Week 6

Question 1

Innate immunity fundamental

Answer 1

Only a limited number of receptors for specific pathogen products (Toll-like receptors/NOD/RIG-I like helicases)
No specific memory generated
However, the innate response is immediate and does not require previous exposure to the pathogen for an effector response
Innate and adaptive immune systems work together to provide immunity

Question 2

The adaptive immune response

Answer 2

Allows exquisite recognition of wide range of varying pathogens
A memory population of cells is created that can respond more rapidly, specifically and efficiently to subsequent infections
The response to a primary infection is relatively slow (days)
Upon re exposure the adaptive response rapid and efficient (principle of vaccination)
Cells of the adaptive immune system recognise specific pathogen antigens
Antigens are molecules that induce an immune response through the activation of antigen specific lymphocytes
Many different structures can act as antigens
-proteins, DNA, lipids, carbohydrates

Question 3

The innate and adaptive immune responses

Answer 3

Do not occur in isolation
The adaptive response is highly dependent on activation of the innate response (eg activation dendritic cells that prime Naive T cells)

Question 4

Key differences between T and B cells

Answer 4

B cells recognise antigen in its native conformation
T cells recognise fragments of antigens- e.g. peptide sequences presented on major histocompatibility complexes

Question 5

Basic structure of antibody molecule

Answer 5

2 heavy chains and 2 light chains
Hinge region -flexibility allows for binding to antigen of different spacing
Antigen binding site on light chains
Hyper variable regions found at sites of antigen binding

Question 6

Response of B lymphocytes to antigen binding

Answer 6

Antigen recognition
Activation of B lymphocytes
Proliferation
Differentiation
Outcome: antibody secretion, isotype switching, affinity maturation, memory B cell
NB: some B cells can respond to repetitive antigens mounting a T cell independent response

Question 7

Antigens adaptive immune response

Answer 7

Cells of the adaptive immune system recognise specific antigens
Antigens are molecules that induce a immune response through activation of antigen specific lymphocytes
Many different structures can act as antigens
But for T cells this must be peptide (from protein) in the context of MHC (major histocompatibility complex)

Question 8

T cell receptor

Answer 8

Resembles a membrane bound FAB fragment
Expression on the surface of T lymphocytes

Question 9

CD8 and CD4 interact with class I and II MHC respectively

Answer 9

2 main classes of MHC:
-MHC class I: HLA, A, B &C
-MHC class II: HLA DR, DP &DQ
HLA= human leukocyte antigen, human version of MHC
CD8 T cells: very important for intracellular infections and viruses, they recognise peptide derived from protein produced within cell, MHC class I is bound with peptides from proteins produced in cell this is then presented to TCR of CD8 T cells, this is a way of dealing with pathogens that have invaded the cell eg viruses and intracellular cytoplasmic pathogens
CD4 T cells: these cells recognise peptides take from proteins outside cell form extracellular pathogen so MHC class II bound with peptides derived from proteins taken up by antigen processing cell, these are from extracellular pathogens or intracellular pathogens in vesicles. This is then presented to TCR of CD4 T cells

Question 10

MHC class I and II are expressed on different cell types

Answer 10

Most cells of body express MHC class I
The main reason for this is to do with NK cell recognition and differentiating self and non self
Only red cells dont express MHC class I
Antigen presenting cells that express MHC class II- when these cells are activated they upregulate class II on their surface enabling them to process and present more antigen to CD4 T cells
Class I and II can be up regulated by inflammatory cytokines (eg IFN gamma)

Question 11

Response of T lymphocytes to antigen binding

Answer 11

Antigen recognition
Lymphocyte activation
Proliferation
Differentiation
Effector functions: activation of macrophages, B cells and other cells; inflammation. Killing of infected cells; macrophage activation
Effector CD4 T cell and memory CD4 T cell
Effector CD8 T cell and memory CD8 T cell

