Antibodies

Question 1

How are antibodies produced ?

Answer 1

By B lymphocytes

Question 2

How are lymphocytes produced ?

Answer 2

Lymphocytes arise from stem cells in bone marrow and differentiate into B cells in bone marrow and T cells in the thymus.

Question 3

Describe naive B cells

Answer 3

These are B cells that have not met antigen, and circulate from the blood into peripheral lymphoid tissues.

Question 4

Function of Peripheral lymphoid tissues

Answer 4

Main site of antigen encounter

Question 5

Function of lymphatics

Answer 5

Drain tissues of fluid, through the lymph nodes and into the thoracic duct.

Recirculating B cells enter back into the bloodstream by the thoracic duct.

Question 6

State the main sites of B cells in the body

Answer 6

Spleen
Lymph nodes

Question 7

Lymph node organisation

Answer 7

Material draining from the site of infection passes through some regions of B/T cells and varieties of antigen presenting cells.

Question 8

Germinal centre

Answer 8

Accumulation of clonal B cells, which are expanding rapidly in response to an infection.

Question 9

Describe the spleen

Answer 9

Site of B cells

Has :

• Red pulp
• White pulp

Question 10

Red pulp

Answer 10

Site of RBC destruction

Question 11

White pulp

Answer 11

Lymphoid

Question 12

Spleen organisation

Where is antigen coming from ?

Answer 12

Antigen is coming through the bloodstream, not the lymphatics (like the lymph nodes)

Question 13

Describe Secondary response

Answer 13

Secondary (memory) response is :

• faster
• can produce more antibody
• does not prevent you from making a response to another antigen.

(multiple antiegns - vaccination)

Question 14

Function of B cells

Answer 14

Form part of the ADAPTIVE immune response, the key features of which are antigen specificity, and memory.

Question 15

Describe some basic features of antibodies

How can they be expressed ?

Answer 15

They can be expressed as membrane bound (B cell receptor)

OR

secreted forms

Question 16

Describe a key feature of B cell antibodies

Answer 16

B cells express a single Ab specificity only

Question 17

State the functions of antibodies (Ab)

Answer 17

1. Bind to the pathogen that elicited its production
2. To recruit other cells and molecules that will lead to clearance or destruction of the pathogen.

Question 18

Describe the structure of antibodies

Answer 18

4 polypeptide chains :

• 2 identical heavy chains
• 2 identical light chains

Question 19

Describe the heavy chains of antibodies

Answer 19

Disulphide bonded to each other
Each H chain is also disulphide bonded to an L chain

Question 20

Describe the light chains of antibodies

Answer 20

2 Light chains exist as lambda and kappa
(either lambda or kappa, never a mix)

In humans ratio is 2:1 in favour of kappa

Question 21

Function of the 2 identical heavy and light chains

Answer 21

Results in 2 identical binding sites

Question 22

Function of the constant region of antibodies

Answer 22

Activates the complement pathway

OR

Can assist with processes like phagocytosis

Question 23

Fab region of antibodies

Answer 23

Contains the binding site for the antigen

Question 24

Function of Fab and F(ab)2 fragments

Answer 24

Very useful tools in the lab, ie.e can be used to label cells without inducing the effects of the Fc region.

Question 25

How are the Fab and F(ab)2 fragments removed

Answer 25

Fab - by papaln F(ab)2 - by pepsin

Question 26

Describe how antigens have specificity

Answer 26

3 hyper-variable loops determine antigen specificity by forming a surface complimentary to the antigens. Final specificity is determined by a combination of loops from H and L chains, not either alone.

Question 27

Germline Theory

Answer 27

Suggested that a separate gene existed for each Ab, which was not really the case.

Question 28

Somatic Diversification Theory

Answer 28

Proposed that repertoire is generated from a limited number of V region genes that undergo alteration. Essentially correct.

Question 29

Chromosomal Rearrangement

Answer 29

The sequence of a V region is generated by the somatic recombination of separate gene segments

Question 30

What are V region genes constructed from ?

