Download Lines of Defense and Immunity

Lines of Defense and Immunity
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1st line of defense –  intact skin
–  mucous membranes & their secretions
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2nd line of defense –  phagocytic white blood cells
–  inflammation
–  fever
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3rd line of defense–  B & T lymphocytes
–  antibodies
Nonspecific/Innate
-complement
-interferon
Specific/Acquired
Formed Elements of Blood
Leukocytes
Characteristics of Leukocytes
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Diapedesis – migration of cells out of blood vessels into the tissues
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Chemotaxis – migration in response to specific chemicals at the site of injury or infection
Cytokines:
Involved in host defenses:
Inflammation!
Chemokines: chemotactic
Surveillance by Leukocytes
Plasma Proteins
Blood plasma contains:
–  Clotting factors
–  Complement
–  Antibodies
–  Molecules not related to defense
Serum is missing clotting proteins
The Lymphatic System
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Provides an auxiliary route for return of extracellular fluid to the circulatory system
Is involved with the inflammatory response
Carries out surveillance, recognition, and protection against foreign material
GALT:
Gut-Associated Lymphatic Tissue
The Reticuloendothelial, Circulatory and Lymphatic Systems
Lymphatic Fluid
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Lymph is a plasma-like liquid carried by lymphatic circulation
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Formed when blood components move out of blood vessels into extracellular spaces
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Made up of water, dissolved salts, 2-5% proteins
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Transports white blood cells, fats, cellular debris & infectious agents (foreign matter)
Lymph nodes
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Small, encapsulated, bean-shaped organs stationed along lymphatic channels &
large blood vessels of the thoracic and abdominal cavities
Lines of Defense and Immunity
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1st line of defense –  intact skin
–  mucous membranes & their secretions
• 
2nd line of defense –  phagocytic white blood cells
–  inflammation
–  fever
• 
3rd line of defense–  B & T lymphocytes
–  antibodies
Nonspecific/Innate
-interferon
-complement
Specific/Acquired
Nonspecific Host Defenses – Innate Immunity
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Always present
Immediately effective
No immune memory – work at the same speed each time
Four Cardinal Symptoms of Inflammation:
1. Rubor (redness)
2. Calor (an increase in temperature)
3. Tumor (swelling/edema)
4. Dolor (pain)
The Wound Response
Enter: Fluid and Macrophages (phagocytes!)
The Wound Response
Contain the
Pathogen!
Ah, Repair…
All Together Now!
1.  Rubor (redness)
2.  Calor (an increase in temperature)
3.
Tumor (swelling/edema)
4.
Dolor (pain)
Phagocytes and Their Activities
Phagocytes = eating cells
–  Neutrophils (PMNs) are present in the highest numbers in blood
–  Macrophages (“big eaters”) in the tissues encounter the pathogen first
•  Secrete cytokines ---> inflammation, systemic responses (e.g. fever)
1. 
2. 
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To survey tissue compartments & discover microbes, particulate matter &
dead or injured cells
To infest and eliminate these materials
To extract immunogenic information from foreign matter
Interferon
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Small protein produced by certain cells
–  Alpha (α) interferon- leukocytes
–  Beta (β) interferon – fibroblasts & epithelial cells
–  Gamma (γ) interferon – T cells
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Produced in response to viruses, RNA, immune products, and various antigens
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Bind to cell surfaces and induce expression of antiviral proteins
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Inhibit expression of cancer genes (γ)
Mechanism of α and β Action
Lines of Defense and Immunity
• 
1st line of defense –  intact skin
–  mucous membranes & their secretions
• 
2nd line of defense –  phagocytic white blood cells
–  inflammation
–  fever
• 
3rd line of defense–  B & T lymphocytes
–  antibodies
Nonspecific/Innate
-interferon
-complement
Specific/Acquired
Lines of Defense and Immunity
• 
1st line of defense –  intact skin
–  mucous membranes & their secretions
• 
2nd line of defense –  phagocytic white blood cells
–  inflammation
–  fever
• 
3rd line of defense–  B & T lymphocytes
–  antibodies
Nonspecific/Innate
-interferon
-complement
Specific/Acquired
The Complement System
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Consists of 26 blood proteins that work in concert to destroy bacteria and viruses
Complement proteins are activated by cleavage
Classical pathway
Alternative pathway
General Functions of the Complement System:
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2. 
3. 
