Transcript Chapter 43 - The Immune System

Chapter 43:
The
Immune
System
Essential Knowledge
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2.d.2 - Homeostatic mechanisms reflect both
common ancestry and divergence due to
adaptation to different environments (43.3).
2.d.3 – Biological systems are affected by
disruptions to their dynamic homeostasis
(43.2-43.4).
2.d.4 – Plants and animals have a variety of
chemical defenses against infections that
affect dynamic homeostasis (43.1-43.4).
3.d.2 Cells communicate with each other
through direct contact with other cells or
from a distance via chemical signaling (43.2).
Focus Topics
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Immunological responses to pathogens, toxins,
and allergens
Vertebrate immune systems have nonspecific and
nonheritable defense mechanisms against
pathogens
The mammalian immune system includes two
types of specific responses: cell mediated and
humoral
In the cell-mediated response, cytotoxic T cells, a
type of lymphocytic white blood cell, “target”
intracellular pathogens when antigens are
displayed on the outside of the cells.
Focus Topics
In the humoral response, B cells, a type of
lymphocytic white blood cell, produce
antibodies against specific antigens.
 Antigens are recognized by antibodies to the
antigen.
 Antibodies are proteins produced by B cells,
and each antibody is specific to a particular
antigen.
 A second exposure to an antigen results in a
more rapid and enhanced immune response.
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Introduction to Immunity
Defense system
 Protects from bacteria, viruses, other
pathogens, early-stage cancer cells
 Three types of immunity:
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1. Innate: nonspecific defense mechanisms
 external physical barriers of skin mucous
membranes
 internal defenses of chemicals and phagocytic cells
 Ex: gastric juices, histamines, inflammatory
response
Introduction to Immunity
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Three types of immunity:
2. Acquired: adaptive immunity, line of
defense in which lymphocytes react
specifically to threat, two types
 Humoral – antibodies produced by cells mark
microbes for destruction, involves B cells
 Cell-mediated – cytotoxic lymphocytes destroy
infected body cells, cancer cells and foreign
tissue, involves helper T cells
3.
Passive: acquired temporarily
◦ Ex: through breast-feeding
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Organs/Tissues/
Glands involved:
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Bone/bone marrow
Spleen
Stomach/Intestines
Skin
Lungs
Lymph nodes
Introduction to Immunity
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Leukocytes are the cells which are the bulk
of your immune system.
◦ Produced or stored in:
 Thymus, spleen, and bone marrow (called the
lymphoid organs)
 There are also clumps of lymphoid tissue throughout
the body (primarily as lymph nodes) that hold
leukocytes
Introduction to Immunity
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The two basic types of leukocytes
are:
◦ Phagocytes, cells that chew up invading
organisms
 Ex: neutrophils
◦ Lymphocytes, cells that allow the body to
remember and recognize previous invaders and
help the body destroy them
 Ex: B and T cells
Introduction to Immunity
The leukocytes circulate through the
body between the organs and nodes via
lymphatic vessels and blood vessels.
 In this way, the immune system works in a
coordinated manner to monitor the body
for germs or substances that might cause
problems.