Question 12

Diversity is generated by rearranging germline DNA of heavy and light/ alpha & beta chains

Answer 12

The germline coding for heavy and light chains/ alpha and beta chain variable regions contains multiple segments
These segments are called V, D, J segments
Mechanism:
-the V, D regions and J segments can rearrange this is called VDJ recombination
-this variation in the genes is then attached to constant domain
-this generates diversity
-this occurs as B and T cells develop
-the diversity of VDJ genes are on different chromosomes:
-heavy chain genes of antibody are on C15 and kapa and lambda light chain genes are on C22 and C2
-alpha and beta chains of T cell receptors are also on different chromosomes

Question 13

Order of gene rearrangement

Answer 13

B cells:
-the heavy chain rearranges its gene segments first and then the light chain rearranges their gene segments
-heavy chains have V,D,J segments
-light chains are either kappa or lambda- both have only V and J segments no D segments
T cells:
-beta chain rearrangement occurs first with V,D,J segments then light alpha chains rearrange their gene segments
-alpha chains also have only V and J segments no D segments
Therefore you have to have heavy/beta chain successful rearrangement before you get alpha/light chain rearrangement

Question 14

Generation of diversity

Answer 14

Diversity is primarily generated by the recombination of gene segments dependent on the activity of the recombinase activating genes RAG-1 and RAG-2
Further variability is introduced at the joining regions of each segment by an enzyme terminal deoxynucleotidyl transferase tdt.
For B cells somatic hypermutation will further increase diversity
Each cell expresses an antigen-specific receptor of a single specificity through a process of allelic exclusion

Question 15

Diversity of lymphocyte antigen receptor genes

Answer 15

Immunoglobin (B cells): heavy chains- IgM, IgA, IgD, IgE, IgG. Light chains- kappa k and lambda l
T cell receptors: TCR beta, TCR alpha, TCR gamma, TCR delta

Question 16

Generation of diversity: rearrangement of antigen receptor genes

Answer 16

Normally one gene encodes 1 mRNA which then goes on to produce 1 protein
The antigen receptor genes of lymphocytes do not behave like that
Antigen receptor genes are made up of various regions:
-variable V regions, diversity D regions, joining J regions, constant C regions
During T cell and B cells development the antigen receptor genes undergo rearrangement:
-the cell randomly choose a particular variable, diversity , joining and constant region from the ones present in the genome
-these are then joined to give a fully rearranged gene by ignoring part of the genome
-because these gene regions contain different nucleotides a distinct mRNA will be produced for the distinct rearranged gene
-therefore the antigen receptor protein will be distinct
-different cells make different choice-how diversity can be obtained
For the TCR-beta TCR-gamma and Ig heavy chain gene we have 4 components: variable, diversity, joining and constant
Whereas for TCR-alpha TCR-delta and Ig light chain we have 3 components; variable, joining and constant
However the process for their production remains the same

Question 17

Types of antigen receptors

Answer 17

Because rearrangement occurs randomly every lymphocyte expresses a different antigen receptor
But how do you avoid lymphocytes that will target your own body tissues causing autoimmune disease
The randomly generated fall into 3 categories:
the bad ones:
-these might recognise self antigens so may lead to an autoimmune disease need to get rid of these via negative selection process
The good ones:
-recognise foreign antigens e.g present on virus or bacteria
-we need to encourage the immune system to retain these through positive selection
The ugly ones:
-the useless ones that encode proteins that wont see antigens, no need to retain these in immune system so die by neglect

Question 18

B cell selection

Answer 18

For B cells negative selection of autoreactive B cells can occur in bone marrow
During development B cells in an immature stage (express surface immunoglobulin) are auditioned for self antigens on the stromal cells that make up bone marrow
These allow B cells to check specificity for self antigens
If there are no recognition of self antigens by this particular antigen-receptor complex the cell receives a survival signal so undergoes positive selection its then able to leave bone marrow and develop further
However if B cell recognises self antigen this could be harmful so cell is triggered to undergo deletion via apoptosis

