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11_innate_adaptive_integration.md

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Integration of innate and adaptive immunity

The distinct phases of infection

innate sensor cells:

  • epithelial

  • tissue resident mast

  • dendritic

  • macrophage

  • obligate intracellular

  • facultative intracellular

  • focus of infection


    luminal

    basal

All three of these layers are called the mucosal layer:

  • epithelial
  • laminal propria {house immune cells}
  • smooth muscle

Present in organ systems respiratory, digestive, urogenital.

Epithelial activation -> innate cells traffic through post-capillary venules -> inflammation from cells leads to more cells + leaky epithelial cells provide complement

general, non-specific cytokine response (eg. TNF) specific cytokine distribution from sensor cells dependent on molecular pattern of pathogen

ILCs:

  • recruit monocytes and granulocytes
  • differentiate specific T-cell effector types

Innate immune system keeps pathogen under control until the active has time to step in

Different effector "compartments" for different pathogens

ILCs, effector T, B -> myelomonocytes

myelomonocytes:

  • neutrophils
  • monocytes
  • eosinophils
  • basophils

ILC1

Intracellular pathogens

IL-12 / IL-18

_ ILC1 respond to IL-12 / IL-18. Mostly produced by macrophages.

  • NK cells are grouped with ILC1. Considered innate and part of this intermediate response?

IFN-\gamma

_ IgG _ Macrophages, respond to IFN-\gamma, for cell killing _ T_H1, respond to IFN-\gamma

ILC2

TSLP and IL-33/IL-25

multi-cellular / Helminth parasites

  • ILC2

IL-5

  • goblet cells in epithelium to produce mucus

  • IgE

IL-13

  • Eosinophils, basophils, mast

Unclear how ILC2 recruit T_H2, but likely through IL-4 produced by eosinophil et. al

  • T_H2

ILC3

IL-23 IL-1\beta

Activate ILC3, releasing IL-17/IL-22, with following effect on environment:

IL-17, pro-inflammatory, releasing further IL-1\beta, IL-6 IL-22, induces antimicrobrial peptides

Effector T-cells

Changes in adhesion molecule and chemokine receptor expression

T_FH:

  • up CXCR5 (home to follicles / B-cell zones)
  • down CCR7 (directs T-cells to T-cell zones)
  • down S1PR1

Other effectors:

  • up S1PR1
  • down CCR7

sphingosine 1-phosphate

S1PR1 -> sphingosine 1-phosphate CCR7

L-selectin glycosylated -> PSLG-1