Immune Responses to Infectious Agents

Immune Responses to Infectious Agents Overview

• This chapter goes into the roles of the immunologic actors and their characteristics in host protection against infection.
• It also includes their interactions, and the immunopathogenic consequences that may arise as a result of the response.

Controlling Infections

• Innate responses control most infections before immune responses begin.
• Immune responses are necessary to resolve more troublesome infections.
• Both innate and immune responses regulate constituents and restrict normal flora to their niche in the body. Additionally, they restrict virulent species.
• The importance of each component of the host response differs for different types of infectious agents.
• It becomes obvious when it is genetically deficient or diminished by chemotherapy, disease, or infection such as acquired immunodeficiency syndrome (AIDS).

Human Defense Lines

Human beings have four basic lines of protection against inappropriate microbial infection:

• Natural barriers, including skin, mucus, ciliated epithelium, gastric acid, and bile restrict entry of the agent.
• Competition with normal flora.
• Innate antigen-nonspecific immune defenses such as fever, antimicrobial peptides, interferon, complement, neutrophils, macrophages, dendritic cells (DCs), innate lymphoid cells, innate T cells, and B-1 B cells provide continuous or rapid local responses at body surfaces, and at the infection site to restrict the growth and spread of the agent.
• Adaptive antigen-specific immune responses like antibody and T cells reinforce innate protections; specifically they target, attack, and eliminate the invaders that succeed in passing the first two defenses, as well as the infected cells; and they remember the pathogen for future challenges.

Symptoms and Disease

• Symptoms and disease occur when barrier functions and innate responses are insufficient to keep normal flora within its niche or control infections.
• Infections can grow, spread, and cause damage during the time period required to initiate a new antigen-specific immune response.
• Microbial and immunopathogenesis initiated by the infection determine the extent of the disease.
• The more extensive and established the infection, the more immunopathogenesis.
• Elicited immune memory by prior infection or vaccination can be activated quickly enough to control most infections before symptoms occur.

Antibacterial Responses

• Protection is initiated by activation of local innate and inflammatory responses and progresses to system-wide acute-phase and antigen-specific responses.
• The barrier functions, antimicrobial peptides, phagocytic killing by neutrophils/macrophages, antitoxin, and opsonizing antibodies are the most important antibacterial host responses.
• Complement and antibody facilitate phagocytes uptake of microbes.
• TH17 and TH1 CD4 T-cell responses enhance phagocytes functions.

Antimicrobial Response Initiation

• Multiple responses during the early stages of a bacterial infection are triggered by the bacteria surface structures/metabolites, stress, and tissue damage.
• Small molecules, such as adenosine triphosphate (ATP), nuclear/cytosolic proteins, respond to cell damage with damage-associated molecular pattern (DAMP) receptors during skin or mucous membrane infections.
• Bacterial cell wall molecules, including teichoic acid, lipoteichoic acid, peptidoglycan fragments (gram-positive bacteria), and lipid A of lipopolysaccharide (LPS) bind and activate pathogen-associated molecular pattern (PAMP) receptors.
• Lipid A (endotoxin) binds to TLR4, other PAMP receptors, and acts as a strong activator of DCs, macrophages, B cells, and selected other cells.
• Innate lymphoid cells and natural T cells also respond, yield cytokines, and reinforce antimicrobial peptide production and cellular responses via interleukin release.
• γ δ T cells in tissue sense phosphorylated amine metabolites from most bacteria.
• NKT cells respond to bacterial glycolipids presented on CD1 molecules by DCs, and MAIT cells respond to vitamin B derivatives produced by many bacteria.
• Natural T cells also respond to PAMPs.
• B-1 B cells are also activated by repetitive bacteria surface structures binding to PAMP receptors and surface immunoglobulin.
• The cells proliferate and produce immunoglobulin (Ig)M, which is especially important for capsular polysaccharides.
• Natural T cells release reinforced antimicrobial peptides such as defensins that protect skin and mucoepithelial surfaces via IL-17 and IL-22.