AP BIOLOGY NOTES ON THE IMMUNE SYSTEM – CH. 43
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INTRODUCTION
Pathogens – infectious agents that cause disease, can be viruses, bacteria, fungi, protists. They
strive in the animal body because they get all of their needs to live and reproduce.
All defenses against these pathogens make up the immune system
Types of immunity:
o Innate immunity – found in all animals. These immune responses occur the same way
whether or not the pathogen has been encountered previously. The activation of these
defenses relies on recognition of pathogens. The recognition occurs by using a small
group of receptors that detect signal molecules that are common among microbes but
are mostly absent from the animal body.
o Acquired immunity – found only in vertebrate animals. This type of immunity develops
slowly and gets stronger by each exposure. This requires a large range of receptors,
each of which recognizes a very specific signal molecule that is only found in a
particular part of a specific microbe.
Lines of defense:
o 1st line of defense: physical and chemical barriers of the body (unbroken skin, secretions
of the skin, mucus, saliva, tears, flow of urine, vaginal secretions, vomiting, defecation) –
these prevent pathogens from getting into the blood stream or among cells of tissues.
o 2nd line of defense (these responses react to the presence of any pathogen):
 antimicrobial proteins (interferons that fight against viruses; complement
system – lyse invading cells),
 Phagocytic white blood cells (neutrophils,monocytes, eosionophils – break
down the cuticle of parasitic worms)
 natural killer cells – help to recognize and remove diseased cells
 inflammation, fever;
http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html
o 3rd line of defense: Specific resistance (immunity) – Develops in response to a specific
invader that was identified by the immune system. Slower but more powerful than the
first, it involves the activation of lymphocytes.
II.
INNATE IMMUNITY IN INVERTEBRATES
 In all environments, insects rely on the exoskeleton as the first line of defense to provide a
barrier against pathogens. This exoskeleton also covers the intestines of insects for protection
against food-borne pathogens.
 Lysozyme – an enzyme that digests microbial cell walls in the digestive system
 If a pathogen enters the body of an insect, they have many ways to fight off the pathogen:
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Hemocytes – immune cells that circulate in the hemolymph and perform phagocytosis
of bacteria
o Other hemocytes -- produce chemicals that destroy pathogenic bacteria and
multicellular parasites.
o Antimicrobial peptides – are also produced to punch holes on the cell membrane of
bacteria and fungi.
Insects recognize fungi and bacteria by the unique polymers of their cell walls.
Check your understanding:
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Differentiate between innate and acquired immunity.
List and describe the three lines of defense of the immune system
Name three methods of fighting pathogens in invertebrate animals.
In 2002, Lemaitre and colleagues in France devised a strategy to test the function of a single
antimicrobial peptide. They began with a mutant fruit fly strain in which pathogens are
recognized but the signaling pathway afterwards is blocked. As a result, the mutant flies do
not make any antimicrobial peptides. Than the researchers genetically engineered some of
these mutant flies to produce only one type of antimicrobial protein, either drosomycin or
defensin. The scientists infected some flies with a fungus (N. crassa) and others with a
bacterium (M. luteus). The results are graphed below. What would you conclude from the
data? Even if a particular antimicrobial peptide showed no beneficial effect in such an
experiment, why might it still be beneficial to flies?
III.
INNATE IMMUNITY IN VERTEBRATES:
 Barrier defenses – epithelial tissue, with its tight arrangement blocks to entry of many
pathogens. They may also create secretions that create a hostile environment for pathogens.
Lysozymes in saliva, mucus and tear destroy susceptible bacteria. The acidic environment of the
stomach will kill most microorganisms. Oil gland and sweat gland secretions also make the skin
more acidic so it can harm bacteria.
