Innate immunity and antigen presentation

Question 1

Phagocytosis promoted by

Answer 1

• 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)

Question 2

PAMPs

Answer 2

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)

Question 3

What is the key process of out immune system in helping us deal with extracellular bacteria?

Answer 3

phagocytosis

Question 4

What are acute phase proteins

Answer 4

a bunch of molecules that are increased in the blood doing acute phase of an infectious process

Question 5

Acute phase proteins

• produced by?
• Activated by?
• Actions?

Answer 5

• liver
• By tissue injury alarm systems (i.e. danger signals)
• promote resolution and repair, limit tissue injury, enhance host resistance

Question 6

Steps of the complement cascade

Answer 6

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.

Question 7

What cells make the adaptive immune response

Answer 7

lymphocytes

Question 8

The difference between B and T lymphocytes

Answer 8

Bone marrow (completely developed here) 
Thymus (bone marrow precursors migrated to the thymus to mature)

Question 9

percentage of lymphoid pool in circulation at any time

Answer 9

10% the other 90% is sitting resident in our secondary lymphoid organs = lymph nodes (tissues), spleen (blood), tonsils, adenoids, peyers patches (mucosal surfaces)

Question 10

Lymphocyte sub population: effector functions

Answer 10

antibody production (B lymphocytes)
Antigen specific cytotoxicity (CD8 T lymphocytes)
Natural killer cell activity (NK lymphocytes)
Antibody dependant cellular cytotoxicity (ADCC) (K lymphocytes)

Question 11

Lymphocyte sub population: regulator functions

Answer 11

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)

Question 12

general method of antigen transport and presentation

Answer 12

Antigen uptake - dendritic cells
Transport through lymphatics
Antigen held in lymph node
Antigen specific cells recruited (lymphocytes)

Question 13

APC functions

Answer 13

Antigen collection and transport 
Antigen concentration 
Antigen processing 
Present processed antigen to lymphocytes 
co-stimulation 
- surface molecules 
- pro inflammatory cytokines 
Tolerance induction

Question 14

Differences between the endogenous and exogenous pathways

Answer 14

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

Question 15

The exogenous pathway process

Answer 15

• 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

Question 16

The endogenous pathway process

Answer 16

• In our cytoplasm we have this things called big enzyme proteasomes, which break down proteins all the time to allow us to recycle
• Some of the fragments produced (which are about 10-20aa long) are transported through the TAP transporter system, out of the cytoplasm and into the Endoplasmic reticulum, where some of the fragments might be able to associate with HLA-A, B or C
• The the MHC I-antigen complex gets taken off to be fused with the cell surface membrane