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Reminders

Reminders. Exam 4- Friday April Ch. 6- effector T cells (lecture 3/28) Ch. 7- Humoral Immunity Ch. 8- Defense against infection material on the adaptive immune response- self learning- p 260-268. Selected material from Ch. 12 if time permits. NK cell activation.

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Reminders

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  1. Reminders • Exam 4- Friday April • Ch. 6- effector T cells (lecture 3/28) • Ch. 7- Humoral Immunity • Ch. 8- Defense against infection • material on the adaptive immune response- self learning- p 260-268. • Selected material from Ch. 12 if time permits.

  2. NK cell activation

  3. Killer Cell Ig Like Receptor (KIRs): Killer Lectin-like Receptors- Similar to C-type lectins/ not limited to carbohydrate binding.

  4. LRC = leukocyte Receptor Complex NK cell Receptors are encoded in 2 gene complexes: • Chromosome 12= Natural Killer Complex (NKC). • Chromosome 19= KIR complex. • Alleles demonstrate polymorphism in the human population.

  5. CD94/NKG2A Heterodimer- Binds HLA-E HLA-E functions as an indicator of the level of HLA-A, -B, & -C on the cell surface. Inhibitory Signals: • Various KIRs: • Specific for HLA-A,-B- & -C alleles. • > 50 discovered

  6. Activating Receptors • Engage “abnormal” ligands: • Different glycosylation • Tumor Ag/viral glycoproteins • NKp46- binds heparan sulfate proteoglycans & viral proteins. • Engage stress induced ligands: • NKG2D

  7. NK cell mediated killing resembles the CTLs.

  8. Mf: Supplies IL-12 early. TNF-alpha Dendritic cells & B cells- IL-12 IFN-a, b IL-12: NK cell proliferation Activation- Increased cytotoxicity Cytokines produced by macrophages, virally infected cells, & B cells activate NK cells.

  9. Th1 cells produce cytokines that will drive CD8 + t cell & macrophage response A viral infection & the presence of IL-12 early will drive TH1 cell development

  10. Vaccines Active Immunization

  11. Development of an immune response does not necessarily mean that a state of protective immunity has been achieved. Must consider pathogens point of entry &/or growth site.

  12. Types of vaccines: • A. Whole Organism Vaccines: 1. Inactivated vaccines: • Heat or Chemical- • Considerations: • Maintain antigenic determinants. • Viruses- nucleic acid must be inactivated. • Large amount of pathogen must be propagated. • Humoral immune response.

  13. Whole organism vaccine continued: • 2. Live attenuated viral or bacterial vaccines: • Attenuated strains • Related pathogen that causes illness in other animal species: • Smallpox vaccine Vesicle formation on skin. TH2 response B cell & T cell memory.

  14. How are attenuated viruses obtained in the laboratory?

  15. Attenuation by genetic modification of virulence genes.

  16. Bacterial attenuation: • Vaccine for tuberculosis: • Mycobacterium bovis- cultured for >13 years on synthetic medium containing bile ----- BCG. • BCG- Bacille Calmette-Guerin.

  17. Attenuated live vaccines demonstrate: • 1. Longer growth time in host: • Increased immunogenicity. • Increased memory cell response. • Cell Mediated Immune Response. • Example: Polio sabin vaccine- 3 attenuated viruses. • Replicated in intestinal epithelium. • IgA response + IgM + IgG. • 2. Generally does not require boosters.

  18. 3. Attenuated generally less stable than inactive. • 4. Concern for attenuated strain reversion & the presence of contaminants.

  19. B. Subunit Vaccines- • Composed of purified macromolecules from the pathogen. • 1. polysaccharide vaccines- Capsules from bacteria. • 2. Toxoid Vaccines- • bacterial exotoxins- diphtheria / tetanus. • purified toxin is inactivated (formaldehyde).

  20. A single isolated constituent of the microbial pathogen cannot alone provide an effective immune response. • Polysaccharides- • T- Independent type Antigen. • Stimulates B cells to produce IgM. • No isotype switching. • No affinity maturation. • No memory. • Proteins-

  21. How can the subunit vaccine be made more useful? • Adjuvant addition to the macromolecule- • Tricks the immune system into thinking that it is under microbial attack. • Role for dendritic cells. • Role for cytokines. • Conjugated Vaccines: Ag is conjugated to a carrier, usually protein. • Converts a T- independent antigenic response into a T dependent antigenic response.

  22. Current Vaccine development: • 1. Use of attenuated microbes as vaccine vehicles for recombinant antigens. • Requires attenuated strain. • Requires knowledge of genes responsible for virulence & immunity. • Requires Biotechnology.

  23. Plasmid DNA containing the gene encoding for a pathogens surface protein. Muscle cells + dendritic cells take in DNA and express the gene. DNA vaccines: Inject intramuscularly

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