Question 19

T cell selection

Answer 19

More complex than B cells
T cells cant see an antigen in the same way
B cells recognise self antigens in native form (dont need to be processed or presented)
T cells only recognise processed antigen fragments presented by MHC molecules of an antigen presenting cell

Question 20

T cell selection in the thymus

Answer 20

The good (positive selection): T cell receptors that will see foreign antigens undergo positive selection
The bad (negative selection): T cell receptors that will see self antigens need to be removed via negative selection as they can generate autoimmune responses
The ugly (death by neglect): T cell receptors that dont see anything at all die by neglect

Question 21

The anatomical compartmentalisation of T cell selection in the thymus

Answer 21

The thymus is divided into individual lobules
Each lobule has an outer cortex and a medulla
The cortex is responsible for driving positive selection
The medulla is responsible for destroying harmful cells by negative selection

Question 22

Stromal microenvironments in the thymus

Answer 22

The epithelial cells in medulla and cortex of the thymus are important for driving the T cell development process- they provide key signals
In the cortex:
-cortical epithelial cells
-cortico-medulla junction: blood vessels found at this junction allow progenitors at beginning of T cell development into the thymus and let mature T cells out and the end of development. Also have APC- dendritic cells sit here
In the medulla: medullary epithelial cells
T cell selection in cortex:
-set of developing T cells that express both CD4, CD8 at same time and express TCR at this time of a random specificity
-can the TCR bind to MHC: if yes undergo positive selection if no undergo death by neglect
T cell selection in medulla:
-do they bind MHC too strongly; if yes the immune cell is cautious and assumes these cells could cause autoimmune response so destroy via negative selection. If no no risk and cells mature further
-if cells recognise MCH class II then they become CD4 T cell switch off CD8 gene
-if cells recognise MHC class I become CD8 T cell switch off CD4 gene

Question 23

T cell tolerance

Answer 23

Central tolerance (thymus):
-this is where positive and negative selection in thymus eliminates self reactive cells. Not 100% efficient
Peripheral tolerance:
-multiple forms of tolerance that happen in peripheral tissue that help mop up problems with thymus not being 100% efficient
-ignorance
-Anergy- switching off cells not killing them
-cell death
-regulatory T cells: these type of T cell regulate and control autoreactive cells that escape from thymus

Question 24

Production of regulatory T cells

Answer 24

Regulatory T cells develop intra-thymically alongside CD4 and CD8 T cells
Goldilocks hypothesis:
-some T cells that have a strong interaction (negative selection) and others have a weak interaction (positive selection) with MHC
-regulatory T cells are those that fit in the middle of this MHC interaction
-if we think about recognition of MHC as being strength of T cell receptor signal we can say that:
- a very good fit will give you strong T cell receptor signal -> negative selection
-a weak T cell receptor signal> positive selection
- a moderate T cell receptor signal-> T regulatory cell selection

Question 25

Regulatory T cells

Answer 25

Subset of CD4 T cells so will recognise MHC class II
They also express:
-CD25 (IL2 receptor)
-transcription factor foxP3 (signature gene for regulatory T cells)
Regulatory T cells are here to help prevent self reactive T cells that have escaped negative selection in the thymus from generating auto immunity
How might they do this:
-might secrete cytokines that help prevent T cell from becoming activated (cytokine-mediated: IL-10, TGF-beta)
-competition for T cell growth factors e.g. IL-2 (this is where CD25 expression is relevant this suppresses autoreactive T cell responses)
-T reg can also regulate and suppress T cell response via contact dependent manner

Question 26

Tolerance to tissue-specific proteins: another function of the thymus

Answer 26

If all tolerance occurs in the thymus then how is tolerance to tissue-specific proteins achieved
E.g how does the thymus enable tolerance to insulin
- T1DM-self receive T cell response to beta cells in pancreas
The thymus is a site where all genes are being expressed at once
This is a very effective way for thymus to control tolerance
This mechanism is under control of AIRE (autoimmune regulator)