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Cellular Innate Defenses – phagocytic white blood cells (neutrophils and macrophages)
recognize microbes by using receptors called TLR (Toll-like receptor), these recognize molecules
that are typically found in some pathogens but not in humans. There is a different type of TLR
for molecules such as double stranded RNA, flagellin protein, liposaccharides etc. that can be
found in some bacteria, fungi and viruses. Once these receptors are activated, they trigger a
series of intracellular defenses, such as phagocytosis. Some of the phagocytic cells remain in
certain organs and tissues, while others migrate all over the body. Major organs of the immune
system are particularly rich in macrophages. These organs are:
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Lymph nodes – microbes and foreign particles present in the circulating lymph get here
and encounter macrophages here that destroy them
o Lymph – fluid that is collected back from in between the cells
o Lymph vessels – collect lymph and lead it to large veins
Antimicrobial Peptides and Proteins – these molecules attack pathogens or disable their
reproduction. The following two are specific peptides to vertebrates:
o Interpherons – proteins that are secreted by virus-infected body cells. These act as local
(paracrine) signals because they induce uninfected cells to produce chemicals that
inhibit viral reproduction and the spread of viruses. Other types of interpherons
activate macrophages to enhance their phagocytic ability. Manufactured interpherons
today are used as antiviral drugs.
o Complement system – These proteins are found in the blood plasma in inactive form all
the time. They get activated by the surface molecules of pathogens. The activation of
these proteins (frequently phosphorylation) results in a cascade of protein activation
that usually results in the lysis of the invading cells. The complement system is also
important in activating inflammatory response.
Inflammatory responses – triggered by an injury or infection. On the site of an infection, the
following steps take place:
o The entry of pathogens activates special immune cells called mast cells that release
some inflammatory signaling molecules – histamines.
o The nearby blood vessels dilate as a response to the histamine signals. During the
dilation, the blood vessels also become more permeable and release phagocytic white
blood cells.
o The activated phagocytic cells start to destroy the bacteria in the area and also release
further signal molecules to further increase blood flow into the area.
o More blood flow results in redness, heat and swelling – typical symptoms of an
inflammation
o All this results in the formation of pus that is composed of fluid rich in white blood cells,
dead microbes and cell debris.
o If the inflammation is caused by major tissue damage, the entire body may respond with
greatly increased white blood cell production, fever (caused by the release of pyrogens).
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An overreaction of the entire system to various bacterial infections can result in septic
shock which is a deadly condition.
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Natural Killer Cells – Normal cells express a surface protein called class I MHC on their surface.
However, cells that are infected by viruses or are cancerous, do not express this protein. NK
cells patrol a body and if they find cells without their proper MHC proteins, they attach to the
diseased cells and release chemicals that destroys these cells.
http://www.youtube.com/watch?v=HNP1EAYLhOs
In spite of all these defenses, it is possible that pathogens avoid recognition by the innate immune
system , because they may have mutations, that hide them or do not allow them to be broken down by
chemicals.
IV.
ACQUIRED IMMUNITY
 This type of immunity is found only in vertebrate animals. The main cells to perform acquired
immunity are lymphocytes. These cells are also produced in the red bone marrow from stem
cells. The lymphocytes that migrate to the thymus after production and mature there are called
T cells. The lymphocytes that mature in the bone marrow are called B cells.
 Both of these cells recognize foreign molecules and cells and inactivate them. Lymphocytes also
have immunological memory – recognize pathogens that they encountered previously and
respond to them faster. This memory can exist for decades for some pathogens.
 Acquired immunity is activated by the signaling molecules of phagocytic cells so the two types of
immunity interact with each other.
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Each T and B cell has a set of surface receptors that can each bind to a particular foreign
molecule. The receptors of one lymphocyte are all the same but different lymphocytes have
different receptors that recognize different foreign molecules. When a molecule fits these
receptors, the T and B cells become activated, undergo cell division to create clones of
themselves to fight the antigen. Some T cells alarm other lymphocytes, others detect and kill
the pathogen. Specialized B cells release proteins that attack pathogens in the body fluids.
The following sections detail the cell’s types, behavior and activation during an immune
response generated by acquired immunity.
V.
