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Function of the immune system.
- Recognise self from non-self
- Defend body against non-self
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2 Divisions of the immune system
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Non Specific Immunity
- Not specific against one specific disease.
- Immunity that is innate or inborn
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3 Catagories of non-specific immunity
- Nonsusceptability.
- Naturally Occuring Antibodies.
- Resistance.
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2 Types of resistance
- Passive resistance
- Active resistance
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Passive resistance
- Called external defense system.
- Includes Structural Barriers.
- First line of defense in intact skin & mucous membranes.
- Skin temp
- body secretions
- cilia
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Active Resistance
- Called Internal defense system
- body responds to foreign antigen
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Types of actuve resistance.
- Phagocytosis.
- NK Cells.
- Acute Phase reactants.
- Soluble Mediators
- Inflammation
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Acute phase reactants.
- Soluble proteins produced in the liver in response to Antigen stimulation.
- 2 most common are: C reactive proteins and complement.
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C Reactive Protein (CRP)
- Globulin produced during inflammation.
- Not found in normal serum.
- Production begins within 4 hours of onset of inflammation
- disappears from serum rapidly after inflammation is gone.
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Complement
- Beta globulin found in serum in active from.
- Series of 9-18 plasma proteins (complements)
- Also called soluble mediator
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Function of complement
- Opsonin
- Chemotaxic
- Complement Fixation
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Soluble Mediators
- Plasma proteins produced in response to antigen stimulation.
- 2 catagories : complement & cytokines.
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Cytokines
plasma proteins produced by activated cells that regulate immune responses.
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What are cytokines that are produced by lymphocytes called?
Lymphokines
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Types of Cytokines
- Lymphokines
- Interleukin
- Interferon
- Tumor necrosis Factor (TNF)
- Colony Stimulating Factor (CFS)
- Transforming Growth factor
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Interleukin
- Group of 12 cytokines
- act between leukocytes
- do not bind to antigen
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Interferon
- Produced by virally infected cells
- proteins that interfere with viral replication
- 3 major calles are alpha beta gamma
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Tumor Necrosis Factor (TNF)
- Cytokines that can destroy tumor cells.
- 2 types: alpha beta
- Can cause shock and death if they reach the blood stream.
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Colony Stimulating Factor (CSF)
- Proteins that stimulate production of non-lymphoid cells.
- Some of the CSF are produced by T-lymphocytes.
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Transforming Growth Factor.
- Protein product produce by virally infected cells
- 2 forms alpha and beta
- transforms neoplastic cells
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Specific Immunity
- Also called aquired or adaptive immunity.
- Immunity against specific disease.
- 2 catagories: cell mediated and humoral.
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Cell mediated immunity
- Involves T-Lymphocytes
- Organ/ Graft rejection
- delayed hyper sensitivity
- contact dermititis
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Humoral Immunity
- Involves both T-Lymphs and B-lymphs
- antibody prodection by b-lymphs
- can be actively or passively aquired
- aquired through artificial or natural means
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Actively aquired humoral immunity
- Antibody production following antigen stimulation
- Antigen stimulation may be natural or artificial.
- Natural = contracting the disease
- Artificial = Vaccine
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Passively Aquired Humoral Immunity
- Antibodies are not prduced in an individual.
- Individual aquires antibody through natural or artificial means.
- Antibody aquired through placnta or brest milk.
- Antibody acquired artificially in anitibody shots (injections)
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Antigens
- Any foreign substance that causes immune response.
- Immune response can be cell-mediated or humoral.
- Protein carrier with 3D surface structures called epitopes.
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Types of Antigens
- Autoantigen (self)
- Heteroantigen (different, but related species)
- Heterophile (different, unrelated species)
- Allo or Iso antigens (same species)
- HLA (human leukocyte antigen)
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HLA (human leukocyte antigen)
- On surface of all cells, not just WBCs.
- MHC ( major histocompatability complex) antigens make up HLA.
- 2nd ABO group in determining success of grafts or transplants.
- MHC antigens are genetically determined.
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Antigen Charactaristics
- Complex Chemical Structure.
- Must be considered foreign
- Degradability / Stability
- Molecular weight over 10,000
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Antibodies
- Gamma Globulin with immune functions
- Called immunoglobulins (IG)
- Produced by transformed B-Lymphocytes in lymphoid tissue.
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Functions of Antibodies
- Combine with antigens and neutralize it.
- Combine with antigen an lyze it.
- Some antibodies are complement dependant.
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IgG
- 70-75% of circulating antibodies.
- 1 basic unit with 150,000 mole wt
- Crosses the placenta.
- 4 subclasses with different heavy chain composition.
- Neutralize and bind antigen.
- React at 37 C following incubation or enhancement.
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IgM
- 10% of circulating antibodies are IgM.
- 5 basic units & a J chain with 900,000 mole wt.
- Does not cross the placenta.
- No subclasses.
- Agglutination antigen and are cytolytic.
