Cell Mediated Immunity

CELL-MEDIATED IMMUNITY: Antibody-independent immunity, mediated by T_H1 cells.
Examples: Type-IV Hypersensitivity Responses, mycobacterium tuberculosis and other intracellular pathogens.

• MACROPHAGE ACTIVATION: IFN-gamma, secreted by T_H1 cells, activates macrophages. Effects are generally anaphylactic:
• Increase expression of MHC-II molecules in macrophages, to enhance their roles as APC's.
• Increase expression of Fc-receptors and CR3-receptors, to enhance opsonization.
• Increase oxidative-burst ------> reactive O₂-intermediates and reactive N₂ intermediates (such as NO).
• Increase synthesis of eicosanoids: PGD₂, PGI₂, TXA₂, LTB₄
• CYTOTOXIC LYMPHOCYTE (CTL) ACTIVATION: IL-2 converts CTL-Precursors ------> Active CTL
• IL-2 is secreted by T_H1 cells.
• Antigen activation of a CD8 cell causes it to up-regulate its expression of IL-2 Receptors. Subsequent IL-2 activation (by T_H1 cells) causes CTL proliferation.
• After antigen activation, both CTL's and T_H-Cells are dependent on IL-2 for their proliferation.
• TERMINATION: After antigen clearance, the levels of IL-2 decline and CTL's die by apoptosis. This ensures that the immune response is limited and help to prevent excessive tissue damage.
• CTL-MEDIATED CYTOTOXICITY:
• CONJUGATE FORMATION: CTL binds to MHC-I of the target cell (which is expressing antigen and is therefore targeted for destruction).
• TCR-CD3 complex on CD8-Cell binds to HLA-I of target cell
• Additional binding by LFA-1 of CD8 cell with ICAM-1 of target cell.
• PERFORIN MONOMERS: After conjugate formation, the CD8 cell releases perforin monomers from storage granules.
• These monomers polymerize within the membrane to form perforin pores ------> target-cell membrane lysis.
• DEATH BY APOPTOSIS: Some evidence exists that the CTL cell sends a signal to target cell which causes the target-cell to die by apoptosis.
• TNF-beta has been a signal that is implicated in this apoptosis signal.
  
• NATURAL KILLER (NK) CELLS: Non-specific (natural) killing of tumors and some virally infected cells.
• They are believed to derive from null cells. Strange cell lineage.
• KILLING METHOD: Similar to CTL's.
• They degranulate perforin-like monomers to cause target-cell lysis.
• They kill cells by apoptosis (mediated by TNF-alpha)
• NK-CELL PROPERTIES:
• They do not express CD8, CD3 or any other CD lymphocyte markers on their membranes.
• They have no immunologic memory.
• ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY (ADCC): Many cytotoxic cells express Fc-receptors on their membranes. They can then kill an antibody(IgG)-coated cell by a non-specific process.
• Cells involved: Most natural immunity cells have Fc-Receptors and can thus partake in ADCC. Neutrophils, Eosinophils, Macrophages, NK-Cells, Monocytes
• Cells coated with IgM are not subject to ADCC because IgM has no available Fc region! Primarily IgG is the antibody responsible for ADCC.