B and T cell immunity

Question 1

Where do B cells develop?

Answer 1

In the bone marrow from the haematopoietic stem cell precursor, They receive signals to proliferate into a pro-B cells, then a pre-B cell to form a mature B cell in the bone marrow. B cells remain in the bone marrow or move into the peripheral tissue.

Question 2

Where are memory B cells found?

Answer 2

In the lymphoid organs, such as the spleen. They act as a defence against reinfection.

Question 3

What are antibodies?

Answer 3

B cells produce immunogoblins proteins called antibodies which act as a receptor for antigens. They are soluble recognition factors for a high level of molecular detail for pathogens. They are found in the plasma.

Question 4

What is the function of antibodies?

Answer 4

Antibodies are responsible for directing phagocytes, clearing microbes, mediating the allergic response and the cause of autoimmune disease against self cells.

Question 5

What is valency?

Answer 5

Valency is the number of epitopes (binding sites) that the antibody has for an antigen.

Question 6

What are the antibody isotypes?

Answer 6

There are five classes of immunogoblin antibodies: IgA, IgM, IgG, IgD and IgE.

Question 7

What are the most polymorphic antibodies?

Answer 7

IgG and IgA. They vary greatly between individuals and the variances are called allotypes.

Question 8

What are the classes of IgG?

Answer 8

It has 4 subclasses which have variances numbered based on abundance in the plasma/serum. IgG1, IgG2, IgG3 and IgG4.

Question 9

What are the classes of IgA?

Answer 9

It has two classes: IgA1 and IgA2 which differentiate due to the extensive hinge region present in IgA1.

Question 10

What is the function of IgG?

Answer 10

It has the same basic function of immunogoblins for enhancing phagocytosis, clearing microbes but it specifically activates the complement cascade.

Question 11

What is the structure of antibodies?

Answer 11

It has four polypeptide chains: two heavy and two light chains. Divided into a constant region for recognition by phagocytes which has a transmembrane portion and variable region for antigen binding

Question 12

What is the Fab region?

Answer 12

Part of the variable region for antigen specificity binding site.

Question 13

What is the Fc region?

Answer 13

Part of the constant region for binding to other cells such as phagocytes. Acts as transmembrane portion for antibodies

Question 14

What are the regions of the light chain?

Answer 14

VL (variable light chain) and CL (constant light region)

Question 15

What are the regions of the heavy chain?

Answer 15

VH (variable heavy chain) and CY 1( constant heavy region 1), CY2 (Constant heavy 2) and CY 3 ( constnat heavy 3)

Question 16

What are the features and roles of IgG antibodies?

Answer 16

Cryoelectron tomography reveals the flexibility of IgG due to its hinge region which vary in each subclass for antigen recognition. It is responsible uniquely for activating the complement cascade.

Question 17

How are antibodies synthesised?

Answer 17

1) Germline diversity
2) Somatic recombination of genes which is split into combinatorial diversity and junctional diversity
Following antigen contact and clonal selection, somatic hypermutation occurs

Question 18

What is germline diversity?

Answer 18

Variance between antibodies due to different variable domains inherited from the parents via germ cells.

Question 19

What is somatic recombination?

Answer 19

The combination of the gene segments V, D and J. V for the variable region in the heavy or light chain which determines subclass, D for diversity and J for the junction gene segment connecting V and D. Junctional diversity is the difference between the joining of the gene segments that occurs during the addition of nucleotides to the DNA sequence. This is responsible for the fixed specificity of B cells.

Question 20

How are the immunoglobin genes rearranged?

Answer 20

Somatic recombination which creates fixed specificity of B cells prior to antigen contact

Question 21

What is clonal selection?

Answer 21

During infection, antigen contact stimulates selection and binding of complementary T or B cells to the antigen depending on the epitope

Question 22

What is somatic hypermutation?

Answer 22

The point mutations introduced following antigen contact and binding of the lymphocyte in order to increase the antibody affinity for clonal differentiation. This uses the enzyme activated cytidine deaminase.

Question 23

How do mutations affect antibody affinity?

Answer 23

Somatic hypermutation aims to increase Ab affinity but may decrease or have no effect which can be identified by the clones produced during clonal differentiation.

