Week 2: B and T cell Mediated Immunity

Question 1

What is an immunoglobulin?

Answer 1

They function as the B lymphocyte receptor for antigen
Soluble recognition molecules secreted by B lymphocytes
High capacity for recognizing fine molecular detail

Question 2

What are important functions of Immunoglobulins?

Answer 2

Directly kill or neutralize microbes
Help target phagocytes to microbes
Regulation of Immune responses (indirectly)
clearance of antigens and termination of immune response

Question 3

What happens if antibodies recognize host proteins or host cells (immunopathologies)?

Answer 3

They mediate allergic responses
Cause immune complex diseases
Mediate autoimmune cell destruction

Question 4

What are the 5 main classes(isotypes) of antibody?

Answer 4

IgA, IgD, IgE, IgG, IgM

Question 5

How do classes of antibody differ?

Answer 5

They differ in valency and function

Question 6

What are the 4 subclasses of IgG?

Answer 6

IgG1, IgG2, IgG3, IgG4,
Decreasing order of abundance in serum ie) IgG1 > IgG2

Question 7

What are the 2 subclasses of IgA?

Answer 7

IgA1> IgGA2

Question 8

What are polymorphic variants of IgG and IgA antibodies referred to as?

Answer 8

allotypes
An allotype would be a good way of distinguishing between antibodies in different individuals.

Question 9

How can subclasses of IgG antibodies differ?

Answer 9

They can have same valency but different function.

Question 10

What are domains in antibodies?

Answer 10

Within the light and heavy chains of the antibodies, there are structural regions of the molecule with a particular function

Question 11

What is an antigen?

Answer 11

Any molecule that can be recognized by an antibody and doesn’t need to be immunogenic

Question 12

What is an epitope?

Answer 12

The portion of the antigen which is recognised specifically at a molecular level by the antigen binding site

Question 13

What is the antigen binding site described as being due to involvement of both light and heavy chains?

Answer 13

combinatorial

Question 14

Affinity

Answer 14

The ability of one binding site to interact with each ligand

Question 15

Avidity

Answer 15

The combined ability/ strength of having multiple binding sites to a specific epitope

Question 16

What is the purpose of the constant chain?

Answer 16

They are important for determining the function of the antibody.

Question 17

Basic structure of antibody

Answer 17

Question 18

What are the further nomenclature in antibodies?

Answer 18

Fab = Fragment antigen binding - the 4 domains of the terminal part of the heavy chain and the light chain
Fc- Fragment crystalizable - termnial portions of the heavy chain -binding site for receptors on other cells
VL - variable light
CL - Control light
cy1 = constant gamma 1 , etc

Question 19

What does the hinge in antibodies help with?

Answer 19

Flexibility

Question 20

How are antibodies of infinitely different specificities created?

Answer 20

Antibody molecule is encoded by multiple gene segments

1) Germ line diversity of genes
2) Combinatorial diversity
3) Junctional Diversity

Question 21

What is somatic recombination?

Answer 21

It is the rearrangement of DNA where gene segments can be put together in different ways to generate proteins with different structures using the processes of combinatorial diversity and junctional diversity.

Question 22

What chromosome is the genes for heavy and light chains found on?

Answer 22

Heavy - Ch14

Kappa Light - Ch2

Lambda Light - Ch22

Question 23

What is somatic hypermutation?

Answer 23

When the B cells increase their affinity of antibodies over time of an immune response by affinity maturation using the enzyme AID,

Question 24

Basic principle of somatic recombination?

Answer 24

The unwanted DNA is excised out of the gene and the desired genes are “glued together”

Each B cell undergoes this during maturation independently of all other B cells.

Recombination only occurs once in the life of a B cell so each B cell has specificity

Question 25

What happens if you have enzyme defects that are responsible for somatic recombination?

Answer 25

You cannot recombine your antibody molecules and B cell maturation cannot be completed an therefore have primary immunodifficiemcy diseases

Question 26

Stages of Clonal selection of b cells

Answer 26

Proliferation and diversification of Progeny cells (specificity)

Antigen binds to specific B cell

Proliferation and Differentiation of B cell (amplification)

Somatic Hypermutation acts after

Question 27

How does somatic hypermutation work?

Answer 27

It introduces random changes into the antibody binding site

Activation induced cytidine deaminase (AID) directs replacement mutations

Sequences in the antibody binding site accumulates point mutations

Mutations can increase, decrease or not change Ab affinity

Selection mechanism for higher affinity clones is called affinity maturation

Question 28

Where does somatic hypermutation take place?

Answer 28

Germinal centres in lymphoid tissue

Light zone = site for selection of high-affinity clones

Dark Zone = site for somatic hypermutation

Question 29

Recognise that different classes and subclasses of immunogloblins have different functions

Answer 29

Question 30

Isotype switching (class switching recombination) allows for what

Answer 30

change of function but specificity stays the same that was developed during antibody maturation

Question 31

IgA and IgM have increased valency through …..

Answer 31

multi-merisation

*valency changes but same specificity

Question 32

What is the structure of IgM and its valency?

Answer 32

pentameric structure and valency of 10

Question 33

Structure of IgA and valency?

Answer 33

Dimeric structure and valency of 4

Question 34

multimeric IgM has increased capacity to interact with….

Answer 34

complement

A multimeric IgM means that a C1q molecule can cross link all of its components on the same antibody molecule and become activated whereas with a non multimeric antibody only some of the C1q molecule components can cross link and becomes less activated so a multimeric IgM increases the efficiency of activation of complement and increased avidity for actual surface.

Question 35

Ig Isotypes have differential tissue distribution

Answer 35

Question 36

Revise complement with classical and alternative pathway

Question 37

Where do T cells come from?

Answer 37

Derived from bone marrow derived hematopoietic stems cells that migrate to thymus

98% of t cells die in thymus by positive and negative selection

only T cells with TCR able to recognise foreign peptides bound by MHC escape to periphery

Question 38

Structural similarity between t cell and b cell receptors

Answer 38

Question 39

How do T cells recognise antigens differently to B cells?

Answer 39

B cells use Ab to recognize conformational epitopes or tertiary structure. Conformational epitopes can be made up from discontinuous stretches of AAs.

T cells use TCR to recognize linear epitopes enzymatically digested out of antigens (“antigen processing”).

Question 40

What are MHC molecules?

Answer 40

Major Histocompatibility complex molecules are very specialized peptide transporters that transfer pepides/antigen pieces from the phagosome to the cell surface so T cell receptors can bind to them.

Question 41

Structure of class 1 and 2

Answer 41

class 1

Made of single heavy chain with 3 domains bound to accessory protein called Beta 2 microgloblin

class 2

Made up of 2 polypeptide chain each with 2 domains with each chain being alpha and beta

Question 42

What is the effect of MHC molecules being highly polymorphic peptide transporters?

Answer 42

Shape of transporter is different in everyone so picks up slightly different peptides but should be able to pick up some peptides from antigen that is digested

Question 43

Difference between MHC class 1 and class 2 molecules?

Answer 43