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• Acute and Chronic inflammation


  Not at two ends of a spectrum, nor does Acute inflammation necessarily lead into Chronic inflammation with the progression of time
• Sometimes the acute phase is so quick that it doesn't cause symptoms/disease (meaning we might not realise there is an Acute inflammation phase)
• Each disease has a specific pattern of acute and chronic inflammation
• Causes of Chronic Inflammation

  • Persistent exposures
  • Abnormal immune responses
  • Irritants
  • Infections
  • Harmless environmental agents
  • Commensal microbes
  • Components of the body
  • Novel cells
  • Grafts/transplants
  • 'Wound that do not heal'
• Chronic inflammatory conditions


  • Bronchitis, Emphysema (from smoke/particles)
  • Hepatitis B virus (HBV), H. pylori gastritis, M. tuberculosis
  • Allergies hayfever (pollen), asthma
  • Inflammatory bowel disease (Crohn's disease)
  • Autoimmune diseases - Rheumatoid Arthritis, Systemic Lupus
  • Cancers in a proliferative stage
  • Rejection of organ transplants if not completely histocompatible
• Lifestyle factors that are protective against chronic inflammation

  • Plant based fibre-rich diet
  • Helminths
  • SCFA
  • Probiotics
  • Omega-3-FA
  • Increased barrier function
  • Increased mucus
  • Exercise
  • IL-10
  • TReg
  • TGFB
• Lifestyle factors that are causative of chronic inflammation

  • Excessive hygiene
  • Antibiotics
  • Western diet
  • Pathobionts
  • Stress
  • Obesity
  • Nervous system
• Psychological stress


  Stress prepares the body for 'fight or flight' and acts partly through the sympathetic nervous system via noradrenalin release from adrenal glands, influences mood and increases risk of inflammatory diseases
• Obesity (diet)


  Hypertrophic (thickened) adipose tissue releases proinflammatory cytokines, saturated fatty acids (SFA) which stimulate TLRs, ROS from malfunctioning mitochondria, DAMPS from necrotic adipocytes. SFA, ROS and DAMPS recruit pro-inflammatory macrophages and T1 cells.
• Microbial Balance


  Changes to the microbes associated with our guts and skin due to diet, antibiotics and excessive hygiene. Pathobionts are harmful, colonise the gut, alter mucus production and induce pro-inflammatory cytokines.
• Anti-inflammatory factors


  • Can counteract pro-inflammatory factors, produce anti-inflammatory cytokines IL-10 and TGFB
• Microbial Balance - Protective

  Symbionts and Probiotics rebalance the commensal microbes on our body. Symbionts are beneficial and promote Treg activity. Probiotics aim to restore the balance. Fecal transplants can rebalance the microbes. Helminths (worms) are anti-inflammatory and can be used to treat chronic inflammatory gut conditions like IBD.
• Diet - Protective


  Diet enriched in short-chain fatty acids (SCFA) such as butyrate are produced from fermentation of plant fibre in the colon -> bind to GPR43 receptors. Omega-3-fatty acids (from seeds and fish) also bind and activate GPR120 receptors. These G-protein coupled receptors regulate metabolism and inflammation through improving mucus production and epithelial barrier function.
• Exercise - Protective


  Suppresses inflammatory cytokines - TNFa, reduces risk of chronic metabolic and cardiovascular diseases, can also lead to a reduction in adiposity.
• Acute Inflammation: Innate Immune System


  • Circulating Neutrophils and Monocytes -> Macrophages recruited to sites of damage within tissues. Phagocytose debris, DAMPS, microbes. Kill microbes. Regulate Inflammation and Repair. Pro-Inflammatory Cytokines and Chemokines (IL-6, TNF, IL-1ẞ) attract immune cells. Proteases (Matrix Metalloproteases) digest ECM.
• Chronic Inflammation: Adaptive Immune System

  • Lymphocytes recognize antigen epitopes as 'foreign' by surface receptors. T Cells: include Cytotoxic T cells (killer; CD8) and T helper cells (CD4). B cells: differentiate into plasma cells to produce antibodies.
• T helper Cells - TH1


  TH1 cells secrete IFNg to stimulate T1 (self)development and macrophage response to intracellular pathogens. Abnormal responses lead to autoimmunity.
• T helper Cells - TH2

  T2 cells secrete IL-4 to stimulate TH2 and eosinophil response to helminths. Abnormal response cause allergy.
• Cytotoxic T cells (killer; CD8)

  T cells that can directly kill infected or cancerous cells
• T helper cells (CD4)


  T cells that help coordinate the immune response
• B cells


  Cells that differentiate into plasma cells to produce antibodies
• Antigen Presenting Cell (APC)
• TH1 cells secrete IFNg to


  Stimulate T1 development and macrophage response to intracellular pathogens
• TH2 cells secrete cytokines including IL-4 to


  Stimulate T2 development and activate eosinophil response to helminths
• TH17 cells secrete IL-21 and IL-17 to


  Stimulate TH17 development and epithelial response to extracellular microbes to secrete anti-microbial peptides and recruit neutrophils
• Treg cells secrete IL-10 and TGFB to


  Stimulate Treg development and suppress inflammation by dampening the activities of other T Helper cells
• Response to foreign material:

  Bone fragments, silica, thorns
• Response to infectious material:

  Mycobacteria tuberculosis, M. leprae
• A balance between neutrophil and T1 responses to

  Prevent/eliminate infection but to avoid severe tissue damage
• Mtb bacteria inhaled into the lung alveoli ->


  Alveolar macrophages phagocytose and enter the lung interstitium (fluid). Bacteria replicate in the macrophage endosome.
• Release of TNFa and IL-1

  Recruits neutrophils -> early innate immunity/ acute inflammation
• Bacteria destroyed by


  Autophagy, ROS and anti-microbial peptides
• Apoptotic death of infected cells induced by PAMPS/PRR, TNFa, IFNg ->

  Releases Mtb in apoptotic bodies
• Efferocytosis of apoptotic bodies -

  Bacteria is killed by phagosomes fusing with lysosomes (oxidative burst). Macrophages switch to be anti-inflammatory (M2, TNF↓↓, TGFß^-> repair).
• Macrophages migrate to the lymph nodes as antigen presenting cells (APC) to


  Activate TH1 cells. These arrive in the lung after several weeks. They release IFNy to activate macrophage bactericidal mechanisms (leading to apoptosis of infected cells).
• TH17 cells are also involved, releasing IL-17 which


  Recruits neutrophils to kill bacteria but this also causes tissue necrosis (as collateral damage).
• Mtb lipids inhibit MO activation to

  Generate 'permissive macrophages' that support intracellular proliferation
• These associate into granulomas to


  Impede T cell penetration and antigen presentation
• Neutrophil toxins (e.g. ROS) and high-dose TNFa cause

  Macrophage necroptosis freeing intact Mtb which is phagocyosed by nearby macrophages. Propagates intracellular and extracellular Mtb.
• T2 release IL-4 to

  Generate fibrosis (scar) to block access of TH1 cells