Week 2 Flashcards
What are the main components of innate immunity?
Soluble Factors: - antibacterial factors - complement system Cellular Factors: - scavenger phagocytes - neutrophils - macrophages
What are the main antibody isotypes?
IgM: main antibody of primary response
IgG: main antibody of secondary response
IgA: present in secretions and lines epithelial surfaces
IgE: high affinity binding to mast cells (role in allergy)
What is the general structure of antibodies?
- Fab region: antigen binding region
- Light chains
- Heavy chain (longer)
- Fc region: binds to Fc receptors on phagocytes, activates complement
What is the function of antibodies?
- Opsonise for phagocytosis
- Activate complement for lysis
- Neutralise toxins and pathogen binding sites
What are the main differences between class I and II MHC?
- Class I presents to CD8 T cells, class II to CD4
- Class I presents intra-cellular antigen, class II extracellular
- Class II found on APCs, class I on all nucleated cells
What is type 1 hypersensitivity?
Immediate, atopic reaction mediated by IgE binding to mast cells
Mast cell degranulation of;
- histamine (smooth muscle contraction)
- proteinase
- cytokines, chemokines, PGs (smooth muscle contraction) and leukotrienes (pro-inflammatory)
What is anaphylaxis?
- Severe, systemic type 1 hypersensitivity
- Widespread mast cell degranulation caused by systemic exposure to antigen (e.g. penicillin)
- Vascular permeability is principal immediate danger
- Can be rapidly fatal
What are type 2 and 5 hypersensitivity?
- Caused by binding of ABs directed against human cells (IgG usual cause)
- Common cause of autoimmune disease
- Steps:
- sensitisation
- opsonisation of cells (as cells are different, no longer recognised as self)
- cytotoxicity (complement, inflammation-> tissue destruction)
- Type V is direct activation with receptor/antigen
What is type 3 hypersensitivity?
- Mediated by immune complexes bound to soluble antigen
- AB complexes aggregate in small blood vessels
What is type 4 hypersensitivity?
Lymphocytes infiltrate area and cause injury several days after (contact dermatitis- contact alters cells so no longer recognised as self-antigen)
What causes rheumatoid arthritis?
- Inflammation leads to release of PAD from inflammatory cells
- Alters variety of proteins by converting alanine to citrulline
- Hence inflammation as proteins no longer recognised as self
- Inflammatory pannus aggregates in joints
What are the systemic effects of RA?
- Pulmonary nodules and fibrosis
- Pericarditis and valvular inflammation
- Small vessel vasculitis
- Soft tissue nodules
- Skin inflammation
- Weight loss, anaemia
What is disease?
Loss of (normal) homeostasis, and a combination of the causative agent and the body’s response to it
What are broad categories of disease?
MEDIC HAT PINE
- Metabolic
- Endocrine
- Degenerative
- Inflammatory
- Congenital
- Haematological
- Autoimmune
- Trauma
- Psychological
- Idiopathic/Iatrogenic
- Neoplastic
- Environmental
What are the broad causes of cell injury?
- Physical agents
- Chemicals/drugs
- Infections
- Hypoxia/ischaemia
- Immunological reactions
- Nutritional imbalance
- Genetic disease
What is reversible cell injury?
- Changes due to stress in environment
- Return to normal once stimulus removed
What is irreversible cell injury?
- Permanent
- Cell death, usually necrosis, follows
- Threshold between reversible and irreversible
Give examples of reversible cell injury:
- “Cloudy swelling” is osmotic disturbance, loss of energy-dependent Na pump leads to Na influx and build up of intracellular metabolites
- Cytoplasmic blebs, disrupted microvilli and swollen mitochondria
- “Fatty change”: accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism, especially in liver
What are the broad mechanisms of cell injury?
Damage to:
- mitochondria: disrupted aerobic respiration/ATP synthesis
- cell membrane: disrupted ion concentrations, esp. increases Ca2+ ions
- cytoplasm including ribosomes: disrupted enzyme and structural protein synthesis and architecture
- nucleus: disrupted DNA maintenance and DNA damage
- oxidative stress: caused by reactive oxygen species, formed pathologically by absorption of radiation, toxic chemicals, hypoxia and damage made more likely by lack of antioxidants
What is necrosis?
Unprogrammed cell death following injury due to external stimuli. Always pathological
What are the histological changes upon cell necrosis
- Cell swelling, vacuolation, and disruption of membranes of cell and its organelles including mitochondria, lysosomes and ER
- Release of cell contents (cell lysis) including enzymes causes adjacent damage and acute inflammation
- DNA disruption and hydrolysis
What are the types and main features of necrosis?
Coagulative:
- firm, tissue outline retained
- haemorrhagic: due to blockage of venous drainage
- gangrenous
Colliquitive:
- tissue becomes liquid and its structure is lost (e.g. infective abscess, cerebral infarct)
Caseous:
- combination of coagulative and colliquitive, appearing “cheese-like”: classical for granulomatous inflammation, especially TB
Fat:
- due to action of lipase on fatty tissue
What are depositions?
Abnormal accumulations of substances, located either intra or extracellularly, or in CT
Describe amyloid:
- Organisation of soluble protein fibrils into specific abnormal, insoluble aggregates
- Can be systemic or localised
- Occurs due to excessive production/accumulation of a normal protein, production/accumulation of an abnormal protein or tendency of protein to misfold
- Clinical effects depend on site of deposition (brain = dementia)
What are the two main types of normal protein that forms amyloid?
- AL amyloid
- immuonglobin light chain
- produced in B-cell neoplasms
- AA amyloid
- serum amyloid associated protein, produced in liver
- produced in prolonged chronic inflammation (RA)
Describe pathological calcification:
- Deposition of calcium salts
- May be:
- dystrophic (in abnormal tissue with normal serum Ca) or metastatic (deposition on normal tissue with raised serum Ca)
What causes pathological calcification?
- Increased levels of parathyroid hormone (PTH)
- primary: PT gland tumour
- secondary: kidney disease
- May be systemic effect with cancer (most common)
How does vascular dilatation occur?
- Histamine from mast cells, prostaglandins and NO released
- Arterioles dilate increasing blood flow in response
- Stasis of blood flow
- Fluid passes into tissue causing swelling
How does neutrophil activation occur?
- C5a, leukotriene B4, bacterial products accumulate
- Activation of neutrophils
- Rolling, adhesion, pass between endothelial cells
- Chemotaxis
- Phagocytosis and bactericidal
How does endothelial activation occur?
- 5-HT, histamine, C3a, C5a, bradykinin leukotriene involved
- Activates vascular endothelium
- Increased cell adhesion molecules
- Increased leakiness of endothelium
- Plasma proteins travel into tissues including immunoglobulins, complement and fibrinogen