Question 27

Autoimmune regulator AIRE

Answer 27

AIRE is a transcription factor expressed by medullary thymic epithelial cells
AIRE allows thousands of genes to be expressed in thymus medulla through a process called ‘ promiscuous gene expression’ (it regulates this process)
This is so tolerance to proteins expressed in peripheral tissues can occur in thymus
Example:
-beta cells of the pancreas make insulin
-AIRE directs insulin expression in the thymus so that T cells developing that recognise insulin undergo negative selection
-this protects against diabetes as we are killing cells that would normally kill beta cells

Question 28

Autoimmune diseases caused by gene mutations that affect tolerance

Answer 28

FoxP3 deficiency in man:
-causes IPEX, deficiency in T-reg —> results in autoimmunity
AIRE deficiency in man:
-prevents pernicious gene expression in the thymus medulla which results in APECED—> Also results in autoimmunity
These are 2 of the commonest monoallelic autoimmune diseases in man

Question 29

When thymus function goes wrong

Answer 29

The cause of improper thymus function can be natural or genetic
Natural:
-aged related thymus atrophy:
— the thymus is not constant organ in life most thymic tissue is present when you’re a child when 40+ most replaced with fat we can tolerate this decline in thymus function as T cells have long life
Genetic :
-thymus aplasia
-FoxN1deficiency in man
-complete diGeorge syndrome (thymus fully absent)

Question 30

Thymic function influences the success of bone marrow transplantation

Answer 30

If we need bone marrow transplant for people with blood borne cancer eg leukaemia we first perform ablative therapy- wipe out immune system and cancer and start fresh by giving people new bone marrow progenitors
This can have limitations eg if provide bone marrow transplant to young people thymus function is still significant and so can still produce new T cells
However if we give bone marrow transplant to older people because their thymus is small cant process bone marrow into new T cells
Can combat this via thymus transplantation
The thymus tissue transplanted into quadricep femoris muscle, these fragments now reconstituted with bone marrow progenitors of infants
This allows us to improve immune system of babies with defective immune system and maybe with a similar approach increase efficiency of bone marrow transplantation in older patients

Question 31

Antibody specificity

Answer 31

Each antibody recognises one specific target molecule
To achieve this the antibody has 2 regions:
-a part that recognises the target- antigen binding site
-a part that imbues its effector function- fc receptor binding site
B cells produce antibodies by going through a differentiation process to become plasma cells

Question 32

Why are B cells and antibody important

Answer 32

Some immune deficiencies caused by gene defects or diseases or infections can affect antibody production (XLA, CVID, hyper IgM)
Children with antibody defects experience more disease
Individuals without antibody who do not receive treatment are likely to die at a younger age
Even lacking some types of IgG (eg IgG2) increases susceptibility to some infections (eg with encapsulated bacteria)
Many cancers derive from B cells
B cells play a regulatory role in diseases such as autoimmunity and in maintaining memory

Question 33

Genetic conditions associated with B cells and antibody production

Answer 33

X-linked agammaglobulinemia (XLA, 1 in 200000 male newborns):
-mutations in the BTK (Bruton tyrosine kinase) gene
-very few B cells, lack of antibody
-comes through after maternal antibody wanes
-this then results in increased risk of susceptibility to mainly bacterial, less viral, infections- lung, ear, eye, chronic diarrhoea
-treatment: intravenous immunoglobulin therapy IVIg
Hyper IgM syndrome ( 1 in 500000 usually males):
-present with abnormally high (sometimes normal) levels of IgM antibodies
-occurs due to mutations in CD40 ligand gene. (70% Xlinked) more rarely AICDA gene (autosomal) activation induced cytidine deaminase AID
-very low levels of IgG, IgA, IgE
-present in infancy with mainly bacterial, less viral infections- lung, ear, eye, sinuses, chronic diarrhoea, sometimes develop autoimmune disorders
-treatment: immunoglobulin replacement therapy

