innate immunity Flashcards
what is innate immunity?
fast (1-4 days) first line of non-specific defence
what is adaptive immunity?
slow long lived specific and acquired
what do both innate and adaptive immunity have?
cellular components and humoral components
what are humoral components?
antibodies
what is tissue homeostasis?
A homeostatic process involved in the maintenance of an internal steady state within a defined tissue of an organism, including control of cellular proliferation and death and control of metabolic function.
what is immune response in healthy indiviuals?
low to prevent uneccessary inflammation
what happens to the immune system during disease?
homeostasis is shifted to prevent infectious pathogens from entering the body and causing disease
is the innate immune system effective?
yes- regular contact with potential pathogens which are destroyed within minutes or hours, only rarely causing disease
what are non professional immune cells?
epithelial/endothelial cells + fibroblasts (contribute to innate immune system to prevent infection)
what are the three parts of the innate immune system?
- epithelium
- innate cell subsets and compliment
- chemokines/cytokines
what is epithelium’s role in innate immunity?
Physical barrier
Produces antimicrobial peptides
Produces cytokines/chemokines
what are the innate cell subsets?
Phagocytic cells (macrophages, neutrophils)
Antigen-presenting cells (dendritic cells)
what are the roles of chemokines and cytokines in innate immunity?
Chemokine – Cell recruitment
Cytokine – Cell activation/proliferation
what are the components of innate immunity?
what is the role of physical barriers (epithelium) in innate immunity?
Epithelial barriers produce a number of different compounds e.g., in the oral cavity the following are produced;
Antimicrobial peptides
Immunoglobulins (secretory IgA)
Lactoferrin
Lysozyme
Cystatins
Epithelium provides structural/mechanical support
what do antimicrobial peptides do?
help to destroy the pathogens (kill microbes by binding to their membrane) or inform the immune system to respond (neutralise microbial virulence factors)
what are examples of antimicrobial peptides?
β-defensins
Human Neutrophil Peptides (HNPs)
Cathelicidins (e.g., LL-37)
Psoriasin proteins (S100 family)
what do SIgAs do?
secretory immunoglobulin A
- coat microbes for host recognition
- produced at mucosal surfaces
- binds to flagella and can prevent motility
- binds to and neutralizes bacterial toxins
- cross links target macromolecules and bacteria therefore trapping them and preventing effects on mucosa
- prevents attachment of bacteria to mucosal surfaces
what does lactoferrin do?
glycoprotein that transports iron ions, has antimicrobial activity
- present in saliva
- produced by neutrophils
what do lysozymes do?
target cell walls of bacteria
- present in saliva
- produced by macrophages and neutrophils
what do cystatins do?
anti-protease activity and support remineralisation of teeth
what is microbial recognition by the host?
- Cells involved in immune responses have receptors for components of microorganisms (antigens)
- Toxins and virulence factors = microbial antigens
- Receptor activation orchestrates the immune response
- Different receptors recognize different antigens from different pathogens
what is an example of a receptor which recognises microbes?
toll-like receptors
What do toll like receptors recognise?
recognise bacteria and fungi
what do intracellular receptors do?
recognise viruses
what are examples of toll-like receptors?
TLR2 TLR4
what do dectin and glucan receptors recognise?
fungi
what do NOD receptors recognise?
bacteria
what is PRR?
pattern recognition receptor
- recognise microbes
what is PAMPS?
pathogen associated molecular patterns
describe the host cell pathogen interaction sequence
what are cytokines?
- small proteins
what are examples 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 three function categories of cytokines?
autocrine
paracrine
endocrine
describe cytokine binding
- induces conformational changes in a majority of receptors intracellularly
- signal transduction – leads to the activation of transcription factors that leads to control of gene regulation
what can both PRR signalling and cytokine receptor signalling lead to?
the transcription and subsequent translation of certain proteins
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 the four classes of chemokines?
- C chemokines (2 members)
- CC chemokines (31 members)
- CXC chemokines (18 members)
- CX3C chemokines (1 member)
which chemokine plays an important role in oral mucosa?
CXCL8
what is the most prominent cell at the oral mucosa?
neutrophils
what happens to neutrophils during inflammation?
- increase in number
- attracted along a CXL8 (IL-8) (interleukin 8) gradient to site of inflammation
what is the name of cells which control interactions between immune cells and endothelial cells?
cell adhesion molecules
what are the three main families of adhesions/receptors?
Selectins (e.g., P and E- selectins)
Integrins (e.g., LFA-I)
Immunoglobulin superfamily
which receptor types are generally found of endothelial cells?
selectins and immunoglobin
which receptor types are generally found on migrating immune cells?
integrins
what is degranulation by neutrophils?
Granules in cell (known as vesicles) containing numerous antimicrobial peptides and enzymes
Released upon activation of receptors (e.g. TLRs)
what are neutrophil extracellular traps?
Activation induces neutrophils to release proteins and some genetic material (chromatin) to form extra-cellular fibril matrix
Trap pathogens
Many antimicrobials also associated with the NET so bacteria ‘held’ whilst ‘administered’
how do monocytes migrate to tissues?
similarly to neutrophils, via cell adhesion molecules
what are the pro-inflammatory machrophages?
M1
what are the anti-inflammatory macrophages?
M2
what are the two types of antigen presenting cells?
non-professional
professional
what are examples of non-professional antigen presenting cells?
Epithelial cells/fibroblasts/endothelial cells
what are examples of professional antigen presenting cells?
macrophages and dendritic cells
what are examples of professional antigen presenting cells?
macrophages and dendritic cells
phagocytosis
antigen presentation
Antigen presentation is the expression of antigen molecules on the surface of a macrophage or other antigen-presenting cell in association with MHC class II molecules when the antigen is being presented to a CD4+ helper T cell or in association with MHC class I molecules when presentation is to CD8+ cytotoxic T cells.
degranulation
which cell types can drive degranulation?
mast
natural killer
monocyte
macrophage
neutrophil
what is the largest component of human blood?
plasma (composes 55%)
what are the four enzymatic cascades systems in plasma?
- complement
- kinins
- coagulation factors
- fibrinolytic system
what is the complement cascade system in plasma?
- A collection of soluble proteins present in circulation.
- Drives inflammation or opsonisation
- Opsonisation refers to coating of pathogens by antibodies or complement proteins
- Three pathways; classical, alternative or lectin pathway
what is the classical pathway of complement?
antibody attached to microbe
what is the alternative pathway of complement?
microbial cell wall
what is the mannose binding lectin pathway of complement?
carbohydrates on pathogen surface
what are anaphylotoxins?
- lead to smooth muscle contraction and capillary leakage – allowing increased infiltration of immune cells to site of infection
what triggers the complement cascade?
initiating factor
C3- C5
what are the functions of anaphylatoxins?
- Promote immune cell recruitment
- Increase adhesion of cells to vessel walls
- Induces granulation
- Promotes cytokine production
- Induces antigen presentation
- Regulate adaptive immune responses
