Specific Defense
IMMUNITY
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Innate immunity
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Nonspecific
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Adaptive Immunity
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Specific
- Induced resistance to a specific pathogen
Humoral Immunity
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Antibody-mediated
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Found in blood, lymphatic system,
and mucus
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Antibodies produced by B cells
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Defense against bacteria, viruses,
and toxins, and transplanted (foreign) tissues.
Cell-Mediated Immunity
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T cells that act against foreign
tissue or organisms
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Regulate macrophage release
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Defense against bacteria and
viruses inside of phagocytes and fungi, protozoa and transplanted tissue
ANTIGENS
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A substance that causes the body to produce specific antibodies or sensitized T
cells
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“Self” versus “non-self”
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Protein or polysaccharide (lipids and nucleic acids when combined with proteins
or polysaccharides)
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Found in capsule, cell walls, flagella, fimbrae, and toxins of microbes
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Pollen, egg white, blood cell surface, tissue surface
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Antigenic determinants (epitopes)
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Specificity
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Each bacterial cell has many different epitopes
HAPTEN
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Haptens require carriers at first
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Example - Penicillin
ANTIBODIES
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Globular proteins (immunoglobulins) made by
B cells in response to an antigen
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Highly specific
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Neutralize and destroy
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Antigen-binding sites
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Valence: number of sites
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Bivalent antibody (monomer)
structure
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Monomers have 2 antigenic binding
sites
Antibody Structure
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2 Heavy and 2 Light Chains
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Joined by disulfide links
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Variable regions
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Constant regions
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Fc region (stem)
Immunoglobulin Classes
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IgG (80%): Monomer found in
blood, lymph and intestine
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Most abundant antibody found in
blood
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23 day ½-life, can fix complement,
can cross placenta
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Enhances phagocytosis, neutralizes
toxins and viruses, and protects fetus (or newborn)
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IgD (0.2%): Monomer found on
B-cell surface, blood and lymph
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3 day ½- life
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Serum function unknown; initiation
of B-cell response
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IgE (0.002%): monomer found bound
to mast and basophil cells, and in blood
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2 day ½-life
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Allergic reactions; lysis of
parasitic worms, and attracts IgG, complement and phagocytic cells
Immunoglobin Classes
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IgM (5-10%): pentamer found in
blood, lymph, and B-cell surface
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5 day ½-life, fix complement, stay
in blood, and very large
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First antibodies produced at
initial infection
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Response to ABO blood group
antigens
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Enhance phagocytosis
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Important in diagnosis
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Short lived and at initial
infection
Immunoglobin Classes
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IgA (10-15%): Dimer with
secretory component found in secretions
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A monomer when in blood serum
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Not very abundant in blood, but
very abundant in secretions
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6 day ½ life, complement fixation
(alternative pathway)
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Defense against respiratory
infections and infant GI infection
Humoral Immunity
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B cells develop from stem cells
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Red bone marrow (adults)
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Liver (fetus)
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Travel to lymph tissue and lymph
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Are not activated until
recognition of specific antigen (clonal selection)
Clonal Selection
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B cell surface receptor recognizes
antigen
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Proliferation : same
immunological specificity
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Memory cells: long-term immunity
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Plasma cells: secrete antibodies
(2000/sec)
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Why we don’t attack our own cells
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Self tolerance
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Clonal deletion in embryo (thymus)
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Dangerous versus Nondangerous
(recognition of inflammation response)
Antibody Activities
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Enhancing
phagocytosis
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Agglutination:
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IgG and IgM
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Aggregation of
antigens for more efficient phagocytosis
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Opsonization:
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Stimulation of
phagocytosis
Antibody Activities
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Antibody
dependent cell-mediated cytotoxicity
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Antibodies coat
infecting cell (large parasite usually)—FC facing out
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NK (lysing
ability), Macrophage, neutrophils, and eosinophils have receptors for FC region
of antibody
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Secretion of
lytic enzymes to destroy parasite
Antibody Activities
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Neutralization:
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IgG antibodies
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Block attachment
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Block active
sites (or binding sites) of toxins
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Activation of
complement for lysis, inflammation, opsonization
Complement System
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Nonspecific response often
stimulated by a specific response
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Causes lysis, inflammation, and
phagocytosis
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Can occur by 2 pathways:
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Antigen-antibody reaction (classical)
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Proteins B, D, P and a pathogen (alternative)
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Serum proteins activated in a cascade
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Components
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Classical: C1 through C9 proteins
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Alternative: Factor B, D and P
Complement System
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Classical Pathway
Complement System
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Alternative Pathway
Complement Activation
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Inflammation
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C3a and C5a
bind to mast cells, basophils and platelets and triggers histamine release
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Increases
permeability of blood vessel and increases emigration
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C5a can also be
a strong chemotactic factor
MEMORY
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Antibody titer
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Primary response: after 1st
exposure
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Antigenàslow
rise in antibody titeràdecline
in antibody titer
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Secondary (memory) response:
after 2nd exposure
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Memory cells change to plasma
cells for an intense response
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Years or decades later
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This time IgG peaks first and most
Acquired Immunity
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Immunity you develop to a specific
antigen
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Active vs. Passive immunity
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Naturally acquired immunity
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Active
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Passive
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Transplacental or via colostrum
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Artificially acquired immunity
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Active
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Vaccination
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Passive
CYTOKINES
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Especially important to cell
mediated response (T cell response)
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Chemical messengers that regulate
other immune cell responses (ex. chemotaxis, NK activation, phagocyte activity)
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Interleukins: communication
between different leukocytes
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IL-1involved in stimulation of T
helper cells
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IL-2 involved in proliferation of
lymphocytes
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Interferons: viral infections
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Chemokines: chemotaxis of
leukocytes
Cell Mediated Immunity
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Also develop from stem cells,
mature in thymus, and migrate to lymphatic system
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TCRs - antigen receptors (recognition and
reaction)
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Antigen specific
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Clonal selection: effector cells
are memory cells and plasma cells
Cell Mediated Immunity
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Three types:
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Helper (TH, CD4)
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Cytotoxic (TC, CD8)
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Regulatory (TR)
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Suppress other T cells
T Cells
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Helper T cells
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A macrophage (antigen presenting
cell) contacts an antigen, ingests and processes it, and displays antigen on
surface with self molecule to make MHC
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TH cell receptor (TCRs) binds
to MHC II and stimulates APC to produce IL-1 cytokine
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IL-1 activates TH cell
to make IL-2, which stimulates maturation (TH clone)
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Mature TH cell makes
other cytokines which stimulates other TH cells, Tc cells
and B cells
T Cells
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Cytotoxic T cells
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Destroy target cell on contact
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Useful for destroying
intracellular parasites that cannot be attacked by antibodies
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TC cell binds to MHC I of
infected cell and secretes perforin which lyses infected cell
Nonspecific Cellular Components
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Part of cell mediated immunity
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Less specific than T cells
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Activated macrophage
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Activated by antigen and by TH
cells
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Natural killer cells
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Contact cell to lyse
Cell Mediated and Humoral Immunity
Relationships
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T-dependent antigen
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Sometimes B cells need help from TH
cells to make antibody to an antigens
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Antibody-dependent cell-mediated
cytotoxicity (ADCC)
SUMMARY