Immune Response Initiation

1.0 Antigens: The Key to Recognition

1.1 What are Antigens?

• Antigens are molecules or parts of molecules that stimulate an immune response.
• They are recognized by the adaptive immune system, specifically by antibodies and T cell receptors.
• Antigens can be proteins, carbohydrates, lipids, or nucleic acids.
• They are typically found on the surface of cells, viruses, fungi, bacteria, and other substances, including toxins and foreign bodies.

1.2 Self vs. Non-Self Antigens

• A critical function of the immune system is to distinguish between self-antigens (molecules belonging to the organism’s own cells) and non-self antigens (foreign molecules).
• Self-antigens are present on the surface of an organism’s own cells and are recognized as “self,” preventing an immune response against the body’s own tissues.
• Non-self antigens are recognized as foreign and trigger an immune response.
• The ability to differentiate between self and non-self is crucial to prevent autoimmune diseases, where the immune system attacks the body’s own cells.

KEY TAKEAWAY: The immune system distinguishes between self and non-self antigens to avoid attacking the body’s own tissues.

2.0 Pathogens and Allergens: Triggers of Immune Responses

2.1 Pathogens: Disease-Causing Agents

• Pathogens are agents that cause disease in their hosts.

• They can be cellular or non-cellular:

  • Cellular Pathogens:
    • Bacteria: Single-celled prokaryotic organisms (e.g., Streptococcus, E. coli).
    • Fungi: Eukaryotic organisms that can be unicellular (yeasts) or multicellular (molds) (e.g., Candida, Aspergillus).
    • Protozoa: Single-celled eukaryotic organisms (e.g., Plasmodium, Giardia).
    • Parasites: Multicellular organisms that live in or on a host and cause harm (e.g., worms, ticks).
  • Non-Cellular Pathogens:
    • Viruses: Non-cellular infectious agents consisting of nucleic acid (DNA or RNA) enclosed in a protein coat (e.g., influenza virus, HIV).
    • Prions: Misfolded proteins that can cause other normal proteins to misfold, leading to disease (e.g., Creutzfeldt-Jakob disease).
    • Viroids: Small infectious RNA molecules that can infect plants.

2.2 Allergens: Overzealous Immune Triggers

• Allergens are non-parasitic antigens that provoke an exaggerated immune response called an allergic reaction in susceptible individuals.
• Common allergens include:
  • Pollen
  • Dust mites
  • Pet dander
  • Certain foods (e.g., peanuts, shellfish)
  • Insect stings
  • Certain medications
• The immune response to allergens involves the production of IgE antibodies, which bind to mast cells and basophils, leading to the release of histamine and other inflammatory mediators upon subsequent exposure.

EXAM TIP: Be able to classify pathogens as cellular or non-cellular.

3.0 Antigen Presentation: Activating the Immune Response

3.1 The Process of Antigen Presentation

• Antigen presentation is the process by which cells display antigens on their surface, where they can be recognized by T cells.
• This is a crucial step in initiating the adaptive immune response.
• Two main types of cells are involved in antigen presentation:
  • Antigen-Presenting Cells (APCs): Specialized cells that engulf pathogens or antigens and present them on their surface. Examples include dendritic cells, macrophages, and B cells.
  • Infected Cells: Any cell infected with a virus or other intracellular pathogen can present viral antigens on its surface.

3.2 Major Histocompatibility Complex (MHC) Molecules

• Antigens are presented on the cell surface bound to MHC molecules (Major Histocompatibility Complex).
• There are two main classes of MHC molecules:
  • MHC Class I:
    • Present on all nucleated cells.
    • Present antigens derived from the cytoplasm (e.g., viral proteins).
    • Present antigens to cytotoxic T cells (CD8+ T cells), which kill infected cells.
  • MHC Class II:
    • Present on APCs (dendritic cells, macrophages, B cells).
    • Present antigens derived from extracellular sources (e.g., bacteria, toxins) that have been engulfed by the APC.
    • Present antigens to helper T cells (CD4+ T cells), which activate other immune cells.

3.3 Steps in Antigen Presentation

1. Antigen Uptake: APCs engulf pathogens or antigens through phagocytosis or endocytosis.
2. Antigen Processing: The antigen is broken down into smaller peptide fragments inside the cell.
3. MHC Loading: Peptide fragments bind to MHC molecules inside the cell.
4. Cell Surface Display: MHC-peptide complexes are transported to the cell surface, where they can be recognized by T cells.

3.4 T Cell Activation

• T cells recognize antigen-MHC complexes on the surface of APCs or infected cells via their T cell receptors (TCRs).
• The interaction between the TCR and the MHC-peptide complex, along with co-stimulatory signals, activates the T cell.
• Activated T cells then differentiate into effector cells that carry out specific immune functions (e.g., killing infected cells, activating B cells).

STUDY HINT: Create a flow chart to visualize the antigen presentation process from antigen uptake to T cell activation.

4.0 Summary Table

COMMON MISTAKE: Confusing antigens, pathogens and allergens. Remember that all allergens are antigens, but not all antigens are allergens. Pathogens carry antigens.

5.0 The Role of Cytokines

• Cytokines are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis.
• They include interleukins (ILs), interferons (IFNs), tumor necrosis factor (TNF), and chemokines.
• Cytokines are produced by a variety of immune cells, including T cells, B cells, macrophages, and dendritic cells.
• They act by binding to specific receptors on target cells, triggering intracellular signaling pathways that alter gene expression and cellular function.
• Cytokines play a critical role in:
  • Activating and differentiating immune cells: For example, IL-2 promotes T cell proliferation, while IL-4 promotes B cell class switching to IgE.
  • Recruiting immune cells to sites of infection: Chemokines attract leukocytes to areas of inflammation.
  • Regulating the intensity and duration of immune responses: Some cytokines, such as IL-10 and TGF-β, suppress immune responses to prevent excessive inflammation and autoimmunity.

VCAA FOCUS: Understand the role of MHC I and MHC II in antigen presentation and how they activate different types of T cells.