factor – a cytokine protein that kills
target cells and activates immune cells
• Prostaglandins – fatty acid derivative that initiates
inflammation in nearby tissues
• Histamine – amino acid derivative that increases the
permeability of blood vessels to white blood cells so
they can act in nearby tissues
OH NO! A Splinter!!
• Damaged tissue attract
mast cells, which
release histamine that
diffuses into the blood
vessels
• Also tumor necrosis
factor is released that
diffuses to phagocytes
• Histamine causes the
vessels to dilate and
become leaky
• Complement proteins
leave the blood vessels
and attract and activate
phagocytes
• Tumor necrosis factor
stimulates phagocytosis
• Blood plasma and
phagocytes move into
infected tissue from the
blood vessels
• Phagocytosis engulfs
bacteria and dead cells
• Histamine and
complement signaling
cease; phagocytes are
no longer attracted
• A growth factor from
platelets stimulates
epithelial cell division,
healing the wound
Following Inflammation
• Pus
– Mixture of leaked fluid and dead cells (bacteria,
WBC’s, and damaged body cells
– Normal result of body’s fighting a disease or
inflammation
– Gradually removed by macrophages
Inflammation can cause medical
problems
• Allergic Reaction
– Nonself molecule that is normally harmless, could
bind to a mast cell causing the release of
histamine and subsequent inflammation (along
with itchy, watery eyes and possible rash)
– The nonself molecule could come from food or
from the environment
Inflammation can cause medical
problems
• Autoimmune Disease
– Immune system fails to distinguish between self
and nonself
– Ends up attacking tissues in own organism’s body
• Sepsis
– Inflammation does not remain local and extends
throughout the body with the dilation of blood
vessels
– If bp drops during this, it could be lethal
• In most cases Innate immunity is good enough
• But in some cases, when the pathogen is in
large numbers, adaptive immunity must take
over.
31.3 Adaptive Immunity Response
in Specific
Key features of Adaptive Immunity
• Specific – allows it to focus its responses on
pathogens that are actually present
• Diverse – enables it to respond to a variety of
pathogens
• Distinguishes self from nonself – prevents it
from destroying self cells
• Immunological memory – allows it to respond
more effectively in later exposures to the
same pathogen
Specificity
• Reason why its specific is because of B and T
lymphocytes
• T cell receptors and the antibodies produces
by B cells recognize and bind to specific
nonself substances called antigens.
• This interaction initiates a specific immune
response
• Each T cell and each antibody-producing B cell
is specific for a single antigen
Antigens
• Have sites that the
immune system
(antibodies) recognizes
called antigenic
determinants or
epitopes
• Usually proteins or
polysaccharides
• A bacterium can have
multiple antigens on
them
An antigenic
determinant is a specific
portion of the antigen,
like a certain sequence
of amino acids
Diversity
• Pathogens can be:
–
–
–
–
–
–
Viruses
Bacteria
Protists
Fungi
Multicellular parasites
Toxins made by these organisms
• Human can respond specifically to 10 million
different antigens – by activating lymphocytes
– So humans need to generate a vast diversity of
lymphocytes that are specific for different antigens
Diversity Continued…
• Diversity is generated primarily by DNA
changes
• Each B cell is able to produce only one kind of
antibody; thus there are millions of different B
cells
• There are also millions of different T cells with
specific T cell receptors
Diversity continued…
• Antigen binding “selects” a particular B or T
cell for proliferation (growth/spreading)
• For example, when an antigen fits the surface
receptor on a B cell and bind to it, the B cell is
activated. It divides to form a clone of cells,
(clonal selection) all of which produce and /or
secrete antibodies with the same specificity as
the receptor
• This also applies to T lymphocytes
Distinguish self from nonself
• The human body contains thousands of
different molecules, each with a specific 3D
