An introduction to innate immunity - unfinished Flashcards
name some components of innate immunity
non-specific, no antigen recognition
Physical barriers
Skin, mucosal surfaces
Chemical barriers
pH, secreted factors-tears e.g.,
Phagocytes
Monocytes/granulocytes
Inflammation; acute phase response
Complement
Cytokines/chemokines
specific/adaptive immunity
Involves very specific recognition of precipitating agent
T lymphocytes
B lymphocytes (antibody)
Cytokines
Neutrophils
Large cells (10-20 microns); only live about 2-3 days
90% of granulocytes are neutrophils
Neutral staining cytoplasmic granules containing enzymes
e.g. lysozyme
Phagocytic, kill bacteria by microbicidal mechanisms
Most important cell in non-viral infections
Eosinophils
Contain prominent granules, which stain red with eosin
Granules contain a crystalline core cytotoxic for parasites; EOSINOPHIL BASIC PROTEIN
Important in immunity to helminth infections
Phagocytic, though this is not a major function
Basophils
<0.2% white blood cells, only go into tissues during inflammation
When stimulated, release substances that promote inflammation
Important in allergy
Not thought to phagocytose
Monocytes
in blood 1-2 days
Mononuclear leukocytes
Phagocytic
APC
Macrophages
APC
MCs in tissues = macrophages
Up to 10x larger than MCs
can live months or years
Characteristics of macrophages depend on tissue e.g. Kupffer cells in liver, microglia of brain
Phagocytic (like neutrophils and eosinophils), adherent
what maintains immune response after innate?
Adaptive seems to be important in maintaining the immune response after the innate
Recognition receptors on innate cells - 2 categories
Specificity from host molecule
- IgG, complement components, chemokines
Inherent specificity (pattern recognition) - those that have an inherent specificity for a pattern, looking for conserved patterns on bacteria or virus
- germline-encoded receptors for conserved molecular patterns
- detects foreign invaders or aged/damaged host cells (apoptotic)
Opsonic receptor vs non-opsonic receptor
opsonic - – recognises host molecule to cause phagocytosis – the phagocytic capabilities are enhanced by IgG or complement bound to that bacterial or viral organism
non-opsonic - recognises pattern conserved molecules
Fc Receptors
Receptors for the Fc region of Ig
Expressed on many cell types
FcγR, αR, εR
Results in internalisation of Ab coated Ag
On Mφ results in activation and production of reactive oxygen species
Complement receptors
CR1-5
Diverse structures
CR1, CR3 (CR4) bind C3 cleavage products which are bound to pathogens, Immune complexes or other complement activators
Endocytic and activatory
Chemokine receptors
7 transmembrane receptors Common family of membrane proteins G-protein coupled Recognise host chemokines and also microbial formyl-met peptides (starting sequence in protein synth) Result in cell migration
General properties of pathogen-associated molecular patterns
Present only on pathogens and not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens
Pattern recognition receptors
-examples?
Mannose receptors
Scavenger receptors
Toll-like receptors (TLRs) (surface and endosomal)
NOD-like receptors (NLRs) (cytoplasm)
RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)
7-transmembrane receptors (G-protein-coupled)
Lectin receptors
Eg Mannose receptor
Lectins bind carbohydrates
MR recognises terminal mannose and fucose (not present in human molecules)
MR is membrane bound cf soluble Mannan Binding Lectin in complement
Results in phagocytosis
Scavenger receptors
Membrane bound PRRs
Bind to apoptotic cells/modified self molecules and responsible for ‘clearing up’ after an immune response.
After e.g. viral infection where you’ve had a lot of cellular debris
Also bind bacterial cell walls
Recognise lipoproteins (lps)
Can mediate endocytosis
Main role is fine tuning TLR signalling (eg SR-A and TLR4 and TLR2 and CD36 in S.aureus and M.tb recognition).
PAMPs & DAMPs
Pattern recognition and Damage recognition
PAMPs such as TLR ligands
DAMPs such as ‘alarmins’, inc defensins, HMGB-1, ATP etc.
Toll-like receptors
Discovered in Drosophila sp, important in development but also in defence
Pattern recognition molecules for bacterial and viral ligands
Most Mammalian Sp: 10-15
Stimulate cytokine release
Other Intracellular receptors
Recognise intracellular bacteria and viruses
NOD-like receptors (nucleotide binding and oligomerization domain)- bind dsRNA and also peptidoglycan
RIG-1- (retinoic acid inducible gene-1) like helicases (RLH)- recognise dsRNA intermediate of viral replication (also MDA-5)
Some NLRs can form the inflammasome.
Inflammasome
A multiprotein oligomer complex which assembles in the cytoplasm after PAMP/DAMP detection. Can lead to activation of Caspases inc Caspase 1 which cleaves precursors to IL-1 and also IL-18
Composed of several intracellular PRRs including NOD-like receptor and can be triggered by PAMPs and DAMPs (DAMPs leading to ‘sterile’ inflammation.).
Leads to pyroptosis; Inflammatory cell death.
Linked to autoimmunity (MS, diabetes) and inflammation such as atherosclerosis. May simply be an exaggerated response to host-derived factors.
Natural Killer cells
Large granular lymphocytes
4% white blood cells
Collection of cells playing role between innate & specific immunity
Lymphocyte-like but larger with granular cytoplasm
Kill certain tumour & virally infected cells
Activated by FcR and KIR
Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
Treat cancer using LAK cells
Lymphokine activated killer cells
Take peripheral blood, separate the white cells out
Give them IL-2 to activate the cells that have the IL-2 receptor, the reason it will have IL-2 receptor because its been partially activated by tumour they’ve seen the tumour
This generates LAK or NK cells which you reinfuse the patient with
These can kill tumou
NKT cells
Express NK and T cell markers, NK1.1 and TCR
Restricted TCR α-chain usage
Intermediate TCR expression.
Recognises through CD1d (non-classical MHC1)
Produces Th1 and Th2 cytokines
Recognises lipids, glycolipids, hydrophobic peptides.
α-galactosylceramide and anti-tumour effect.
