Lecture 11: Intro to T cells; MHC structure, function and genetics in T cell recognition of antigen Flashcards
Where are T-cells born?
Bone marrow
T-cells originate from hematopoietic stem cells in the bone marrow.
Where do T-cell precursors travel to mature?
Thymus
The thymus is critical for the development of T-cells.
What are the secondary lymphoid tissues where mature T cells travel?
Lymph nodes, spleen, GALT
Secondary lymphoid tissues are essential for immune response activation.
What type of white blood cell are T-cells?
T lymphocytes
T-cells are a crucial component of the adaptive immune system.
What are the two main types of mature T-cells?
CD4+ (helper T cells) and CD8+ (cytotoxic T cells)
These T-cells have distinct roles in immune response.
What is the primary function of CD4 helper T cells?
Help B cells become plasma cells
CD4 cells assist in B-cell development and antibody production.
What do CD8 cytotoxic T cells do?
Directly kill infected or cancerous cells
CD8 T-cells recognize and eliminate cells presenting non-self antigens.
True or False: T-cells can develop into multiple types with unique functions.
True
T-cells can differentiate into various subtypes based on signals received.
Fill in the blank: T-cells travel via the _______.
Bloodstream
T-cells circulate through the body in the blood to reach lymphoid tissues.
What type of immune response do regulatory T cells provide?
Immune inhibition
Regulatory T cells help maintain immune tolerance and prevent overactive responses.
What is the role of Th1 cells?
Help macrophages become more phagocytic
Th1 cells enhance the ability of macrophages to engulf pathogens.
What is the function of lymph nodes?
Filters for lymph
Lymph nodes trap pathogens and activate T and B cells.
What is the function of the spleen?
Filter for blood
The spleen removes old or damaged blood cells and pathogens.
What does GALT stand for?
Gut-associated lymphoid tissue
GALT plays a vital role in immune function in the gastrointestinal tract.
What are the types of CD4 helper T cells?
Th1, Th2, Th17, Treg, and Tfh
Each subtype has distinct roles in regulating immune responses.
What do BCRs recognize?
BCRs recognize any solvable protein.
What do TCRs recognize?
TCRs can only recognize peptide portions of antigens presented by MHC.
What does MHC stand for?
MHC stands for Major Histocompatibility Complex.
What are T-cell receptors (TCRs) made up of?
TCRs are made up of two polypeptide chains that compose one antigen binding region.
What percentage of TCRs are composed of alpha and beta chains?
Approximately 95% of TCRs are composed of an alpha and a beta chain.
What percentage of TCRs are made up of gamma and delta chains?
The remaining 5% of TCRs are made up of gamma and delta chains.
Where are gamma delta cells usually distributed?
cells are usually distributed in peripheral tissue.
What is the function gamma delta T cells?
have a similar function to NK cells and play a role in innate immunity.
What is sometimes needed for a functional T cell?
Sometimes a CD3 co-molecule is needed to help transduce a signal to activate the T cell.
What do T cells secrete?
T cells secrete cytokines and toxic proteins.
What is similar to the FAB fragment on antibodies?
The variable region (V) of TCRs is similar to the FAB fragment on antibodies.
What is the constant region (C) of TCRs similar to?
The constant region (C) of TCRs is similar to an Ig-like domain.
What is the size of the alpha chain of TCRs?
The alpha chain is approximately 40-50 kDa.
What is the size of the beta chain of TCRs?
The beta chain is approximately 35-46 kDa.
What region of TCRs is exposed for specificity?
TCRs have a CDR exposed region for specificity.
What do BCRs recognize?
can recognize antigens via either an energy segment or a 3D structure.
How do T-cell receptors (TCRs) recognize proteins?
TCRs do not recognize soluble proteins; they recognize a complex made by peptide and MHC.
What is the primary function of the T-cell receptor?
The primary function of the T-cell receptor is to recognize and bind to specific antigens presented by MHC molecules.
What is involved in antigen processing?
Antigen processing involves the breakdown of proteins and the presentation of peptides by MHC molecules.
What is recognized by the T-cell receptor?
The T-cell receptor recognizes the antigen-MHC complex on the cell surface.
What is the ligand for a TCR?
The ligand for a TCR is the combination of peptide and MHC molecule at the cell surface.