Question 24

Where does somatic hypermutation take place?

Answer 24

In the germinal centres of the lymphoid tissues in the dark region.

Question 25

Where does clonal selection take place?

Answer 25

In the light regions of the germinal centre of lymphoid tissue.

Question 26

What is the difference between clonal selection and somatic hypermutation?

Answer 26

Clonal selection is finding the lymphocyte complementary to the antigen which binds. Somatic hypermutation is the introduction of point mutations using activated cytidine deaminase to increase antibody affinity for clonal differentiation. Both processes occur in different regions of the germinal centre in lymphoid tissue.

Question 27

What is the difference between somatic hypermutation and somatic recombination?

Answer 27

Somatic hypermutation is the introduction of point mutations using activated cytidine deaminase to increase antibody affinity for clonal differentiation following antigen contact. Somatic recombination occurs prior to antigen contact where the V, D and J segments inherited are rearranged to produce the antibodies with a fixed specificity.

Question 28

What is isotype switching?

Answer 28

Changing of classes such as IgG to IgA for a change of function.

Question 29

Where does isotype switching take place?

Answer 29

Germinal centre

Question 30

How to increase valency?

Answer 30

To increase the number of epitopes, multimerisation is effective for antibodies.

Question 31

Which antibodies have increased valency?

Answer 31

IgM which has a pentameric structure and IgA which has a dimeric structure.

Question 32

What is the function of secretory piece of IgA?

Answer 32

Allows it to cross the plasma membrane without damage to the mucosa.

Question 33

How does multimeric IgG interact with antigens?’

Answer 33

It binds to antigens on bacterial surface and increased valency allows increased affinity for C1q to bind and cleave C1r and C1s and associate with serine protease to form C1 complex for classical pathway immune response.

Question 34

How do Ig isotypes change during development and why?

Answer 34

Foetus receives maternal IgG, which drops as it synthesises its own IgM, IgG and IgA following birth.

Question 35

Which antibodies are the foetuses commonly in contact with?

Answer 35

IgE which lines the membranes, IgA within organs and IgM in the heart.

Question 36

How are antibodies involved in the complement pathway?

Answer 36

IgG is responsible for providing surface via the Fc region for C1q to bind and cleave C1r and C1s for the classical pathway initiation.

Question 37

What are Fc receptors?

Answer 37

Region below hinge in antibodies which allows antibody to interact with different antibodies or cells. It is part of the constant region and can initiate phagocytosis or allergic response through its interactions.

Question 38

How are cellular responses to antibodies mediated?

Answer 38

Binding to the Fc region

Question 39

Why is cellular recognition of FcR important?

Answer 39

For the effector to function such as phagocytic cells.

Question 40

How does a B cell produce a plasma cell?

Answer 40

Stimulated by cytokines, chemokines, follicular dendritic cells and CD4+ T helper cells.

Question 41

What is the role of follicular dendritic cells?

Answer 41

B cell activation to form a plasma cell producing antibodies. It is a stromal cell (which makes up connective tissue.)

Question 42

What is the origin of T cells?

Answer 42

Haematopoeitic stem cell precursor in the bone marrow which moves into peripheral tissue and enters the thymus. The progenitor produces thymocytes which bind to the epithelia in the cortex and are majorly negatively selected. The positively selected produce clones which undergo selection again in the medulla of the thymus before being released into peripheral tissue.

Question 43

What is the structure of a T cell?

Answer 43

Two polypeptide chains with an alpha and beta chain of similar molecular weight. it has a constant region and a variable region.

Question 44

How do B cells bind to antigens?

Answer 44

They have antibodies which bind to the conformational epitope of the antigen.

Question 45

What are conformational epitopes?

Answer 45

Discontinuous stretches of amino acid.

Question 46

How do T cells bind to antigens?

Answer 46

It has TCR receptor which binds to the linear epitope of antigens, which are antigen fragments that have undergone phagocytosis. MHC molecules present this on the surface for T cells.

Question 47

What are MHC molecules?

Answer 47

Peptide transporters which present antigen fragments on phagocyte surfaces for T cell activation.