Initiation of Acquired Immune Responses (B cells and Antibodies)

Question 1

What are the two types of lymphocytes?

Answer 1

T cells and B cells

Question 2

What is the role of B cells?

Answer 2

Mature in the bone marrow (Primary lymphoid tissue).
Responsible for humoral immune responses.
“humors” = body fluids
Produce antibodies that attack pathogens circulating in the blood and lymph.
Key role in defence against extracellular (and intracellular) pathogens.

Question 3

What happens if B cells and T cells react to self-antigens?

Answer 3

As they develop, B cells and T cells learn to distinguish self form non-self.
If they react to self-antigens they are (usually) destroyed or inactivated.

Question 4

What is the role of T cells?

Answer 4

Mature in the thymus (Primary lymphoid tissue).
Responsible for cellular immune responses.
Key role in defence against intracellular pathogens
- CD4+ T cells which are key regulators of the entire immune system.
- CD8+ T cells kill virally infected body cells.

Question 5

What are antibodies and what are their roles?

Answer 5

An antibody is a protein that is produced in response to a particular molecule (antigen), and has the property of binding specifically to tat antigen.
Antibodies are also known as immunoglobins.
Antibodies are proteins that bind to one specific antigen.
They are a complex of 4 polypeptide chains (2xlight chain + 2x Heavy chain).
Each antibody as unique variable region that binds to one specific antigen.
Millions of different antibodies are present I our bodies - able to respond to millions of different antigens.
Antibodies exist in membrane bound and soluble forms.
Different classes of antibodies exist
- IgM
- IgG
- IgA
- IgE
- IgD

Question 6

What are Antigens and what are their roles in the body?

Answer 6

An antigen is any substance which can cause an adaptive immune response by activating B cells and T cells.
Adaptive immune responses are induced by specific structures called antigens.
Individual cells/pathogens can contain many different antigens
- Individual antigens can contain many different antigenic epitopes.
- Each specific antibody can bind to only one specific antigenic epitope.

Question 7

How do B cells use antibodies and antigens?

Answer 7

B cells use membrane-bound antibodies as a receptor to recognise and bind to antigens.

• Different B cells express different antibodies.
• One B cell expresses ~50000 copies of one specific antibody.

Question 8

In what way does the adaptive immune system have specificity and how is each response unique to an individual pathogen?

Answer 8

individual B cells and T cell express only one type of antigen receptor on their cell surface - so each individual cell can only respond to one specific antigen.
There are a limited number of each antigen-specific cell type within the human body (space) - these few antigen-cells are not sufficient to kill and eliminate an antigen-carrying pathogen.

Question 9

How are PAMPs recognized by non-specific recognition?

Answer 9

There are a limited number of PAMPs, which are common to many different pathogens.
Only a small number of different PRRs are required to stimulate innate immune cells.
Common structures (PAMPs) recognized by innate leukocytes.

Question 10

How are antigens recognized by specific recognition?

Answer 10

Millions of different antigens - unique to individual pathogenic species.
Individual T cells and B cells only express one specific antigen receptor, which binds to only one specific antigenic epitope.
Unique structures (antigens) recognized by adaptive leukocytes.

Question 11

Adaptive immune responses occur in secondary lymphoid tissues. Where do the T cells and B cells develop?

Answer 11

Antigen-specific cells and B cells develop in primary lymphoid tissues
- Bone marrow
- Spleen
Lymphocytes develop initially in the bone marrow and then mature in either the bone marrow (B cells) or in the thymus (T cells).

Question 12

Where do B cells and T cells circulate within the body?

Answer 12

Mature, quiescent, antigen-specific T cells and B cells constantly re-circulate between different the blood, secondary lymphoid tissues and lymphatic vessels.

Question 13

What state do lymphocytes remain in, where do they meet their antigen and become activated?

Answer 13

Lymphocytes are inactive until they meet their specific partner antigen within a secondary lymphoid tissue.
Secondary lymphoid tissues are sites where T cells and B cells are activated by antigens
Lymph nodes - important stations for monitoring tissues infections.
Spleen - important in monitoring blood-borne infections.
Mucosal - associated lymphoid tissues - important in monitoring throat/gastrointestinal tract infections.

Question 14

What happens to B and T cells if they don’t encounter a specific antigen?

Answer 14

After several days, if they don’t encounter specific antigen, B cells and T cells return to the blood system via the efferent lymphatics.

Question 15

Naïve T cells and B cells use the process of Transendothelial Migration to enter lymph nodes from High Endothelial Venules (HEV). What is this process?

Answer 15

Lymph nodes are key sites of pathogen detection and are therefore organized into distinct functional areas to facilitate efficient activation of B cells and T cells.

