Immune System

• Fibroblasts create scar tissue --> incomplete healing = not regeneration
• Macrophages are phagocytes that engulf pathogens, dead cells, debris, etc.
• Neutrophils degranulate after doing their job, and this releases free radicals that damage tissue in high numbers
• Eosinophils release toxic chemicals to kill parasites
• Basophils release histamine which causes inflammation (redness)
• Mast cells release histamines as part of the immune response
• principal features of chronic inflammation are cellular infiltrate (contains macrophages, lymphocytes, plasma cells, neutrophils, eosinophils and basophils), repair with new vessel formation, and varying degrees of fibrosis
• granulomas are a stack of macrophages on top of a pathogen that cannot be eradicated (like TB) as part of chronic inflammation
• chronic inflammation can be caused by acute inflammation, persistent infections (eg mycobacterium tuberculosis), persistent exogenous toxins (asbestos) and autoimmune diseases
• Macrophages are the drivers in chronic inflammation. They secrete cytokines and growth factors. They recruit T cells and Fibroblasts. They have direct involvement in destroying foreign invaders
• Chronic inflammation either becomes inactive (scar tissue, disability, recurrence) or persists and becomes fatal (TB) or Amyloidosis occurs or neoplasia
• Neoplasia is the uncontrolled, abnormal growth of cells or tissues in the body, and the abnormal growth itself is called a neoplasm or tumour.
• Amyloidosis occurs when the amyloid protein builds up in organs, affecting funciton
• repair requires cell proliferation from the remains of the injured tissue (stem cells), vascular endothelial cells to produce new vessels, and fibroblasts to produce scar to fill defects not corrected by regeneration.
• Healing adequacy is controlled by polypeptide growth factors, and the ability of cells to divide in response
• regeneration is a tissue response with regrowth of specialised cells (using preserved framework)
• healing is the tissue response to a wound, inflammation in internal organs and cell necrosis (in organs incapable of regeneration)
• regeneration occurs when specialised cells are destroyed but the framework is preserved, surviving somatic cells proliferate and recover the reticulin fibre network
• healing has three phases; inflammation, formation of granulation tissue (intermediary scarring) and epithelial regrowth, and then wound contraction (deposition of extracellular material inc collagen, scar remodelling)
• First Intention healing = minimal scarring --> small, clean, uninfected with severed edges close together (think sutures)
• In healing, tensile strength starts low, slow increase up to ~2 weeks, then rapid increase. ~6 weeks ~50% ultimate strength (can tolerate moderate forces)
• Secondary intention --> large defect, infection, ongoing inflammation, or no opposition of wound edge. CAUSES MAJOR SCARRING
• adaptive growth responses: hyperplasia (one cell type proliferates), hypertrophy (gets bigger), atrophy (smaller), autophagy (cell eats itself, recycles contents), metaplasia (one specialised cell turns into a different specialised cell)
• Neoplasm = new growth of cells
• tumour = neoplasia presenting as a mass/lesion
• Histogenesis of tumours: epithelial = carcinoma, soft tissue/bone = sarcoma, osteosarcoma, angiosarcoma mixed eg metaplasia carcinosarcoma. In glands - adenocarcinoma. CNS = glioma vs neuroepithelial vs meninges. Germ cells (from emrbyotic cells) = blastoma (1 layer) teratoma (multiple). Lymphoid/haemopoeietic. Neuroectodermal = melanoma
• malignant = bad tumour, rapidly growing, not confined by basal lamina, spreads to lymph - CANCER
• benign = good --> can press on important nerves etc. slow growing, not invasive
• Malignant neoplasms are favoured by --> 1. differentiation (looks different to og tissue) + anaplasia (ugly) 2. local invasion (can it move through tissue/produce enzymes to dissolve tissue) 3. Metastasis (spreads to another organ or site, not joined to og)
• well differentiated = low grade = better behaved = less invasive (vice versa also true)
• poor differentiation = high grade differentiation
• anaplastic cells have pleomorphism ie lots of different sizes and shapes, different to og --> generally bigger, with more dna that's mutated
• some malignant tumours won't metastasize
• Cancer is a genetic disorder caused by DNA mutations --> problems with the genetics of the cell. Can happen when it's sitting there, or while dividing. They can get passed one. Think chemo-resistant cancer cells that proliferate - best clone survives
• mutations and epigenetic changes to the cell can cause cancer, giving a set of properties called 'cancer hallmarks'. This phenotype can allow for targeted treatments
• benign tumours can mutate into malignant tumours
• cancer development: hyperplasia/metaplasia (no mut.) > low grade dysplasia (some mut. confined to BM) > high grade dysplasia (more mut. confined to BM) > malignant tumour (mutations facilitate invasion)
• body has a number of checks/repair/apoptosis mechanisms to avoid generating mutations
• oncogenes (cancer gene 1) arise from mutated proto-oncogenes (normal genes part of cell signalling pathway: pro-growth and enhanced survival). Mutation or overexpression activates pathway to constantly switch cell on, increases cell growth and survival, leads it to ignore 'off' signals
• Tumour suppressor genes (cancer gene 2) aim to prevent uncontrolled growth of altered cells. Two copies as a redundancy. Governors stop cells proliferating if too much damage. Guardians sense damage, and try and repair or induce apoptosis if unable