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Saturday, March 18, 2006

Vaccination And Immunology

5.10.05

Features of the immune response:
• Specificity.
• Memory.
• Self-nonself discrimination.
• 'Redundancy.'

Types of immune response:
• Innate response
-rapid, relatively non-specific, no memory, first line of defence.
• Adaptive response
-slower, highly specific, long-lasting memory, ultimately more effective, second line of defence.

Innate response 1: soluble mediators
• Bind to pathogens or their products.
• Opsomise pathogens for phagocytosis.
• Recognise mainly bacterial carbohydrates.
• Eg. complement (alternate pathway), collectins, LPS binding protein.

Innate response 2: phagocytic cells
• Eg. neutrophils, macrophages.
• Bind and engulf (phagocytose) pathogens.
• Use pattern recognition receptors (PRRs) that recognise bacterial, viral and fungal molecules eg. scavenger and toll-like receptors.
• Binding triggers adaptive immune response.

Adaptive immune response 1: soluble mediators - antibodies
• IgM (primary response); pentamer.
• IgG (secondary response); monomer.
• IgA (mucosal surfaces); dimer.
• IgE (parasites/allergy); monomer.
• Made by plasma cells (derived from B cells).
• Bind and neutralise pathogens.
• Stimulate removal by phagocytes and compement.

Antibody responses:
• In primary response, IgM produced.
• Later in response, antibody class switches to IgG, IgA or IgE of same specificity.
• Antibody affinity then further refined to give more efficient response.
• Memory B cells produced; switched on more quickly and produce higher affinity antibodies.

Adaptive reponse 2: cellular mediators - CD4 and T cells
• 'Helper' T cells.
• Recognise exogenous bacterial or viral peptide antigens presented by dendritic cells or macrophages in association with class II HLA.
• Generate help for antibody production and stimulate cell-mediated immunity.

Adaptive response 3: CD8 and T cells
• 'Cytotoxic' T cells.
• Recognise endogenous viral peptide antigens presented in association with class I HLA.
• Generate 'killer' cells that directly kill virus-infected cells.

Antigen presentation
• Dendritic cells and macrophages take up antigen, process it and present it in the form of short peptides to T cells in association with HLA.
• Exogenous antigen processed and presented in association with class II HLA, but can also associate with class I HLA.

Vaccination: designed to mimic natural infection and stimulate immunological memory.

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