1. Lymph flows into lymph nodes through the afferent lymphatic vessels.
2. B cells and T cells enter lymph nodes through high endothelial venules (HEV).
3. Once B cells come through the HEV, they immediately go into the lymphoid follicle.
4. Once T cells come through the HEV, they stay in the -cell area of the lymph node and interact with dendritic cells tat come in through the afferent lymph.
5. Both lymph and lymphocytes leave the lymph node by first going through the medullary sinus and then out through efferent lymphatic vessels. Efferent lymph eventually flows back into blood circulation via the subclavian vein.

Question 16

What is the acquired immune response mediated by B cells (aka: the Humoral Immune response) and how does this process work?

Answer 16

B cells produce specific antibodies in response to specific antibodies in response to specific antigens.
Membrane bound, antigen-specific IgM (or IgD) is used to bind to their target antigens.
Once activated, these B cells clonally proliferate and differentiate into 2 different types of effector cells:
Plasma cells
- Produce and secrete soluble, antigen-specific antibodies
Memory B cells
- Long lived cells that continue to circulate around the body.

Question 17

How do B cells encounter antigens?

Answer 17

Specialized cells within B cell zones can “trap” opsonised antigens - these cells express opsonin receptors.

Question 18

What happens after B cells encounter antigens?

Answer 18

B cells need to receive 2 signals to become fully activated and clonally proliferate in response to protein antigens:
- Antigen
- “Helping” signals
After receiving both signals, antigen-activated B cells clonally proliferate (i.e. enter the cell cycle and divide many times over)
- The resulting daughter cells all express BCRs that have the same antigen-specificity as the parent B cell.
- These highly proliferative cells form a secondary follicle within the B cell zone (known as the Germinal Centre).

Question 19

What are the 2 types of signals in protein antigens?

Answer 19

1. BCR binding to antigen

2. Help from TH(H is subscript) cells

Question 20

What are the 2 types of signals in other types of antigens?

Answer 20

1. BCR + antigen

2. PRR + PAMP

Question 21

What are the 2 types of signals in antigens with repetitive antigenic epitopes?

Answer 21

Signal 1+ 2: Multiple BCRs + antigens engaged

Question 22

The activated B cells once activated, differentiate into plasma cells, how does this occur?

Answer 22

This expanded population of cells now has sufficient numbers to be able to dal with any pathogen tat expresses the specific antigen on their surface

• They stop proliferating and differentiate into antibody-secreting plasma cells.
• These secreted antibodies recognize the same specific antigen as the original parent B cell.

Question 23

How do antibodies help kill and eliminate antigens (i.e. pathogens)?

Answer 23

Antibodies can bind to soluble antigens o to membrane-bound antigens expressed on the surface of microbes or other immune cells.
Antibodies provide immunological defence against extracellular and intracellular microbes (most bacteria, viruses)
- Recognise the microbe as foreign
- Inactive/eliminate the microbe
Recognition Function
- Binding to antigen mediated by variable region sites
Effector function
- Clearance mechanisms mediate interaction of the Heavy chain constant region with effector molecules
- Complement
- Fc receptors

Question 24

What is IgM and what is it’s role?

Answer 24

IgM: present only in plasma and secretions (too large to enter tissues)
In membrane-bound form serves as the B cell antigen receptor (monomer)
- Functions: B cell activation
IgM (in its secreted form is the first Ig type produced during a humoral (adaptive) immune response.
IgM present in plasma and secretory fluids as a pentamer.
Functions of IgM:
- Agglutination (immune complex formation)
- Complement system activation

Question 25

What is the definition of agglutination (Immune complex formation)?

Answer 25

Agglutination: The action of an antibody when it cross-links multiple antigens producing clumps of antigens. The clumping together of particles (e.g. microbes) caused by antibody molecules binding to antigens on the surface of 2 adjacent particles/ cells/ pathogens/ antigens.

Question 26

What is the function of Agglutination (Immune Complex formation)?

Answer 26

Increases the efficacy of microbial elimination by phagocytosis as large clumps of bacteria can be eliminated in one pas, versus the elimination of single microbial antigens.
Different antibodies (recognizing different antigens) can work together, causing virus particles to stick together - agglutinated viruses make an easier target for immune cells than single viral particles (e.g. for phagocytosis).
Agglutination increases the efficacy of pathogen elimination by enhancing phagocytosis
- Phagocytic cells express Fc receptors (i.e. IgM and IgG are very good opsonins).
Can also prevent viruses them from binding to and infecting host cells
- “Neutralisation” function.

Question 27

What antibodies activate the complement system?