Enhance phagocytosis by phagocytes (opsonization)
Directly lyse microbes, bacteria, and enveloped viruses
Generate peptide fragments that regulate inflammation and immune responses
The Complement System
Activation of the Classical Pathway:
Membrane Attack Complexes (MACs)
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Amplification by enzyme activity
Highly regulated so our cells don’t lyse
Summary of Nonspecific Defenses
The Acquisition of Specific Immunity and Its Applications (Chapter 15)
Genetic and Acquired Defenses
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Some hosts are genetically immune to the diseases of other hosts.
Some pathogens have great specificity
Some genetic differences exist in susceptibility
Lines of Defense and Immunity
• 
1st line of defense –  intact skin
–  mucous membranes & their secretions
• 
2nd line of defense –  phagocytic white blood cells
–  inflammation
–  fever
• 
3rd line of defense–  B & T lymphocytes
–  antibodies
Nonspecific/Innate
-interferon
-complement
Specific/Acquired
Acquired/Adaptive Immunity
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Specific resistance to certain pathogens (antigens)
Discriminates foreignness (danger)
Slow starting – needs nonspecific defenses to be engaged
Immune memory – faster response on repeat exposure
Formed Elements of Blood
Leukocytes
Specific Immunities
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B and T lymphocytes
B-Cell and T-Cell Development
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Directed by bone marrow sites that harbor cells, which nurture the lymphocyte stem
cells & provide hormonal signals
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Millions of distinct B cells develop & home to specific sites in the lymph nodes,
spleen, and GALT where they come into contact with antigens throughout life
B and T Lymphocytes
B and T Cells have receptors that recognize (bind) antigens specific to individual pathogens
Specific Immunities
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B and T lymphocytes
Antigens & Antibodies
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Antigens are foreign to host
–  Proteins and large
polysaccharides
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Antibodies are host proteins that
bind specifically to an epitope on
an antigen
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Each antigen has many epitopes
= antibody-binding sites
Antigens & Antibodies
The Hapten-Carrier Phenomenon
Haptens: Small molecules that are too small (by themselves) to elicit an immune response
Examples: industrial/household/environmental chemicals
metals
small drug compounds
hydralazine (blood pressure lowering drug) can cause
drug-induced lupus erythematosus
Antigens & Antibodies
Antigen with four epitopes
Activation of the Humoral Response
Antigen-Antibody Reactions
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Opsonization
Neutralization
Agglutination
Complement fixation
Nature of Antibodies
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Immunoglobulins (Ig)
A large Y-shaped protein (IgG = Immunoglobulin class G)
Consists of 4 polypeptide chains (two heavy chains, two light chains)
Contains 2 identical fragments (Fab) with ends that bind to specific antigen
Fc binds to self through disulfide bridge
Immunoglobulins
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Immunoglobulin genes lie on 3 different chromosomes
Undifferentiated lymphocyte has 150 different genes for the variable region of light
chains & 250 for the variable region and diversity region of the heavy chain
During development, genetic recombination causes only the selected V and D genes
to be active in the mature cell.
Take home message:
Billions and billions of distinct
antibodies can be produced!
Different Classes of Antibodies
Antibodies are Receptors in the Plasma Membrane of B-Cells
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Each B cell has a uniquely specific receptor
(a membrane-bound antibody!)
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B cells with certain receptors are produced
randomly in the bone marrow
So, Where Do All These Different B Cells Come From?
Clonal Selection Theory
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Lymphocytes use 500 genes to produce a tremendous variety of specific receptors (Abs!)
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Undifferentiated lymphocytes (stem cells) undergo genetic mutations & recombinations
while they proliferate in the embryo forming a billion different clones with the ability to react
with a tremendous variety of antigens.
Clonal Selection Theory - continued
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Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen
has ever entered the system.
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Each genetically different type of lymphocyte expresses a single specificity.
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First introduction of each type of antigen into the immune system selects a genetically distinct
lymphocyte and causes it to expand into a clone of cells that can react to that antigen.
Clonal Selection Theory - continued
Clonal Deletion
Apoptosis/Programmed Cell Death
Leads to Immune Tolerance
Activation of the Humoral Response
Antigen-Antibody Reactions
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Opsonization
Neutralization
Agglutination
Complement fixation
Primary and Secondary Immune Responses to an Antigen
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Primary response – after first exposure to an antigen immune system produces IgM
and a gradual increase in antibody titer (amount of substance in a body fluid)
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Secondary response –after second contact with the same antigen, immune system
produces a more rapid, stronger response due to memory cells