Inflammation and Immunity: A Deep Dive

1. Signs and Symptoms of Swelling:

  • Pain
  • Warmth
  • Swelling

Preventing Inflammation Spread: Several factors can prevent the spread of inflammation beyond the initial site, including:

  • Proper hygiene
  • Rest and elevation
  • Medical intervention (if necessary)

Immune System’s Inflammatory Response: The immune system generates an inflammatory response through the release of signaling molecules called cytokines, such as TNF-alpha. These molecules recruit immune cells to the site of injury or infection and initiate the inflammatory process.

Pus Cells: Pus cells are primarily composed of dead neutrophils (PMNs).

2. Definitions:

  • Rookie Lymphocyte: A mature T lymphocyte that has not yet been activated or encountered its specific antigen.
  • Innate Immunity: The body’s non-specific, immediate defense mechanisms against pathogens, without adaptive immune response or memory.
  • TNF-α: A cytokine that induces local or systemic inflammation, produced by macrophages (MCFs).
  • Diapedesis: The extravasation of PMNs and monocytes from blood vessels into tissues.
  • Receptor: Cell membrane proteins that bind to specific molecules, known as ligands.
  • TLR (Toll-Like Receptor): A class of proteins that play a key role in the innate immune system by recognizing conserved molecular patterns associated with pathogens.
  • Allotype: A genetic variation within a population.

3. TLRs and Recognized Products in Mammals:

  • TLR1: Diacylated lipoproteins
  • TLR3: Double-stranded RNA
  • TLR5: Flagellin
  • TLR7: Single-stranded RNA, diacylated lipoproteins
  • TLR9: Unmethylated bacterial CpG DNA

4. Lysozyme: The enzyme lysozyme is found in various bodily fluids, including cerebrospinal fluid (CSF), sweat, tears, and urine.

5. Major Acute Phase Proteins (Serum Protease Inhibitors):

  • Alpha-1-antitrypsin
  • Alpha-1-antichymotrypsin
  • Alpha-2-macroglobulin

6. Systemic Reactions to Inflammation/Tissue Damage: Key mediators of systemic reactions to inflammation and tissue damage, such as fever, neutrophilia, drowsiness, muscle wasting, and production of new proteins, include the macrophage-derived cytokines IL-1, IL-6, and TNF-α.

7. Vasoactive Peptides from C3 and C5: C3a and C5a, derived from complement proteins C3 and C5, respectively, are anaphylatoxins that increase vascular permeability by promoting histamine release from mast cells. C5a is also a potent chemoattractant for PMNs and monocytes.

8. Platelet Activating Factor (PAF): PAF, a phospholipid produced by mast cells, platelets, PMNs, and other cells, promotes PMN aggregation, chemotaxis, oxygen radical release, and smooth muscle contraction.

9. C-Reactive Protein (CRP): CRP, a major acute phase protein in humans and some other species, is a pentraxin that binds to phosphatidylcholine on cell membranes, activating the classical complement pathway.

10. Serum Amyloid P Component (SAP): SAP, a major acute phase protein in rodents, is a pentraxin that binds to nuclear constituents and can activate the complement system.

11. Serum Amyloid A (SAA): SAA, an acute phase protein, is a chemoattractant for PMNs, monocytes, and T lymphocytes.

12. Haptoglobin: Haptoglobin, an acute phase protein, binds free iron, inhibiting bacterial growth.

13. Major Acute Phase Proteins in Pigs: Haptoglobin, acid soluble glycoprotein, α1-acid glycoprotein, ceruloplasmin, and α2-globulin.

14. Negative Acute Phase Proteins in Pigs: Alpha-lipoprotein, transferrin, and fetuin.

15. Mannose-Binding Lectin (MBL): MBL, an important protein in the innate immune system, binds to microbial surfaces and activates the complement pathway.

16. Iron-Binding Protein: Proteins like lactoferrin and transferrin bind iron, limiting its availability to pathogens and inhibiting their growth.

