HUBS191 Lecture 38: The Immune Response to Infection – A Wrap Up

Adaptive and Innate Immunity

• Adaptive and innate immunity work together to protect the body from infection and disease.

Key Concepts

• Phagocyte Mobilization:

  • Inflammation makes capillaries leaky.
  • Neutrophils squeeze out of capillaries and enter tissue.
  • Neutrophils are attracted to the infection site by chemicals.
  • Bacteria are phagocytosed, and lysosomal enzymes kill them.

• Cell-Mediated Immunity and Antibody Production:

  • Optimal antiviral responses require CD4 T cells, CD8 T cells, and B cells (for antibody production, especially neutralizing IgG).

• T Cell and B Cell Activation:

  • Viral proteins can enter both the phagolysosome and cytosol of Dendritic Cells (DCs).
  • Phagosomal antigen will be loaded onto MHC-II for CD4 (helper) T cell stimulation.
  • Cytosolic antigen will be loaded onto MHC-I for CD8 T cell stimulation.
  • Helper T cells stimulate B cells to make antibodies; only B cells that recognize the antigen are activated.
  • Antibody class switching (IgM → IgG → IgA → IgE) alters antibody function, not specificity.

Clonal Selection

• Selective expansion of lymphocytes that interact with the antigen.

MHC Loading

• MHC-I:
  • Viral or bacterial infection triggers antigen presentation by class I MHC proteins.
  • Abnormal peptides in the cytoplasm are displayed by class I MHC proteins on the plasma membrane.
• MHC-II:
  • Phagocytic APCs engulf extracellular pathogens.
  • Lysosomal action produces antigenic fragments displayed by class II MHC proteins.

Antibodies

• Bind native antigens without requiring processing to peptide.
• Epitopes are antibody binding sites on larger structures.
• The isotype switching changes antibody function but not specificity.

Primary vs. Secondary Immune Response

• Secondary response is faster and larger compared to the primary response.
• Class-switched antibodies are predominant in secondary responses (IgG, IgA, IgE).

Vaccines

• Types:
  • Live attenuated, killed, sub-unit protein, sub-unit mRNA.
• Adjuvants:
  • Immune stimulants added to vaccines to enhance APC activation.
  • mRNA SARS-2 vaccine is intrinsically adjuvanted (lipid-encapsulated mRNA is immunostimulatory).

Immune Response Tests

• Clonal selection: selective expansion of lymphocytes able to recognise antigen.
• B cells progress to plasma cell and memory cell stage after recognizing antigen through their B cell receptor (BCR) AND after receiving CD4 T cell help (cytokines).
• In dendritic cells, viral antigens normally access the cytosol and the phagolysosome
• To progress to CTL, naive CD8 T cells require recognition of MHC-I / peptide and help provided by CD4 T cells
• CD8 CTL recognize virus infected cells (and cancer cells) via MHC-I / peptide
• Adjuvants: Enhance the activation of antigen presenting cells
• Cytotoxic T lymphocytes (CTL) kill by releasing: granzyme and perforin