I&I Week 9 B-lymphocytes and Antibody production

What type of APC is a B-lymphocyte?

semi-pro APC

Why is it important that B-lymphocytes are semi-pro APC important?

They become plasma cells and make antibodies and if they get infected they can be present microbial protein antigen to CTLs.

Antibody can bind to what and help destroy what?

Bind to microbial antigens and destroy extracellular pathogens

Antibodys can activate the complement cascade and generate what?

Generate Complement oponins and the MAC

What do opsonins do?

They are antibodies that bind to an antigen marking it as a target microbe for phagocytosis

How do antibodies help the innate immune system?

They bind to infected host cells which helps NK cells target and kill host infected/tumor cells (ADCC)

What happens if antibodies do to good of a job and bind to healthy host cells marking them as a target for NK cells?

Autoimmune disorder

What dies the presence of antibody in the serum to a particular antigen indicate?

Adaptive humoral immune response to that antigen

Why would we want to assess an adaptive humoral immune response to a particular antigen in an animal?

To determine if the animal has been exposed to a particular pathogen

To determine is an animals immune system responded to a vaccine

Help with diagnosis (titer)

How can we assess a humoral immune response in an animal?

Detect antibody to antigen of interest in serum

Why is it important that B-cells are semi-pro APCs and can present peptides to T-helper cells?

Some B-cells have BCRs that recognize non-protein antigens.

B-cells need cytokines help form T-helper cells to make antibodies and memory B-cells specific to these proteins antigens

What are examples of non-protein antigens that some B-cells have BCRs that can recognize them?

Carbohydrates

Lipid epitopes of gram - bacteria

If a B-cell responds to a non-protein antigen how does this effect the help it gets to a T-helper cells?

It does not receive cytokine help from T-helper cells because T-Helper only recognize protein antigens. So there is no memory cells produced and no antibody class switch.

What is the only antibody produced when a B-cell responds to a non-protein antigen?

IgM

What does it mean to not have a memory response to a non-protein antigen?

Each time the non-protein antigen shows up again, it will continue to have an initial response. Like it was seeing it for the first time.

How is the antibodies effected to the limited response from the adaptive immunity?

The antibody produced is specific to the antigen recognized by the BCR

How do B-cell get cytokine help from T-Helper cells?

BCR binds to protein epitope it recognizes

B-cell process and presents peptide to T-helper

B-cell receives cytokine help

B-cell clonal expands (proliferate)

Differentiate into plasma cells to make antibodies or memory cells

Why in any adaptive humoral immune response to a microbe, multiple different B-cells will be activated and clonally expand?

Microbes have multiple antigens/epitopes

Why is there a polycolonal antibody response generated for a single antigen?

Different peptides with different epitopes on the same antigen is presented to T-helper cells to produce antibodies that can be specific for their specific epitope on the antigen.

The class of antibody the plasma cell makes depend on what?

The type of cytokine help they get from Th-1 and Th-2 cells

Cytokines from the T-helper 1 cells promote what kind of antibodies?

Antibodies that help other immune cells do their jobs (opsonizing antibody)

Cytokines from the T-helper 2 cells promote what kind of antibodies?

Promote neutralizing antibodies

What does a neutralizing antibody do?

An antibody that binds to the spike proteins virus and now the virus can’t enter host cell, neutralizing its effects.

Cytokines for the T-helper cells also allow what type of change to antibodies?

Antibody class-switching

What type of antigen does it mean for a class switch in antibodies to occur?

Protein antigen

What part of the antibody changes from one antibody to another and what stays the same?

Fab part of the antibody ( what it recognized) doesn’t change but the Fc part does.

What does the Fc region of the antibody determine?

The class of the antibody and thus what the antibody can do

When the B-cell is activated by a microbial protein antigen what is the first class of antibody is usually made?

IgM

The B-cells during an infection will receive additional cytokine signals from T-helper cells causing what?

The dominant class of antibodies made will change (class switching)

The memory response is a feature of what two responses?

