What is cell mediated immunity?
due to the direct action of T cells
Where did the cell mediated immunity term evolve from?
The finding that immunity to intracellular pathogens could be transferred to other animals by immune cells from infection-recovered animal.
How have T cells evolved?
To protect us against intracellular microbes (viruses and some bacteria)
What do T cells have to help to mount?
A robust Ab-mediated humoral immune responses directed agains extracellular pathogens
What can T cells not do?
Cannot directly recognize unprocessed Ags or bind to microbes
How are Ags in host cells broken up?
Each T cell recognizes only one specific foreign peptide, how does the body over come this?
but there is a large TCR repertoire generated in the body
Where are the T cells educated?
T cells are either?
selected for survival or eliminated if self reactive
What is the general function of different T cells?
each with different functions in the immune response that are dictated by cytokines produced
CD4+ T helper cells recognize?
peptide Ags in the context of MHC class II molecules that are expressed by dendritic cells, Mo, and B cells
CD8+ cytotoxic T cells
recognize peptides associated with MHC class I molecules
What does the CD4 and CD8 attach to?
the non-polymorphic (non variant) part of the MHC class II and MHC class I molecules, respectively.
What needs to happen to T cells in order for them to carry our their function?
they need to be activated
What is not sufficient to activate the T cells?
recognition of the peptide Ag by the TCR
What are required in addition to recognition?
Co-stimulatory molecules, with co receptors involved in signaling events
What does T cells activation lead to?
production of IL-2, which controls clonal expansion of specivic T cells
What does IL-2 control?
clonal expansion of the specific T cell
What does Th1 do?
helps Mo to get rid of intracellular microbes and help the development of cytotoxic T cells to kill virus infected cells
What is IFN gamma produced by?
Th1 cells activates Mo
What are Th2 cells involved in?
Helping B cells to develop into memory cells and plasma cells that produce antibodies
What is IL-4 produced by?
What is IL-4 important for?
B cell proliferation
How is B cell activated?
Self activated, but cannot advance without help from Th cells.
What do B cells develop into?
memory cells and plasma cells
plasma cells produce?
What is the TCR of conventional (alpha, beta T cells)?
It is composed of two polypeptide chains, alpha and beta, which have molecular wights of 50 and 39 kDa
What are the genes coding for TCR polypeptide chains?
members of the Ig super family
What does the T cell receptor complex consist of?
The TCR, the alpha,beta or gamma,epsilon dimer, in association with CD3
What is CD3?
A signaling complex composed of gamma, epsilon, and delta
What is a seperate signaling molecule made up of?
What does CD4 on T cells bind to?
nonpolymorphic region of MHC class II on APCs restricting Th cells to recognizing only peptides presented on MHC class II molecules
CD8 on cytolytic T cells binds to?
the non polymorphic region of MHC class I, restricting...
Know what TCR complex looks like
Proteasome genes structure
Look at Detailed map of Human
Class I major
HLA-B, C, A
Class I region minor
HLA G, F, E
What is the significance of co dominant expression of both parental allels of each MHC gene are expressed?
increases number of different MHC molecules that can presesnt peptides to T cells
What is the significance of polymorphic genes: many different alleles are in the population.
Ensures that different individuals are able to present and respond to different microbial peptides
What is the significance of MHC expressing Cell types: Class II: dendrictic cells, macrophages, B cells
CD4+ helper T lymphocytes interact with dendritic cells, macrophages, B lymphocytes
Class I all nucle
What are the two classes of polymorphic MHC genes encode human leukocyte ?
Class I and II, that can bind peptides and are thus critical to Ag presentations
What are class I genes?
HLA-A, -B, -C
What doe class I genes do?
encode a polymorphic heavy chain which combines with beta2-micro-globulin and is expressed on the surfaces of all nucleated cells
What does the heavy chains of class I genes have?
a binding groove for peptides to be recognized by T cells
What are Class II genes?
What are Class II genes encoded molecules?
What is that alpha chain of the class I molecules?
glycosylated (carbohydrate residues are not shown)
What does the ribbon diagram show??
The stucture of the ex....
What do the anchor residues on the peptides do?
Bind to residues in the class I and II grooves and vary for different MHC alleles.
What are MHC class II molecules expressed on?
professional APCs, only B cells, dendritic cells and macrophages
What are MHC class I molecules expressed on?
all nucleated cells
What is expression of MHC class I and II modulated by?
What are peptides that bind to class I MHC molecules derived from?
viruses that have infected host cells and move as the complexes to the surfac (endogenous pathway)
What doe petides that bind to class I MHC bind to?
recgonized bty CD8+ cytotoxic T lymphocytes CTL
Ags and pathogens taken from the environment primarily present on?
MHC class II molecules to CD4+ helper T cells
What are professional APCs?
B cells macrophages, dendritic cells... They are strongly expressed on MHC class I and II
Dendritic cells recognize?
antigens at the gate..
CD28 does what?
Binds dendritic cell and naive T cells with the costimulator B7