lecture 13

Question 1

how are bacterial toxins in disseminated disease recognised?

Answer 1

this branch of the adaptive immune system requires B cells which make pathogen specific antibodies

Question 2

similarities between t cells and B cells

Answer 2

t cells develop in the thymus and the B cells develop in the bone marrow
both are derived from common lymphoid progenitor cells which are themselves derived from haemopoietic stem cells from the liver (foeutus) or the bone marrow (adults)

Question 3

difference between t cells and b cells recognising antigens

Answer 3

unlike t cells which recognises APC, B cells recognise their antigens as soluble proteins

soluble antigens are present in the blood or the lymph
B cell bcr recognises self antigen - no action is Taken
B cell bcr recognises no antigen - no action is Taken
B cell bcr recognises non self antigen - activation, mitosis and clonal expansion of specific B cells occur

Question 4

what can the activated B cells differentiate into?

Answer 4

activated B cells differentiate into antibody secreting effectors
the resting B cell has membrane bound antibodies that constitutes the b-cell receptor
the effector B cell (plasma cell) has a massive increase in er , which allows the secretion of 5000 antibodies per second

Question 5

describe the structure of the antibody

Answer 5

it has 4 polypeptide chains 2 identical heavy chains and 2 identical light chains, held together by covalent disulfide bonds at the hinge and between h and L chains

the central domains of the heavy chain tails are pushed apart by glycans (big sugars)

Question 6

describe the antibody-antigen interactions

Answer 6

1 intergenic determinant – 1 antibody tetramer can bind two identical antigens

2 identical antigenic determinants – if an antigen has two identical antigenic determinants, the antibodies can cross-link the antigens,making small cyclic complexes or linear complexes

3 or more identical antigenic determinants – with more antigenic determinants expressed on antigens, antibody cross linking can generate large three-dimensional lattices

3 or more different antigenic determinants – if multiple antigenic determinants are available, antibodies with different specificaty can cooperate

Question 7

how does the ability to cross-link antigens allow B cells to trap viruses?

Answer 7

the ability to cross-link antigens coupled with a flexible hinge region that allows different spatial geometries of antigen binding –> means that soluble antigens and viruses can be trapped in large cross-linked networks that often precipitate

this also makes it easier for phagocytic cells to engulf them all at once

these large networks make it easier for phagocytes to engulf pathogens or soluble antigens, which can then be degraded and represented to t-cells, amplifying the immune response

and this shows the interaction between innate and adaptive arms

Question 8

classes if antibodies (5)

Answer 8

the collective name for antibodies is immunoglobulin IG
mammals usually make five classes of IG distinguished by their heavy chains

IgM - mew heavy chain
IgD - delta heavy chain
IgG - gamma heavy chain
IgA - alpha heavy chain
IgE - epson heavy chain

Question 9

some oddities

Answer 9

some mammals from the camel family make unusual antibodies where about 50% of their antibodies have heavy chains that cannot take a light chain partner

sharks make IGM antibodies but also make heavy chain antibodies that can not accept a light chain

invertebrates do not make antibodies

Question 10

IgM (the most primitive Ig)

Answer 10

it is a pentamere of the basic tetrameric unit
held together by a J joining chain
it is thought to aid polymerisation of the complex
it’s valency is 10 and it is an efficient crosslinker

it’s the first antibody that a b cell makes
then the IGM shifts and turns into the other types
overtime many b cells will switch to making other immunoglobulin molecules
but these new antibody forms will retain the same specificity as the original IGM

in a pre-B cell in the bone marrow, IGM are membrane-bound and form b cell receptors

Question 11

similarities between IgM and IgD

Answer 11

IGM and IGD are both bcr - but IGM can be secreted
an immature naive B cell in bone marrow expresses surface IGM
as it migrates to a lymphoid tissue it also expresses membrane-bound IGD
as a response to an antigen, helper t cells go through clonal expansion and differentiation
then the plasma cells start secreting IGM

Question 12

regards IGD as a…

Answer 12

regards igd as a developmental marker because it tells the body how far down a developmental pathway a B cell has gone

Question 13

how does an IGM activate complement proteins?

