lecture 12: antigen uptake and presentation Flashcards
(32 cards)
1
Q
what two components cause immunity
A
- the two interdependent components of the immune response to invading microorganisms and foreign material are innate resistance and adaptive immune responses
- innate resistance mechanisms offer substantial host defence against any microorganism or foreign material. it has no immunological memory and innate responses are always ready for host defence
- the adaptive immune response resists a particular foreign agent; moreover, adaptive immune responses improve on repeated exposure to the agent but must be activated by innate immune mechanisms
2
Q
what is antigen
A
- anything that has the potential to be recognised by the immune system
3
Q
what does foreign antigen include
A
transplants, environmental, pathogens, some chemicals
- anything from ‘outside’
4
Q
self antigen
A
- can be recognised by immune system esp. in autoimmune disorders
5
Q
how do phagocytes and other leukocytes detect microbial macromolecules
A
- by the repetitive structural patterns
6
Q
how does phagocytosis happen
A
- binding triggers phagocytosis as antigen causes a conformational change in the antibody which allows receptors to bind
- there is a wide range of innate receptors that will help trigger phagocytosis
FC receptor –> antibody and antigen
Complement receptor –> complement and antigen
Mannose receptor –> antigen (containing mannose)
7
Q
how does receptor mediated antigen uptake work with antibody and complement
A
- antigen may be tagged by complement (C3B) and/or antibody
- this facilitates recognition and uptake through cell surface receptors eg:
–> complement receptors (CR) bind C3b
–> Fc Receptors (FcR) bind Fc region of antibody
8
Q
MAMPS
A
microbe associated molecular patterns
9
Q
PAMPs
A
pathogen associated molecular patterns
10
Q
how are extracellular infectious agents identified
A
they are identified by cells of innate system because of receptors on their surface
11
Q
how are intracellular infectious agents detected
A
they are detected by host receptors in cytosol
12
Q
PRR
A
= pattern recognition receptors
- recognise PAMPS and damage associated molecular patterns (DAMPS) eg: uric acid (gout), heat shock proteins
13
Q
cellular location of TLR
A
- present on plasma membrane and endosomes
- found on structural cells not just immune cells
14
Q
function of TLR
A
- when they signal they recruit adaptor molecules which facilitate downstream activation of transcription factors which cross into nucleus to trigger inflammatory cytokines
- they are attached to the plasma membrane as well as on membranes of endosomes, lysosomes, endolysosomes and ER where they detect MAMPS/PAMPS
15
Q
what is the effect of TLR signalling
A
- increases cytokine secretion and phagocytic ability: greater pathogen clearance
- dramatically increases the immunostimulatory capacity of Antigen presentign cells (esp. Dendritic cells)
- this results in enhanced T cell stimulation and better ‘memory’ responses
16
Q
MHC defintion
A
MHC = major histocompatibility complex
- MHC proteins present peptides for the stimulation of T cells
- They are expressed at the cell surface
17
Q
MHC class 1 properties
A
- all nucleated cells
- activates CDH8 t cells
- 9-10 amino acids
18
Q
MHC class 2 properties
A
- antigen presenting cells: DC, B cells, monocytes and macrophages
- CDH4 helper t cells
- 11-15 amino acids
19
Q
endogenous response
A
- peptides generated in the cytoplasm bind to newly synthesised MHC-I
- Virus inside the cell, peptides generated in cytoplasm, proteins are digested and loaded onto newly synthesized MHC I
20
Q
Exogenous response
A
- peptides generated in acidic vesicles bind to newly synthesised MHC-II
- viruses swallowed from outside the cell
21
Q
polymorphism
A
mutations that result in alternative forms of genes
22
Q
polymorphisms within MHC
A
- polymorphisms in MHC are useful because they allow different types of peptides to bind
- positions of polymorphisms within MHC-I & II are confined to the peptide binding sites
- polymorphisms add to the diversity of MHC
- they allow a multitude of peptides to bind
- humans express: six types of MHC-I and six types of MHC-II genes
–> expression is co dominant
23
Q
how do MHC-I & II interact with self antigen
A
- stable MHC-I & II requires peptide bound to the antigen binding groove
- most non-peptide bound (‘empty’) MHC is either recycled from the cell surface or does not reach the cell surface
- in the absence of infection, 100% of MHC is loaded with self peptide
24
Q
how does TCR change the affinity state
A
- TCR signalling switched LFA-1 to a high affinity state capable of binding ICAM-
high affinity = more able to bind a molecule on the dendritic cell called ICAM-1 - this allows for adhesion between dendritic cells and T cells
LFA-1 = T cell
ICAM-1 = Dendritic cell
25
what is "signal 1"
- once stable adhesion has been achieved, antigen presentation can begin
- the antigen/MHC binding to the TCR provides the T cell with the first signal ('signal 1') for activation
26
what is serial triggering
- MHC-TCR interactions are very weak and have a high on and off rate
- one MHC molecule may 'serially trigger' hundreds of TCR molecules
- this increases the effciency of antigen presentation, especially for rare MHC/peptide complexes
- serial triggering leads to a sustained activation
- a certain number of t cells must be triggered to lead to a detectable T cell triggering
27
what are the steps of T cell activation
1. Signal 1 = TCR and MHC
2. signal 2 = CD80 and CD28
These two anchor the dendritic cell and Naive T cell which results in T cell activation and proliferation
--> T cell start to divide and make more copies
28
what happens if there is no CD80
- signal 2 wont happen
- this results in anergy (non-responsiveness) or apoptosis
- T cell becomes non functional
29
what is the goal of acute inflammatory response
deliver immune cells to the site of injury or infection
30
chronic inflammation
infiltration of lymphocytes and macrophages into the affected site and formation of new connective tissue = can result in long term damage
31
Innate response to chronic inflammation
- physical and chemical barriers
- phagocytosis
- complement
- PRRs
32
adaptive response to chronic inflammation
- if innate responses are unable to protect the host from ongoing infection the body attempts to wall off and isolate the site --> granuloma
granuloma = a well organized mass of macrophages and other cells
- together, the cells and extracellular matrix proteins form a spherical mass that. can bind calcium making the granuloma harder to break down
