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Antigen
- -molecule with ability to stimulate immune response
- -i.e. foreign protein, polysaccharide, or lipid
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Epitope
the part of an antigen that is bound by a specific antibody/T-cell receptor
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Cytokines
-proteins used as signaling molecules or as chemoattractants for leukocytes
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Micro-Organism
- -Local proliferation (Phagocytes, Complement lysis and metabolite transport blocked)
- -Invasion (Antibody to aggressions, antibody to organism, complement lysis, phagocyte)
- -Toxin production (antibody to toxin)
- -Intracellular growth (Chronic infection) (Cell-mediated immunity)
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Cytokines and Chemokines (Interleukins)
- -IL-6: proinflammatory, made in
- response to bacterial products, Induces acute phase of response in liver,
- promotes B-cell proliferation
- -IL-12: Heterodimer of IL-12
- alpha/beta, disulphide linked, promotes conversion Th0->Th1
- -IFN-γ: Activates macrophages and T-cells, produces by Th1/NK cells
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Macrophages and Cytokines
- -Important component of innate and adaptive immune response
- -Important antibacterial phagocytic cell
- -Produce IL-1, IL-6, IL-12, TNF-α/β and interferon-α
- -Activation of acute-phase and inflammation responses
- -Presentation of antigen to CD4 T cell
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T-cells Recognize Antigens in Presence of:
MHC Class I/II
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B cells and T cells proliferate in response to
Specific antigens
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Postulates of Lymphocyte Clonal Selection hypothesis
- -Each lymphocyte bears a single type receptor of a unique specificity
- -Interaction between a foreign
- molecule with high affinity leads to lymphocyte activation
- -Differentiated effector cells derived
- from activated lymphocyte bear receptors of identical specificity to those of
- parental cell from which that lymphocyte was derived
- -Lymphocytes bearing receptors
- specific for self molecules are deleted at an early stage in lymphoid cell
- development and are therefore absent from the repertoire of mature lymphocytes.
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T-cell precursors/B-cell originate in
Bone Marrow
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T cells selected for in
Thymus
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Self-Tolerance
- -In Thymic medulla
- -Includes at least two cell populations
- -Medullary thymic epithelial cells (mTECs): Delete self-antigens
- -Haematopoietic antigen-presenting cells (APCs): Deletes but needs help
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Recognition of antigen bound MHC class II
- -Along with a second signal from the APC
- -Leads to conversion of Th0 cells to Th1 or Th2 effector cells:
- -Pathogen binds APC
- -Antigens fed to naïve T cell via MHC/TCR, naïve T cell become effector
- -Cytokines released from APC go to effector
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Five Classes of Antibodies
IgM, IgG, IgA, IgE, IgD
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IgM
- Intravascular;
- -complement activation, agglutination (5 IgGs)
- -Mainly in bloodstream, B-cell
- surface, responses to polysaccharides in bacterial surfaces
- -First responder
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IgG
- Intravascular Interstitial fluid,
- Transplacental complement activation, Neutralization, opsonization, Immunity to neonate
- -Bloodstream and extracellular, can get
- to mucous membranes, most abundant
- -Bulk of secondary response
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IgA
- Luminal secretions, Breast milk
- Neutralization at body surface,
- Intestinal immunity in neonates (2 IgGs)
- -Protects gut, respiratory tract, other
- secretory surfaces such as tear ducts
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IgE
- Subcutaneous Submucosal;
- -Mast-cell sensitization, Eosinophil activation
- -Mainly bound to mast cells, involved
- in allergic response
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IgD
- B-cell surface
- -Not known (B-cellantigen receptor)
- -Helps initiate B-cell response
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T-independent Response
- -Does not require T-cells for B-cell proliferation
- -Shorter lived/weaker response then T-dependent responses
- -No isotype switching (get IgM)
- -B-cells become plasma cells, release cytokines
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T-dependent Response
- -Requires T-cells for B-cell proliferation
- -T-cell signals using cytokines IL-2, IL-4, IL-5
- -Get isotype switching to IgG, IgA, IgE
- -Get stronger response and memory response
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Antibodies
- -Binding to surface structures of bacteria (pili, lipoteichoic acid, capsule)
- -Blocking of attachment
- -Opsonization
- -Promotion of complement action
- -Promotion of clearance of bacteria
- -Neutralization of toxins and toxic enzymes
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Candidates for Vaccination
- -Causes significant illness
- -Exists as only one Serotype
- -Antibody blocks infection/systemic spread
- -Organism does not have oncogenic potential
- -Vaccine is heat-stable so can be transported to endemic areas
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What do Vaccine Do
- -Neutralize toxins (diphtheria and tetanus)
- -Prevent adherence (experimental cholera vaccine)
- -Opsonize encapsulated organisms (pneumonia, influenza)
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Why Can Vaccines not work
- -Pathogens rapidly change surface structure
- -Immune responses can elicit damaging sequelae
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Properties of Good Vaccine
- -Generate rapid memory response without disease symptoms
- -Elicit strong response in vaccine (adjuvants)
- -Correct immune response is elicited
- -systemic vrs. mucosal
- -antibody vrs. T cell
- -reasonable cost
- -safe
- -Live vaccine better than inactivated
- -Not storable, can be more volatile in response
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