Blood and Immune: Cellular Immunity and Histocompatibility Flashcards
Where do T lymphocytes mature
the thymus
where do the precursor of T cells get produced before migrating to the thymus
bone marrow
What is a thymocyte
Immature T cell found in the thymus
The coreceptors (cell surface markers) on a T cell
CD4+, CD8+ (or just CD4 and CD8)
What is the name for a T cell expressing both CD4 and CD8 on its surface
a double positive immature thymocyte
Name of T cells that only express CD4+
CD4+ helper T cells
Name of T cells that only express CD8+
CD8+ cytotoxic T cells
What % of T lymphocytes in blood are CD8+ + cytotoxic
20%
What % of T lymphocytes in blood are CD4+ helper
80%
The four subgroups of CD4 T helper cells
Treg, Th1, Th2, Th17
What is the function of Tregs
to regulate immune response
What is the function of Th1
drive cellular response
What is the function of Th2
drive antibody response (B cells)
What is the function of Th17
control inflammatory response
If a pathogen demands a cellular immune response, which T helper cell subgroup will predominate?
Th1
How are T cells distinguished
by their antigen (CD4 or CD8)
What is CD in CD4 and CD8
cluster differentiation
How can T cells be marked
by the monoclonal antibody that binds to the antigen CD4 or CD8
When is the thymus at its largest size and why
largest at birth then shrinks with age (cellular immune response developed before and just after birth)
What is the function of the thymus
Location where T cells are ‘educated’ to recognise self MHC molecules and where they become CD4 or CD8 (its important in immune response development)
Where is the thymus located
It sits at the top of the pericardium above the heart
Name of precursor to T lymphocytes
Hematopoietic lymphoid precursors
What is negative selection
when T cells die from “neglect”, have not recognised the correct antigen to activate and undergo mitosis
What is positive selection
Some cells recognise the correct antigen but are activated too strongly which are killed by apoptosis
What is Apoptosis
is a form of programmed cell death, or “cellular suicide
What happens to T cells that survive the thymus
“educated” to recognise self MHC molecules expressed in thymic tissue
What system is MHC important for
adaptive immune response/system
What type of pathogens are viruses
intracellular
Where do viruses replicate
inside cells
What do T cells do when they recognise infected cells
either kill them or provide help to other cells that reduce the ability of the virus to replicate and produce copies of itself which infect other cells
What does MHC stand for
Major Histocompatibility Complex
What is MHC
A set of highly polymorphic genes that code for Human Leukocyte Antigens on the cell surface
What antigen on a cell will express parts of a virus if infected
MHC
What antigen controls tissue transplantation
MHC
What is and isn’t “self”
MHC, “not self” is if MHC changed (due to virus or bacteria)
What does CTL stand for
Cytotoxic T lymphocytes (CD8 T cells)
Function of CTL
stimulate immune response which actively kills cells
What do CTL generate?
perforin molecules that are inserted into target cells to kill them
What do CTL do if they recognise a “non-self cell”
CTL binds tightly to cells that have altered class 1 MHC (expressing a neo-antigen that is viral or altered self antigen) and release perforin molecules which form pores into target cells causing the release of internal innards of the cell = cell death
What is a neo-antigen
are mutated antigens specifically expressed by tumour tissue and are not expressed on the surface of normal cells
meaning of congenic
Strains that are genetically identical except for one or more MHC locus/loci
What are congenic mice
Congenic mice is when you isolate particular genes that regulate certain phenotypes (e.g. tissue rejection)
What is MHC restriction
The fact that a T cell can interact with a self-MHC molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule
viral immunity requires both these antigens
SELF Antigen(s) encoded by MHC NON-SELF Antigen(s) encoded by the virus
what is HLA
human leukocyte antigen coded for by MHC
What does a T cell form with a target cell?
synapse so it can insert signal into target cell so it undergoes apoptosis
How is MHC changed by a target cell
MHC has been changed because of a new peptide antigen that has been inserted into groove on the top of the MHC (HLA) molecule
What a T cell receptor
a membrane bound Ig-like molecule on T lymphocytes
Classes of MHC
class 1 and 2
Names of antigen/loci in class 1
A, B and C
Names of antigen/loci in class 2
DR, DP, DQ
How many types of each antigen in both class 1 and 2 exist
two possible types (paternal and maternal alleles)
How many types of antigens in total are expressed on the surface of cells
12
What does H2 refer too
the MHC antigens on mouse cells
What can MHC molecules be used for in medicine
you can transplant and store tissues in case someone needs a bone marrow transplant
What part of MHC class 1 is polymorphic
the top (the 2 alpha helices on top of the heavy chain), amino acid sequences vary from individuals
Where does a viral peptide sit in MHC class 1
in groove between the two alpha helices
What part of MHC class 1 is invariant
lower part (bound by CD8)
What holds MHC class 1 molecules in the right conformation
Beta 2M
What part of MHC class 2 is polymorphic
The top (1 beta and 1 alpha strand)
Where does a viral peptide sit in MHC class 2
in groove between alpha and beta strand
Is the viral peptide longer in class 1 or 2
class 2
Where does viral peptide come from in MHC class 1
from virus inside the cell or altered self antigen
Where does viral peptide come from in MHC class 2
antigens that have come from extracellular pathogens like bacteria that have been taken up by phagocytosis and broken down so pieces attach groove
What type of cell recognises antigens in MHC class 1
CD8 cytotoxin T cells
What type of cell recognises antigens in MHC class 2
CD4 Helper T cells
What is intracellular tyrosine kinases
CD8 and CD4 have these receptors associated with their cytoplasmic tails. These initiate T cell signalling through phosphorylation
What do CD4+ T Helper cells do when they recognise MHC class 2 antigens
T cells proliferate and produce cytokines that “help” other cells
What do CD8+ T Helper cells do when they recognise MHC class 1 antigens
CTL produces granzyme and perforins that punch holes in the target cell membrane and destroy cell viability
Type of pathogen antigen expressed by MHC class 1
virus
Type of pathogen antigen expressed by MHC class 2
bacteria
Peptide source in MHC class 1
intracellular
Peptide source in MHC class 2
extracellular
What is polymorphism
genes that encode for the MHC complex are all different across individuals
Is tissue rejection learned
yes
What are haplotypes
a set of genetic determinants located on a single chromosome (lots of differing variations of aa sequence at each MHC locus)
What is polymorphism restricted to
the protein domains that form the peptide groove
What are anchor amino acids
the few points in peptides that are invariant (amino acid side chains point down into MHC molecule and anchor)
What is the evolutionary purpose of polymorphism in MHC
Polyphormism is designed to create the broadest capacity for protection of a species as a whole (MHC in a community is for what they are most likely to encounter). When communities do not have the right MHC haplotypes, new diseases can devastate communities
Two major consequences of MHC polymorphism
Tissue transplantation and autoimmune diseases
What did the congenic mice experiment show
viral immunity requires both self MHC and foreign antigen
