Innate Immunity 1 Flashcards
What is innate immunity?
first line of defence (non specific). it is fast
When does immediate innate immunity response occur?
0-4 hours
When does early innate immunity response occur?
4-96 hours
When does adaptive immunity response occur?
> 96 hours
What are the 5 groups that can cause diseases?
Bacteria
Viruses
Fungi
Protozoa
Helminths (worms)
What are the characteristics of innate immunity response?
No-memory or lasting protective immunity
Present from birth
Effective: regular contact with potential pathogens which are destroyed within minutes or hours, only rarely causing disease
Responses are broad spectrum: non-specific
What are the 3 types of innate immunity?
Epithelium (physical barrier)
Innate cell subsets & complement
Chemokines/Cytokines
What does epithelium produce?
Produces antimicrobial peptides
Produces cytokines/chemokines
What are the cell subsets and complements?
Phagocytic cells (macrophages, neutrophils)
Antigen-presenting cells (dendritic cells)
What do chemokine and cytokines do?
Chemokine – Cell recruitment
Cytokine – Cell activation/proliferation
What are the non-professional immune cells?
epithelial cells
endothelial cells
fibroblasts
What are the compounds present in the oral cavity?
Antimicrobial peptides
Immunoglobulins (secretory IgA)
Lactoferrin
Lysozyme
Cystatins
What are the major families of antimicrobial peptides?
β-defensins
Human Neutrophil Peptides (HNPs)
Cathelicidins (e.g., LL-37)
Psoriasin proteins (S100 family)
What are the main functions of AMPs?
Kill microbes
Modulate immune response –
neutralize microbial virulence factors by activating immunocytes,
neutralising bacterial products,
enhancing nucleic acid recognition to promote auto-inflammation
Where is secretary IgA produced?
Produced at mucosal surfaces
What form does SIgA have and why is it useful?
Dimeric form allows attachment to multiple microbes
What is the function of SIgA?
Binds to flagella and can prevent motility (microorganisms)
Binds to and neutralizes bacterial toxins (microorganisms)
Cross links target macromolecules and bacteria therefore trapping them and preventing effects on mucosa
Prevents attachment of bacteria to mucosal surfaces
What is lactoferrin, where is it and what does it do?
Glycoprotein that transports ions
Present in saliva and produced by neutrophils/macrophages
Prevents microbes using iron to grow
What does lysozyme do and where is it present?
Present in saliva and produced by macrophages/neutrophils. Targets cell walls of bacteria.
Lyzozyme implants in the cell wall cleaving part of peptidoglycan which makes up the cell wall.
What do cystatins do?
Anti-protease activity and supports re-mineralization of the teeth
bind to hydroxyapatite on tooth surface aiding mineralization
What antimicrobial peptides are most effective?
SIgA
What do immune cells have for antigens?
receptors
Where are the toxins and virulence factors in a microbe?
in the antigen
What do different receptors detect?
different antigens from different pathogens
What are the receptors generally?
proteins but can be sugars
What are the main receptors called?
toll-like receptors
What are the main toll-like receptors expressed in periodontal disease?
TLR2 and TLR4
What are the other receptors present and what do they recognise?
Dectin and glucan receptors – Fungal recognition
NOD-like receptors – Bacterial recognition
Protease-activated receptors (PARs) - Microbial and allergen recognition
What is an example of a PAMP (pathogen associated molecular pattern)?
LPS
What do these receptors promote?
Promote phagocytosis of microbes
Promote activation of immune cells
What happens when the receptor attaches to LPS?
results in signaling cascades in host cell that tells the cell what to do (e.g., produce cytokines, chemokines to attract and tell other cells they need help)
What do cytokines do and why are they important?
cytokines instruct the target cell “what to do” – important in differentiation of naïve T cells into different T helper subsets
What are cytokines?
small proteins that are signalling molecules that coordinate the cell what to do
What are the main families of cytokines?
Interleukin family (e.g. IL-1α, IL-1β, IL-6, IL-8 etc)
TNF family (e.g. TNF-α)
Interferons (e.g., IFN-γ)
“unassigned” (e.g., TGF-β)
What are the types of cytokines according to function?
Autocrine – alter behavior of cell from which they were secreted e.g., self-regulating
Paracrine – alter behavior of neighboring cells
Endocrine – enter circulation and alter behavior of distant cells
What is present on target cells?
cytokine receptors
What happens when cytokines attach to the receptors?
Signal transduction leads to the activation of transcription factors that leads to control of gene regulation e.g., inducing expression of a certain gene that encodes a certain protein
What proteins can the transduction produce?
antimicrobial
growth factors (tissue remodelling)
receptors (differentiation/ proliferation)
cytokines and chemokines
What is chemotaxis?
the movement of a cell in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance (e.g., chemokines)
What are chemokines?
small signalling proteins
Whats the difference between chemokines and cytokines?
Chemokines tell cells where to go, cytokines tell cells what to do
What are the classes of chemokines based on?
the spacing of their first 2 cysteine residues
What are the classes of chemokines and how many members do they have?
C chemokines (2 members)
CC chemokines (31 members)
CXC chemokines (18 members)
CX3C chemokines (1 member)
Where are chemokine receptors present?
a range of innate and adaptive immune cells
What is the main chemokine found to play a role in oral mucosa?
CXCL8
IL-8
What is the main role of IL-8?
mobilises, activates and degranulates neutrophils
angiogenesis
What is the homeostasis of the immune reaction dictated by?
cytokine responses
What can cytokine responses be?
Some are pro-inflammatory others are anti-inflammatory (anti-inflammatory cell subsets can include T regulatory cells)
What are the variety of receptors that recognise ‘unique’ features of microbes known as?
Pattern Recognition Receptors (PRRs)
