L2. Antigen presentation Flashcards
What are the main cells of the innate immune system.
what do they recognise with their cell receptors that promotes their main action
Neutrophils (and Macrophages) ; recognise
- Common bacterial cell wall structures - weak binding
- C3b complement component (complement mediated opsonisation)
- Fc region of antibodies (immune complex-mediated opsonisation)
What is the 3 main steps of actions after recognition by the innate immune cell
- Adheres to the thing it recognises which triggers activation of the membrane to engulf it
- Forms a phagosome which then fuses with vesicles containing digestive enzymes
- Releases the degraded products outside
What are the different types of Pathogen associated molecular pattern (PAMP) and what does their recognition by dendritic cell trigger
- Common bacterial cell wall components
- Bacterial metabolic products - (f-me-leu-phe which is bacteria only )
- Heat shock proteins released by stressed cells
Causes release of cytokines which act on liver to produce acute phase plasma proteins
When are acute phase proteins released after infection and what do they do
Released 4-10 days after cell injury/infection to help
- enhance host resistance - eg. opsonins, coagulation factors, haem and iron binding proteins
- minimise tissue injury
- promote resolution and repair of inflammatory lesions
How does complement work and the 3 outcomes
- Complement components bind to PAMP
- form an enzyme that activates other complement components and through an enzyme cascade.
- Leads to recruitment and movement of neutrophils to phagocytose the bacteria.
Outcomes
- Increased vascular permeability
- Chemotaxic protein (5a)
- Opsonisation of bacteria with C3B.
What are the cells associated with the adaptive immune system.
Where are they made and where do they circulate
*Not all classes circulate to the same extent- t cells and memory cells are the most mobile
Lymphocytes
They are all made in the 1’ lymphoid organs
- Bone marrow (B lymphocyte), with T lymphocyte also maturing in the thymus
Found in 2ndary lymphoid organs where they are presented with antigens
- Spleen for bloodborne
- Lymph nodes for tissue borne antigens
- GALT: Tonsils, adenoids, peyer’s patches for mucosal antigens
or circulating in the blood (10%) with fluctuations in numbers in response to stress - enter tissues via high endothelial venules
What type of lymphocyte is
- natural killer lymphocyte,
- antibody dependent Cellular cytotoxicity.
What are the other lymphocytes that are in this type
Effector lymphocyte.
B lymphocyte : APC and makes antibodies
CD8 T- lymphocyte: antigen specific cytotoxic cells
What are the cells that present antigens to the lymphocytes.
What roles do they play
Dendritic cells/ Professional antigen presenting cells - different names for different tissues
they
1. Collect antigen, process it into recognisable fragments, concentrate it for triggering signal
- Transport through afferent lymphatics to 2ndary lymphoid organ - eg. lymph node or insitu where it can present to naive lymphocytes, causing the ones that recognise it to be activated and leave as effectors after several days. Others just leave
- They produce co-stimulation through surface molecules and pro-inflammatory cytokines to activate the lymphocyte that has bound
- Or can switch lymphocytes that respond to an antigen off: Inducting tolerance
What are the 4 categories of the Regulator lymphocyte. Which CD protein
CD4 T lymphocyte: produces cytokines
- TH1 for fighting intracellular agents
- TH2 for fighting multicellular agents
- Treg for down regulation of immune response
- TH17 for mucosal inflammation
How are peptides derived from cytoplasmic proteins through viral infection/cancer presented - which MHC protein used
Which cells present these, and which lymphocyte responds by binding to the non polymorphic regions of the MHC
All nucleated cells present cytoplasmic peptides via normal metabolism.
Presented via Endogenous pathway
- Proteosomes degrade cytoplasmic proteins into peptides
- Peptides transported to lumen of ER via TAP transporter
- There it binds to Class 1 MHC which is bound to TAP-1 transporter complex.
- Upon binding, Class 1 MHC folds around the peptide and released from TAP-1 to be transported to the cell membrane
It is recognised by CD8 T lymphocyte (killer)
How are peptides derived from ingested material - bacteria, foreign material which MHC protein used
Which cells present these, and which lymphocyte responds by binding to the non polymorphic regions of the MHC
Only specialised APC - such as B cells and Dendritic cells present via Class 2 MHC
- Antigen is taken up into APC into intracellular vesicles
- Acidification of vesicle activates protease to degrade antigen into peptide fragments
- Vesicles containing peptide fragments fuse with vesicles containing MHC class 2 and the peptides with an affinity for the antigen binding groove bind to it
- Bound peptide is transported by Class 2 MHC to the surface
It is recognised by CD4 T lymphocytes (helper)
What 2 things limit the ability of antigens to activate an immune response/lymphocyte
- Not all peptide fragments are immunogenic- only those with affinity to peptide binding groove of MHC will be able to be presented to lymphocytes
- There are many different alleles for MHC (HLA in humans) proteins, meaning not everyone will present the same epitopes to the immune system.
What does the CD3 found on all T lymphocytes do
Transduces antigen binding event into activation signal within the cell
What cell can do both types of antigen presenting to both types of lymphocytes
APCs/b cells are only cells that can present ingested material on Class 2 HLA
But they are also nucleated so have Class 1 HLA although they are also able to have cross presentation of their phagosomed material too
What are the other names for Class 1 and 2 MHC and what are 2 common features
Class 1 (to helper on APC): HLA DP, DQ, DR Class 2 (to killer on every1): HLA-A, B, C
Both types are polymorphic - many different types of DP, DQ, DR.
+ co-dominantly expressed: both maternal and paternal versions
