Humoral Immunity (Habal)

Question 1

The majority of intracellular pathogens are targeted by what kinds of cells?

Answer 1

T cells

Question 2

How does the humoral response begin?

Answer 2

It’s launched against extracellular pathogens.

Question 3

What happens during the humoral response?

Answer 3

B cell activates against a specific antigen. It then undergoes clonal expansion & differentiation. Plasma cells secrete antibodies, which once produced have only a limited shelf-life (although they may persist longer). Memory B cells come along to provide long-lasting immunity.

Question 4

Genes for heavy chains of antibodies come from which chromosome?

Answer 4

14

Question 5

Genes for light chains of antibodies come from which chromosomes?

Answer 5

2-kappa & 22-lambda

Question 6

What is the first Ig to be produced?

Answer 6

IgM

Question 7

How do you go from IgM to IgG?

Answer 7

Get IgM first as it is genetically encoded in constant region. Post-rearrangement you get class switching - a loop forms, bringing the constant region for IgG or IgA closer to VDJ region, forming the class.

Question 8

What are the effector mechanisms of the humoral response?

Answer 8

Agglutination (enhances phagocytosis), opsonization, neutralization (blocks toxin binding), inflammation, antibody-dependent cell-mediated cytotoxicity (NK cells), and activation of complement.

Question 9

What are the 3 subsets of B cells?

Answer 9

Follicular, marginal zone, B-1

Question 10

Describe follicular B cells.

Answer 10

T-dependent, isotype-switched (IgD & IgM), high-affinity antibodies; long-lived plasma cells. Found in spleen, other lymphoid organs. Respond to protein antigen and helper T cell.

Question 11

Describe marginal zone B cells.

Answer 11

T-independent, mainly IgM; short-lived plasma cells. Found in white pulp of spleen. Respond to polysaccharides, lipids, nucleic acids.

Question 12

Describe B1 B cells.

Answer 12

T-independent, mainly IgM; short-lived plasma cells. Found in mucosal tissues, peritoneal cavity. Respond to polysaccharides, lipids, nucleic acids.

Question 13

What does class switching require?

Answer 13

T cell activation

Question 14

What is the signal for class switching?

Answer 14

CD40 ligand

Question 15

What do avidity and affinity of Ig refer to?

Answer 15

Avidity = strength of binding; affinity = specificty

Question 16

What causes affinity maturation?

Answer 16

Continued exposure to antigens increases affinity over time, causing an increase in antibody specificity.

Question 17

What are the secondary immune organs?

Answer 17

Lymph nodes, spleen

Question 18

What is the main job of the red pulp of the spleen?

Answer 18

Filtration - RBC may be attached to opsonins that need to get cleared out.

Question 19

What are people without spleens susceptible to?

Answer 19

Encapsulated organisms - no marginal zone B cells present to encounter them.

Question 20

Where does class switching occur in the secondary immune organs?

Answer 20

Medulla

Question 21

In the generation of antibody diversity, the heavy chain is rearranged first. With this rearrangement of BCR, you will have hypermutation. Define this, and explain its presence/absence in TCR.

Answer 21

Hypermutation - changes to the gene that enhance its specificity, but do not get transmitted to offspring. This is not seen in T cells.

Question 22

B cells must be what in terms of T cells to class switch?

Answer 22

Be T-dependent.

Question 23

What happens in Hyper IgM Syndrome?

Answer 23

Results from mutations affecting class switching (rare). Get a decrease in IgG, IgA, and IgE.

Question 24

What would happen if you had a T Cell that doesn’t express CD40L?

Answer 24

B cell is activated by T cell, but cannot class switch, so you’d only have an IgM response - but this decreases after about a week (not long-lasting). Thus you have a strong initial response that can knock out the organism, but not memory to fight it off at a strengthened initial attack should it come back - susceptible to repeated chronic infections.

Question 25

If you have low levels of any specific Ig, what would you suspect to find in terms of levels of IgM?

Answer 25

They would be increased.

Question 26

Describe IgM.

Answer 26

Pentamer when soluble , 1st Ig made by fetus and B cells, expressed as membrane-bound Ig, Fc receptor on phagocytes binds IgM (opsonization), present in colostrum & mother’s milk to protect newborn, fixes complement. Higher avidity, lower affinity.

Question 27

Describe IgG.

Answer 27

Monomer, major serum Ig, major Ig of secondary immune response, magor Ig in extravascular spaces, transported across placenta, fixes complement, opsonization. Longer lasting immune response because of memory and affinity maturation.

Question 28

Which Ig gives an infant the immunity it needs during the 1st 6 months of its life?

Answer 28

IgG

Question 29

Describe IgA.

Answer 29

Found in serum and body secretions - tears saliva, gastric, pulmonary (major secretory Ig); does not fix complement unless aggregated; present in colostrum & mother’s milk (protects newborn); exists as dimer; gives infant some immunity.

Question 30

Describe IgE.

Answer 30

Least common serum Ig (binds basophils & mast cells without needing Ag), allergic & hypersensitivity reactions, parasitic infections, does not fix complement; precipitates corsslinking after it has encountered antigen 2nd time after initial binding - get degranulation.

Question 31

Describe IgD.

Answer 31

Found on membrane of mature B cells, present in very small amount in serum, does not bind complement, biological function not really understood.

Question 32

How does T cell get activated?

Answer 32

When MHC presents (antigen) peptide to it.

Question 33

What tells the B cell to start class switching?

Answer 33

CD40L on the antigen-specific T cell.

Question 34

What stimulates the costimulatory signal?

Answer 34

CD28 on T cell binds to CD80/86/B7 of B cell.

Question 35

What cytokine from which T cell is responsible for signaling clonal expansion of the B cell?

Answer 35

IL-4 from Th2

Question 36

What cytokine from which T cell is responsible for signaling clonal differentiation of the B cell?

Answer 36

IL-5 from Th2

Question 37

What triggers the process of B cell apoptosis and why?

Answer 37

FasL - kill the B cell if it interacts with something it’s not supposed to, e.g. self-interaction.

Question 38

Explain the classical complement pathway.

Answer 38

C1 binds to antibody complex, allowing it to cleave C2 & C4. C2b joins C4b to make C3 convertase, which either cleaves C3 or makes C35 convertase (in the presence of Properdin). Cleaved C3a creates an inflammatory response. Cleaved C3b opsonizes the antigen. C5 convertase cleaves C5. C5a creates an inflammatory response. C5b forms MAC when it reacts with C6-9. MAC makes a hole in cell membrane, leading to cell lysis.

Question 39

Explain the alternative complement pathway.

Answer 39

Antigen reacts to C3b (always a little bit floating around). In presence of Factor B, Factor D, and Properdin, it forms a complex with these proteins to become C3 convertase. At this point it follows the same steps of the classical pathway, but either cleaving C3 or making C35 convertase (in the presence of Properdin). Cleaved C3a creates an inflammatory response. Cleaved C3b opsonizes the antigen. C5 convertase cleaves C5. C5a creates an inflammatory response. C5b forms MAC when it reacts with C6-9. MAC makes a hole in cell membrane, leading to cell lysis.