Innate immunity and antigen presentation Flashcards
Phagocytosis promoted by
- Receptors for common bacterial cell wall components - PAMPs (pathogen associated molecular patterns), generally weak interactions
- receptors for C3b complement component
(complement mediated opsonisation) - Receptors for Fc region of antibodies (immune complex mediated opsonisation)
PAMPs
pathogen associated molecular patterns, all have different properties but all referred to as immunological danger signals, act as signal for phagocytosis by neutrophils and as foreign invasion by dendritic cells to stimulate inflammatory response
Common cell wall structures
- lipopolysaccharides (LPS)
- Peptidoglycan’s (e.g. manna’s and mannoproteins)
Bacterial metabolic products
- N-formyl-methionine-peptides
Heat shock proteins (released by stressed cells)
What is the key process of out immune system in helping us deal with extracellular bacteria?
phagocytosis
What are acute phase proteins
a bunch of molecules that are increased in the blood doing acute phase of an infectious process
Acute phase proteins
- produced by?
- Activated by?
- Actions?
- liver
- By tissue injury alarm systems (i.e. danger signals)
- promote resolution and repair, limit tissue injury, enhance host resistance
Steps of the complement cascade
common cell wall components on bacteria/viruses
first complement components: proteins in our blood that can recognise some of the lipopolysaccharides and other signatures on bacterial cell walls, assemble themselves on that signature and consequently form an enzyme
This enzyme acts on other proteins of the complement cascade, usually to cut them in two and give two active components from what was previously an inactive molecule. Because its enzymatic it can amplify the initial interaction with the staph bacteria
Active complement components do a number of things:
1. increase vascular permeability - allows BV’s to become more leaky, fluid and cells can get out more easily = swelling, heat and redness
2. Attract neutrophils to the site of production (chemotaxis)
3. Opsonisation via C3b fragment, a very reactive component that covalently attaches to anything close by, neutrophils have a high receptor affinity for and will phagocytose.
What cells make the adaptive immune response
lymphocytes
The difference between B and T lymphocytes
Bone marrow (completely developed here) Thymus (bone marrow precursors migrated to the thymus to mature)
percentage of lymphoid pool in circulation at any time
10% the other 90% is sitting resident in our secondary lymphoid organs = lymph nodes (tissues), spleen (blood), tonsils, adenoids, peyers patches (mucosal surfaces)
Lymphocyte sub population: effector functions
antibody production (B lymphocytes)
Antigen specific cytotoxicity (CD8 T lymphocytes)
Natural killer cell activity (NK lymphocytes)
Antibody dependant cellular cytotoxicity (ADCC) (K lymphocytes)
Lymphocyte sub population: regulator functions
cytokine production (CD4 T lymphocytes)
TH1 (viruses, bacteria, intracellular agents)
TH2 (parasites, allergies, multi-cellular)
Treg (regulatory T cells - down regulation)
TH17 (mucosa and inflammation)
general method of antigen transport and presentation
Antigen uptake - dendritic cells
Transport through lymphatics
Antigen held in lymph node
Antigen specific cells recruited (lymphocytes)
APC functions
Antigen collection and transport Antigen concentration Antigen processing Present processed antigen to lymphocytes co-stimulation - surface molecules - pro inflammatory cytokines Tolerance induction
Differences between the endogenous and exogenous pathways
Exogenous
- peptides drives from ingested material
- Only specialised APC’s (dendritic cells/ reticuloendothelial, B cells)
- presented by MHC II
Endogenous Pathway
- Peptides derived from cytoplasmic proteins
- Normal metabolism (viral peptides, modified self peptides (tumours),
- Presented by MHC I
The exogenous pathway process
- Material phagocytized, which involves the release of material from within a vesicle, which can break down the foreign material, these cells all the time are synthysizing new surface molecules of the HLA-DP, DQ, DR type (last year we called them MHC (major histocompatibility complex) molecules… the Human MHC is HLA)
- Vesicles containing HLA molecules and those containing the broken down foreign material fuse together, bacterial proteins bind to HLA presentation groove
- New vesicle get taken to the surface and fuses with the cell surface membrane