Adaptive immune response and the response to protein antigens

What are the difference between Memory T and B cells vs Naive T and B cells?

Memory cells are long lived cells and activated much more quickly than naive cells

How long does the primary adaptive immune response take?

7-10 days

A memory adaptive immune response takes how long to detect?

-1-2 days

What are the B-lymphocytes capable of becoming?

Plasma cells that can make antibodies

What can B-lymphocytes do if they become infected?

They are like any other infected host cell with a nucleus and can present microbial protein antigens to CTLs

What are the two main parts of an antibody that can be distinguished?

The Fab part and the Fc part

What part of the antibody is identical to the antigen recognition part of the B-cell receptor?

The Fab region

What are three ways antibody can help destroy extracellular pathogens?

Activate the Complement Cascade, generate Complement opsonins, and generate MAC

What is another way antibodies can target microbes for destruction?

By targeting microbes for phagocytosis (opsonin)

How do antibodies help NK cells?

They help NK cells target and kill host infected/tumor cells (ADCC).

What does the presence of antibody in the serum to a particular antigen indicate

An adaptive immune response

What is one reason why we would want to assess an adaptive humoral immune response to a particular antigen in an animal?

To determine if the animal has been exposed to a particular pathogen.

What is another reason why we would want to assess an adaptive humoral immune response in an animal?

To determine if the animal’s immune system was able to respond to a vaccine

Assessing a humoral immune response can help with what?

Diagnosis

What two characteristics of the antibody response can be helpful to determine for diagnosis?

The amount/titer and the kind of antibody class made to a particular pathogen of interest

How can we assess a humoral immune response in an animal?

Detect antibody to antigen of interest in serum.

Why is it important that B-cells are semi-pro APCs and can present peptides from protein antigens to T-helper cells?

B-cells need cytokine help from T-helper cells to make antibody and memory B-cells specific to these protein antigens

What type of antigens can some B-cells recognize with their BCRs?

Non-protein antigens

What are two examples of non-protein antigens that B-cells can recognize?

Carbohydrate and Lipid molecules, such as epitopes on lipopolysaccharide (LPS) molecules of Gram-negative bacteria

What type of help do B-cells responding to non-protein antigens not receive?

Cytokine help from T-helper cells

What are two limitations of the B-cell response to non-protein antigens due to the lack of T-helper cell help?

No memory cells produced (thus, no memory response), and no antibody class switch (only IgM is made)

What is a key characteristic of the antibody produced in response to non-protein antigens?

The antibody produced is SPECIFIC to the antigen recognized by the BCR

What class of antibody is exclusively made in response to non-protein antigens?

IgM

What are non-protein antigens often composed of?

Simple, repeating polymers, such as LPS of gram-negative bacteria.

What is the first step in a B-cell response to a protein epitope?

BCR binds the protein epitope it recognizes

Following BCR binding of a protein epitope, what does the B-cell do?

Processes and presents peptide to a Th-cell.

What does a B-cell receive from a Th-cell after presenting a peptide from a protein antigen?

Cytokine help

What are three outcomes of a B-cell receiving cytokine help from a Th-cell after recognizing a protein antigen?

Clonal expansion, memory B-cells, and plasma cells that make antibody

What is the end result of the cytokine help B-cells receive from T-helper cells?

Clonal expansion, becoming plasma cells and making antibody, antibody class switching, antibody affinity maturation, and generation of antigen-specific memory B-cells

What is a key difference in the B-cell response to protein vs. non-protein antigens regarding memory cells?

Memory B-cells are generated in response to protein antigens but usually not to non-protein antigens

What is a key difference in the B-cell response to protein vs. non-protein antigens regarding antibody class?

Antibody class switching occurs in response to protein antigens, while only IgM is usually made in response to non-protein antigens

What is a key difference in the B-cell response to protein vs. non-protein antigens regarding T-cell help?

B-cell responses to protein antigens require help from Th-cells, while responses to non-protein antigens do not

What is clonal expansion?

