B-cells, T cells and antibodies

Question 1

B cell function

Answer 1

Antibody production

Question 2

Antibody production

Answer 2

1. Endocytosis of antigen
2. Processing of antigen
3. Presentation of antigen to T cells

Question 3

B cells

Answer 3

• 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

Question 4

B cell activation and downregulation

Answer 4

1. B cell presents antigen to helper t cell
2. T cells presents CD40 ligand and releases cytokines
3. Both CD40 and cytokines bind to B cell activating it
4. B cell proliferates and differentiates

Complement coreceptor also enhances signal
Signal is downregulated by binding of Fc coreceptor

Question 5

Antibodies

Answer 5

Represents 20% of plasma protein and helps in specific recongnition of antigens

Target circulating microbes/toxins for phagocytosis

Question 6

Antibody structure

Answer 6

-Unit consists of two heavy chains and two light chains joined by disulphide bonds

Question 7

5 Types of antibody

Answer 7

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

Question 8

Physiological changes in B cells

Answer 8

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

Question 9

Antibody diversity

Answer 9

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

Question 10

Hypervariable regions

Answer 10

Variable regions on the end of heavy/light chains where antigens bind

Question 11

Specific antibody production process

Answer 11

1. B cells do irreversible genetic recombination during maturation that make it produce specific antibodies
2. Membrane bound IgM first forms then IgD
3. Antibodies bind antigens with weak affinity/high avidity
4. B cell activation leads to Ig class switching and somatic hypermutation
5. The bcells become plasma cells while some become memory cells

Question 12

Fc region

Answer 12

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

Question 13

Antibody uses

Answer 13

Lab detection of proteins

Diagnostic detection of antibodies in patient serum

Prevention/treatment of disease- vaccinations, antibody therapies

Question 14

Antibodies as blockers

Answer 14

Can bind to receptor or ligand to prevent binding/activation

used in anti TNF’s, anti VEGF and herceptin

Question 15

Challenges of antibody therapies

Answer 15

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

Question 16

T-cells

Answer 16

Removes infected cells

‘Helps’ activate B cells

Responds to antigens presented by dendritic (APC) cells

Question 17

Types of T cells

Answer 17

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

Question 18

TCR- T cell receptor

Answer 18

Similar to antibodies

No somatic hypermutation therefore low affinity

Binds across both peptide and MHC residues

Question 19

MHC- Major histocompatibilty complex

Answer 19

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

Question 20

Antigen recognition

Answer 20

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

Question 21

Thymic selection

Answer 21

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)

Question 22

How are t cells kept alive?

Answer 22

Continual interaction with self peptide/MHC

Activated only when encountering foreign antigen presented on self MHC

Question 23

Co-stimulation of T cells

Answer 23

Antigen presentation is not enough, on its own would cause t cells to die therefore needs co stimulation

Question 24

Co-stimulation process

Answer 24

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

Question 25

Effector responses of t cells

Answer 25

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

Question 26

Cytotoxic t cells

Answer 26

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