B-cell 1: Intro to Humoral Immunity

Question 1

Adaptive immune response

Answer 1

Swat team - highly specialized cells to target pathogens by recognizing very specific antigens

Question 2

General functions of adaptive immune response (3)

Answer 2

1. Recognition of specific “non-self” antigens in the presence of self antigens
2. Generation of pathogen-specific immunologic effector pathways that eliminate specific pathogens or pathogen-infected cells
3. Development of immunologic memory to quickly eliminate pathogens in subsequent infection

Question 3

Principles of adaptive immunity

Answer 3

• each developing lymphocyte (B and T) generates a unique antigen receptor
• adaptive immunity is initiated when antigens or antigen presenting cells (APCs) reach the secondary lymphoid organs where lymphocytes reside
• lymphocytes (B and T cells) are activated by antigens, and then give rise to clones of antigen specific effector cells

Question 4

Adaptive immunity: 2 main components?

Answer 4

• humoral response (B-cells)

- cell mediated response (T-cells)

Question 5

Where do antibodies come from?

Answer 5

• activated b-cells will differentiate into plasma cells; need T-cells to help get activated
• plasma cells secrete antibodies

Question 6

Antigen receptors

Answer 6

• B and T cells have specific antigen receptors
• B cells have antibodies (that are attached to the B cell surface membrane)….plasma cells antibodies are secreted
• T cells have T-cell receptors (TCRs)
• Antibodies and TCRs have variable region (antigen binding site) and constant regions

Question 7

Antibodies

- 3 main functions? (fourth function on next slide)

Answer 7

• aka immunoglobulin
  Functions:
  1) neutralization of microbial toxins (mop up toxins), then macrophages have receptors that bind the antibodies and signal for the macrophages to engulf the neutralized toxins
  2) opsonization: antibodies bind to pathogens (phagocytes have antibody receptors and engulf pathogen)
  3) complement activation: antibodies bind to the pathogen to initiate the complement cascade (look to previous videos for exact mechanism) –> this further enhances opsonization and leads to cell lysis of microbes

Question 8

Fourth function of antibodies

Answer 8

Antibody dependent cell-mediated cytotoxicity (ADCC)

• falls more under innate immune response
• virus can affect a host cell, hijacks host cell machinery to make its own proteins; some of these viral proteins will be displayed on the surface of the host cell
• an antibody might recognize viral proteins on the host cell and bind
• and the natural killer cell has antibody receptors (Fc receptors) that recognize the antibodies and bind
• cross-linking of Fc receptors signals the NK cells to kill the target cell –> cell dies from apoptosis

Question 9

Antibody structure

Answer 9

2 heavy chains:

• structure of heavy chains determines function and isotype
• IgG is the most abundant isotype (4 subclasses - IgG1, IgG2, IgG3, IgG4)

2 light chains:
- 2 types, kappa light chains or lambda light chains (kappa are more common in humans - ratio 2:1)

Variable and Constant regions:

• heavy and light chains are composed of variable and constant regions
• Variable region (with heavy and light chain) is the antigen binding site

Parts of antibodies:
Cl
Ch1, Ch2, Ch3
Vl
Vh

Question 10

Antibody isotypes

- list all

Answer 10

IgM (acute infection)

• large, pentameric (5 IgGs)
• important for activation of complement
• first antibody produced in immune response
• elevated IgM titres indicate recent infection

IgG

• smallest and most abundant
• most important for protection from infections (neutralization and opsonization)
• crosses the placenta (important for autoimmune conditions)

IgE (allergy)

• found in acute allergic reactions and protection against parasites
• binds mast cells and basophils
• IgE develops an antigen binding site for parasite or benign protein (that someone can become allergic to)
• once the b-cell makes the IgE, IgE will bind to an IgE receptor on a mast cell. If antigen is not encountered, mast cell will sit at rest. But if there is an antigen, it will bind to the IgE antibody (which is attached to the IgE receptor on the mast cell). This causes cross-linking of the IgE, which sends a signal to the mast cell to be activated and send off granules with mediators that will give rise to symptoms

IgA

• dimer
• found in respiratory and gut mucosa secretions
• found in secretions and other bodily fluids such as tears, saliva, and breast milk

IgD

• produced early in the immune response (with IgM)
• present in very low levels (generally not measured)
• can also fix complement
• not as important

Question 11

QUESTION
- what are the 4 functions of antibodies?

• what are the 5 antibody isotypes?
• what antibody isotype is most abundant and important in protection against pathogens?

Answer 11

1) Neutralization of microbe toxins
2) Opsonization
3) Activation of complement
4) Antibody dependent cell-mediated cytotoxicity

• IgM (large, pentameric, first one made, activation of complement, signals recent infection)
• IgG (smallest, most abundant, most important for protection from infection - opsonization and neutralization, can cross placenta - autoimmune issues)
• IgE (allergy and parasites. IgE receptors on mast cells and basophils, IgE made by b-cells goes onto IgE receptors, antigen binds to IgE and mast cell degranulation)
• IgA (dimer, on mucous membranes - resp and gut, secretions: tears, saliva, breast milk)
• IgD (released early like IgM, low numbers, can fix complement, not important)

Already answered - IgG