Lecture 28 - Innate Immunity 1 Flashcards
What are the major features of innate immunity?
- Present at birth
- Rapid response
- No memory
- Non specific
Components:
• Physical barriers
• Chemical defences
• Cells
Responding to change in equilibrium: not necessarily infection. Can be, for example, a response to a bruise
What are the chemical defences of innate immunity?
- Fatty acids
- Low pH
- Pulmonary surfactant
- Defensins
Which cells play a role in innate immunity?
- Granulocytes: neutrophils, eosinophils, basophils
- Monocytes / macrophages
- Mast cells
- DCs
- NK cells
What is the stem cell line of innate immune cells?
CMP: common myeloid progenitor
Describe the innate defences in the skin
- Mechanical
• Epithelial cells w/ tight junctions
• Longitudinal flow of air or fluid
2. Chemical • Fatty acids • β defensins • Lamellar bodies • Cathelicidin
- Microbiological
• Normal microbiota
Describe the innate defences in the gut
- Mechanical
• Epithelial cells w/ tight junctions
• Longitudinal flow of air or fluid
2. Chemical • Low pH • Enzymes (pepsin) • α-defensins (cryptidins) • Cathelicidin • RegIII (Lecticidins)
- Microbiological
• Normal microbiota
Describe first line of defence in lungs
- Mechanical
• Epithelial cells w/ tight junctions
• Mucociliary escalator - Chemical
• Pulmonary surfactant
• α-defensins
• Cathelicidin - Microbiological
• Normal microbiota
Describe the innate barriers in the ear/nose and oral cavities
- Mechanical
• Epithelial cells w/ tight junctions
• Tears
• Nasal cilia - Chemical
• Lysozyme in tears and saliva
• Histatins
• β defensins - Microbiological
• Normal microbiota
What is the general life span of the following cells:
• Granulocytes
• Monocytes / macrophages
Neutrophils: short lived (8-10 hours to days)
Monocytes / macrophages: long lived
What is the function of the following cells:
• Neutrophils
• Eosinophils
• Basophils
Neutrophils:
• Phagocytosis of extracellular pathogens
• Activation of bactericidal mechanisms
Eosinophils:
• Killing of antibody coated parasites
Basophils:
• Promotion of allergic response
• Anti-parasitic immunity
Which cell is responsible for chronic granulomatous disease?
Neutrophils
Where are neutrophils normally found?
In the blood
Which diseases can neutrophils cause?
Chromic granulomatous disease
• Mutations in NADPH oxidase
• Cannot kill phagocytosed bacteria
Myeloid leukaemias
Describe the process of neutrophil extravasation
- Rolling adhesion
• Selectin mediated - Tight binding
• Integrin mediated - Diapedesis
• PECAM1 - Migration
• Chemokines
Describe phagocytosis by neutrophils
- Microbe binds receptors on the surface of neutrophils
- RME
- Microbe in phagosome
- Fusion of lysosomes with phagosomes
- ROS burst and NADPH oxidase activation
- Intracellular killing of the pathogens
Describe NET formation
Effector function of neutrophils
- Neutrophil engages extracellular bacterium
- Release of molecules (DNA etc.)
- DNA precipitates with many other proteins
- Bacteria become entangled and thus opsonised
- Macrophages come and phagocytose these bacteria
What are the two types of granules in eosinophils?
Toxic granules containing:
• Arginine-rich basic protein
Microbicidal:
• Toxic proteins
• Radicals
Immunomodulatory:
• Leukotrienes
• Prostaglandins
• Cytokines
Where are eosinophils found?
Mainly in tissues
Small numbers in the blood
Describe effector function of eosinophils
Parasite immunity
Granule release
• Microbicidal
• Immunomodulatory
Killing of antibody coated parasites
Role in allergic disease
What is the important structural feature of eosinophils?
Many granules visible in the cytoplasm
To which other cells do basophils have a similar function?
Eosinophils
Mast cells
(possibly)
Describe the function of basophils
- Recruitment to site of IgE-mediated allergic reactions
- Release of histamine and cytokines (IL-4, IL-13)
- Involved in ‘helper’ T cell differentiation
- Important role in allergic diseases
Where are basophils found?
Circulation
Compare location of the following cells: • Neutrophils • Eosinophils • Basophils • Monocytes / macrophages • Mast cells • NK cells • DCs
Neutrophils: circulation
Eosinophils: tissues (also some in circulation)
Basophils: circulation (?)
Monocytes: circulation
Macrophages: tissues
Mast cells: connective tissues
NK cells: * (?)
DCs: tissue resident
What is NADPH oxidase?
Complex of enzymes that become auto-catalytically activated
Generate oxygen radicals
Found in neutrophils to kill phagocytosed microbes
Which cytokines do basophils release?
IL-4
IL-13
Which is usually the first cell to arrive in an area of injury?
Neutrophils
normally within 10 minutes
What is pus made of?
80% Neutrophils
What are the functions of macrophages?
Phagocytosis: clearance of:
• Microbes
• Debris
• Dead cells
Presentation of antigen
Orchestration of immune responses
Describe the function of Mast cells
Histamine release:
• Increased VP
Sensitisation with IgE
• IgE binds Ig(e)R on Mast cells
• Cross linking once antigen binds
• Toxic granule release
Which other cell is really important for Mast cell function?
B cells
The B cells produce the Ab that sensitise mast cells and allow them to perform their main function
What is the ‘concerted inflammatory response’?
What are the cardinal signs?
Involvement of all the components of the innate immune response
Cardinal signs: • Calor • Dolor • Rubour • Tumour • Function laesa
