Innate immunity 1 Flashcards
Examples of inciting causes
invading microorganisms, particulate materials (allergens, prostheses), altered self cells (growth disorders/cell injury), transformed malignant cells (neoplasia)
What is inflammation?
an immune response aimed at eliminating the inciting cause
4 stages of inflammation
initiation (response to harmful agents), progression (containment of agent), amplification (modulation of immune response), resolution (healing or failure to resolve)
What is acute inflammation?
Inflamed tissue that can heal itself (e.g. gingivitis)
What is chronic inflammation?
inflammation that cannot be resolved - e.g. periodontitis (alveolar recession)
What is innate immunity?
an effective, first line of non-specific immunological defence against an inciting cause
Which cells are involved in innate immunity?
Innate immune cells (leucocytes), and non-professional immune cells
Mechanisms of action of innate immune cells
phagocytosis, degranulation, antigen presentation, mediator release
what are the 4 types of epithelium in the oral cavity?
lining/buccal mucosa, masticatory epithelia, gustatory mucosa, crevicular/junctional epithelia
Function of the epithelium
structural, mechanical and immunological support
What are the compounds produced by epithelial barriers?
Antimicrobial peptides, secretory IgA, lactoferrin, lysozyme, cystatins
Where are the compounds produced by epithelial barriers found?
In oral secretions (saliva, gingival crevicular fluid - GCF)
Which of the 5 types of antibodies are produced by the epithelium?
Secretory IgA (produced by B cells)
What is the main type of antimicrobial peptide (AMP) produced by the epithelium?
Cathelicidins (e.g. LL-37)
Function of cathelicidins
attach and disrupt microbial membranes causing lysis
What is the structure of IgA?
double headed with 4 antibody binding sites
What is lysozyme?
an enzyme found in saliva that targets components of bacterial cells walls (e.g. peptidoglycan) causing lysis
Name of peptide cell wall components/virulence factors that immune cell receptors bind to
antigens
Main receptors for microbial recognition
toll-like receptors
Where can toll-like receptors be located?
on plasma membrane to recognise external microorganism, on organelles to recognise intracellular/invading pathogens (e.g. viruses)
How many toll-like receptors have been identified in humans?
10
What are the types of receptors on immune cells?
toll-like receptors, dectin and glucan receptors (fungal pathogens), NOD-like receptors (intracellular pathogens - viruses), protease-activated receptors (PARs)
What do dectin and glucan receptors recognise?
Fungal pathogens
What do NOD-like receptors recognise?
intracellular pathogens (viruses)
What do protease-activated receptors (PARs) detect?
allergens (non-microbial)
What are the receptors that recognise unique components of microbes (PAMP) collectively known as?
Pattern Recognition Receptors (PRRs)
What are PAMPs?
Pathogen associated molecular patterns are unique components of microbes e.g. lipopolysaccharide
What happens when a receptor detects a PAMP (microbial recognition)?
Microbial recognition -> cell activation -> effector response
Examples of cellular responses (depends on cell type)
production of soluble mediators (protein/chemical release e.g. cytokines), phagocytosis, antigen presentation, degranulation
Examples of soluble mediators produced by immune cells
antimicrobial peptides, enzymes (e.g. lysozyme, granzyme), cytokines, chemokines, immunoglobulins (B cells)
What are cytokines?
small proteins that are soluble mediators produced by immune cells in response to microbial recognition.
Function of cytokines
signalling molecules that coordinate immune responses. Either anti-inflammatory or pro-inflammatory (dampen/drive inflammation)
How are cytokines grouped?
Grouped into families by structure (e.g. interleukin family, TNF family, Interferons)
3 types of cytokines (depending on target cell)
autocrine, paracrine, endocrine
What are autocrine cytokines?
Cytokines that alter behaviour of the cell they are secreted from e.g. self-regulating
What are paracrine cytokines?
Cytokines that alter behaviour of neighbouring cells
What are endocrine cytokines?
Cytokines that enter the circulation and alter behaviour of distant cells
How are cytokines detected by target cells?
Via cytokine receptors (not microbial / PRRs receptors)
What happens when cytokines bind to target immune cells?
Signal transduction occurs resulting in effector responses similar to microbial recognition responses
What are the potential cellular responses as a result of cytokines binding?
Increased production of cytokines, chemokines, antimicrobial peptides, growth factors, receptors and degranulation
What are chemokines?
Chemotactic cytokines (proteins) that are involved in immune cell recruitment/trafficking
What is chemotaxis?
The movement of a cell in a direction corresponding to a gradient of increasing concentration of a substance (e.g. immune cell moving towards an increasing concentration of chemokines).
How are chemokines detected by target cells?
Via chemokine receptors on immune cells
Out of all the different classes of chemokines, which is the main example?
IL-8 (CXCL8)
Function of chemokines and cytokines
tissue homeostasis - promote balance between pro-inflammatory and anti-inflammatory
Consequences of an immune over-reaction
autoimmune problem (internal threat), allergic reaction (external threat)
Consequences of an immune under-reaction
cancer, infection