Immune system - immune processes

• How are lymphocytes activated?

  Cytotoxic lymphocytes require activation from infected cell.

  T helper cells are activated by antigen presenting cells
• how is an antigen presented to cells?

  by MHC molecules
• Describe T cell activation

  Cytotoxic lymphocytes contain a TCR (T cell receptor) which binds to a MHC-1 expressed on infected cells

  T helper cells also contain a TCR but this is complementary to MHC-II
• Where is MHC-I found?

  expressed by all nucleated cells
• Where is MHC-II found?

  Expressed by specialised antigen presenting cells
• where is CD8+ found?

  Nowhere, CD8+ are a type of cytotoxic lymphocyte that recognise MHC-I presented by an infected cell
• where is CD4+ found?

  Nowhere, CD4+ are a type of T helper cell that recognise MHC-II found on antigen presenting cells
• What are professional antigen presenting cells?

  dendritic cell
• What is a professional antigen presenting cell?

  immune cells that specialise in presenting to T cells
• antigen presenting cell: dendritic cells, macrophages, B cells
• Can macrophages present antigens?

  yes, but are less able to activate naive T-cells than dendritic cells
• What are important in activation of the secondary immune response?

  macrophages
• Describe B cells as antigen present cells

  1. B cells bind antigen by B cell receptor
  2. receptor and antigen endocytosed
  3. B cells present antigens via MHC II to helper with same epitope recognition
  4. activated helper T cell secretes cytokines
  5. cytokines activate B cells to produce memory B cells and plasma cells
• What is an epitope?

  An epitope is the specific part of an antigen that is recognized and bound by an antibody.
• What is mediated by the humoral response?

  B-cell mediate, antibody-antigen mediates, phagocytosis and complement -mediated killing
• Describe antigen-driven cloning of lymphocytes (clonal selection)

  1. variety of b cell all with different antigen specificity
  2. BCR bind to specific antigens
• Humoral response:

  Free pathogens binds to B cell receptors (specific epitope recognition)

  B cell activated to produce clones of plasma cells and memory B cells

  Antibody production from plasma cells

  elimination of pathogen
• Humoral response

  1. Macrophage or dendritic cell phagocytoses pathogen
  2. Antigen processed in macrophage or DC & presented on surface via MHC II
  3. Specific helper T cell recognises processed antigen and binds (aided by CD4 binding to MHC II)
  4. Helper T cell activated
  5. B-cell phagocytoses BCR & antigen, presents antigen on MHC-II
  6. Helper T cell recognises antigen presented by B cell
  7. Cytokines from activated helper T cell fully activate B cell.
  8. B cell activated to produce clones of plasma cells and memory B cells
  9. Antibody production from plasma cells.
  10. Elimination of pathogen.
• antibodies mediated antigen inactivation (opsonisation)

  • neutralization
  • agglutination of antigen-bearing particles
  • precipitation of soluble antigens
• what does opsonisation mean?


  Enhancement of phagocytosis
• Antibodies mediate antigen inactivation (killing)

  complement fixation of complement
• complement: a pathway composed of more than 30 different soluble proteins that are in the blood
• activation of complement: classical, lectin and alternative
• what do the lectin, classical and alternative pathway all end in?

  formation of Membrane attack complex (MAC)
• Parts of a C1 complement: C1r, C1s, C1q
• complement binds to antigen-antibody complexes on cell surface and activates complement cascade
• Complement cascade activated, several complement proteins from membrane attack complex - a hole is formed in foreign cell
• how is the membrane attack complex formed?

  Complement cascade.

  C5b, generated by the cleavage of C5, serves as the initiator of the MAC formation. C5b binds to the surface of the pathogen or target cell, where it recruits other complement proteins (C6, C7, C8, and multiple copies of C9) to assemble into a transmembrane pore-like structure.
• how is the MAC inserted into the membrane?

  The assembled MAC complex inserts itself into the lipid bilayer membrane of the target cell, forming a channel or pore. This disrupts the integrity of the membrane, leading to osmotic lysis of the cell. Essentially, the MAC creates holes in the membrane, causing the target cell to swell and burst, ultimately leading to its destruction.
• Describe the split washer structure of MAC: This configuration comprises 4 asymmetric and 18 symmetric staves. The assembly of the MAC involves sequential association of complement proteins C5b, C6, C7, C8, and C9. The structure reveals that the MAC is an asymmetric pore, with differences in stacking between symmetric and asymmetric staves
• What does the cell mediated response involve?

  T-cell mediated (CLT for cell mediated response, aided by T helper cells)

  recognition of foreign material (MHC I antigen-T-cell receptor mediated)

  killing mechanism: cytotoxic T cell mediated killind anf humoral response activation by Helper T cells
• Cell mediated response:

  Infected cell presents antigen on MHC I to CTL

  T cell receptor (TCR) binds presented antigen

  CD8 binds to MHC I (MHC I on all somatic cells)

  CTL cell activated

  Perforin – forms pores in target cell membrane

  Granzymes – initiate apoptosis in target cell