Ch. 3. Innate Immunity Anatomical barriers epidermis, dermis, cilia, cough, sneeze, outward flow of urine Chemical b

1. Ch. 3. Innate Immunity Anatomical barriers epidermis, dermis, cilia, cough, sneeze, outward flow of urine Chemical barriers psoriasin on skin, acid pH of stomach, lysozyme in tears But some organisms can evade these barriers, e.g., by attaching firmly to epithelial cells by fimbriae or pili Ch. 3

2. Vertebrates - Two Systems of Immunity 1. Innate immunity (early in infection) physical, chemical, cellular barriers 2. Adaptive immunity (or acquired immunity) - specific response by B and T lymphocytes memory; future exposures quicker and more vigorous “sensors” = specific antibodies (Ab’s) and T cell receptors (TCR’s) Ch. 3

3. p. 53 Ch. 3

4. Ch. 3 p. 54

5. Ch. 3

6. Connections Between Innate and Adaptive Immunity Invaders must be sensed and destroyed Invaders are recognized by soluble or membrane-bound molecules These molecules recognize broad structural motifs that are in germs, but not in self Ch. 3

7. PRRs and PAMPs PRRs = Pattern Recognition Receptors PAMPs = Pathogen-Associated Molecular Patterns - combinations of sugars, certain proteins, some lipid-bearing molecules, and some nucleic acid motifs - found only on microbes, never on self Ch. 3

8. In contrast, Ab’s and TCR’s of adaptive immunity recognize finer details of molecular structure Summary: PRRs recognize broad, essential motifs, present on many groups of microbes; Ab’s and T-cells recognize fine differences among different microbes Ch. 3

9. Examples of soluble mediators of innate immunity • Mannose-binding lectin (MBL) • C-reactive protein (CRP) • When these bind to microbes with PAMPs they • recognize, the complement system may be • activated to opsonize microbes or lyse them Ch. 3

10. Ch. 3 p. 58

11. p. 58 Ch. 3

12. Dendritic cell and macrophages have Toll-like receptors (TLRs) which detect microbial products 11 discovered in humans, 12 in mice When TLR combines with microbe, macrophage: -has increased phagocytic activity -makes toxic chemicals -makes cytokines, like IL-1, IL-6, TNF-alpha -thus inflammatory response is induced Ch. 3

13. p. 58 Ch. 3

14. Immature dendritic cells internalize antigen, process it, mature, migrate to lymph node, and present processed Ag to T cells for adaptive immune response. Dendritic cells also secrete a variety of cytokines that promote inflammation. Ch. 3

15. p. 56 Ch. 3

16. Inflammation Can be acute or chronic Acute: redness, heat, swelling (edema), pain Chemoattractants cause extravasation of leukocytes (white blood cells); examples are - chemokines (subclass of cytokines) - C3a, C5a (from complement) - N-formyl peptides (from microbes) Ch. 3

17. p. 60 Ch. 3

18. Ch. 3

19. Ch. 3

20. Soluble Molecules and Membrane-associated Receptors Antimicrobial peptides contribute to the defense against bacteria and fungi Proteins of the acute phase response contribute to innate immunity Innate immunity uses a variety of receptors to detect infection (e.g., MBL, CRP, LBP, NOD) Ch. 3

21. p. 61 Ch. 3

22. Ch. 3

23. Toll-like Receptors (TLRs) Membrane-spanning proteins that share a common structural element in their extracellular region (24-29 aa’s, xLxxLxLxx, called leucine-rich repeats, LRRs) Intracellular domain is called the TIR domain Complete set of TLR’s can detect many viruses, bacteria, fungi, and some protozoa Ch. 3

24. p. 63 Ch. 3

25. p. 63 Ch. 3

26. p. 64 Ch. 3

27. Ch. 3

28. Cell Types of Innate Immunity Neutrophils – in blood Macrophages – in tissues NK cells – in blood Dendritic cells – in lymph Ch. 3

29. Ch. 3

30. p. 68 Ch. 3

31. Signal Transduction Pathways Signal  receptor  signal transduction  effector mechanism TLR signaling is typical of signal transduction pathways Ch. 3

32. Initiation by interaction of signal with receptor • 2. Signal-induced assembly of pathway components / Involvement of an adaptor molecule • 3. Protein kinase-mediated phosphorylation • 4. Initiation of an enzyme cascade Ch. 3

33. p. 70 Ch. 3

34. Ch. 3

35. Ch. 3

36. p. 72 Ch. 3