A guide to Clinical Infectious Disease
17th Edition
Levinson
TABLE OF CONTENTS:
1. The Barrier
2. Phagocytes and Other myeloid cells
3. PRRs of Innate Immune Cells
4. Effector Mechanisms of Innate Immune Cells
5. Inflammatory Mediators
6. Acute Phase Response
7. Trained Innate Immunity
, Chapter 58: Innate Immunity
THE BARRIER: skin and its mechanical, chemical and biological components. “First line of Defense”
Defensins: Antimicrobial peptide
An example of chemical barriers produced by gastrointestinal and lower respiratory tracts.
Creates pores in lipid membranes of microbes
Antivarial: alpha defensins (by neutrophils and paneth cells in intestinal crypts.)
Antibacterial: beta defensins (by respiratory tract)
PHAGOCYTES AND OTHER MYELOID CELLS
Second line of defense - Innate immune cells/leukocytes/WBCs.
Includes myeloid cells. Most importantly: phagocytes.
1. Tissue macrophages encounter invaders
2. Neutrophils migrate and contribute to inflammation
3. Dendritic cells take microbial material to spleen and lymph nodes (activate adaptive immune
response)
4. Monocyte: Are a special type of myeloid cell that can differentiate into macrophages or dendritic
cells when needed. Thus can also be recruited to inflammation site to take over their roles.
Innate immune response:
Invasion by microbes
Innate recognition
Proinflammatory signals produced (APCs, granulocytes, NK cells)
, PATTERN RECOGNITION RECEPTORS OF INNATE IMMUNE CELLS
- Innate immune cells: PRRs recognize PAMP.
PAMP: eg carbohydrates, lipids, nucleic acids (eg double-stranded RNAs)
● Significance of PAMP:
1. Is not present in human cells and is difficult for those microbes to alter through mutation.
2. Reduced specificity but can broadly distinguish what is foreign from what is “self.”
Extracellular PRRs: recognize microbes that are outside of cells or within the cells’ vesicle
Intracellular PRRs: recognize microbes that have invaded the cell’s cytoplasm
The immune response is shaped by the PRRs activated during the initial encounter with innate immunity.
Antibody-mediated responses are most effective against extracellular bacteria.
T cell–mediated responses are required against intracellular microbes.
TLRs: antibacterial and antiviral
different receptor types but innate cell activation is the same.
TLR4 -> binds to endotoxin/LPS.
1. LPS released from -ve bacteria
2. Binds to LPS-binding protein