Antigen Presentation Flashcards
How were Major Histocompatibility Complexes discovered
Due to their importance during tissue rejection
Major Histocompatibility Complex is encoded where
Human Leukocyte Antigen Complex on Chromosome 6
What are Major Histocompatibility Complex genes
Polygenic, extremely polymorphic, Codominantly expressed
Major Histocompatibility Complex molecules are neccessary to
Present Ag to T cells
Who has MHC Class I
All nucleated cells
What do MHC Class I display
Endogenous peptides
What do MHC Class I present to
CD8+ T cells
Who expresses MHC Class II
on professional antigen presenting cells
What do MHC Class II present
exogenous peptides
Who do MHC CLass II present to
CD4+ T cells
Strucutural difference between Class I and Class II MHC structures
Class I, only in membrane once, where class II enters cell membrane twice
MHC Peptide Binding region for Class I and Class II
Class I: 8-10 amino acids
Class II: 13-18 amino acids
The breakdown of macromolecules into amller fragments in order to prepare for presentation to a t cell
Antigen Processing
4 ways of Ag Processing
Exogenous, Endogenous, Cross-presentation, autophagic
endogenous pathway
Infection by bacteria, antigen degraded in ctosol, peptide association with MHC Class I, activation of CD8 Tc Cells
Exogenous Pathway
Internalization by APCs, antigen degradation in endocytic compartment, peptide assocation with MHC class II, Activation of CD4 Th cells
Cross presentation
Starts in exogenous pathway and ends in endogenous pathway (outside but MHC class I)
Autophagic
Starts in endogenous pathway and ends in exogenous pathway (inside but MHC class II)
Naive T Cell Activation
Uses a Dendritic cell to take up antigen, and results in Clonal expansion and differentiation into effector T cells
Effector T cell activation
Marcrophase presnts, leading to T cell activation and activation of macrophages for Cell-mediated Immunity
And B cell activation and antibody production leading to humoral immunity
What i contained in the Alpha subunit of MHC Class I
Enter into the membrane and have the peptide binding chain
Subunits of MHC CLass I
Alpha and Beta subunits both insert into the membrane and also have a peptide binding cleft
3 types of Antigen Presenting Cells
Mature DC, Macrophages, B cells
What is the best at presenting to a T cell
Dendritic cells (high MHC II and constimulary molecules)
What can activate a Naive T cell
Dendritic cells
What are macrophages and B cells good activating
Effector cells and memory T cells
Action of Dendritic Cells
Recognize antigen, Phagocytosis it, activating DC cell. Begins processing, drain through lymphatics , to find the correct T cell, to activate that T cell
Exogenous Pathway
Internatlize antigen by phagocytosis to form phagosome. This fuses with lysosome to bread down antigen. At the same time the RER begins making Class II MHC. Passes throught the SER, Golgi, then heads to Lysosome, to degrade invariant chain. HLA-DM removed clip and peptide from antigen to be presented on the outside of the cell.
What parts are uniquie to the exogenous pathway
Invariant chain, Clip, HLA-DM, MHC II
Endogenous Pathway
Internal peptide has a tag added to it from the Ubiquitin Protein. Tis tells the protein to be degraded by the proteosome. TAP puts these fragments into the endoplasmic reticulum and is loaded into MHC Class I
Cross Presentation pathway
APC ingest and processes virally infected cell. Viral Proteins enter the cytosol and is processes via endogenous pathway(protesome) to activate a CD8 cell via MHC I
Autophagic Pathway
Uses internal stuff and degrades it with lysosome and presented in MHC II
Receptor responsible for antigen recognition on t Cells
T cell Receptor
Alpha Beta T cells recognize
MHC/Ag
Where Alpha-Beta T cells Reside
In secondary Lymphoid tissue
Gamma delta T cells recognize
Processed/unprocessed ligands (innate immune cells)
Where gamma delta T cells are found
Intraepithelial Tissues
Structure of T cell Receptor
1 variable region on each chain(2 total)
1 constant region on each chain (two total)
The T Cell receptors need to recognize
Peptide + MHC
What helps to start an intracellular chain of events in a T cell Receptor
CD3 (zeta chains)
What recognizes MHC class I
CD8 T Cell
What recognizes MHC Class II
CD4 T cell
What are CD4 T cells
And CD8
Helper T cells
Cytotoxic
How TCR Complex is activated
MHC interacts with T cell receptor. CD4 or CD8 recognizes when this becomes activated and this activates Lck which phosphorylates tyrosines in ITAMs
Can a TCR undergo VDJ recombination
Yes
V(D) J recombination occures where
In the Variable region
HOw T cell and B cell development is similar
Begin in bone marrow
V(D)J recombination of variable region of TCR leads to antigenic diversity
At one point cells express both CD4 and CD8
Undergo positive and negative selection
What do T cell development begin with
NK/T precursor cell
Where do T cells (thymocytes) move to finish development
leave bone marrow to go to thymus
What molcules of T cell development are involved in Establishing central tolerance
MHC molecules
Can Somatic hypermutation occur in T cells
No
Role of Rag genes
do V(D)J recombination
What surface molecules are expressed by T cell stem cells
Adhesion molecules
Does Recombination of V(D)J occure during stem cell stage of T cells
No
1st tell cell stage in the thymus
Pro-T cell
When does the Beta Chain first recombo for T-cell
At the end of the Pro-T cell
When the Beta chain recombo for T cells end and alpha begins
Pre-T (alpha at the end)
DOuble positive T cell
full T receptor and CD4 and CD8
When T cells go through positve and negative selection
Double possitive
What separates Single possitve T cell
when it only recognizes as a CD4 or CD8 cell
Negative selection
Dies because reacts to much to MHC
Cell involved in Naive T cell activation
Dendritic Cells
Naive T cell activation steps
Dendritic cells process antigen, present to a CD4 T cell and co-stimulatory factors
The Best epitope of activating a T Cells
immunodominant
Steps of signalling T cells
- Ag recognition
- Costimulation(IL-2 needed to activate)
- Cytokines
- Differentiation (cytokines)
B7 is related to
Found on the antigen presenting cells to adhere to CD28 for signal transduction via costimulation
IL-2 is needed for
Survial, proliferation, and differentiation of T cells
Roll of CD4 T cell
Activation of Macrophages, B cells, and others, plus inflammation
Roll of CD8 T cells
Killing of infected cells, macrophage activation
CD4 subsets
Subsets of Helper T cells that match for which type of problem you have
FUnction of Th1 helper t cells
T help for Tc response against intracellular pathogens (activate macrophages) (IFN7)
Function of Th2 helper t cells
T cell for B cell responses against extraceullar pathogens and humoral activation (IL-4)
Th17 roll
Inflammation and mucosal immune response(antimicrobial peptides), recruit nutrophils (IL-17)
Treg roll
Peripheral tollerance, make sure immune response does not get out of control (IL-10)
The Cytotoxic Cells
CD8 T cells
Ctokines needed for CD8 T cells
IL-2, IL-12, and type 1 IFN
interaction of cytotoxic T Lymphocytes
Interacts with Anitgen bound to MHC class 1. GRanule exocytosis to kill target. Releases and taget cell dies
What is left after Contraction of Immune system
Memory T cells
