Chapter 57
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The Immune System
Chapter 57
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Skin: First Line of Defense
• Three Lines Of Defense Skin – barrier to penetration
- Mucous membranes also important Cellular Counterattack – cells engulf
and/or produce chemicals to kill microbes Immune Response – immunoglobulins, B
cells and T cells attack foreign antigens
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Skin: First Line of Defense
• Skin is largest vertebrate organ, provides first line of defense against microbe invasion Also barrier to dehydration
• Skin has three layers 1) Epidermis
- 10-30 cells thick Stratum corneum - Outer layer
Continuously shed Basal Layer - Innermost layer
Rapid division, replace lost cells of stratum corneum
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Skin: First Line of Defense
2) Dermis- 15-40 times thicker than epidermis- Provides structural support for epidermis- Contains sensory receptors, blood
vessels, etc. 3) Subcutaneous layer
- Composed of fat-rich cells acting as shock absorbers and insulators
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Other External Body Surfaces
Digestive Tract- Saliva/lysozyme- Acidic environment of stomach
Respiratory Tract- Thick mucus layer traps microbes- Cilia “flush” microbes out to be
swallowed into digestive tract Vomiting, diarrhea, coughing and sneezing
also expel microbes, etc.
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Cellular Counterttack: Second Line of Defense
• Lymphatic System - Central location for the collection and distribution of immune system cells Consists of a network of lymphatic
capillaries, ducts, nodes, and lymphatic organs.
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White Blood Cells That Kill Invading Microbes• Macrophages
Ingest bacteria Fuse with lysosome
• Neutrophils Ingest microbes like macrophage Also release chemicals
- Create “kill zone”, includes releasing cell• Natural Killer Cells –
Attack body cells infected by invading microbes Also kill cancer cells, before detectable tumor Puncture plasma membrane with perforins
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Proteins That Kill Invading Microbes
• Complement System Approximately 20 different proteins
circulating freely in blood plasma- Some aggregate to form membrane
attack complex Insert into cell’s plasma membrane
and form pore, allowing water to rush in and burst cell
Others attract phagocytes to infection area or make cells easier to phagocytose
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Interferons
• Alpha, beta and gamma varieties• Produced by viral-infected cells• Act on neighboring cells to prevent
replication of new viruses which might infect them
• Gamma interferon may be involved in defense against cancer
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The Inflammatory Response
• Localized, nonspecific response to infection• Injured cells release chemical alarm signals
(histamine and prostaglandins) that cause blood vessels to dilate Increased blood flow to site of injury
- Stretches capillary walls increasing permeability
Redness and swelling of affected area due to increased blood flow
- Phagocyte migration into tissue
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Local Inflammation
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The Inflammatory Response
• Temperature Response When macrophages initiate counterattack,
they send a message to brain to raise body temperature
- Fever inhibits microbial growth- But body temperature over 103 F
dangerous and over 105 often fatal
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The Immune Response: Third Line of Defense
• Key Concepts Antigen - molecule that provokes a specific
immune response- Antigenic Determinant Sites - Different
portions/shapes of a large antigen, each stimulating a different immune response
Lymphocytes called B cells respond to antigens by producing antibodies
- Antibody proteins are secreted into the blood and other body fluids and thus provide humoral immunity
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The Immune Response: Third Line of Defense
• T cells directly attack cells carrying specific antigens Cell-mediated immunity
• Active or Acquired Immunity– use antibodies readily produced as a result of this or a previous exposure
• Passive Immunity - immunity gained by transference of antibodies via placenta, breast feeding or injection
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Immune System
• Involve actions of leukocytes T and B Cells are lymphocytes
- T Cells originate in bone marrow and migrate to thymus
Develop ability to identify foreign particles by antigens exposed on their surfaces
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Cells of the Immune System
• T Cell types Inducer - Oversee T cell development Helper - Initiate immune response Cytotoxic - Lyse infected cells Supressor - Terminate immune response
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Cells of the Immune System
• B Cells Are produced and complete maturation in
bone marrow- Circulate in blood and lymph
When bind antigen can convert to plasma cells and produce large quantities of antibodies
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Initiating the Immune Response
• Macrophages inspect surfaces of cells encountered for MHC (major histocompatability complex) proteins Self versus nonself recognition MHC genes highly polymorphic (170+ alleles) T cells only bind to antigens presented to them
on surface of cells- Foreign particles are taken in and partially
digested Antigens are processed and moved to the
surface of plasma membrane Antigen Presenting Cells
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Initiating the Immune Response
• Macrophages that encounter pathogens lacking proper MHC proteins, or a virus-infected cell with viral proteins stuck to surface, secrete alarm signal Interleukin-1
- Stimulates helper T cells to initiate: Cellular response of T cells Humoral response of B cells
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T Cells: Cell-Mediated Immune Response
• Helper T cells become activated when they bind to complex of MHC proteins and antigens presented by macrophages. Helper T cells secrete interleukin-2.