Answer 13

the IGM has 10 binding sites and makes crosslinks and contacts with the pathogen surface
it binds to the target and activates complement proteins via two pathways:
- lectin pathway where lectin is any protein that will bind to a sugar
- classical pathway that is activated by the tails of IGM
( - alternative pathway)

these pathways cleave and activate C until they reach C3
C3 is cleaved into c3b and c3a
c3b binds to the membraneand acts as a nucleation point for a further enzymatic cascade that will end in a c9 pore. it doesn’t have to attach to the pathogen membrane it’s can also attached to the IGM
c3a calls for help

Question 14

why is IGM very efficient at activating complements?

Answer 14

phagocytic cells do not have a receptor for IGM so they do not recognise pathogens / antigens cross-linked or coated with IGM

so IGM acts alone which is ineffective in assisting phagocytosis
but it is very efficient at activating complements and so is considered an opsonin (a molecule that targets antigens for phagocytosis like complements)
opsonisation is the process of coating a target with IGM or other antibodies
IGM molecules of the humoral arm of the adaptive system interact with the innate immune system (directing complement for direct killing or making antigens with complement for phagocytosis)

Question 15

IgM secreting B cells (plasma cells) switch to IgG secretion.
what are similarities even after switching, and what are the functions of IgG?

Answer 15

Some IgM making cells switch to making IgG which maintains the same binding specificity
IgG has the standard tetrameric structure (2H chains and 2L chains)
IgG has 4 different subclasses IgG1-IgG4

FUNCTIONS
toxin neutralisation, binding to microorganisms, opsonisation by coating a pathogen and by activating complement, leading to phagocytosis and provision of passive immunity to foetuses and newborns

Question 16

which immunoglobulin can cross the placenta?

Answer 16

Only IgG can cross the placenta (IgG2 is the poorest at this)
Placental cells have Fc receptors for IgG (they bind to the Fc tail region of IgG)

Question 17

what is transcytosis? what is natural passive immunity?

Answer 17

after the binding of placenta cells to Fc of IgG, the IgG is secreted into the mother’s milk, taken up by neonate’s gut, into neonatal blood by TRANSCYTOSIS
so some IgG sub-classes provide passive immunity to the developing foetus and to newborns

Question 18

how is IgG an opsonin as well?

Answer 18

IgG can bind and coat pathogens.
phagocytotic cells (macrophages) have receptors (Fc) that recognise and bind the tail region Fc of IgG antibodies
the result is the stimulation of phagocytosis.

Question 19

IgM secreting plasma cells can switch to IgA secretion. describe the IgA structure and its role.

Answer 19

IgA is a dimer of 2 tetrameric structures held together by a J chain and an S chain (joining and secretory chains), which allows secretion into saliva / tears / milk / mucus

after switching, the IgS has the same binding specificity as the IgM

IgA protects our mucosal surfaces (genital tracts, respiratory tracts and alimentary canal) from pathogen attack
Newborns also passively benefit from IgA

Question 20

IgM secreting plasma cells can switch to IgE secretion

Answer 20

IgE has the standard tetrameric structure (2H, 2L). after switching, the IgE has the same binding specificity as the IgM

IgE binds Fc receptors on mast cells in tissues / basophils in blood / eosinophils

Then, they act as passive receptors for the antigens to which the original clonal expansion took place

Question 21

IgE triggers mast cell / basophil de-granulation.

Answer 21

Mast cells and basophils have a secretory vesicles that contain histamine
when the IgE binds the the Fc receptors on a mast cell’s membrane, an antigen can now bind to them and cause the release of histamine by exocytosis
Histamine stimulate inflammation and blood vessel dilation
(uncontrolled IgE reactions cause hay fever and asthma)

Question 22

IgE also acts as receptors for eosinophils. explain how

Answer 22

Eosinophils are the ones that work in gangs on cells
the pathogen cell has to be opsonised/coated with complement OR the eosinophils have to use IgE as a passively required receptor for the eosinophils to recognise it and collectively kill it

Question 23

what do IgE-specific Fc receptors allow?

Answer 23

IgE-specific Fc receptors (on mast cells, basophils or eosinophils) allow these cells to be targeted to different antigens/pathogens

the antibody arm of the adaptive immune system can direct parts of the innate immune system, as and when required.