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Immunology > B-cells and antibodies > Flashcards

B-cells and antibodies Flashcards

1
Q

B-cells

A
  • Important for adaptive immune system
  • Express the B-cell receptor (antibody) on their surface which allows them to recognize antigen directly
  • When activated by antigen, they develop into plasma cells
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2
Q

Plasma cells

A
  • Antibody-secreting cells
  • Antibodies are produced in the golgi vesicles
  • Proliferate in response to infection
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3
Q

What part of the immune response are the B-cells and antibodies secreted from plasma cells from?

A

Humoral part

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4
Q

Plasma cells appearance

A
  • Pan-fried egg
  • Nucleus pushed to side and plasma filled with golgi vesicles
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5
Q

B-cell functions

A
  • Antibody production
  • Antigen presenting cells (they express MHCI and MHC II)
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6
Q

Where were B-cells first identified?

A

Bursa fabricius of birds

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7
Q

Antibodies

A

Immunoglobulin molecules that are secreted into the blood by plasma cells

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8
Q

B-cell stages

A
  • Progenitor
  • Naïve B cell
  • Activated B cell
  • Plasma cell
  • Memory B cell
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9
Q

Progenitor B cell

A

Derive from hematopoietic stem cells (HSCs) and common lymphoid progenitor cells

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10
Q

Naïve B cells

A
  • Hasn’t encountered antigen yet
  • Develops in bone marrow before migrating to peripheral lymphoid organ
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11
Q

Where are naïve B cells primarily found?

A
  • Spleen
  • Peripheral lymphoid organs
  • Peyer’s patch
  • Bone marrow
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12
Q

Activated B cell

A
  • Has encountered antigen
  • Differentiates into plasma cells and memory B cells
  • Undergoes affinity maturation in germinal centre
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13
Q

Memory B cell

A
  • Long lived
  • Secondary response to re-infection
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14
Q

B cell activation

A
  1. Naïve B cells in peripheral lymphoid organs recognize antigen
  2. They phagocytose antigen and present via MHC II to the T helper cells
  3. T helper cells secreted cytokines that allow B cell to mature

**B cells need to be activated by cytokines from T helper cells (BUT T-helper cells can be told to release cytokines by both the B-cells presenting antigen on MHCII or by the dendritic cells presenting antigen on their MHCII)

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15
Q

What factor decides the type of antibodies produced by the plasma cells?

A

Depends on the type of T helper cell and the cytokines they release

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16
Q

Class (Isotype) Switching

A

B cells during the course of an antibody response can change their class of antibody. No matter what class, the B cell would recognize the same epitope

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17
Q

How does class switching of antibodies occur?

A
  • Change in the cytokines of T helper cells can cause in a change in the antibody class being produced although they will still recognize the same epitope
  • The daughter cells secrete other heavy chain antibodies
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18
Q

B cell receptor

A
  • Each B cell has a single receptor for a specific epitope only.
  • Multiple copies of the BCRs on each B cell (but all for the same epitope)
  • Interact directly with antigen (no need for presentation)
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19
Q

Monoclonal

A

A mature B cell produces antibodies to one epitope only

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20
Q

Polyclonal

A

If we have multiple B cells secreting antibodies against multiple epitopes

21
Q

Parts of antibody

A
  • Two heavy chains- variable region, helps make up paratope
  • Two light chains- variable region, helps make up paratope
  • Constant Regions (Fc fragment)- structure of antibody
22
Q

Paratope

A
  • Recognizes the epitope on the antigen
  • Made by 1 light and 1 dark chain of antibody
23
Q

Constant region of antibody

A
  • Determines the antibody class or isotype
  • Also considered the Fc fragment which is recognized by Fc-receptors on the surface of immune cells
24
Q

Variable regions of antibody

A

Involves the heavy and light chains; They are folded to form a groove that acts as the antigen binding site

25
Q

Classes or isotypes of antibodies

A
  • IgA
  • IgD
  • IgE
  • IgG
  • IgM
  • IgT and IgY for horses
26
Q

How are antibodies classified?

A

Classified based on the heavy chain that they contain in their constant region (alpha, delta, epsilon, gamma, mu)
- They differ in their sequence and number of constant domains, their hinge structure and the valency of the antibody

27
Q

What is the purpose of having different antibody isotypes?