- Stimulates production of cytotoxic T cells Any cytotoxic T cell whose receptor
fits the particular antigen-MHC protein complex begins to multiply rapidly
Any cells bearing traces of viral infection are destroyed
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B Cells: Humoral Immune Response
• B cells recognize invading microbes and use proteins (antibodies) to mark pathogen for destruction Can bind to free, unprocessed antigens Antigen particles enter B cells by
endocytosis and get processed- Helper T cells that recognize the specific
antigen bind to the complex and stimulate B cells to divide
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B Cells: Humoral Immune Response
• Antibodies are proteins in class immunoglobulins (Ig), which is subdivided into subclasses based on structure and function of the specific proteins IgM - Secreted during primary response IgG - Secreted during secondary response IgD - Receptors for antigens on B cells IgA - Found in external secretions IgF - Promote histamine release
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Antibodies
• Structure of Antibodies Each antibody consists of two short
polypeptides, light chains, and two identical long chains, heavy chains.
- Antibodies with the same variable segments have identical clefts and therefore recognize the same antigen.
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Antibodies
• Antibody Diversity Estimated human B cells can make
between 106 and 109 different antibody molecules.
Immune receptor genes are assembled by stitching together three or four DNA segments that code for different parts of the receptor molecule.
- Somatic Rearrangement- And a lot more…
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Immunological Tolerance
• Immune response does not respond to the animal’s own tissue Immune system of an embryo is able to
respond to both foreign and self molecules- Loses ability to respond to self
molecules as development proceeds- If regained as adult result is autoimmune
disease
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Active Immunity Through Clonal Selection• Binding of antigen to its receptor on the
lymphocyte surface stimulates cell division and produces a clone (clonal selection) of memory cells Primary Immune Response carried out by
“original cells from this proliferation Secondary Immune Response occurs
when body is again invaded by same pathogen/antigen and this time body starts with a large clone of lymphocytes that recognize the pathogen
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Antibodies in Medical Diagnosis
• Blood Typing • (ABO System)
The immune system is tolerant to its own red blood cell antigens.
- People with type A blood make antibodies against the B antigen and vise-versa.
- People who are type AB do not produce anti-A or anti-B antibodies.
- People who are type O have both anti-A and anti-B antibodies.
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Antibodies in Medical Diagnosis
• Rh Factor People who have Rh antigen are Rh-
Positive and people who do not have the antigen are Rh-Negative
- If a mother produces antibodies against the Rh factor and her second child is Rh-positive, the antibodies can cause hemolysis of the Rh-Positive red blood cells of the fetus
Erythroblastosis fetalis
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Antibodies in Medical Diagnosis
• Monoclonal Antibodies Monoclonal antibodies exhibit specificity
for one antigenic determinant Animal is injected with an antigen, and
subsequently killed- B lymphocytes are then obtained from
the animal’s spleen and placed in incubation vessels
Hybridized with cancerous multiple myeloma cells
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Antibodies in Medical Diagnosis
• Development of much more sensitive clinical laboratory tests Monoclonal antibodies react against one
specific antigen- Modern pregnancy tests
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(hCG)
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Evolution of the Immune System
• Bacteria Defend against viral invasion through
restriction endonucleases that degrade foreign DNA lacking specific DNA pattern
• Invertebrates Mark cell surfaces with self labels
- Employ negative test May not recognize cells that resemble
self marker as foreign
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Evolution of the Immune System
• Shared Elements of Invertebrate and Vertebrate Immune Responses Phagocytes Distinguishing Self from Non-Self Lymphocytes Immunoglobulins
- Antibodies in vertebrates- Lectins in invertebrates
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Evolution of the Immune System
• Vertebrates Modern vertebrate immune system first
arose in fish with jaws- Sharks are oldest surviving group
Have immune response much like that in mammals
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T Cell Destruction: AIDS
• The AIDS retrovirus (HIV) mounts a direct attack on CD4+ T cells
• HIV’s attack on CD4+ T cells cripples the immune system in at least three ways: HIV-infected cells die only after releasing
replicated viruses HIV causes infected cells to secrete a
soluble suppressing factor that blocks other T cells from responding
May block transcription of MHC genes
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T Cell Destruction: AIDS
• Treatment was limited to drugs that inhibit reverse transcriptase (AZT) Recently, protease inhibitors have become
available- Inhibit enzyme necessary for viral
assembly Like the influenza virus, HIV engages in
some form of antigen shifting, making it difficult to develop an effective vaccine.
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Antigen Shifting
• Pathogen may defeat the immune system by mutating frequently so that it varies the nature of its surface antigens. By the time a significant number of
antibodies have been generated against one form of a protein, another form is already present in the population.
- Survives immunological attack and reproduces
- Trypanosomes/sleeping sickness
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Autoimmunity and Allergy• Autoimmune diseases are produced by a
failure of the immune system to recognize and tolerate self antigens Results in the activation of autoreactive T
cells and production on of autoantibodies by B cells
More than 40 known human autoimmune diseases
Treated by suppressing immune system and/or antiinflammatory drugs (e.g. aspirin)
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Autoimmunity and Allergy
• Allergy refers to particular types of abnormal immune responses to antigens - allergens Immediate Hypersensitivity - Due to an
abnormal B cell response to an allergen that produces symptoms within seconds or minutes, IgE involved
Delayed Hypersensitivity - Abnormal T cell response that produces symptoms within about 48 hours after allergen exposure
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Autoimmunity and Allergy
• Mast cells initiate inflammatory response Release histamine causing capillaries to
swell- Widespread and excessive release of
histamine may cause Anaphylactic Shock (an uncontrolled fall in blood pressure)
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