Answer 27

The classical complement is activated by the Fc region of IgM and IgG antibodies when they are bound to antigens.
Initiated by specific antigen binding to IgM (and IgG) antibodies.
Induces a conformational change in the Fc regions of IgM and IgG antibodies which exposes multiple binding sites for C1, the first component of the classical activation pathway of the complement system.
Each C1 molecule must bind via it’s globular heads to at least two Fc sites for a stable interaction.
This results in a conformational change within the Fc region of the antobody, exposing a inding site for downstream complement proteins that eventually end in the production of a C3 cleaving enzyme.
A single IgM pentamer is sufficient to activate the Classical pathway since it binds multiple antigens at once.
However, several different IgG antibodies must bind closely located antigens in order to recruit and activate the C1 complex.

Question 28

What IgG, and what is it’s role?

Answer 28

The most abundant antibody in normal human serum (70-85% of the total Ig pool) - monomeric.
The dominant Ig type produced during a secondary (memory) immune response.
Functions of IgG;
- Agglutination
- Complement system activation
- Foetal immune protection
- Neutralisation
- Opsonisation
- Natural killer cell activation
IgG has the longest half-life (20-24 days) of the 5 immunoglobulin classes.
IgG consists of 4 human subclasses (IgG1, IgG2, IgG3 and IgG4) each containing a different heavy chain.
These are highly homologous and differ mainly in the hinge region and the extent to which they activate the host immune system.

Question 29

What is Foetal immune protection and how does it occur?

Answer 29

IgG antibodies are transported across the placenta, directly into the foetal blood circulation.
At birth human babies have as high a level of circulating maternal IgG antibodies - collectively these are able to recognise a wide range of different antigen specificities.
- Helps protect the neonate against many different pathogens until it’s own adaptive immune system develops fully (approx. 6 months of age).
Not: maternally derived IgG wanes over time (due to the natural half-life of IgG proteins) resulting in a period of transient hypogammaglobulinaemia (this is the most common type of immunodeficiency condition).

Question 30

What is the process of neutralisation?

Answer 30

Antibodies can neutralize viral infectivity in a number of ways, as summarized in the illustration.
They may interfere with virus binding to receptors, they may block entry of viruses or toxins into cells, they ay prevent uncoating of viral genomes in endosomes, or they may cause aggregation of virus particles in the extracellular environment.
Mediated by specific antigen binding.
Binding of high affinity neutralising antibodies to antigens is protective
- IgG
- Secretory IgA (sIgA)
Prevent viruses from infecting host cells
Prevent microbial Toxins from disrupting normal cell function.

Question 31

What is the process of opsonisation?

Answer 31

Opsonisation: the coating of pathogens by immune proteins (opsonins) to enhance phagocytosis.
Earlier, in the context of innate immunity, we encountered the concept of an opsonin and opsonisation
- C3b
IgG antibodies are excellent opsonins.
Phagocytes express a type of Fc receptor that binds specifically to the constant region of the IgG heavy chain.
Opsonisation enhances phagocytosis, especially important for encapsulated bacterial species.

Question 32

Natural Killer cell activation

Antibody-Dependent cell-Mediated Cytotoxicity (ADCC). What is the process?

Answer 32

Innate Immune response:
Intracellular pathogens Infect Host Cells -PAMPS -> Secrete interferons alpha/beta (IFNalpha/beta) -> Natural killer cells -> Killing of infected host cells.
Production of pro-inflammatory mediators.

Adaptive (humoral) Immune response:
IgG is another very good activator of Natural Killer cells.

Question 33

What is IgD and what is it’s role?

Answer 33

Extremely low concentrations in blood. The least well characterised immunoglobin.
In membrane-bound form serves as the B cell antigen receptor (monomer)
- Functions: B cell activation
Function of the secreted form is not well understood
- Found at extremely low concentrations in blood
- Function = ?

Question 34

What is IgD and what is it’s role?

Answer 34

Extremely low concentrations in blood. The least well characterised immunoglobin.
In membrane-bound form serves as the B cell antigen receptor (monomer)
- Functions: B cell activation
Function of the secreted form is not well understood
- Found at extremely low concentrations in blood
- Function = ?

Question 35

What is Neonatal immune protection and what role does it play?

Answer 35

Colostrum is a form of milk produced by the mammary glands of mammals (including humans) in late pregnancy. Most species will generate colostrum just prior to giving birth. Colostrum contains antibodies to protect the newborn against disease. In general, protein concentration in colostrum is substantially higher than in milk.
sIgA in brast milk can help protect during periods of transient hypogammaglobulinaemia.
sIgA antibodies are transported into colostrum and breast milk in order to protect the GI tract of neonates.

Question 36

Can IgE trigger allergic responses or not?

Answer 36

IgE antibodies can trigger allergic responses

- allergy, asthma, anaphylaxis