structure capable of generating immune
responses
• Thus every cell in the body bears a
tremendous number of antigens
• Hopefully the individuals immune system can
recognize it’s own body’s antigens and not
attack them
Clonal Deletion
• Any immature B or T cell that shows the
potential to mount a strong immune response
against self-antigens undergoes apoptosis
within a short time
• A failure of clonal delection leads to an
immune response or autoimmunity
Autoimmune Diseases
• SLE – Systemic Lupus erythrematosis
– Their antibodies can cause serious damage when
they bind to normal tissue antigens and form large
circulating antigen-antibody complexes
– They become stuck in tissues and provoke
inflammation
• Hashimoto’s thyroiditis
– Most common in women over 50
– Immune cells attack thyroid tissue, resulting in
fatigue, depression, weight gain, and other
symptoms
Immunological Memory
• After responding to a particular type of
pathogen once, it will remember that
pathogen and will respond faster to same
threat in the future
• Saves us from repeats of childhood infectious
diseases
• First exposure – primary immune response
• Second exposure – secondary immune
response
Primary Immune Response
• Activated lymphocytes divide and differentiate
to produce 2 types of daughter cells
1. Effector cells – carry out the attack on the
antigen
•
•
•
Effector B cells (plasma cells) secrete antibodies
Effector T cells release cytokines
Live only a few days
2. Memory cells – long lived cells that retain the
ability to start dividing on short notice to
produce more effector and more memory cells
•
Memory B and T cells may survive decades
Secondary Immune Response
• More rapid and more powerful
• The memory cells that bind with that antigen
proliferate and launch a huge army of plasma
cells and effector T cells
The principle behind vaccination is to trigger the
primary immune response that prepares the body to
mount a stronger, quicker secondary response if it
encounters the actual pathogen again.
3 phases to adaptive immune response
1. Recognition – organism discriminates
between self and nonself to detect pathogen
2. Activation – The recognition event leads to a
mobilization of cells and molecules to fight
the invader
3. Effector phase – mobilized cells and
molecules destroy the invader
A T cell with a
specific receptor
binds to an antigen
presenting cell. The
T cell then makes
cytokines, which
stimulate other cells
to divide
The specific B
cell that binds
the antigen is
stimulated to
form a clone.
B cells form
specific
antibodies
that bind
to free
antigens
T cell that binds
to the antigen on
the antigen
presenting cell is
stimulated to
form a clone
T cells bind to
and destroy cells
bearing the
antigen
31.4 Adaptive Humoral Response
involves specific antibodies
Humoral Response
• Basis is B cells
• Billions of B cells survive the test of clonal
deletion and are released from the bone marrow
into the circulatory system
• Remember it has a receptor protein on its cell
surface that is specific for a particular antigen
• It gets activated by antigen binding to this
receptor and then after stimulation from a T cell,
it produces a clone of plasma cells that make
antibodies as well as memory cells
Each B cell makes a different
specific antibody and displays it
on its cell surface
The specific antigen
also binds to a T cell,
which stimulates the
B cell to divide,
resulting in a clone
of cells
Primary immune
response – some
cells develop into
plasma cells (effector
B cells) that secrete
the same antibody as
the parent cell
This B cell makes an
antibody that binds this
specific antigen
Potential
Secondary
Immune
Response – a few
cells develop
into nonsecreting
memory cells
that divide at a
low rate.
Antibodies
• Also called immunoglobulins
• Two of the polypeptides are identical light chains and
two are identical heavy chains
• Held together by disulfide bonds
• Each chain has a
– Constant region – amino acid sequence determines the
general structure and function (class) of the
immunoglobulin
– Variable region – amino acid sequence is different for each
specific immunoglobulin.