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Innate Immunity
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External defenses
◦ Skin – secretions lower pH (discourage
microbial attack)
◦ Mucous membranes (line digestive,
respiratory, genitourinary tracts)
 Gastric juice – lowers pH to acidic
 Epilethial lining of respiratory – traps microbes
◦ Lysozyme – enzyme that attacks bacterial cell
walls
 Present in tears, saliva, and mucus
◦ Serve as physical barriers to microbes
Innate Immunity
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Internal defenses
◦ Systemic response may include:
 Increase in number of circulating WBCs
 Fever
 Triggered by toxins produced by pathogen or chemicals
released by immune system
 Stimulates phagocytosis and thus tissue repair and immune
response
 Inflammation
 Redness, swelling, heat
 Occurs when damaged mast cells (in connective tissue)
release histamine
 Histamine: triggers dilation and leakiness of blood vessels
Innate Immunity
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Internal defenses
◦ Relies upon phagocytosis by special WBCs
(phagocytes)
 These cells release antimicrobial proteins to help
initiate an inflammation response
 Rely upon cell surface rectors to bind to microbial surface
receptors
 Then, engulfs microbe and kill them using lysosome toxins
 Neutrophils: most numerous phagocytic WBCs
 Eosinophils: WBCs that attack multicellular
parasites
 Dendritic cells: stimulate acquired immunity
Innate Immunity
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Internal defenses
◦ Natural killer (NK) cells: nonphagocytic
cells that also participate in innate defenses
 Recognize general features of viral-infected or
cancer cells
 Attaches to them and triggers apoptosis
◦ Complement system: 30 proteins that can
lyse microbes, trigger inflammation or assist in
acquired immunity
◦ Interferons: stimulate neighboring cell to
produce anti-viral reproduction substances
Acquired Immunity
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Introduction
◦ First visit: Immune System Preview
◦ Key cells: lymphocytes (WBCs)
◦ Activated by contact with microbes OR by
cytokines (proteins secreted by macrophages)
◦ Recognizes antigens (foreign molecules)
 Most are large proteins or polysaccharides
 Often protrude from surface of microbe
 Epitope: region of antigen to which lymphocyte
attaches
Acquired Immunity
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Antigen Recognition
◦ Performed by B and T cells
 B lymphocytes (B cells) and T lymphocytes (T cells)
circulate in blood and lymph
 Found in spleen and lymph nodes
 Recognized by antibodies to the particular antigen
 Both contain membrane-bound antigen receptors
which allows them to recognize specific epitopes
(where they will bind)
Acquired Immunity
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Antigen Recognition
◦ B cell receptor
 Y-shaped
 Consists of 4 polypeptide chains (two light chains
and two heavy chains)
◦ T cell receptor
 One alpha chain and one beta chain
 Recognize special cell-surface proteins made by
MHC (major histocompatibility complex – a family
of genes)
Acquired Immunity
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Primary immune response
◦ Begins this response upon first exposure to an
antigen (foreign molecule)
◦ Requires about 10-17 days to yield maximum
response via T and B-cells
◦ Immunological memory: secondary immune
response that provides long-term protection
against a previously encountered pathogen
 “To avoid illness, expose yourself to germs, enabling your
immune system to develop antibodies. I don’t know why
everyone doesn’t do this. Maybe they have something
against living forever.” ~Dwight Schrute
Acquired Immunity
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Two types:
◦ Humoral immune response
 Involves B cell activation and production of
antibodies
 Antibodies then circulate in blood and lymph
 Provide defense against pathogens and toxins in the
extracellular fluid
◦ Cell-mediated response
 Involves cytotoxic T cells that destroy infected body
cells, cancer cells and transplanted tissues
 Relies upon Helper T cells to activate B cells and
cytotoxic T cells
Acquired Immunity
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Only found in vertebrates
T cells and B cells
◦ Types of WBCs called lymphocytes
◦ Originate from stem cells in the bone marrow
◦ Some lymphocytes migrate from the marrow to
the thymus
 These mature into T cells
◦ Some lymphocytes remain in the marrow
 These develop into B cells
◦ Other lymphocytes stay in the blood and become
the natural killer cells of innate immunity
Acquired Immunity
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Antigens are substances that prompt a
response from a B or T cell
Antigen receptor proteins allow B and T
cells to bind to antigens
◦ Specific enough to bind to just one part of one
molecule from a particular pathogen
◦ Millions of antigen receptors (AR) are produced,
but all AR’s are identical on each B and T cell
◦ Up to 100,000 AR’s on the surface of each B and
T cell!