A
  • They differ in size which makes it easier for them to be transported across mucosal surfaces, get into small niche tissues or form large networks in serum
  • Different advantages and disadvantages to each class
28
Q

IgM

A
  • mu
  • Primary response antibody
  • Monomer on surface of B cell (BCR)
  • Secreted as pentamer (5 antibodies together, act like a fishing net)
  • Mechanisms of action: opsonization, complement activation, agglutination
29
Q

IgG

A
  • gamma
  • B cell has undergone isotype switching
  • Found in spleen, lymph nodes, bone marrow
  • Mechanisms of action: opsonization, neutralization, complement activation, agglutation
  • Small and easy to get through surface
30
Q

IgA

A
  • Alpha
  • Mucosal antibody
  • Secreted as a dimer at mucosal surfaces
  • Transport through epithelium via Fc receptor or secretory component
  • Mechanisms: neutralization, agglutination
31
Q

IgE

A
  • Epsilon
  • Allergies, inflammation, parasites
  • Beneath mucosal surfaces, and in serum
  • Signal transducer (mast cell and basophil degranulation)
    Binds antigen and interacts with Fc(epsilon)RI on surface of mast cells and basophils
32
Q

IgD

A
  • Delta
  • Respiratory tract defence
  • Low to near undetectable prevalence in serum
  • Undergoes class switching similar to IgM
  • Species specific structural differences
33
Q

Subclasses of antibodies

A

Within each class, there are also subclasses
- Same type of heavy chain but from different alleles
- Differences less pronounced, conferring slightly different properties

Specific for the type of immune response being raised to make them more efficient
- Ex. Th1= IgG2a and Th2 = IgG1

34
Q

Functions of antibodies

A
  1. Neutralization
  2. Opsonization
  3. Agglutination
35
Q

Neutralization

A

They bind to pathogen and neutralize its effect by blocking binding sites or neutralizing toxins (eg. Pathogen neutralization on mucosal surfaces OR act as anti-toxins to a snake bite= passive immunity)

36
Q

Opsonization

A
  • Antibodies bind to antigen and activate the complement through Fc-fragment
  • Antibody dependent cell mediated cytotoxicity by NK cells
  • Phagocytosis
37
Q

Agglutination

A
  • Neutralization
  • Phagocytosis
  • Complement activation
38
Q

Avidity

A

Measure of the overall strength of an antibody-antigen complex
- Number of binding sites on an antibody able to bind an antigen
- Dependent on affinity of the antibody for its epitope

39
Q

Affinity

A

The strength of the interaction between an epitope and the antibody’s antigen binding site
- More specific antibody binding grooves for the antigen (matching amino acids compared to mismatched amino acids)

Immune system is working to find the highest affinity!

40
Q

Examples of avidity vs. affinity

A

IgM: 5 antibodies joined together (decavalent)
- Low affinity
- High avidity

IgG: bivalent
- High affinity
- Low avidity

41
Q

Immune response and receptor diversity

A
  • We are born with naïve lymphocytes that express specific receptors on their surface for only one antigen
  • For every epitope of an antigen, we have a specific cell expressing the specific receptor for it. This is done by combining different amino acid chains for the receptor composition
  • Immune response depends on how quickly the cell is activated and cloned into thousands more for the attack
42
Q

Heavy Chain rearrangement

A
  • Have both constant and variable regions.
  • Take only certain parts (alleles) and slice out the other parts. Eventually only a certain few genes are being used for mRNA encoding for the transcript for the actually antibody
43
Q

Light chain rearrangement

A

Specific alleles that are spliced down to form mRNA code. Code will undergo translation to form specific polypeptide chain to form specific antibody on a specific B cell

44
Q

Light and heavy chain loci

A

There are many different loci or libraries to be chosen from and diversity arises from the different combinations of VDJ and VJ sequences
- Point mutations, insertions and deletions further increase diversity

In heavy, there are CH genes that code for different isotypes

45
Q

Somatic hypermutation

A

The process where B cells undergo rounds of mutations which slightly change the binding site in the hopes of finding the perfect fit
- Mutation at the V region of B cell receptor in hopes to increase binding affinity

The mutations that result in a stronger binding to the antigen will be positively selected for while mutations that have diminished affinity for antigen binding are instructed to die by apoptosis

46
Q

Where does somatic hypermutation occur?

A

Germinal centres of lymph nodes

47
Q

Steps of somatic hypermutation

A
  1. Activated Th cells migrate to follicles, differentiating into follicular Th cells
  2. B cells are activated, some enter the germinal centres to undergo isotype switching and affinity maturation. At the same time, some will leave and go make antibodies
  3. B cell somatic hypermutation occurs in the dark zone. Antibody affinity tested in light zone
  4. Follicular Th cells will tell the B cells to undergo further affinity maturation OR to undergo apoptosis if they are not positively selected for
  5. B cells clones with highest antigen affinity differentiate into plasma cells and memory cells
48
Q

Serum therapy

A

Use of immune serum (antibodies) for therapy. Horses were immunized to develop specific antibodies and serum was used to treat patients

49
Q

Monoclonal antibodies

A

Fusion of a B cell clone with a myeloma (tumor cell) forming a hybridoma in order to obtain monoclonal antibodies

Immunology (8 decks)

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