The proliferation of antigen-specific B cells (mitosis... many progeny)

Why are multiple different B-cells activated and clonally expand in an adaptive humoral immune response to a microbe?

A microbe has multiple antigens/epitopes

What is the result of multiple B-cell clones being activated by different epitopes on a single protein antigen?

A polyclonal antibody response is generated

What determines the class of antibody a plasma cell makes?

The type of cytokine help it gets from the Th-1 and Th-2 cells

What type of antibody do cytokines from T-helper 1 cells generally promote?

Antibody that helps other immune cells do their job, such as opsonizing antibody

What type of antibody do cytokines from T-helper 2 cells generally promote?

Neutralizing antibody

What part of the antibody molecule changes during antibody class switching?

The Fc region

What part of the antibody molecule remains the same during antibody class switching?

The Fab region (what it recognized)

What does the Fc region of an antibody determine?

The class of antibody and thus, what the antibody can do (biological activity)

What is the first class of antibody usually made when a population of B-cells is activated by microbial protein antigens?

IgM

What happens to the dominant class of antibody made as the population of B-cells receives additional cytokine signals from T-helper cells?

It changes (antibody class switching)

What type of immune response is the memory response a feature of?

The adaptive immune response

Is the memory response a feature of the response to protein or non-protein antigens?

Protein antigens

How do memory B- and T-cells compare to naïve B- and T-cells in terms of activation speed?

Memory B- and T- cells are activated much more quickly

How long does it typically take to detect a primary adaptive immune response?

~7-10 days

How long does it typically take to detect a memory adaptive immune response

~1-2 days

What are two things that are generated more of in a memory adaptive immune response compared to a primary response?

More memory cells and more plasma cells

What are two things that can be detected to assess a memory response?

Antigen-specific antibody in the serum (serology) and antigen-specific T-cells in the blood

What is a key feature of the antibody response to protein antigens related to antibody binding strength?

A progressive increase in the affinity of the antibody (affinity = strength of antibody binding to antigen)

What is required for B-cells to become plasma cells that make higher and higher affinity antibody to protein epitopes?

Cytokine help from Th-cells

What is the main function of B-lymphocytes

To become plasma cells and make antibody

What else can B-lymphocytes do besides making antibodies?

Present protein antigens acquired from the extracellular environment and present peptides of these proteins to T-helper cells

What is the feedback regarding non-protein antigens and B-cell responses?

When B cells have BCRs that recognize non-protein antigens they will clonally expand and make specific antibody but no memory B-cells are generated and antibody class switching and affinity maturation does not occur

What is polyclonal antibody?

Antibodies made to many/most/all of the different epitopes of an antigen with varying degrees of affinity

What type of immune response typically results in polyclonal antibody?

The serum from an animal exposed to a pathogen (or vaccinated) contains polyclonal antibody to the pathogen or vaccine antigens because the pathogen expresses many different epitopes

What is monoclonal antibody (MoAbs)?

Antibody from a single B-cell clone

How are monoclonal antibodies typically made in the lab?

By fusing a plasma cell (makes antibody to one epitope) with a cancer B cell (lives forever) to create a hybridoma

What is a hybridoma?

An immortalized cell line that will live forever and continue to make a specific antibody

What are immunoglobulins (Ig)?

Antibody; glycoproteins

Where are immunoglobulins primarily found?

In serum (serum = blood with cells and clotting factors removed)

Where else can antibodies be found in the body?

Joint fluid, CSF, colostrum, etc

How are proteins in serum separated during electrophoresis?

Based on charge

Towards which electrode do immunoglobulins migrate during electrophoresis?

The negative cathode because they have a positive charge

In which fraction of serum protein electrophoresis is most antibody found?

The Gamma Globulin fraction

hat else besides antibody can be found in the gamma globulin fraction?

Some acute phase proteins

What is the synonym for Gamma Globulin in the context of this material?

Antibody

What is the antigen recognition part of the antibody molecule?

The Fab region

What part of the antibody molecule determines the class of antibody?

The Fc region