- React at 22c immediatly
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IgA
- 15-20% of circulating antibodies
- Exists as monomer in serum.
- Exists as dimer in body fluids.
- Both forms posses a J chain
- Mole weight of dimer is 360,000
- 2 subclasses
- Does not cross the placenta
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IgD
- <1% of circulating antibodies
- Cell membrane immunoglobulin
- 160,000 mole wt
- 1 basic unit with no J chain
- No interchain S-S bonds
- Hinge region is exposed
- Does not cross the placenta
- no subclasses
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IgE
- present in serum and plasma in trace amounts
- 1 basic unit with no J chain
- 180,000 mole weight
- Fc portion can bind with mast cell
- does not cross the placenta
- no known classes
- takes part in hypersensitive reactions
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4 polypeptide chains in Y shape
- 2 light chains ( kappa and lambda)
- 65% of light chains are kappa
- 35% lambda
- 2 heavy chains (A,G,D,E,M)
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Light and heavy chains are linked by?
non covalent S-S bonds
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Hinge region composed of?
15 amino acids between CH1 and CH2 region
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Variable protion are fist _____ amino acids
110-120 on NH2 end
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Folding within chain disulfide bonds are?
Domains
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What portion contains antibody binding sites?
FAB
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What portion has ability to crystalize?
FC
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Isotype
- Iso=same
- part of Antibody structure that is the same in all humans
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allotype
- Structure of antibodies that is found on some but not all antibodies.
- structure of ab that is genetically determined.
- used as genetic markers
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Idiotype
Unique variations of the variable portions of an AB
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AB Synthesis sequence.
- Macrophage phagocytizes foreign antigen.
- Breaks down AG and collects info.
- Receptor appears on Macrophage.
- Macrophage finds T helper cell w/ compatible receptor.
- T-cell combines and downloads info.
- T helper secretes lymphokines and stimulates b-cell activation
- B-cell transforms into Plasma cell
- starts AB production
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Long Lag phase
7-10 days (primary)
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Short lag phase
48 hours (secondary)
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Factors affecting AB production
- Age
- Nutrician / diet
- Stress and Hormones
- Underlying Diseases
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When does bone marrow take over lymphocyte production?
6-8 months
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Hormone that stimulates maturation of T-Lymphs
Thymosin
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T cells are tested for what during maturation?
Self recognition
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2 types of t-lymphs
- T-helper
- T-suppresor/cytotoxic
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TH cells make up what percent of lymphocytes?
55-70%
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TS makes up what percent of lymphocytes
25-40%
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what is CD?
- Cluster of differentiations
- t cell surface markers
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CD3
marker need to pass self recognition test
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CD4
Class 2 MHC is on T helper cells
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CD8
Class 1 MHC is on T-S cells
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B-lymphs make up what percent of circulating lymphocytes?
20%
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Surface Receptors on B-lymphs are called?
Ig receptor
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Ig receptors are specific to what?
Various antigens prior to exposure.
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NK cells
- 5-10% of circulating lymphs
- Lack surface markers of T and B cells
- Used to be called Null Cells
- Destroys target cells directly
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Primary immune disorders
- 75% affect beofre age 5
- Defects in T or B line
- Aids
- SLE
- Hodgkins
- DiGeorge's Syndrome
- Multiple Myeloma
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Secondary Immune disorders
- Underlying disease that impares that immune system.
- Temorary or perminant
- Viral Infections
- Diabetes Mellitus
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Leukocytes communicate how?
- Physical contact
- or siluble mediators (chemical substances)
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AG and AB bonding creates what?
- Complex
- Bond is non-covalent and reversible
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Types of Bonds AB-AG reactions
- Hydrogen
- Hydrophilic
- Van Der Waals forces.
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Specificity
Ability of an AB to combine with one specific AG
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Affinity
Bond that forms between AB and AG
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Avidity
Strength of bond between AG - AB
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Cross reactivity
- AB can combine with AG tht has similar epitopes.
- Heterophile antibodies
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Radioimmunoassay (RIA)
- Uses isotope lable
- Competative binding
- Labled AB vs. unlabled AB competeing with binding with known antigen
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Enzyme Immunoassay (EIA)
- Enzyme labeled antibody conjugate (AHG)
- competative binding (sandwich principle)
- Enzyme causes a color change
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Common Colloidal particls used with Sol particle Immunoassay.
Gold, Silver, Iodine, barium, sulfate
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Nephlometry
Light scatter of macro immune complexes
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Flow symetry
- stained cell passes single file through laser
- cell flourecents a distinctive color of light
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Hapton
- <5000 daltons
- can combine with protein to become Antigen
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How many classes does MHC have?
3
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final visible result of a soluble Antigen to it's antiserum?
Precipitation
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Plasma cell that makes one specific AB
Monocolonal
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Neutralizes toxins
Antitoxen
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lysosime
enzyme found in tears and other secretions
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