ANTIGEN RECOGNITION BY LYMPHOCYTES
 Any foreign molecule that is recognized by a lymphocyte and starts a response is called an
antigen. Antigens can be macromolecules, such as proteins or polysaccharides.
 These antigens are recognized by antigen specific receptors on the surface of the T and B cells.
B cells also release these receptors into the plasma of the blood in soluble form. These released
receptors are called antibodies or immune globulins (Ig). The receptors recognize a small
portion of the antigen, this portion that is called an epitope. One single antigen can have
several different epitopes that are recognized by different lymphocytes. But all of the antigen
receptors of a single lymphocyte are the same, they recognize only one epitope.
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Each B cell receptor for an antigen is a Y-shaped protein, consisting of 4 polypeptide chains, 2
identical heavy chains and 2 identical light chains. These chains are liked together by disulfide
bridges. One end of the heavy chain anchors the receptor into the B cell's membrane. The
constant (C) region of the heavy and light chains vary very little among different B cells.
However, the V region of the light chain and the V region of the end of the heavy chain, vary
extensively among the B cells. These V-regions form an asymmetric binding site for antigens.
Antibodies are similar to the membrane receptors, but they are lacking the membrane binding
sites.
T cell receptors for antigens consist of two different polypeptide chains, an α chain and a β
chain, linked by disulfide bridges. These receptors also have a membrane-binding region, a C
regions, and V regions.
Both the T and B cell receptors bind with antigens but have different functions. B cell receptors
bind with the antigen whether that antigen is free or on the surface of a pathogen. T cell
receptors only bind with antigen fragments if they are displayed on the surface of a host cell.
The host cell has a special group of genes called the major histocompatibility complex (MHC)
that produces host cell proteins that present the antigen fragments to T cell receptors.
Once a phagocytic cell engulfs a pathogen, it breaks down the pathogen proteins to small
peptides by using lysososmes. The small antigen fragments than bind to MHC molecules. The
MHC molecule binds to the surface membrane of the phagocytic cell where it can be recognized
by T cells. This process is called antigen presentation.
The antigen presentation can result in immune actions against the antigen or against the cell
that displays the antigen. Destroying the presenting cell may be necessary to stop the spread of
infection.
There are two classes of MHC molecules:
o Class I MHC molecules -- are found in almost all cells of the body. After the cells are
infected by a pathogen, they displayed antigens will be recognized by cytotoxic T
cells and that will kill infected cells by releasing toxins into them.
o Class II MHC molecules -- made by only a few immune cells (macrophages, B cells)
that are commonly known as antigen presenting cells. After these cells phagocytize
the pathogen, the present the antigen on their surface. These antigens will be
recognized by cytotoxic T cells and helper T cells (cells that when activated, are able
to activate cytotoxic T cells and B cells for further action against the pathogen.)
VI. LYMPHOCYTE DEVELOPMENT
 Three major properties of the acquired immune system are:
o Diversity -- mostly recognizable by the number of different receptors that can be
displayed on the surface of lymphocytes. This ensures that all pathogens, even the
ones that we have never encountered before can be recognized.
o Self-recognition and tolerance -- even with the great diversity, under normal
conditions, lymphocytes do not attack the body's own cells.
o Immunological memory -- infections that we encountered previously, are
recognized and a stronger action is expressed against them.
 Lymphocyte diversity is enormous. Each human has about 1 million different B cells and about
10 million different T cells. This variety is due to the random combination of several different
segments of the C, J, and V region of the surface receptors and immunoglobulins. Once a B or T
cell is formed, it has to mature to become active. During the maturation process, the
lymphocyte DNA gets cut by enzymes. Some cut regions will not be expressed in the particular
maturing B or T cells. Other regions will become introns and will be cut out during RNA
modification. Only a few of the many genes that originally were present to form a surface
receptor will become genes that will be active in each cell. (Review transcription, translation and
RNA editing for this section)
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Because lymphocytes randomly generate new versions of surface receptors, they can always
generate receptors that would be active against the body's own surface receptors. However,
during maturation, the lymphocytes are tested for self-reactivity and if they are reactive against
the body's own surface receptors, they are destroyed by apoptosis or inactivated. If this system
fails, autoimmune diseases can occur. These diseases cause the body to destroy its own tissues.
