B and T Cells Flashcards
what are the four stages of adaptive immune response
antigen recognition, lymphocyte activation, effector responses, homeostasis
what are T-cell effector responses
cell mediated cytotoxicity, activation macrophages, recruitment of neutrophils
what are B-cell effector responses
antibody production
what are cytokine effector responses
IL-2/4/5/13, IFNgamma, TGFbeta, lymphotoxin, all produced by T-cells
most activate other cells, stimulate antibody production
TGFbeta inhibitory
what is the process of B cell action
microbial protein antigen attaches to B cell -> receptor mediated endocytosis of antigen -> antigen processing and presentation -> class 2 MHC-peptide complex attaches to B7 on B cell -> T-cell recognition of antigen
what are B cells
mature in the bone marrow and express IgD receptors on surface
antigenic challenge (in lymph node) results in processing and presentation of antigenic fragments to Th cells
Th2 cells provide costimulatory signals required for B cell activation and ab production (CD40L and IL-4)
class switching and somatic hypermutation improve antibody affinity and function
some remain after antigen elimination as memory cells
how are B cells activated
by engagement of surface antibodies plus costimulatory signals from T-cells
the signal is enhanced by engagement of complement coreceptor
what is B cell action
antigen presentation to T-helper cells, activation of T cell (expression of CD40 ligand, cytokine secretion), activation of B cell by cytokines and CD40 ligation, B cell proliferation and differentiation
what is down regulation of B cell activation
signals for B cells are down regulated by engagement of Fc coreceptor
what are antibodies
produced by B cells - humoral immunity
20% plasma protein, specific recognition of antigen, target circulating microbes and toxins for phagocytosis, provide active and passive immunity
what are the hypervariable regions
regions on antibodies that vary to accommodate antigens
how are antibodies produced
during maturation in the bone marrow B cells undergo irriversible genetic recombination to produce an antibody of restricted specificity
membrane bound IgM form, then IgD
antibody generally binds antigen with weak affinity/high avidity
activation of B cell leads to Ig class switching (G, A, E) and somatic hypermutation
activated B cells become plasma cells and some become memory cells
what are Fc mediaed effects
mediates many of the effector functions of antibodies; variability in Ig class affects function
IgG binds FcR on neutrophils and mac to promote phagocytosis
IgE Fc causes eosinophil activation and mast cell degranulation
IgG and IgM can trigger complement activation by binding C1q
all require bound antigens to initiate cross linking of antibodies
how are antibodies used as tools
can detect proteins in a lab
can detect antibodies in patients
prevent/treat diseases - vaccines, antibody therapies
what are blocking antibodies (ADCC)
antibody binds to receptor or ligand to prevent receptor binding and activation (anti TNF)
called antibody dependent cellular cytotoxicity
where are B cells stored
lymph nodes
what are B cell receptors made of
antibodies; recognises, engulfs and breaks up an antigen and keeps the fragment on the surface so it can be recognised by a Tcell
where are t cells stored
lymph nodes
what is somatic hypermutation
growing collection of antibodies can cause mutation
what is passive immunity
e.g. travel vaccinations that provide antibodies but do not stimulate the immune system
what is active immunity
active intake of pathogen to trigger memory cell formation
what are T cells
thymus selected lymphocytes, required for cell mediated immunity
removal of intracellular pathogens by killing infeced cells, respond to antigenetic fragments presented by MHC molecules
required to help B cells become activated and produce antibodies
what do helper T-cells (CD4+) do
recognise antigenic fragments presented on class II MHC
what do Th1 cells do
activate macrophages and cytotoxic T cells (IFNgamma, TNFalpha)
what do Th2 cells do
provide costimulatory help to B cells (IL-4, IL-5, IL-10)
what regulates T cell differentiation
cytokine production
what is the role of cytotoxic T cells (CD8+)
recognise antigenic fragments presented on class I MHC, kill infected cells
what is TCR
similar structure and assembly as antibodies
associated with CD3 signalling chains and CD4/8
undergo thymic selection for self tolerance
no somatic hypermutation - ag affinity remains low
what is the major histocompatibility complex
human leukocyte antigens
two classes; MHC I and MHC II
large number of different alleles, inherit 12 genes with no individual likely o be the same
what is MHC class I
recognised by CD8+ T cells
what is MHC class II
recognised by CD4+ T cells
what is antigen recognition
T cells only recognise a small fragment of antigen
it requires endocytosis, processing and presentation by APC in conjunction with MHC molecule; peptide fragments bind in groove of MHC; TCR binds across both peptide and MHC residues
CD4/8 bind MHC to prevent T cells killing APCs
what is positive T cell selection
if T cell does not recognise and bind MHC it is signalled to die by apoptosis
what is negative T cell selection
T cell binds strongly and is activated - signalled to die by apoptosis
where are T cells kept alive
in peripheral lymphoid organs by continual interaction with self peptide/MHC
they become activated when encountering foreign antigen presented on self MHC
what is co-stimulation
peripheral tolerance
T cells do not activate in response to an antigen alone, normal T cell activation required a second signal which is generated by co-stimulatory molecules
engagement of TcR signal without co-stimulation causes T cell to become unresponsive and probably undergoes apoptosis
what is the inihibitory signal in costimulation
CD28 expressed on resting T cells, B7-2 expressedon resting APCs
antigenic engagement of TCR leads to activation of CD28 by binding B7-2
folowed by upregulation of CTLA-4 and B7-1
engagement of these acts as inhibitory signal
what are TH1 effector responses
migrate to site of infection, release IFNgamma to activate macrophages, simulate production of monocytes in bone marrow, increase expression of adhesion molecules on endothelium, induce leukocyte migration via chemokine release
what are the TH2 effector responses
provides signal two to B cells