17. Pentraxins: Pentraxins, including CRP and SAP, are acute phase proteins with diverse biological functions, including complement activation and stimulation of phagocytic leukocytes.

18. Listeria: A facultative intracellular, Gram-positive bacterium that neutralizes oxidative respiration for intracellular survival.

19. Mycobacterium: A facultative intracellular, acid-fast bacterium that blocks phagosome-lysosome fusion for intracellular survival.

20. Salmonella typhimurium: A facultative intracellular, Gram-negative bacterium with lipopolysaccharide in its cell wall.

21. IL-12: A cytokine produced by antigen-presenting cells that promotes Th1 cell activity and stimulates T and NK cell proliferation.

22. Flagellar Antigen: The flagellar antigen of bacteria is designated as the “H” antigen.

23. Selectins: Adhesion proteins that bind to glycoproteins on vascular endothelial cells.

24. Chemotaxis: The phase of phagocytosis where immune cells are attracted to the site of inflammation by chemoattractants like C5a, fibrinopeptide B, chemokines, and leukotriene B4.

25. PMNs (Neutrophils): Short-lived, first-line defense cells that rapidly phagocytose invading organisms.

26. MCFs (Macrophages): Long-lived phagocytic cells that contribute to tissue repair and immune regulation.

27. IL-1: A cytokine that causes lethargy and malaise and mobilizes amino acids for protein production.

28. IL-1: A cytokine that activates lymphocytes and promotes immune responses.

29. IL-6: A cytokine involved in lymphocyte activation and acute phase protein production.

30. TNF-α: A cytokine that causes fever, stimulates acute phase protein production, and enhances chemotaxis and phagocytosis.

31. Macrophages: Cells essential for wound healing, phagocytosing bacteria and regulating collagen production.

32. Histiocytes: Activated macrophages in inflamed tissues with increased lysosomal enzyme activity and phagocytic capacity.

33. FcgRI: A high-affinity Fc receptor expressed on macrophages and monocytes that binds to the Fc region of antibodies.

34. Fcg2R: A bovine Fc receptor that binds to IgG2a antibodies.

35. Defensins: Antimicrobial peptides found in neutrophil granules that disrupt microbial cell membranes.

36. Chemokines: Proteins involved in leukocyte maturation, trafficking, and diapedesis.

37. Innate vs. Acquired Immunity:

InnateAcquired
Cells InvolvedMacrophages, dendritic cells, neutrophils, NK cellsT and B lymphocytes
Evolutionary HistoryOldRecent
AppearanceRapid (minutes-hours)Slow (days-weeks)
SpecificityCommon bacterial structuresUnique antigens

38. Tissue Macrophages:

  • Kupffer cells (liver)
  • Microglia (brain)
  • Alveolar macrophages (lungs)

39. MHC Class I Molecule:

  • Name and Function: Major Histocompatibility Complex class I, presents antigens to cytotoxic T cells.
  • Part 1: Beta-2 microglobulin
  • Part 2: Alpha-3 domain
  • Part 3: Alpha-1 domain
  • Part 4: Alpha-2 domain

40. MHC Class I Peptide-Binding Groove: The peptide-binding groove of MHC class I is formed by the alpha-1 and alpha-2 domains.

Vasoactive Molecules and Their Roles:

Histamine: Increased vascular permeability, pain
Thromboxanes: Increased vascular permeability, platelet aggregation
Kinins: Vasodilation, increased vascular permeability, pain
Leukotrienes C, D, E: Smooth muscle contraction, increased vascular permeability
Serotonin: Increased vascular permeability
Leukotriene B4: PMN chemotaxis, increased vascular permeability
C3a and C5a: Degranulation of mast cells, smooth muscle contraction, neutrophil chemotaxis
Platelet-Activating Factor (PAF): Platelet secretion, PMN secretion
Products that Destroy Fibrinogen: (e.g., plasmin)
Nitric Oxide: Vasodilation
P-selectin: Leukocyte rolling and adhesion