Question 34

B cells are really important

Answer 34

Antibodies ultimately derived from B cells and can protect against infection
There are >10^10 unique B cells, each expressing >10^5 copies of the B cell receptor (BCR or surface immunoglobulin)- each BCR recognises only one target
Foetal B cells are made in the liver- by birth B cells are made in bone marrow
B cells can develop into plasma cells or memory B cells
Inducing antibody is a key aim of vaccination
A failure to induce functional antibody responses increases risk of infection/childhood death
Poor control of B cell responses results in diseases such as autoimmunity and cancer

Question 35

Individual naive B cells differ most

Answer 35

By the different specificities of the BCR they express- one B cell recognises one target

Question 36

Inducing adaptive immune response is dangerous if poorly controlled

Answer 36

3 poor outcomes:
-don’t make an appropriate response against target pathogen so not protected
-don’t control what you’re making in terms of antibody can produce ones that recognise you, self autoimmunity
- B cells can’t switch off proliferative capacity causing cancer

Question 37

Overview of the (possible) life of a B cell

Answer 37

B cell starts from a B cell precursor found in the bone marrow
The B cell precursor has to rearrange its immunoglobulin genes
The immature B cell undergoes screening to make sure it does not recognise self
If B cell survives and then encounters its foreign antigen it stimulates an immune response
The activated B cell can then go on to become a plasma cell or memory B cell
Development requires the successive acquisition of properties that are essential for function:
-the rearrangement of immunoglobulin gene
-minimal recognition of self
-encounter antigen
-undergo selection

Question 38

Antibody formation

Answer 38

Made up of 2 heavy chains and 2 light chains
How these combine provides specificity and functionality

Question 39

How B cells develop

Answer 39

Development of B cell defined by Ig rearrangement and H or L chain expression (heavy chains first)
B cells start as a stem cell in the bone marrow:
-here the heavy and light chain genes are germline
-theres no surface Ig
Early pro-B cell stage:
-theres D-J gene rearrangement in the H chain genes
Late pro-B cell stage:
-the DJ genes joins, rearrangement of V gene
Large pre-B cell stage:
-heavy chain VDJ is fully rearranged
-at this stage we have functional heavy chain
-need to test H chain to see if it works
-Heavy chain is transiently expressed on surface of B cell in a non-functional way (can’t bind antigen) this informs cell that we can get it to surface so we can say the heavy chain is correct and start making light chain

Small pre-B cell stage:
-V-J rearranging of light chain genes
Immature B cell:
-light chain VJ fully rearranged
-need to check light chain is functional so it’s expressed at IgM on surface of cell
Mature B cell:
-B cell is mature, leaves bone marrow to go into secondary lymphoid tissue
-the hall mark of being mature (functioning) B cell is co-expression of IgM and IgD on the surface- this is via alternatively spliced H-chain transcripts
-IgM and IgD although having different heavy chains recognise same antigen- Same specificity

Question 40

Overview of B cell development by gene rearrangement

Answer 40

Because recombination events of variable genes are random- there are lots of opportunities for failure. Many joins are not productive- 70% fail for each chain
Recombination needs RAG genes
Rearrangements can occur from either inherited chromosome but only one chromosome is used at a time
There are 2 light chains, kappa and lambda to choose from
The two kappa genes are used first then the two lambda genes
- this is called allelic exclusion and ensures that one B cell produces antibody of one specificity
If you had one kappa and one lambda active at the same time then you could have 1 B cell with 2 specificities, this could be a problem if one antibodies recognises bacterial antigen and the other recognises self
In humans the k:l ratio 2-3:1 used clinically- if big change indicative of issue such as cancer etc
Using all potential genes raises the chance of making a successful BCR this leads to lots of individual B cells that differ in their B cell receptor
Further recombination is stopped by preventing RAG expression or function

