Cell mediated immunity (year 2) Flashcards
what is required for antibody to be produced?
T and B cells
if antibody can’t be produced what can this lead to?
higher mortality rates and great susceptibility to disease
what are T and B cells?
circular cells with T cell receptors (TCR) and B cell receptors (BCR) on them
what are the three main regions on the receptors?
constant, variable and transmembrane
what are the two forms of T cell receptors?
alpha/beta heterodimers
gamma/delta heterodimers
where are alpha/beta heterodimers found?
they are membrane bound and the classic MHC class I or II
where are gamma/delta heterodimers found?
these are non-membrane bound and bind to free specialised antigens - lots found in cattle
what letter do B cell receptors resemble and what is this structure similar to?
Y - an antigen
where does T cell selection occur?
in the thymus
what does MHC stand for?
major histocompatibility complex
describe the process of T cell selection
arrive as double negative - lack CD4/CD8
T cells get given both CD4 and CD8 surface markers so are now double positive
T cell then undergoes positive selection in response to whether they recognise MHC (the way antigen is presented)
they then undergo negative selection in response to whether they recognise self-proteins
finally move into the medulla where they become single positive for either CD4 or CD8
what does MHC do?
presents the antigen to a host T cell
how is MHC classified?
class I and II
which class of MHC does CD4+ T cells recognise?
class II
which class of MHC does CD8+ T cells recognise?
class I
on what cells in MHC class I expressed?
all nucleated cells except RBCs, platelets and nerve cells
what cells express MHC class II?
all professional antigen presenting cells
give examples of some professional antigen presenting cells (APCs)
dendritic cells
macrophages
B cells
MHC shows heterozygosity. what significancy does this have?
there is huge genetic diversity which can lead to disease resistance
where is the MHC complex assembles?
inside the cell, it is then transported to the surface where T cells can recognise the proteins
what determines if the antigen is presented as class I or II?
the route of entry
what antigens are presented as as class I?
intracellular pathogens that directly enter the cytosol and undergo endogenous antigen processing
what antigens are presented as class II?
extracellular pathogens that enter the cells via endocytosis or phagocytosis and undergo exogenous antigen processing
describe the process of exogenous antigen processing
extracellular pathogens enter the cell and are processed via the endocytic pathway, the peptides are then presented by MHC class II molecules these are recognised by T cell receptors of CD4+ T helper lymphocytes and cytokines are secreted which enhances the humeral (antibody) and cellular immune responses
describe the process of endogenous antigen processing
intracellular pathogens are processed via cytosol and proteasome and the resulting peptides are presented by MHC class I
these are recognised by T cell receptors of CD8+ T cytotoxic lymphocytes
cytokines are then secreted which enhances cell mediated immunity
what are the 3 types of T cell?
cytotoxic CD8
T helper 1 CD4
T helper 2 CD4
lymphocytes express thousands of identical receptors unique for what?
a single epitope
cytotoxic T lymphocytes are restricted to which MHC class?
class I - they are CD8 positive
what do cytotoxic T cells do?
kill cells that are infected with intracellular pathogens
T-helper lymphocytes are restricted to which MHC class?
class II - they are CD4+
what is the role of T-helper cell 1 (Th1)?
proinflammatory - activates cytotoxic T lymphocytes to kill intracellular pathogens
what is the role of T-helper cell 2 (Th2)?
anti-inflammatory - stimulate antibody production and switching
what is Th0?
an undifferentiated T helper cell
what can Th0 differentiate into?
Th1, Th17 and Th2
what drive Th0 differentiation?
cytokines
what are cytokines?
soluble protein messengers of the immune system
what T helper cells are involved in cell mediated immunity?
Th1 and Th17
what factors dictate the type of cellular immune response?
type of pathogen (intra/extracellular)
cytokine microenvironment
what is a cytokine microenvironment?
small localised part of a lymph node, spleen or intestine
what microorganisms will cause Th0 to differentiate into Th1?
bacteria and viruses
what microorganisms will cause Th0 to differentiate into Th1?
bacteria and fungi
what microorganisms will cause Th0 to differentiate into Th2?
helminths, yeast, bacteria
name the effectors released from CD8 cells
IFN-gamma TNF-beta perforin granzymes fas ligand
name the effectors released from Th1 cells
IFN-gamme IL-3 IL-2 TNF-alpha TNF-beta
name the effectors released from Th2 cells
IL-4 IL-5 IL-10 IL-13 CD40-ligand
Th1 and Th2 have antagonistic mechanisms, what are these?
Th1 - IFN-gamma antagonises Th2
Th2 - IL-4 and IL-13 antagonises Th1
why is the antagonism of Th1 and Th2 a problem?
often with responses are needed to clear an infection so the first pathway that is triggered needs to be over come
what happens once antigen is presented?
clonal expansion
describe the process of clinical expansion
the single T/B cell proliferates
the cells enlarge and stop migrating
chromatin becomes less dense to allow protein synthesis
within a few hours lymphoblasts have formed
lymphoblasts give rise to 2-4 daughter cells each day producing memory lymphocytes and effector cells
what cells need activation to survive and which don’t?
effector cells do
memory cells don’t