Lymphocyte receptors, B cells and antibodies

Question 1

T cell structure

Answer 1

-T cell receptor is heterodimer
-Alpha and Beta chain
-One binding site for antigen

Question 2

B cell structure

Answer 2

-B cell receptor is an antibody
-2 identical heavy chains and 2 identical light chains
-2 antigen binding sites for antigen

Question 3

Memory in adaptive immunity

Answer 3

-Same principle for B cells and T cells
-Higher frequency of specific cells
-Respond more rapidly
-Memory only in adaptive immunity

Question 4

Timeframe of Innate vs Adaptive immunity

Answer 4

Innate: Minutes to hours

Adaptive:
-First exposure (primary response) 12 days
-Booster (secondary response) 5-7 days

Question 5

Constant vs Variable region in T cells and B cells

Answer 5

Question 6

What 3 parts make up the variable region of the heavy chain

Answer 6

-Variable
-Diversity
-Joining

Question 7

How many combinations of the antibody heavy chain?

Answer 7

Question 8

What 2 parts make up the variable region of the light chain

Answer 8

-Variable
-Joining

Question 9

What is junctional diversity

Answer 9

-Joining of the 3 regions in heavy chains and 2 regions in light chains is not precise
-Nucleotides are added and removed from junctions during rearrangement
-This adds further diversity

Question 10

Where does B cell and T cell development and gene rearrangement occur?

Answer 10

-B cell development with gene rearrangement - bone marrow
-T cell development with gene rearrangement - thymus

Question 11

What are the 2 main types of T cells

Answer 11

Cytotoxic T cell
-Differentiate to secrete cytotoxic granules

Helper T cell
-Differentiate to produce different sets of cytokines

-None of these pathways involve the T cell receptor beyond recognition of antigen

Question 12

What happens when B cells recognises antigen

Answer 12

-It differentiates to become antibody producing plasma cell
-Plasma cell secretes antibody that has same specificity expressed by B cell
-B cell receptor ultimately becomes effector molecule

Question 13

Antibody (immunoglobulin) structure

Answer 13

-2 identical light chains (Kappa or Lambda)
-2 identical heavy chains
-Variable regions determine specificity
-Constant regions of the heavy chain determine if antibody is IgA, IgD, IgE… and therefore determines function

Question 14

Antibody terminology

Answer 14

-IgA, IgD, IgE are
referred to as classes/isotypes
-The classes are defined by the constant regions of
their heavy chains
-IgG1, IgG2, IgG3 and IgA1, IgA2 are subclasses
-The subclasses are coded by
different constant region gene

Question 15

Fc receptors

Answer 15

-Some cells such as macrophages have Fc receptors that can bind antibodies
-Fc = the paired constant region
segments

Question 16

How do antibodies bind antigens

Answer 16

-Through the tip of variable regions
-Lock and key, electrostatic, hydrostatic
-Antibody must stick to antigen on the surface of the pathogen

Question 17

General functions of antibodies

Answer 17

-Neutralise toxins and viruses by binding to them and blocking their interaction with other cells
-Opsonise pathogens by binding to them to promote phagocytosis and killing activity by other cells by recognition of Fc receptors
-Activate the complement cascade which helps kill pathogens
-Agglutinates particles (pathogen debris, viruses etc)

Question 18

What is the main serum antibody?

Answer 18

IgG
-Measurement of antibody titre in
serum in response to vaccine is often a measurement of specific
IgG

Question 19

Features of IgG antibody

Answer 19

-Good at opsonisation - coating pathogens so
that phagocytic cells can recognise them
-Pathogens coated in IgG also become targets for
killing by NK cells - antibodydependent cellular cytotoxicity
-4 subclasses of IgG (IgG1,IgG2,IgG3,IgG4 - descending concentration in serum)

Question 20

IgA structure

Answer 20

2 IgA monomers join by a joining J chain to form a dimer

Question 21

How does dimeric IgA regulate bacteria in the gut?

