B-cells, T cells and antibodies Flashcards
B cell function
Antibody production
Antibody production
- Endocytosis of antigen
- Processing of antigen
- Presentation of antigen to T cells
B cells
- Mature in bone marrow and express IgD receptors
- Class switching and somatic hypermutation antibody affinity and function to improve antibody affinity and function
- Some remain even after antigen elimination as memory cell
B cell activation and downregulation
- B cell presents antigen to helper t cell
- T cells presents CD40 ligand and releases cytokines
- Both CD40 and cytokines bind to B cell activating it
- B cell proliferates and differentiates
Complement coreceptor also enhances signal
Signal is downregulated by binding of Fc coreceptor
Antibodies
Represents 20% of plasma protein and helps in specific recongnition of antigens
Target circulating microbes/toxins for phagocytosis
Antibody structure
-Unit consists of two heavy chains and two light chains joined by disulphide bonds
5 Types of antibody
IgM- iMMature antibodies
IgA- used against Airborne microbes found in epithelia/mucousa
IgE- Used in allergiEs and against helminths
IgD- a B cell surface receptor
IgG- used in General immunity, neonates
If many types of B cell are activated then polyclonal antibody response is found. If a single type of anitbody is activated then a monoclonal response occurs
Physiological changes in B cells
At resting B cell vol is mostly nucleus but when activated the amount of cytoplasm increases. Known as ‘blasting’
Activated B cells have more ER to increase production of antibodies
Antibody diversity
10^7 functional antibodies due to gene rearrangement
Multiple V,D and J alleles due to gene duplication
Conserved sections are joined when mRNA is made allowing for class switching
Hypervariable regions
Variable regions on the end of heavy/light chains where antigens bind
Specific antibody production process
- B cells do irreversible genetic recombination during maturation that make it produce specific antibodies
- Membrane bound IgM first forms then IgD
- Antibodies bind antigens with weak affinity/high avidity
- B cell activation leads to Ig class switching and somatic hypermutation
- The bcells become plasma cells while some become memory cells
Fc region
Mediates many effector functions of antibodies that vary with Ig class
IgG FcR binds to neutro and mac to stim phagocytosis
IgE FcR causes eosinophil activation and mast cell degranulation
IgM and IgG can trigger complement by binding to Cq1
Requires bound antigen to initiate crosslinking of antibodies
Antibody uses
Lab detection of proteins
Diagnostic detection of antibodies in patient serum
Prevention/treatment of disease- vaccinations, antibody therapies
Antibodies as blockers
Can bind to receptor or ligand to prevent binding/activation
used in anti TNF’s, anti VEGF and herceptin
Challenges of antibody therapies
quick but expensive to produce
can only be given pareneterally as it is a protien
resistance as a result of mutations are common
Is a type of immunotherapy hence anaphylactic shock is a major issue
Treatments decrease in effectiveness over time
T-cells
Removes infected cells
‘Helps’ activate B cells
Responds to antigens presented by dendritic (APC) cells
Types of T cells
Helper T cells- recognises antigens presented by MHC
Th1- Activates macrophages and cytotoxic T cells
Th2- provides cosimulatory help to B cells
Cytotoxic t cells (CD8+) recognise class 1 MHC antigens and kill infected cells
Differentiation controlled by cytokine production
TCR- T cell receptor
Similar to antibodies
No somatic hypermutation therefore low affinity
Binds across both peptide and MHC residues
MHC- Major histocompatibilty complex
Human antigens
Class 1 recognised by cytotoxic cells
class 2 recognised by helper t cells
Defines the self antigens and inherits 12 genes with many alleles therefore unlikely that any one individual is the same
Antigen recognition
T cells only recognise a small part of the antigen and requires endocytosis and processing of antigens with MHC’s
Peptides bind in the groove of MHC’s and TCR binds across both of them
T cells bind to MHC to prevent them from dendritic cells
Thymic selection
T cells encounter self antigen on self MHC on thymic epithelial cells
if it does not recognise and bind MHC then apoptosis occurs-known as positive selection (primary response)
if it binds strongly and is activated then apoptosis occurs- known as negative selection (secondary response)
How are t cells kept alive?
Continual interaction with self peptide/MHC
Activated only when encountering foreign antigen presented on self MHC
Co-stimulation of T cells
Antigen presentation is not enough, on its own would cause t cells to die therefore needs co stimulation
Co-stimulation process
Resting t cell presents CD28 and resting APCs present B7-2
TCR binding causes CD28 to become active and bind to B7-2
Causes upregulation of CTLA-4 and B7-1
These acts act as an inhibitory signal
Effector responses of t cells
TH1- goes to site of infection
activates macrophages with IFNalpha
releases chemokines to induce leucocytes
stimulates production of monocytes in bone marrow
TH2- Provides signal to B cells
Cytotoxic t cells
2 types
Perforin dependant- releases perforin to open channel allowing in caspase to wreck the fucking microbe
Fas dependant- fas trimer ligand activates inactive pro-caspase within microbe to activate and then shit hits the fan
