Lecture 10 -- Extracellular Immunity

A set of vocabulary flashcards covering key concepts about extracellular immunity, parasite interactions, and immune responses.

Describe the process of the adaptive immune response against extracellular parasites, which the body has not been exposed to.

1. Antigen capture and presentation

   • Neutrophils and macrophages may attempt phagocytosis and degrade parasites into peptide fragments using enzymes (e.g. defensins, lysozyme, MPO)

   • Dendritic cells itself may also phagocytose those parasites

   • Peptides are loaded onto MHC class II molecules in the endoplasmic reticulum of dendritic cells → Transported via Golgi → Expressed on the cell surface

2. Activation of naïve CD4⁺ T cells

   • Dendritic cells migrate to secondary lymphoid organs (lymph nodes, spleen) and present antigen–MHC II complexes to naïve CD4⁺ Th0 cells

   • Co-stimulation is required for activation of T cells: CD28 (T cell) binds CD80/CD86 (APC)

   • APCs release IL-4 and IL-6 → Drive differentiation into Th2 cells

3. Early innate signalling (alarmins)

   • Parasite damage to epithelium triggers release of alarmins (e.g. IL-33) → Activates innate lymphoid cells (ILCs) → Release IL-4 and IL-13

     • IL-4 promotes Th2 differentiation

     • IL-13 enhances dendritic cell migration to lymphoid tissues

4. Th2-mediated cytokine response

   • Promote activation and differentiation of B cells into plasma cells → antibody production

   • Secrete key cytokines: IL-4, IL-5, IL-9, IL-10, IL-13

Describe the role of IL-4 and IL-13 produced by Th2 cells in the immune response against extracellular parasites.

• Increases goblet cell production

  • Increases mucus secretion → Mucus prevents attachment of parasites to the lumen

• Produce RELM-β → Inhibits parasite feeding on the host → Starvation

• Shift macrophages from M1 → M2 phenotype

  • M2 macrophages produce:

    • IL-10 → Self regulatory

    • RELM-α → Promotes extracellular matrix deposition and tissue repair (wound healing)

Describe the role of IL-4 produced by Th2 cells in the immune response against extracellular parasites.

• Induces B cell class switching → production of IgE (and some IgG)

• Fc region of IgE binds Fc receptors on mast cells and eosinophils

Describe the role of IL-5 produced by Th2 cells in the immune response against extracellular parasites.

• Stimulates production and activation of eosinophils from bone marrow → Promotes eosinophil accumulation in blood

• Eosinophils kill parasites via degranulation:

  • Reactive oxygen species (ROS) → oxidative stress

  • Major basic protein (MBP) and eosinophil cationic protein (ECP) → Damage parasite cuticles

• OR via Antibody-dependent cellular cytotoxicity (ADCC)

Describe the role of IL-9 produced by Th2 cells in the immune response against extracellular parasites.

• Promotes mast cell growth and activation

• When IgE bound to mast cells binds to an antigen, it leads to degranulation of mast cells:

  • Proteases

    • Damage parasite cuticles or interfere with larval stage of parasite

    • Opens tight junctions → Allow fluid egress 離開

  • Histamine

    • Increases vascular permeability → Allows plasma proteins, antibodies, and immune cells to exit blood vessels into tissues

  • Cytokines

Describe the role of IL-10 produced by Th2 cells in the immune response against extracellular parasites.

• Self regulatory → Prevents excessive inflammation and tissue damage

Describe the role of IL-13 produced by Th2 cells in the immune response against extracellular parasites.

• Increases intestinal smooth muscle contraction → helps expel parasites

• Promotes epithelial turnover from the stem cells at the crypt in the intestinal lumen → Physically removes parasite or disrupt their attachment sites

Describe the process of the adaptive immune response against extracellular bacteria.

1. Antigen capture and presentation

   • Neutrophils and macrophages may attempt phagocytosis and degrade bacteria into peptide fragments using enzymes (e.g. defensins, lysozyme, MPO)

   • Dendritic cells itself may also phagocytose those parasites

   • Peptides are loaded onto MHC class II molecules in the endoplasmic reticulum of dendritic cells → Transported via Golgi → Expressed on the cell surface

2. T cell differentiation

   • Dendritic cells migrate to secondary lymphoid organs (lymph nodes, spleen) and present antigen–MHC II complexes to naïve CD4⁺ Th0 cells

   • Co-stimulation is required for activation of T cells: CD28 (T cell) binds CD80/CD86 (APC)

   • Dendritic cells secrete cytokines → Naïve CD4⁺ Th0 cells differentiate into:

     • Th2 cells (driven by IL-4, IL-6)

     • Th17 cells (driven by IL-6, IL-23, TGF-β)

Describe the role of Th2 cells in extracellular bacterial infections

Th2 cells secrete IL-4 (and other cytokines)

• IL-4 functions:

  • Promotes antibody class switching (From IgM to IgG)

    • Neutralisation of bacterial toxins and virulence factors

    • Opsonisation = Coats bacteria to enhance recognition and uptake by phagocytes

    • Fc region of IgG binds to Fc receptor on neutrophils and macrophages, leading to:

      • Enhanced phagocytosis → Degranulation of neutrophils and macrophages = Activation of intracellular killing mechanisms

      • Antibody dependent cellular cytotoxicity (ADCC)

What specific types of tissues do Th17 cells particularly defend?

Mucosal and barrier tissues