• There are 2 antigen binding sites, making the antibody
bivalent. – This allows the antibodies to form large
complexes with the antigens
5 Classes of Immunoglobulins (Ig)
• Differ in function and in the type of heavy chain
• IgG – secreted by B cells and constitutes about 80%
of circulating antibodies
• IgD – cell surface receptor on a B cell
• IgM – initial surface and circulating antibody
released by a B cell
• IgA – protects mucosa on epithelia exposed to the
environment
• IgE – binds to mast cells and is involved with
inflammation
Antibodies have 2 roles in B cells
1. Acts as a receptor for an antigen in the
recognition phase of the humoral response
2. In the effector phase, they can be produced
in large amounts by a clone of B cells
– They are then secreted and enter the
bloodstream
– Can then do 2 actions
2 actions of antibodies in bloodstream
1. Bind to antigen that is expressed on the
surface of a pathogen – this stimulates
macrophages to ingest, or natural killer cells
to destroy the pathogen
2. If the antigen is free in the bloodstream, then
antibodies may bind to it to form large,
insoluble antibody-antigen complexes, which
are then ingested and destroyed by
phagocytic cells
31.5 Cellular Immune
Response involves T cells
and their receptors
T Cells
• Like B Cells, also possess
specific membrane receptors
• Not a immunoglobulin
• Glycoprotein made up of 2
polypeptide chains
– Each chain has a constant and
a variable region
• Variable region provides the site
for specific binding to antigens
Two types of T Cells
• TH is a T-helper cell
• When they bind to an
antigen, it results in the
activation of the
adaptive immune
response
• Tc is a cytotoxic T cell
• When they bind to an
antigen, it results in
death of the cell
The MHC proteins form complexes with antigens on cell
surfaces and assist with the recognition by the T cells, so that
the appropriate type of T cell binds. There are 2 types of
MHC proteins.
2 Types of MHC Proteins
1. Class 1 MHC – on the surface of every
nucleated cells in the mammalian body
– Present antigens to Tc cells
– These antigens can be fragments of viral proteins
or abnormal proteins made by cancer cells
2. Class 2 MHC – on the surface of
macrophages, B cells, and dendritic cells
– Present antigens to TH cells
Death of target cells
Infected Cell
• TC cells can produce
perforin, which
lyses the bound A Tcell receptor
recognizes an
target cell
antigenic
fragment bound
• TC cells stimulate to a class I MHC
apoptosis in the protein
target cell
Perforin lyses the
infected cell
before the viruses
can multiply!
T cell
releases
perforin
Regulatory T Cells (Tregs)
• Third class of T cells
• Ensures that the immune response does not
spiral out of control
• Similar to other T cells in that
– It is made in the thymus gland
– It expresses the T cell receptor
– It becomes activated if they bind to antigen-MHC
complexes
Tregs continued…
• Different than other T cells in that
– The antigens they recognize are self antigens
• The activation of Tregs causes them to secrete
cytokine interleukin-10, which blocks T cell
activation and leads to apoptosis of the TC and
TH cells that are bound to it
• Main role is to mediate tolerance to self
antigens
A self antigen binds to MHC
and is exposed on the cell
surface
A T cell has the T cell
receptor for the self antigen
A Treg cell binds to the
antigen-MHC complex
Binding stimulates Treg to
make interleuken-10,
which suppresses the TH
or TC cell and causes it to
undergo apoptosis
2 Experimental Evidence for the role of
Tregs
1. If Tregs are experimentally destroyed during
development in the thymus of a mouse, then
the mouse grows up with an out-of-control
immune system – autoimmunity.
2. IPEX – rare x linked disease in infants mounts
an immune response that attacks the
pancreas, thyroid, and intestine. Most
affected individuals die within the first few
years of life
AIDS
• Acquired Immune Deficiency Syndrome
• Results from HIV – human immunodeficiency
virus
• Transmitted from person to person in blood,
semen, vaginal fluid or breast milk
• Initially infects macrophages, TH cells, and
antigen presenting dendritic cells in blood and
tissues
AIDS continued..
• At first there is an immune response to the
viral infection, and some TH cells are activated
• But because HIV infects the TH cells, they are
killed both by HIV itself and by TC cells that
lyse infected TH cells
• So TH cell numbers decline after the first
month or so of infection
• Meanwhile, the humoral immune response is
activated due the extensive production of HIV
by infected cells
AIDS cont…
• Antibodies bind to HIV and the complexes are
removed by phagocytes
• HIV level in blood goes down
• During this dormant stage, people carrying HIV
feel fine, and their TH cell levels are adequate for
them to mount immune responses against other
infections
• Eventually the virus destroys the TH cells and
their numbers fall to the point where they are
susceptible to infections that the TH cells would
normally eliminate
AIDS continued…
• Infections that result now are:
– Kaposi’s sarcoma – skin tumor
– Pneumonia caused by a fungus
– Lymphona tumors – caused by Epstein-Barr virus
• These are opportunistic infections because the
pathogens are taking advantage of the
crippled immune system of the host
• Once this happens, death is within a year or 2