Examples of autoimmune diseases are lupus, Type I diabetes and multiple sclerosis.
Clonal selection: The binding of an antigen to any mature lymphocyte will activate that
particular lymphocyte, because it alone is not able to fight off any pathogen. The activated B or
T cell divide many times, so in a short period of time we have thousands of two types of clones
(identical copies):
o Effector cells -- these are clones that directly attach the antigen or any pathogens
that produce the antigen. These cells are very short-lived.
o Memory cells -- long-lived cells (can survive for 10-15 years) but only a few of them
are produced. These cells bear the receptors for the antigen that we encounter.
These cells build our immunological memory.
The first exposure to an antigen is slower because the immune system does not have memory
cells to that particular antigen yet. It takes longer to generate the clonal selection process and
produce the necessary effector cells and memory cells -- primary immune response.
Secondary immune response occurs when an antigen is encountered the second or multiple
times. This time the response is faster, greater in magnitude and longer. In this case a reservoir
of memory cells is activated.
VII. HUMORAL AND CELL-MEDIATED IMMUNE RESPONSES
 The two basic responses that are generated by lymphocytes are humoral immune response and
cell-mediated immune response.
 Humoral immune response -- involves the activation and clonal selection of B cells, which
secrete antibodies that circulate in the blood and lymph. The key players are antibodies
(basically free moving protein receptors), that are able to bind to antigens, with that neutralizing
pathogens and making them better targets for phagocytic cells and complement proteins. The B
cells get activated by cytokines that are released by helper T cells and by the presence of
antigens. When the antigen first binds to the receptors of the B cells the cell takes in a few of
the antigen molecules by receptor-mediated endocytosis. The B cell expresses an MHC complex
and with that it binds with a helper T cell. The T cell binding results in a full scale activation of
the B cell, that starts to divide and forms antibody secreting plasma cells and memory B cells.
The plasma cells can release as many as 2000 antibody molecules/second for 4-5 days. These
antibody molecules bind with the antigen and destroys it.
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Cell-mediated immune response: Involves the activation and clonal selection of cytotoxic T
cells, which identify and destroy target cells. Helper T cells aid both of the humoral and cellmediated immune responses. The cytotoxic T cells become active when signals (cytokines)
come from helper T cells. Once the cytotoxic T cells are activated, they eliminate body cells that
are infected by viruses or other intracellular pathogens or they are cancerous. Class I MHC
proteins are displayed on the cell surface of these infected or cancerous cells that are
recognized by the cytotoxic T cells. The cytotoxic T cell releases proteins that cause the cell to
rapture. With this the pathogen loses its place to reproduce and also gets exposed to circulating
antibodies that will attack it.
Below is a summary of all processes related to the acquired immune response:
VIII. ACTIVE AND PASSIVE IMMUNIZATION:
 In response to infection, active immunity forms, which is the body produces its own memory
cells that can later respond by a secondary immune response a lot more efficiently when
exposed to the same antigen and/or pathogen.
 Passive immunity: forms when antibodies are transferred into a person either naturally by the
mother during pregnancy or breast feeding or by artificially when antivenin is given to a person
after a snake bite to neutralize the toxins.
 Immunization can also be active when antigens are given through a vaccine (smallpox, polio,
measles, whooping cough etc.)
Video resources:
Acquired immunity: http://www.youtube.com/watch?v=rp7T4IItbtM
Innate immunity:
http://www.youtube.com/results?search_query=innate+immunity&oq=innate+immunity&gs_l=youtube
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Role of phagocytes: http://www.youtube.com/watch?v=O1N2rENXq_Y
Humoral and cell-mediated immune response: http://www.youtube.com/watch?v=YyCWm8WrZJU
All of the above: http://ocw.mit.edu/high-school/biology/structure-and-function-of-plants-andanimals/response-to-the-environment/