Answer 21

-IgA has 4 binding sites so can agglutinate and neutralise bacteria
-Secretory component part of secreted IgA binds well to mucus, retaining antigens on mucus surface, preventing damage

Question 22

What is the first antibody made in immune response?

Answer 22

IgM
-pentameric structure
-10 possible binding sites gives it high avidity - ability of whole molecule to bind rather than 1 binding site
-Can agglutinate pathogens effectively

Question 23

Which antibody is responsible for allergies

Answer 23

-Individuals with allergies have higher concentrations of IgE in serum
-Mast cell has receptors for IgE

Question 24

Features of IgD

Answer 24

-IgD isn’t considered to be a secreted antibody
-Very little IgD in serum
-However, IgM and IgD with the same specificity are expressed on the surface of newly formed B cells

Question 25

What is affinity maturation

Answer 25

-Affinity maturation is the process of improving a cell's specificity for an antigen -Only B cells can undergo affinity maturation

Question 26

Refinement of antibody specificity after meeting antigen

Answer 26

-Lymphocytes constantly recirculate through blood and lymphoid tissues -Secondary lymphoid tissues contain zones of dividing B cells called germinal centres -If B cells encounter specific antigen and they have help from T cells they can enter germinal centres of dividing B cells -B cells in the germinal centre start to divide very rapidly and MUTATE their immunoglobulin variable region genes by somatic hypermutation -High affinity variants are SELECTED in the germinal centre -Somatic hypermutation then selection = AFFINITY MATURATION -B cells can also class switch in germinal centres, so they express isotypes other than IgM and IgD

Question 27

What 2 types of B cell leave the germinal centre?

Answer 27

-Quiescent circulating memory B cells => Affinity matured and possibly class switched -Plasma cells local to bone marrow or intestine =>Bone marrow plasma cells can secrete protective antibodies for a lifetime

Question 28

Primary (initial) vs Secondary (booster) antibody responses

Answer 28

Question 29

What are monoclonal antibodies?

Answer 29

-Powerful laboratory reagents and biological therapeutics -Used to treat autoimmune diseases (rheumatoid arthritis) and inflammatory diseases (Crohn’s, cancer)

Question 30

How were monoclonal antibodies first made and why did this change?

Answer 30

-Monoclonal antibodies were first made using mouse B cells -Mouse monoclonal antibodies are powerful reagents for research and diagnosis -However, mouse monoclonal antibodies don't make good therapeutics because the mouse protein is seen as a foreign antigen -An immune response is generated against it

Question 31

Chimeric antibodies

Answer 31

-A chimeric antibody is one where the mouse monoclonal is engineered so that the mouse variable region of heavy and light chains are associated with human constant regions -Chimeric antibodies have the ending –ximab -E.g. Rituximab - an antibody to CD20. CD20 is expressed by B cells -Rituximab targets B cells for killing and removes them from circulation and lymphoid tissues -Rituximab is effective against B cell lymphomas and some autoimmune diseases (rheumatoid arthritis)

Question 32

Humanised monoclonal antibodies

Answer 32

-A monoclonal antibody can be ‘humanised’ so that only the parts of the variable region that contact antigen are from the mouse -Humanised antibodies have the ending –zumab -E.g. Omalizumab -Omalizumab is specific for IgE and can be used to treat moderate to severe allergic asthma

Question 33

Human monoclonal antibodies

Answer 33

-Monoclonal antibodies can be fully human -Human monoclonal antibodies have the ending -umab -E.g.g Adalimumab is specific for TNFa and is used to treat inflammatory diseases

Question 34

ABO system - antigens and antibodies

Answer 34

-Group O - can only receive O, universal donor -Group A - can donate A, AB -Group B - can donate B, AB -Group AB - universal recipient, can only donate to AB

Question 35

Rhesus

Answer 35

-Mother who is Rh- has IgG antibodies to Rh following exposure to Rh antigen from a first pregnancy -Cross placental transfer of IgG targeting rhesus antigen from mother to foetus causes red blood cell lysis in the foetus and haemolytic disease of the newborn