Immunobiochemistry and Infection: A Molecular Insight into Immune Dynamics and
Disease
Immunobiochemistry, the biochemical basis of immune function, explores how immune cells
detect, respond to, and eliminate pathogens, as well as how errors in these processes lead to
autoimmune diseases. With recent advances in proteomics, metabolomics, and structural biology,
the intricate interactions between immune cells and pathogens are increasingly understood at the
molecular level. This article discusses key areas in current immunobiochemistry research:
metabolic reprogramming in immune cells (immunometabolism), host-pathogen protein
interactions during viral infections, and the biochemical basis of autoimmune diseases,
particularly the role of citrullinated proteins in rheumatoid arthritis.
Metabolic Reprogramming in Immune Cells (Immunometabolism):
Glycolysis vs. Oxidative Phosphorylation in T-cell Activation
T-cells, central players in adaptive immunity, undergo profound metabolic changes upon
activation. Resting T-cells rely primarily on oxidative phosphorylation (OXPHOS) to meet their
energy needs. However, once activated by antigen-presenting cells, T-cells switch their
metabolism from OXPHOS to aerobic glycolysis, a phenomenon known as the "Warburg effect"
in immune cells.
Aerobic Glycolysis: Activated T-cells increase glucose uptake and upregulate enzymes
involved in glycolysis, producing ATP more rapidly despite its lower efficiency
compared to OXPHOS. This shift supports rapid proliferation, cytokine production, and
effector functions.
Oxidative Phosphorylation: In contrast, memory T-cells and regulatory T-cells favor
OXPHOS and fatty acid oxidation, reflecting their roles in long-term immune
surveillance and immune tolerance.
This metabolic flexibility is orchestrated by signaling pathways such as mTOR, HIF-1α, and
AMPK. Dysregulation of immunometabolism has been implicated in chronic infections, cancer,
and autoimmune disorders, making it a target for therapeutic intervention.
Host-Pathogen Protein Interactions: Proteomic Mapping During
Viral Infections Like SARS-CoV-2 or Influenza
Understanding how viral proteins interact with host cell machinery is critical for uncovering
mechanisms of viral entry, replication, and immune evasion. Proteomic mapping has emerged as
a powerful tool in this domain.
SARS-CoV-2: Proteomic studies have identified over 300 host proteins that interact with
the SARS-CoV-2 proteome. For example, the viral non-structural protein NSP1
suppresses host mRNA translation by binding to the 40S ribosomal subunit, impairing
antiviral protein synthesis.
Influenza Virus: Hemagglutinin and neuraminidase are key influenza proteins that
interact with sialic acid residues on host glycoproteins, facilitating viral entry and release.
Additionally, influenza polymerase interacts with host RNA polymerase II, hijacking the
host transcription machinery.
Techniques such as affinity purification-mass spectrometry (AP-MS), proximity labeling, and
cross-linking mass spectrometry (XL-MS) allow high-resolution mapping of these interactions.
The resulting interaction networks reveal potential antiviral drug targets and host factors critical
for viral pathogenesis.
Biochemical Basis of Autoimmune Diseases: Role of Citrullinated
Proteins in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and
joint destruction. A hallmark of RA is the presence of anti-citrullinated protein antibodies
(ACPAs), which target proteins modified by citrullination.
Citrullination: This post-translational modification, catalyzed by peptidylarginine
deiminases (PADs), converts arginine residues into citrulline. Citrullination alters protein
structure and antigenicity, potentially creating neoepitopes that are recognized as foreign
by the immune system.
Pathogenesis in RA: Common citrullinated proteins in RA include vimentin, fibrinogen,
and enolase. These proteins are often found in inflamed synovial tissue and contribute to
the formation of immune complexes, leading to chronic inflammation and tissue damage.
Genetic and Environmental Triggers: HLA-DRB1 shared epitope alleles and
environmental factors like smoking enhance PAD expression and citrullination,
predisposing individuals to RA.
ACPAs serve as both diagnostic biomarkers and predictors of disease severity, and therapies
targeting citrullination pathways are under investigation.
Conclusion
Immunobiochemistry bridges immunology and biochemistry to unravel the molecular
mechanisms underlying immune function and dysfunction. The metabolic shifts in T-cells,
detailed protein interaction networks between host and pathogen, and the pathogenic role of
citrullinated proteins in autoimmunity highlight the complexity and precision of immune
regulation. These insights not only deepen our understanding of immune responses but also open
new avenues for diagnostic and therapeutic advancements in infectious and autoimmune
diseases.
