Innate Immunity Flashcards
Functions of the innate immune system
Prevention of infection
Recognition and response
Activation of adaptive immune system through APCs
What are the primary barriers of the innate immune system
Anatomical (physical) barriers
Chemical defences
Commensal flora
Describe the structure skin
Epidermis - rightly packed cells (mostly dead) full of kerati. Sites
Dermis - connective tissue, blood vessels, hair follicles, sebaceous and sweat glands etc.
- macrophages, dendritic and mast cells
Describe the skin as an anatomical barrier
Low pH ~5.5
Secretion of antimicrobial peptides and proteins
Fatty acid in sebum
Name some anatomical barriers of the innate immune system
Skin
Mucosal epithelium: GI, respiratory and urogenital tracts
Describe the structure of mucosal epithelium
Outer layer of epithelial cells
Mucus: prevents microbial adhesion to epithelium by trapping them
- beating cilia to expel microbes
Describe mucosal epithelia as a biochemical weapon and anatomical barrier
Antibacterial and antiviral substances in saliva, tears and mucus
- lysozyme: attack’s cell walls predominantly gram positive
- defending, cathelicidins, histatins: secreted by phagocytes
- IgA: opsonisation of bacteria and viruses
What is opsonisation
Process whereby opsonins e.g. IgA, make an invading microorganism susceptible to phagocytosis
What is an opsonin
A freely circulating serum molecule which can attach to the surface of microbes or damaged cells thus making them susceptible to ingestion by phagocytosis
How does lysozyme effect bacteria
Hydrolysis of peptidoglycan layer exposing membrane bilayer accessible to antimicrobial proteins e.g. defensins
Name some chemical defences of the innate immune system
Low pH - skin (5.5), stomach (2), vagina (4.5)
Bile - bile acids effective against helibacter
Pulmonary surfactant - 6 lipids and 4 proteins - prevent alveoli from collapsing at exhalation, collectins in surfactant
How does commensal flora act as a primary barrier in the innate immune system
- Compete with pathogens for colonisation space and nutrients
- Promote maturation of immune cells
- Aid polysaccharide digestion and absorption of nutrients by gut cells
- Antimicrobial activist against pathogens e.g. bacterial fatty acids against Candida
What are the two soluble molecules of the innate immune system
Antimicrobial peptides
Pattern recognition molecules
Characteristics of antimicrobial peptides
Attach bacteria, fungus and viruses
Positively charged peptides and proteins up to 60 amino acids
Disrupt microbial membranes, inhibit synthesis of DNA, RNA or proteins
Describe the recognition process of antimicrobial peptides
- Utilises a fixed pathogen recognition battery encoded in human genome
- Microorganisms display particular pathogen associated molecular patterns (PAMPs)
- PAMPs are detected by pattern recognition receptors (PRR) and PR soluble molecules
Name some PR soluble molecules
Mannose-binding lectin (MBL)
C1q
C-reactive protein
Describe what mannose-binding lectin does
Carbohydrate recognition sites recognise mannose, fructose and N-acetylglucosamine residues which are common in bacteria but not humans Ls
- Activation of Lectin complement pathway
True or false: MBL monomers form trimeric clusters of carbohydrate-recognition domains that bind to mannose and fructose residues with high affinity
True
Name some receptors macrophages have
Mannose receptor Complement Scavenger Lipid (CD36) Dectin-1
Describe non-oxidative attack
When lysosomes merge with the phagosome to form a phagolysosome and destroy pathogen
Describe oxidative attack
Employs reactive oxygen and nitrogen species (ROS and RNS)
Describe the process of oxidative attack
- binding of PAMPs leading to activation of NADPH oxidase —> respiratory burst, transient increase in oxygen consumption resulting in prod. Of superoxide O- and Hydrogen peroxide
- Activation of inductive nitric oxide synthase —> reactive nitrogen species (nitric oxide) forming radicals - intracellular messages
True or false: ROS are generated continuously in small amounts in normal cell metabolism
True
What is respiratory burst
The generated ROS are the main mechanism for killing phagocytosis extracellular pathogens
What are the reactive oxygen species
O2- superoxide
OH. Radical
H2O2 peroxide
ClO- hypochlorite anion
What are the reactive nitrogen species
NO nitric acid
NO2 nitrogen dioxide
ONOO- peroxynitrate
What does Rec2 induce
In neutrophils, they induce assembly of NADPH oxidase in the phagolysosome membrane leading to generation of Superoxide.
The resultant acidification releases granule proteases
What are the 4 classifications of inflammation
Location: Local or Systemic
Time: Acute or Chronic
What are the signs of acute inflammation
Swelling (leaky blood vessels)
Redness (attraction of blood)
Heat (blood in area)
Pain (chemicals)
What are the roles of inflammation in the body
To recruit effector molecules at site of infection
To induce local blood clotting to trap pathogens
Initiate tissue repair
What systems does tissue damage activate in the blood
- Kinin system: enzymatic cascade leading to increase in vascular permeability, vasodilation and pain, SM contraction
- Clotting: increase vascular permeability & neutrophil chemotaxis
- Fibrinolytic: complement activation
- Complement: anaphylaxaroxins bind to receptors on mast cells —> degranulation —> release of histamines and other mediators
What are he roles of mast cells and basophils in inflammation
Release of histamine: 23 dif. physiological functions
- dilation of blood vessels
- vascular permeability
- chemotaxis of leukocytes
What is leukocyte extravasation
Movement of leukocytes out of circulation and towards site of damage