Question 41

Removing B cells that recognise self is important to prevent autoimmunity

Answer 41

Once we have made immature B cells they need to undergo further scrutiny to check they don’t recognise self antigens
Theres 3 events that can happen:
-if when the B cell is made it recognises multivalent self molecules usually on bone marrow stroma cells it will bind to them, sends a strong signal inside B cell that leads to apoptosis of itself
-similarly you may have soluble self antigens floating around if the immature B cell recognises these then it can become anergic (non-responsive) and then dies overtime
-no self reaction so the B cell migrates to periphery and becomes full mature B cell
This is the first level of control of process
We need further control processes as both multivalent and soluble self antigen are surface exposed antigens
Theres lots of intracellular antigens inside cells
This becomes important as many of the autoantigens we recognise are intracellular derived e.g. DNA

Question 42

Antibody responses develop through multiple pathways

Answer 42

T- independent antibody response:
-this pathway makes antibodies without involvement of T cells
-the B cell encounters antigens and then it becomes a plasma cell to make antibodies
-this pathway results in you making more IgM than IgG
-antibodies produced are of lower affinity (germline affinity) which means overall they might not hold onto targets as well

T-dependent antibody response:
-vast majority of responses
-involves T cells
-responses have higher affinity, long lived and memory responses
-need a protein in process
-antibodies produced are IgM, IgG, IgA, IgE
-these are the responses we prefer to get out of vaccination

Question 43

Antibody have a region that relates to antigen-recognition and to function

Answer 43

2 heavy 2 light chains
Heavy chain imbues the antibodies effector function and its identity
The Fc portion of the antibody made up by the heavy chain has the Fc receptor binding site- important site for effector function of antibody
The specificity of the antibody is at tip of arms called antigen binding site

Question 44

Ig heavy chain

Answer 44

The function of an antibody is influenced by the Ig heavy chain used
Ig types:
- IgM and IgD are expressed on surface of naive B cells
-IgM is also found in serum
-IgG expressed on surface memory B cells and in serum
-IgG split into 4 subclasses IgG1-4
-IgE found attached to surface of cells eg mast cells so not much in serum
-IgA predominates at mucosal surfaces IgA1-2
Serum levels: IgG1-4»>IgA1-2> IgM»»IgD»»>IgE
IgG 1 higher levels than 2,3,4. All found in blood but differ in structure, flexibility and functional activities
IgG3 long hinge region extreme flexibility. Influences half life

Question 45

The properties of antibodies

Answer 45

Influenced by heavy chain usage
Classical pathway of complement activation:
-IgG1, IgG3 and IgM are very good at activating complement through this pathway. IgG2 less so. IgG4 and IgD very poor
Placental transfer (transfer of Ig from mother to offspring):
-IgG1 found at higher levels than 2,3,4
-these provide protection to infant in first weeks and months of life before weaning off
High affinity binding to mast cells and basophils:
-IgE only efficient at binding to these cells

Question 46

IgM and IgA

Answer 46

IgM and IgA typically exist as multimers- pentamers (IgM) or dimers (IgA) linked by a J chain
Pentameric IgM has 10 arms:
-can therefore bind to 10 identical epitopes (antigen) so has high avidity for its target, harder for antigen to get away
The avidity is how well the grasp is through the numbers of arms which are holding onto its target
Dimeric IgA has 4 arms:
-therefore has lower avidity
The strength of binding of a single Fab is a measure of antibody affinity

Question 47

IgA

Answer 47

Secreted as a dimer and helps protect mucosal sites
Mainly a monomer in the blood but dimerisation is needed for secretion
It’s transported through epithelial cells and it picks up secretory component as it goes through
This allows the antibody (largely found in lumen of gut or surface of lungs) to bind and neutralise its pathogens and toxins
However IgA is not good at activating complement this is important as if it did bind to target it would not be beneficial to host to start inducing a lot of inflammation locally because that can cause additional damage and allow other pathogens in
It binds and labels in a way that does not activate inflammation

