Adaptive immunity mechanisms Flashcards
MHC class processing
1) 2 chains of the MHC class II molecule assemble in the endoplasmic reticulum
2) a portion of a third chain called the invariant chain binds to the peptide binding groove of the MHC II receptor and prevents peptides and unfolded proteins present in the ER from binding
3) The invariant chain also guides the MHC class II molecule to the end of the ER and into a vesicle that eventually becomes part of the endocytic pathway
4) In which pathogens and foreign particles are taken into the cell, and acidification of these vesicles causes destruction of its content
Progressive acidification of these vesicle activates proteases which cleaves the invariant chain in two places leaving a small peptide in the receptor mouth (CLIP)
5) Engulfed pathogens then merge with vesicles containing MHC II receptors
6) These pathogen peptides will not bind to the class 2 molecule due to the CLIP molecules blocking their active sites
7) The removal of the CLIP molecule is the function of a specialised MHC Class II like molecule called HLADM
8) The HLADM acts as a catalyst, coordinating both the release of the CLIP molecule and the binding of pathogen derived peptides
9) This vesicle containing an MHC II molecule with a pathogen derived peptide then fuses with the cell surface and present the peptide to the antigen receptors of CD4 T cells.
dendritic activation of T cells
1) As the T cell contacts the surface of the dendritic cell, little green fluoresce turns into strong fluorescent green (triggered by Calcium), as the T cell becomes activated
2) The T cell continues to move crawling over the surface of the dendritic cell , sampling the cells display of peptide MHC complexes
3) As the T cell loses interest its fluorescence starts to fade
4) The t cell then migrates away from the dendritic cell
dendritic migration and activation of T cells
1) The key antigen presenting cells of the immune system are dendritic cells
2) Generated from progenitors in the bone marrow which migrate via the blood stream into the tissue, where they wait for pathogens to enter the body
3) Dendritic cells display various PRR that can recognise common features of many bacterial and fungal pathogens, which triggers phagocytosis
4) This causes activation and maturation of the dendritic cells
5) In this process they migrate from the tissue and into the lymphatic vessel, where they change their behaviour to stop phagocytosis and to start presenting immune stimulatory molecules
6) This lymphatic tissue drains through lymph nodes, where the dendritic cells are inspected by T cells for the presence of antigens
7) T cells which fail to recognise antigens on one dendritic cell carry on inspecting others
8) Eventually returning to the circulating
9) T cells which do recognise antigens will become activated and proliferate/ differentiate into effector cells
Cytotoxic T cell killing
1) Virus’ are intracellular pathogens which infect host cells
2) E.g. epithelial cells, using their DNA replication machinery to proliferate
3) This process also causes parts of the viral molecule to be presented on the outside of the infected cell via MHC class I Receptors
4) CD8 T cells, recognise these peptide complexes and kill infected cells
5) The killing process:
a. Initiated when the t cell receptor and CD8 together bind to an MHC I molecule baring a viral peptide
b. These produces signals which activate the T cell
c. Cytotoxic T cells contain Cytotoxic granules which package the proteins which kill infected host cells e.g. perforin and granzymes
d. These proteins are complex with a scaffolding protein call serglycin
e. Activation of the T cell triggers the release of the content of these cytotoxic granules
f. Delivering the proteins directly onto the surface of the target cell
g. The perforin facilitates the delivery of the granzymes into the cytosol
h. At this point the target cell is destined for destruction and the T cell can move on to find a new cell to destroy
i. This process granzymes use to kill the cell uses the same machinery as those used in apoptosis
j. Granzymes target proteins which target apoptosis such as BID and pro-caspase-3
k. The granzymes cleave BID, which causes cytochrome C to release from the mitochondria into the cytosol
l. Cytochrome C also activates pro-caspase-3, which in turn cleaves icad, the inhibitor of the caspase activated DNAase (CAD)
m. The CAD- degrades the DNA ensuring the death of the cell
cytotoxic killing process
a. Initiated when the t cell receptor and CD8 together bind to an MHC I molecule baring a viral peptide
b. These produces signals which activate the T cell
c. Cytotoxic T cells contain Cytotoxic granules which package the proteins which kill infected host cells e.g. perforin and granzymes
d. These proteins are complex with a scaffolding protein call serglycin
e. Activation of the T cell triggers the release of the content of these cytotoxic granules
f. Delivering the proteins directly onto the surface of the target cell
g. The perforin facilitates the delivery of the granzymes into the cytosol
h. At this point the target cell is destined for destruction and the T cell can move on to find a new cell to destroy
i. This process granzymes use to kill the cell uses the same machinery as those used in apoptosis
j. Granzymes target proteins which target apoptosis such as BID and pro-caspase-3
k. The granzymes cleave BID, which causes cytochrome C to release from the mitochondria into the cytosol
l. Cytochrome C also activates pro-caspase-3, which in turn cleaves icad, the inhibitor of the caspase activated DNAase (CAD)
m. The CAD- degrades the DNA ensuring the death of the cell
immune-synapse
1) When T cells is able to recognise their antigen on another cell, an immune-synapse is formed
2) The zone f contact between the two cells- immune-synapse
3) This synapse is made out of adhesion molecules (outer ring) and signalling molecules (inner ring) and secretory zone (inner)
4) Mediates fusion of cytotoxic granzymes to synapse- so that T cells can mediate cytotoxic killing
professional APC cells express
both MHC molecules
CD4: MHC II and costimulatory molecules
1) Stimulation of a CD4T cell by APC involves interaction between the T cell receptor and the Co-receptor molecules, with the MHC II molecule, as well as the interaction between CD28 (T cell) and CD80
2)the interaction between the APC and T Cell causes signals to pass in both directions
3)signalling the APC cell to present additional co-stimulatory molecules such as CD86 and CD40
4)this interaction also causes the T cell to express the CD40Ligand and CD86 ligand
the interaction between the CD40L and CD40, as well as the additional stimulation through CD28, mediate a bi-interaction with CD86, resulting in the full activation of the CD4 T
antibody mediated cytotoxicity- 2 widely recognised mechanisms of antibody mediated toxicity
1) antibody dependent cell-mediated cytotoxicity (ADCC)
2) Complement-mediated cytotoxicity
antibody dependent cell-mediated cytotoxicity (ADCC)
antibody attracts cytotoxic cells by means of their Fc receptors
Complement-mediated cytotoxicity
Antibody binding results in the fixation of complement onto the target cell
example of ADCC
- E.g. of a parasite (too big for phagocytosis)
- Fc receptor binds once parasite opsonized (IgE)- which forces eosinophil to degranulation to make life extremely uncomfortable for the parasite.
