Immune Response to Bacterial Infections

Immune Response to Infectious Diseases - Bacteria

• The immune system uses a multifaceted approach to recognize and fight bacterial pathogens.
• Bacterial superantigens are toxins that activate a large number of T cells, which is not specific to one type of bacteria
• These superantigens work by simultaneously binding to the T cell receptor (TCR) and the major histocompatibility complex (MHC) class II molecules
• Massive T cell activation causes the release of pro-inflammatory cytokines
• These cytokines lead to systemic immune dysregulation and potentially severe conditions like toxic shock syndrome.

Learning Objectives

• Describe how the immune system recognizes and responds to bacterial pathogens.
• Identify strategies bacterial pathogens employ to evade the immune system's detection and elimination.
• Understand bacterial superantigens and the immunological consequences of their activation.

Learning Aims and Objectives

• The different immune responses are tailored to various pathogens (bacteria, viruses, parasites).
• The body's response to pathogens and how pathogens exploit their abilities.

Introduction

• Innate and adaptive immunity (humoral and cell-mediated) are involved in the response to infection.
• The extent of involvement depends on the infectious agent.
• Three types of infectious agents: bacteria, viruses, and eukaryotic parasites.

Bacteria

• Prokaryotic cells that do not need a host's machinery to replicate.
• Gram-positive and gram-negative bacteria.
• All bacteria have a cell wall surrounding the plasma membrane, containing peptidoglycan.
• Gram-negative bacteria have an additional outer membrane with lipopolysaccharide (LPS), anchored to the wall by lipoproteins.
• LPS is an endotoxin, causing antigenic variation.

Bacteria (cont'd)

• LPS triggers inflammation and fever by activating phagocytic cells, also activating B1 and mantle zone B cells.
• Gram-positive cells have a cell wall with peptidoglycan combined with teichoic acids, which are antigenic structures
• Capsules are saccharide material, masking underlying antigenic structures.

Immune Response to Bacterial Infection

• Physical barriers (skin, mucosa)
• Commensal organisms prevent colonization by pathogens.
• Lysozyme, found in secretions, digests peptidoglycan (especially in Gram-positive bacteria).
• Activated complement via classical and alternative pathways.
• Phagocytosis (direct or mediated by opsonization with antibody or complement).
• Antibodies (neutralization, opsonization, complement activation).
• Th1 cells activate phagocytes and mediate the inflammatory response.

Immune Response to Bacterial Infection (cont'd)

• Immune responses depend on the specific bacterium.
• Gram-positive bacteria resist lysis by the MAC.
• Complement activation leads to destruction of Gram-positive bacteria through opsonization.
• Encapsulated bacteria are resistant to direct phagocytosis, needing opsonization for uptake.

Mechanisms of Evading Immune Detection

• Capsule (e.g., Streptococcus pneumoniae): a saccharide coating protecting from phagocytosis and complement activation (MAC). Associated with virulence.
• Alteration of antigenic structures (e.g., LPS in Gram-negative bacteria).
• Localization within cells (e.g., Listeria monocytogenes).

Antibody Responses to Bacterial Antigens

• Most protein antigens elicit T-dependent responses.
• Some bacterial polysaccharides, nucleic acids, and polymeric proteins, and LPS can stimulate B cells without T cell help (TI responses).
• Two classes of TI antigens:
  • TI-1: Stimulate B cell division through TLR binding, leading to specific antibody response, predominantly IgM, early response, poor inducer of class switching.
  • TI-2: Do not have mitogenic activity but stimulate B1 and marginal zone B cells, cross-linking BCR, producing specific IgM response early in anti-bacterial response, important in response to encapsulated bacteria, triggering complement activation, opsonization, and eventual uptake and destruction.

Intracellular Bacteria

• Bacteria can be taken up by phagocytes, remaining within a phagosome or escaping into the cytosol.
• Listeria monocytogenes: produces a pore-forming toxin to disintegrate the phagosome membrane allowing it to replicate within the cytosol.
• During the initial extracellular phase, antibodies mediate immunity.
• Inside the phagosome, Listeria antigens are presented to Th1 cells via MHC Class II proteins.
• In the cytosolic phase, Listeria antigens are presented to Tc cells via MHC Class I proteins.

Bacterial Superantigens

• Stimulate T cell responses similar to allogeneic MHC response.
• Recognised by T cells without processing into peptides and binding to MHC.
• Bind to outer surface of Class II proteins and the Vβ region of many TCRs.
• A superantigen can activate 2-20% of all CD4+ T cells, resulting in massive cytokine production and systemic toxicity.
• Examples: Staphylococcal enterotoxins (food poisoning), S. aureus toxic shock syndrome toxin-1 (TSST-1).

This quiz explores how the immune system recognizes and battles bacterial pathogens, focusing on the role of superantigens. Participants will learn about the multifaceted immune response, T cell activation, and the implications of cytokine release. Prepare to deepen your understanding of immunology and the challenges posed by bacterial infections.