-binds targets in lumen: secreted IgA on the gut surface can bind and neutralise pathogens and toxins
-binds targets in gut cells: IgA is able to bind and neutralise antigens internalised in endosomes
-binds and exports targets from tissues: IgA can export toxins and pathogens from the lamina propria while being secreted

Question 48

IgE

Answer 48

Mainly bound to the surface of cells like mast cells- important in hypersensitivity
Serum level not very high
So when IgE located on surface of mast cells binds its target antigen the cell can become activated very quickly and respond to induce an inflammatory reaction
Very beneficial
IgE commonly induced to innocuous antigens and this results in hypersensitivity reactions

Question 49

Antibody binding

Answer 49

Antibodies can function through many pathways: neutralisation, opsonophagocytosis, complement activation
Antibodies bind to a part of antigen called epitope
Antigens can contain more than one epitope so can be recognised and bound by different anitbodies
Most B cell antibodies recognise and build to the 3D shape of antigen and not the linear sequence which T cells recognise

Question 50

Antibody forces

Answer 50

Antibodies are highly flexible molecules that recognise the 3D shape of an antigen and bind non covalently
Forces used:
-electrostatic forces
-hydrogen bonds
-van der waals forces
-hydrophobic forces

Question 51

Cross link

Answer 51

As antibody molecules have 2 arms they can crosslink antigens to form immune complexes for easier removal via phagocytosis
Many Ag contain repeating epitopes (bacterial polysaccharides)
Ab bind antigens on different bacteria to form an immune complex to be removed by phagocytes

Question 52

What happens once binding occurs

Answer 52

Neutralisation: prevents toxin from interacting with receptor and damaging cell. Eg bacterial toxins. Then ingested by macrophage

Opsonisation: bacteria in extracellular space, labelled by antibody alerts immune system, ingested by macrophage

Complement activation: bacteria in plasma, antibodies bind to antigen on bacteria and cause complement activation. Lysis and ingestion
Some people who have defects in complement cascade are at more at risk of certain infections eg meningitis

Question 53

FcR and complement receptors enhance

Answer 53

Antibody function and phagocytosis enhanced by expression of Fc receptors and complement receptors by phagocytes

Question 54

Antibody coated antigens

Answer 54

Antibody coated antigens can be recognised by cells through Fc gamma receptor
There are multiple Fc gamma receptor some of which result in activation and some in inhibition
The type of IgG that is bound to the antigen makes a difference to which FC gamma R is activated
This has a significant effect on enhancing the efficiency and ability of phagocytosis and eliminating the organisms

Question 55

Antibody dependent cellular cytotoxicity ADCC

Answer 55

Sometimes pathogen derived antigens are localised to the host cell membrane if the host cell is infected
Antibody can bind these antigens (i.e infected cells) to enable immune cells such as NK cells to recognise that antibodies are bound
This leads to cross linking of Fc receptors which activates NK cells which then kills the infected cell via apoptosis
This is important to target cancer cells and virally infected cells

Question 56

Monoclonal antibodies

Answer 56

The exquisite specificity of antibodies can be exploited by making monoclonal that are then used to treat a range of diseases
Usually responses contain antibodies with many specificities (polyclonal)
Using a range of technologies antibodies with a single specificity can be made (monoclonals)
These are humanised so they can be given without inducing an immune response to them
They can be used to neutralise/block targets, label cells for killing (C’, ADCC, FcR)
Specificity can reduce potential side effects
Used for infection or cancer (ā-CD20, ā-HER2) and autoimmunity (ā-CD20, ā-TNF, ā-IL6R)
They are increasingly important tools and are the focus of much immunotherapy