◦ See Fig. 43.9, page 935
Antigen Specifics
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Usually foreign
Large molecules
◦ Proteins or polysaccharides
Protrude from the surface of foreign cells or
viruses
 Some, such as bacterial toxins, are released
into the extracellular fluid
 Small, accessible portion that binds to an AR
is called an epitope or antigenic determinant
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◦ Each antigen has several different epitopes, each
binding a receptor with a different specificity
B Cell and Antibody-Antigen
Recognition
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Each B cell AR is a Y-shaped molecule of 4
polypeptide chains
◦ Two identical heavy chains
◦ Two identical light chains
◦ Fig. 43.9, page 935
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Light and heavy chains have a constant
region where amino acid sequences don’t
vary much and a variable region on which
the amino acid sequence varies
extensively from one B cell to another
Formation of Antibodies
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When a B cell AR binds to an antigen, that will elicit B
cell activation eventually leading to the formation of
cells that secrete a soluble form of the receptor
◦ The secreted protein is an antibody or immunoglobulin
(Ig)
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Antibodies are Y-shaped like the B cell AR’s
◦ But are secreted rather than membrane-bound
◦ Antibodies are the proteins that defend against pathogens
◦ Differences in amino acid sequences of variable regions on
the B cell AR’s allow highly specific binding
B cell AR’s and antibodies bind to intact antigens in
the blood and lymph
 Fig. 43.10, page 936
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T Cell Antigen Recognition
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T cell AR’s are two different polypeptide chains,
an α chain and a β chain, linked by a disulfide
bridge (fig. 43.11, page 936)
Outer tips of each chain consist of the variable
region and are where the antigen binds
Remainder of the molecule is the constant region
Bind to fragments of antigens that are presented
on the surface of host cells
◦ The host protein that displays the antigen fragment
on the cell surface is the MHC (major
histocompatibility complex) molecule
Recognition of Protein Antigens by
T Cells
Begins when a pathogen or part of a pathogen either
infects of is taken in by a host cell (Fig. 43.12, page
937)
 Enzymes in the host cell break the antigen into
smaller peptides called antigen fragments
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◦ These bind to MHC molecules inside the cell
◦ MHC molecule with the bound antigen fragment move to
the cell surface resulting in antigen presentation
 This advertises that the host cell contains a foreign substance
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If the cell displaying an antigen fragment encounters a
T cell that is the right match, the AR on the T cell will
bind to the antigen fragment and the MHC molecule
◦ This binding is necessary for a T cell to participate in an
adaptive immune response
Acquired Immunity
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Active immunity: acquired when body
produces antibodies and develops
immunological memory from either
exposure to actual pathogen OR from
immunization/vaccinization
◦ Vaccine can be:
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1) inactive toxic
2) killed/weakened microbe
3) portion of microbe
3) genes for microbial proteins
Passive Immunity
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Passive immunity: temporary immunity
provided by antibodies
◦ Supplied through:
 Placenta to fetus
 Milk to nursing infant
 Antibody injection
Tissue Transplant
Limited by immune system’s ability to
distinguish self from nonself
 Immune system responds negatively to
chemical markers (unlike itself) during
blood transfusions (and tissue
transplantation)
 Mother and fetus: Rh factor
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◦ Rh: protein, RBCs antigen
◦ If fetal blood is different from mother, fetal
blood can leak across placenta (creating
immunological response from mother)
Tissue Transplantation
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Organ and Tissue Transplants
◦ May be rejected b/c the foreign MHC
molecules are antigenic
◦ Triggers immune response
◦ Use closely related donors and immune
system suppressor drugs to minimize risk of
rejection
Immune System Diseases
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Allergies
◦ Hypersensitivity to certain environmental
antigens (allergens)
◦ Releases histamines – creating inflammatory
response that may include:
 Sneezing
 Runny nose
 Difficulty breathing
◦ Antihistamine drugs – those that combat
these symptoms by blocking histamine receptors
◦ Ex: Asthma, eczema (dry skin), environmental
allergies (dust, dust mites, grass)
Immune System Diseases
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Autoimmune Disease
◦ Ex: Lupus, rheumatoid arthritis, insulin-dependent
diabetes mellitus, multiple sclerosis
◦ May be caused by failure in regulation of selfreactive lymphocytes
◦ Causes immune system to turn against itself
◦ Ex: Scleroderma, a chronic autoimmune
disease that can lead to inflammation and damage
of the skin, joints, and internal organs
◦ Ex: Ankylosing spondylitis, a disease that
involves inflammation of the spine and joints,
causing stiffness and pain
Immune System Diseases
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Immunodeficiency diseases
◦ Ex: AIDS (caused by HIV), cancer, Hodgkin’s
disease, stress
◦ Suppress the immune system
◦ Become highly susceptible to opportunitistic
infections (like pneumonia, flu, etc)
◦ Ex: DiGeorge syndrome (thymic dysplasia),
a birth defect in which kids are born without a
thymus gland
◦ Ex: Chediak-Higashi syndrome and chronic
granulomatous disease both involve the
inability of the neutrophils to function normally
Exclusion Statements
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Memorization of the structures of specific
antibodies is beyond the scope of the
course and the AP Exam.