Biochemistry II: Immunity

Innate Immunity vs Acquired Immunity

• Innate immunity is inborn and activated immediately in response to an invading microorganism
• Acquired immunity is adapted by the body to defend against an invading pathogen
• Innate immunity is generic or non-specific in nature, while acquired immunity is specific
• Innate immunity is present from birth, while acquired immunity develops over time
• Aspects of innate immunity, such as mechanical barriers, exert defensive mechanisms regardless of the presence or absence of an invading pathogen
• Innate immunity is triggered immediately in response to infection, while acquired immunity takes time to develop and exert its effects
• Major immune cells involved in innate immunity include NK cells, neutrophils, macrophages, eosinophils, and basophils
• Major immune cells involved in acquired immunity are primarily lymphocytes, including B cells and T cells

Inflammatory Response

• Three major immunological events occur during an inflammatory response:
  • Vascular changes: increased blood flow and fluid and plasma protein leakage into the inflamed tissue
  • Cellular infiltration: leukocytes adhere to vascular endothelium and migrate through the endothelial layer to access surrounding tissues
  • Chemotaxis: leukocytes follow a chemical gradient to the site of insult and unleash potent killing mechanisms

Phagocytosis

• Five processes involved in phagocytosis:
  • Activation of the cell that will perform phagocytosis
  • Chemotaxis occurs in the immune system
  • The cell attaches to the particle that it will ingest
  • The cell ingests the particle, which is enclosed in a vesicle (phagosome)
  • A lysosome fuses with the phagosome, and the particle is digested

Immune Cells

• Examples of immune cells involved in different responses:
  • Allergic response: Mast cells
  • Phagocytosis: Macrophages
  • Production of antibodies: B cells
  • Antigen presentation: Dendritic cells

Complement Activation

• Complement activation leads to the formation of the membrane attack complex (MAC), which kills Gram-negative bacteria
• The MAC is formed through the assembly of C5b, C6, C7, C8, and C9 proteins
• The MAC causes osmotic lysis of bacteria through the influx of Ca2+ and other electrolytes

Cytokines in Bacteria Septic Shock

• Tumour necrotic factor-alpha (TNF-α) and Interleukin-1 (IL-1) are elevated in bacteria septic shock
• Gram-negative bacteria, such as E. coli, K. pneumoniae, P. aeruginosa, and E. aerogenes, have cell wall endotoxins that stimulate macrophages to release TNF-α and IL-1

Membrane Attack Complex (MAC) Formation

• Assembly of the MAC is initiated when the complement protease C5 convertase cleaves C5 into C5a and C5b
• The MAC is formed through the binding of C5b, C6, C7, C8, and C9 proteins, leading to the formation of a transmembrane pore

Tumour Antigens

• Two mechanisms employed by tumour antigens to evade immune responses:
  • Inhibiting the immune system: Tumours inhibit or evade the immune system by accumulating specific metabolites and signal factors, or limiting the nutrients available to immune cells
  • Inducing T cell exhaustion: Cancer cells affect the metabolism of T cells, inhibiting glycolysis and affecting the immune response

Blood Group Antigens

• Blood group antigens are found on N-glycoproteins, O-glycoproteins, and glycolipids on RBCs and other cells
• They are synthesized on type 1, 2, 3, or 4 structures
• Type 1 and 2 structures are Galβ1-3GlcNAc-R and Galβ1-4GlcNAc-R, respectively
• Type 3 and 4 structures are Galβ1-3GalNAc-R, with differing R groups