How is a mature peptide processed to be put in an MHC molecule?
Cut peptides so that multiple inside portions can meet multiple MHCs
What do individual TCRs recognize?
Individual TCRs recognize only individual unique MHC-presented peptides.
What is T-cell recognition of antigens restricted by?
T-cell recognition of antigens is MHC-restricted.
Which T cells can recognize antigens?
Both CD4+ and CD8+ T cells can recognize antigens.
When can T cells recognize antigens?
T cells can recognize antigens only when presented in the groove of an MHC molecule.
What is MHC restriction?
MHC restriction is the dependence of T-cell receptors on self-MHC.
Where does MHC restriction occur?
MHC restriction occurs as T cells are developing in the thymus.
What is the survival dependence of T cells in the thymus?
The survival of T cells is dependent on engagement with self-MHC molecules present in the thymus.
What happens before T cells mature?
Before T cells mature, a sophisticated screening process occurs.
What can T cells weakly bind to during maturation?
Only T cells can weakly bind with their self-MHC and self-peptide.
What happens if T cells don’t recognize self-peptide-MHC?
If T cells don’t recognize self-peptide-MHC, they won’t survive or leave the thymus.
What do T cells show after leaving the thymus?
After leaving the thymus, T cells show weak binding to self-MHC with foreign peptides.
What is a major issue for tissue graft rejection?
Host rejects MHC molecules.
What is the MHC gene in mice called?
H2 - a major immune response gene.
Who originally identified MHC in mice?
R.A. Gorer and G.D. Snell in the 1930s.
What was the basis for defining MHC?
Tissue graft rejection.
Who was awarded the Nobel Prize in 1980 for MHC discoveries?
George D. Snell.
Who discovered the first compatibility antigen in humans?
Jean Dausset.
What did Barui Benacerraf find about immune reactions?
They are controlled by the MHC genes (immune response genes).
What did Rolf Zinkernagel and Peter Doherty reveal about T cells?
It is the complex of MHC molecule plus antigen that is recognized by T cells (MHC restriction of T cell responses).
Who won the Nobel Prize in Physiology or Medicine in 1996?
Rolf Zinkernagel and Peter Doherty.
What was the 1980 Nobel Prize awarded for?
“For their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.”
What are inbred strains of mice?
Genetically identical at all loci
What discovery was made from experiments mapping the genetics of transplantation?
The discovery of the MHC
What are the genotypes of the parental strains?
b/b and k/k
What is the genotype of the F1 progeny?
Heterozygous at all loci (H-2b/k)
What is required for skin transplants?
MHC identity
What is the recipient type for a skin graft from F1 progeny?
Parental recipient
What happens to tissue if MHC identity is not matched?
Tissue will be rejected
How many MHCs does each APC have on the surface of the cell?
100,000 MHCs
What does MHC stand for?
Major Histocompatibility Complex
What is the significance of the experiments mapping the genetics of transplantation?
Led to the discovery of the MHC
What are MHC molecules?
MHC molecules are a set of cell surface proteins.
What are the two broad kinds of microorganisms that infect human tissues?
1) Extracellular, e.g. bacteria which live and replicate in the space between cells.
2) Intracellular, e.g. virus which live and replicate inside human cells.
What is MHC class I associated with?
MHC class I presents endogenous proteins, such as viral or tumor proteins.
What is MHC class II associated with?
MHC class II presents exogenous proteins.
How do MHC class I and class II differ?
The two types have different pathways for presenting antigens.
What forms the peptide binding groove in MHC class I?
MHC class I has a peptide binding groove formed by alpha (α1-3) domains and a beta (β)2-microglobulin domain.
What forms the peptide binding groove in MHC class II?
MHC class II has a peptide binding groove formed by two alpha (α) and two beta (β) domains.
Which chains in MHC 1 molecule bind to the antigen?
Alpha 1 and 2
Which chains in MHC 1 molecule bind to the antigen?
Alpha 1 and 2
What part of the MHC 1 complex has a transmembrane domain?
Alpha 3 is the longer peptide that does this
What chains on the MHC 2 complex binds to the antigen?
Alpha 1 and Beta 1
What chain in the MHC 2 complex is transmembrane?
Alpha 2 and Beta 2 chains
What chain in the MHC 2 complex is transmembrane?
Alpha 2 and Beta 2 chains