Answer 30

Constructed from multiple gene segments.

Question 31

Junctional Diversity

Answer 31

Errors in DNA replication Completely random insertion of bits of DNA/nucleotides to make up a fresh DNA. New loop at the front of antibody CREATES EXTRA VARIABILITY

Question 32

Name the main methods by which you generate antibody diversity EXAM Q

Answer 32

1. Rearranging multiple gene segments 2. Junctional diversity 3. Different combinations of H and L chains 4. Somatic Hypermutation

Question 33

When do methods to generate antibody diversity occur ?

Answer 33

During B cell development (happens in bone marrow)

Question 34

Somatic Hypermutation

Answer 34

Occurs after B cells have become antigen activated in the lymph node. Accumulation of random mutations

Question 35

State the 5 classes of antibodies and what they are defined by

Answer 35

Defined by the heavy chain IgG IgM IgD IgA IgE

Question 36

IgE

Answer 36

Sticks on mast cells and causes the allergic responses. Sequestered away on mast cells.

Question 37

IgA

Answer 37

Present in secretions, tears and saliva Good at being transported across epithelium to get into saliva and tears.

Question 38

IgD

Answer 38

The first B cells that come out of the bone marrow tend to always have IgD

Question 39

IgG

Answer 39

The most common antibody and most prevalent in the bloodstream.

Question 40

Describe IgG subclasses

Answer 40

IgG1 is the body common with up to 10mg per ml in blood. Note : If IgG is increased --> infection, IgG decreased --> deficiency in immune response

Question 41

Why is IgE concentration low in the blood ?

Answer 41

IgE which is very low, because as soon as you make it, it gets sucked out of the bloodstream and sits on muscle cells where its going to be doing its jobs.

Question 42

IgM

Answer 42

All B cells initially express a membrane form of IgM (also some IgD).

Question 43

Describe Antibody multimers

Answer 43

IgA - dimer in secretion IgM - pentamer in secretion

Question 44

What antibodies are dimers ?

Answer 44

IgA

Question 45

What antibodies are pentamers ?

Answer 45

IgM (can also be a monomer)

Question 46

Function of dimeric form of IgA

Answer 46

Enables it to get across an epithelial cell and secreted via a transport mechanism.

Question 47

Where is IgE found ?

Answer 47

Mostly near epithelial surfaces, especially gut, lungs and skin.

Question 48

Where are IgG and IgM found ?

Answer 48

Predominate in plasma

Question 49

Where are IgG and monomeric IgA found ?

Answer 49

MAin isotypes in extracellular fluid

Question 50

Where is dimeric IgA found ?

Answer 50

Secretions across epithelia, including breastmilk. Found in intestinal tract and respiratory tract.

Question 51

Brain

Answer 51

Normally free from antibodies, due to blood brain barrier

Question 52

Function of antibodies

Answer 52

Blocking binding to virus receptor

Question 53

Opsonisation

Answer 53

Enhances phagocytosis into cells for degradation

Question 54

What is high in autoimmune diseases ?

Answer 54

High levels of Antibody-Antigen complexes Ab-Ag complexes Major cause of glomerulonephritis

Question 55

Function of Ab-Ag complexes

Answer 55

Important mechanisms for clearing soluble antigens. Taken up by phagocytes.

Question 56

Monoclonal Antibodies

Answer 56

A powerful tool for research, diagnosis and maybe treatment. Antibodies of just one specificity. Grown in LAB.

Question 57

New Biologicals

Answer 57

Infliximab Herceptin Tocilizumab

Question 58

Infliximab

Answer 58

Anti-tumour necrosis factor (inflammatory mediators) Used in rheumatoid arthritis Psoriasis Ankylosing Spondylitis Inflammatory Bowel disease

Question 59

Herecptin

Answer 59

Anti HER2 Can block growth and lead to destruction of breast tumour cells that express high levels of HER2.

Question 60

Tocilizumab

Answer 60

Anti-interleukin 6 Used in Inflammatory conditions Covid-19