Cellular Communication and Inflammation

Cytokines
1. Activity
  1. Autocrine
  2. Paracrine
  3. Endocrine
2. IL-4
  1. B-cell
    1. Activation
    2. Proliferation
    3. Differentiation
  2. Thymocyte and Mast cell
    1. Proliferation
3. IL-2 and IL-5
  1. B-cell proliferation
4. IL-4 + IL-5
  1. Induces B-cell class switch to IgE
Recognition and assessment
1. PRR activation
  1. TLR receptors sense infection inside and outside the cell
    1. TLR 4 and TLR1:TLR2 heterodimer sense bacterial infection outside the cell
    2. TLR3 detects viruses
    3. Horseshoe shaped
    4. Transmembrane
    5. Can be homo or hetero-dimers
2. Assessment
  1. 1. Soluble pathogen-associated molecular patters (PAMPs) and dead microorganisms pose a low threat
    1. Recognised by pattern-recognition receptors PRRs
    2. Induces the production of pro-inflammatory cytokines (IL-6, IL-12 and TNF), as well as other cellular responses
    3. PAMPs and microbial debris removed from the tissue
  2. 2. Viable microorganisms, which are by definition infectious, pose a significant threat and elicit robust inflammatory responses
    1. Bacterial viability is sensed through detection of 'vita-PAMPs', and possibly though other mechanisms
    2. Leads to the activation of additional PRR pathways, including those involving interferon-regulatory factors, NOD-, LRR- and pyrin domain-comtainin 3
      1. Induces IL-1-beta production and pyroptosis
    3. Increased IFN-beta production
  3. 3. Classical pathogens are extremely dangerous for the host organism and usually trigger immediate and strong inflammatory responses
    1. PRR activation
    2. Direct and indirect effects of virulence are sensed triggering rapid mobilisation of multiple PRR systems
      1. Include TLRs and NLRs
    3. Inflammatory response is scaled to the microbial threat
Activation of cytokine signalling and recruitment of neutrophils and diapedesis
1. General PRR activation activates an intracellular signal cascade that turns on relevant gene transcription of cytokines
2. Initiation of inflammatory response
  1. Activated macrophages release pro-inflammatory cytokines
3. Neutrophils migrate to the site of inflammation by 'rolling'
  1. Rolling along the capillary endothelium slows leukocytes down and facilitates stronger intractions
4. Diapedesis (extravation)
  1. Neutrophils follow the IL-8 gradient to the site of the infection
Systemic signalling
1. Initiation of the inflammatory resopnse
  1. Activated macrophages release pro-inflammatory cytokines
    1. IL-6
      1. Fever. Induces acute-phase protein production by hepatocytes
    2. TNF-alpha
      1. Activates vascular endothelium and increases vascular permeability, which leads to increased entry of complement and cells to tissues
      2. Increased fluid drain to lymph nodes
      3. Fever. Mobilisation of metabolites. Sock
      4. 185 amino acid glycoprotein peptide released by many leukocytes
      5. Increases vascular permeability for cells and humoral components (IgG and complement)
      6. Also acts on hypothalamus
        stimulates release of corticotropon releasing hormone (CRH)
        suppresses appetite
        Causes a fever
      7. Enough TNF is good
      8. Too much TNF is bad
    3. IL-1-beta
      1. Activates vascular endothelium
      2. Activates lymphocytes
      3. Local tissue destruction
      4. Increases access of effector cells
      5. Fever. Produciton of IL-6
    4. CXCL8
      1. Chemotactic factor recruits neutrophils and basophils to site of infection
    5. IL-12
      1. Activates NK cells

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Cellular Communication and Inflammation

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	Created by zambrella about 11 years ago