Bms 501

Overview of Immune Response Mechanisms

Activation of Signaling Pathways

  • Acids activate chloride receptors, influencing signaling pathways.

  • Primary focus on Toll-like receptors (TLRs) activating NF kappa B.

  • TLRs help in recognizing pathogens and activating immune responses.

Recognition of Cytoplasmic Nucleic Acids

  • RIG-I and MB-5 bind viral RNA.

  • Interaction leads to movement towards mitochondria where antiviral systems are activated.

  • This pathway initiates kinase activation that leads to phosphorylation mechanisms.

Interferon Regulatory Factors (IRFs)

  • Key immune modulators: IRF3 and IRF7.

  • Phosphorylated IRFs migrate to nucleus to initiate transcription of Type 1 interferons (alpha and beta).

  • IRFs serve as transcription factors crucial for immune signaling.

Pathways for DNA Recognition

  • Viral and bacterial DNA initiates the cGAS pathway.

  • Cyclic AMP (cAMP) and GMP are important signaling molecules motivating IRF activation.

  • IRFs play roles in expressing Type 1 interferons as a response to these viral components.

Interferon Functionality

  • Interferons are secreted proteins crucial in inhibiting viral replication.

  • They bind to specific receptors invoking JAK-STAT pathways to signal cellular defenses.

Mechanisms of Viral Suppression

  • Interferons trigger an autocrine response where infected cells also gain protection.

  • Infected cells produce signals to nearby cells indicating the presence of a virus.

  • Results in downregulation of protein synthesis to limit viral replication.

Role of EIF2 and PKR in Protein Synthesis Regulation

  • EIF2: An initiation factor critical for the protein synthesis process.

  • Interferons upregulate key proteins that bind to EIF2, inhibiting its function and thus protein production.

  • Protein Kinase R (PKR) is activated by interferons, contributing to the inhibition of viral protein synthesis.

Endoribonucleases and Targeting Viral RNA

  • Endoribonucleases selectively degrade viral RNAs, which are typically longer than host RNAs.

  • This mechanism helps in reducing the viral load and the effectiveness of viral replication.

Natural Killer (NK) Cells

Activation and Role of NK Cells

  • NK cells detect MHC I molecules on host cells.

  • Absence of MHC I signals target cells for destruction by activating NK cell mechanisms.

  • Activated NK cells release cytotoxic granules to induce apoptosis in infected cells.

Cytokine Release and Communication with Macrophages

  • NK cells enhance macrophage activity through cytokine signaling.

  • Interleukin 12 from macrophages stimulates NK cell proliferation and activity.

  • NK cells release interferon-gamma, enhancing the immune response.

Dendritic Cells and Adaptive Immune Activation

  • Dendritic cells play crucial roles as antigen-presenting cells.

  • Interactions between NK cells and dendritic cells can lead to population dynamics where either NK cells activate proliferation or they balance each other.

  • When dendritic cells outnumber NK cells, they migrate to secondary lymphoid tissues to initiate adaptive immune responses involving T cells.

Relationships in Immune Response Dynamics

  • Interferons signal NK cells and enhance their readiness to combat viral infections.

  • The balance between immune components ensures effective control of infections, with adaptive immune responses engaged if innate responses fail.

  • This hierarchical immune response provides layers of defense against pathogens, promoting both immediate and long-term immunity.