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Chapter 73: Immune Dysfunction and Dysregulation

BALANCED INFLAMMATORY RESPONSE

Immune system components: balanced response by these components ensures elimination of threat with minimal damage to surrounding tissues (Table 73-1).

  • Innate immunity:

    • Pattern recognition receptors (PRRs) = present on most cells, recognize pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Lead to the production of cytokines and chemokines to contain threat and recruit cellular components of the immune system. Include the toll-like receptors (Table 73-2), Toll-like and Nod-like receptors, RIG-like receptors, and C-type lectin receptors.

    • Opsonins = mark pathogens or cells for clearance by phagocytes.

    • Complement = opsonize or directly lyse pathogens via assembly of the membrane attack complex.

    • Cells = including neutrophils, monocytes/macrophages, dendritic cells, and natural killer cells.

  • Adaptive immunity:

    • T cells.

      • CD4+ helper T cells:

        • Th1: Triggered by bacteria and viruses. Primary cytokines include IL-2, IFN-γ, TNF.

        • Th2: Triggered by parasites and allergic reactions. Primary cytokines include IL-4, IL-5, IL-10.

        • Th17: Very inflammatory. Primary cytokine is IL-17.

      • CD8+ cytotoxic T cells: Kill infected cells.

    • B cells.

      • Plasma B cells: Antibody factories.

      • Memory B cells: Provide long-term protection.

TABLE 73-1

Examples of Key Effector Molecules of the Innate Immune System

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TABLE 73-1

Examples of Key Effector Molecules of the Innate Immune System
Effector Molecules Primary Source Critical Function
Pro-inflammatory cytokines IL-1β Macrophages, endothelial and epithelial cells Fever, induces other cytokines, stimulates bone marrow to release neutrophils and platelets, inhibited by anakinra (IL-1 receptor antagonist)
TNF-α Macrophages Fever, induces other cytokines, recruits neutrophils and monocytes, inhibited by infliximab and etanercept
IL-2 T cells Induces T-cell proliferation, activates B cells
IL-6 Macrophages, endothelial and epithelial cells Mediator of the acute phase response, inhibited by tocilizumab
IL-12 Macrophages and dendritic cells Stimulates production of interferons (IFNs)
Chemokines C-X-C family Many cells Chemotactic to neutrophils
C-C family Many cells Chemotactic to monocytes and T cells
Anti-inflammatory cytokines IL-4 T cells Inhibits T cells, macrophages, IFN, and IL-12
IL-10 Monocytes Suppresses pro-inflammatory cytokines
TGF-β Macrophages, many cells Inhibits phagocytosis, induces inflammatory cell apoptosis
Antiviral interferons Type I interferon (IFN-α and IFN-β) Most cell types Inhibit viral replication through transcription of IFN-regulated genes
Type II interferon (IFN-γ) T cells (Th1), NK cells Inhibits viral replication directly, supports Th1 response, promotes cellular immunity
TABLE 73-2

Key Pattern Recognition Receptors from the Toll-Like Receptor Family

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TABLE 73-2

Key Pattern Recognition Receptors from the Toll-Like Receptor Family
Toll-like Receptor Classic Ligand(s) Source of Ligand
TLR1 Lipopeptides Bacteria
TLR2 Lipoteichoic acid Gram-positive bacteria
TLR3 Double-stranded RNA RNA viruses
TLR4 Lipopolysaccharide (LPS) Gram-negative bacteria
TLR5 Flagellin Bacteria
TLR6 Diacyl lipopeptides Mycoplasma
TLR7 Single-stranded RNA RNA viruses
TLR8 Single-stranded RNA RNA viruses
TLR9 Unmethylated CpG DNA Bacteria, DNA viruses

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS)

Excessive inflammation: can cause collateral damage to tissues.

  • Symptoms: fever or hypothermia, tachycardia, tachypnea, abnormally ...

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