Chapter 5: Overview of lymphocyte activation and adaptive immune responses

Question 1

It is impossible for lymphocytes of every specificity to patrol every possible portal
of antigen entry. How is this problem overcome?

Answer 1

Antigens in epithelia and other tissues are captured by resident dendritic cells, which then carry their antigenic cargo to draining lymph nodes through which T cells constantly recirculate. Here the antigens are processed and displayed complexed with MHC molecules on the cell surface, where the antigens are recognized by T cells.

Question 2

What happens at the same time as microbial antigens are recognized by T and B lymphocytes?

Answer 2

The microbe activates innate immune cells expressing pattern recognition receptors.

Question 3

What is a microbial mimic called in a vaccine?

Answer 3

An adjuvant.

Question 4

What happens when a microbe enters the body?

Answer 4

APCs, like dendritic cells, recognise the antigen and bind with it. The APCs bring the antigen towards peripheral lymphoid organs. Here, the antigen activates APCs to express costimulators (so that the APC can bind with a lymphoid cell) and it also stimulates the secretion of cytokines that stimulate the proliferation and differentiation of T lymphocytes.

Question 5

What is signal 1 of T- cell activation?

Answer 5

When an APC brings the antigen to peripheral organs, it binds with a T cell (either CD4+ or CD8+) through the MHC complex on the APC. This triggers initial activation (signal 1).

Question 6

What is signal 2 of T-cell activation?

Answer 6

This signal is provided by a co-stimulatory molecule called CD28 on the T cell which binds with APC. Upon binding it initiates T cell proliferation.

Question 7

What happens first after a naive CD4+ T cell is bound to an antigen via an APC?

Answer 7

It secretes the cytokine IL-2 and expresses a receptor for IL-2. The growthfactor stimulates their proliferation, leiding to an increase in the number of antigen-specific lymphocytes.

Question 8

What else happens when a CD4+

helper T cell recognizes a antigen being displayed by macrophages or B lymphocytes?

Answer 8

The T cell expresses CD40L (ligand), which can interact/bind with CD40 (receptor) on the macrophages or B cells and activates these cells.

Question 9

What is meant by a classical macrophage activation?

Answer 9

The combination of CD40- and IFN-γ–mediated activation results in the activation of macrophages. This causes macrophages to take up microbial substances and destroy them.

Question 10

What is meant by an alternative macrophage activation?

Answer 10

Th2 cells produces IL-13 (among others) which induces the activation of macrophages. These macrophages play a role in tissue repair and fibrosis.

Question 11

In response to stimuli (mainly cytokines) present at the time of antigen recognition (with the help of an APC), naive CD4+ T cells may differentiate into populations of effector cells that produce distinct sets of cytokines that act on different cells and mediate different

functions. Answer the following questions about Th1:
1. What cytokines induce the production of Th1 cells?
2. What cytokines do they produce?
3. What is activated as reaction to the cytokines produced by Th1?
4. Against what kind of pathogens are Th1 cells produced?
5. In which disease do Th1 cells play a role?

Answer 11

1. They are produced when IFN-γ or IL-12 is present.
2. They produce IFN-γ
3. Cytokine IFN-γ activates macrophages, antibody IgG is produced.
4. Their host defense is against intracellular microbes.
5. They play a role in autoimmune and other chronic inflammatory diseases.

Question 12

In response to stimuli (mainly cytokines) present at the time of antigen recognition (with the help of an APC), naive CD4+ T cells may differentiate into populations of effector cells that produce distinct sets of cytokines that act on different cells and mediate different

functions. Answer the following questions about Th2:
1. What cytokines induce the production of Th2 cells?
2. What cytokines do they produce?
3. What is activated as reaction to the cytokines produced by Th2?
4. Against what kind of pathogens are Th2 cells produced?
5. In which disease do Th2 cells play a role?

Answer 12

1. They are produced when IL-4 is present.
2. They produce IL-4, IL-5, IL-13.
3. They stimulate IgE production and activate mast cells and eosinophils.
4. Their host defense is against helminthic parasites.
5. They play a role during allergies.

Question 13

In response to stimuli (mainly cytokines) present at the time of antigen recognition (with the help of an APC), naive CD4+ T cells may differentiate into populations of effector cells that produce distinct sets of cytokines that act on different cells and mediate different

functions. Answer the following questions about Th17:
1. What cytokines induce the production of Th17 cells?
2. What cytokines do they produce?
3. What is activated as reaction to the cytokines produced by Th17?
4. Against what kind of pathogens are Th17 cells produced?
5. In which disease do Th17 cells play a role?

Answer 13

1. They are produced when TGF-b, IL-6, IL-1, IL-23 is present.
2. They produce IL-17 and IL-22.
3. They recruit neutrophils and monocytes.
4. Their host defense is against extracellular microbes.
5. They play a role in autoimmune and other chronic inflammatory diseases.

Question 14

Activated CD8+ T lymphocytes differentiate into CTLs that kill cells harboring cytoplasmic microbes. This is based on a perforin-granzyme system, how does this system work?

Answer 14

Perforin and granzymes are stored in granules. When a CTL binds with its target, the granules are released. Here, perforing binds to the plasma membrane of the target which promotes the entry of granzymes. Granzymes are proteases that specifically cleave and activate cellular caspases which induces apoptosis of the target cell.

Question 15

While CD28 provides the second co-stimulatory signal that induces proliferation of lymphocytes when bound to APC, there are also inhibitory receptors that can terminate/block the signal from CD28. Name two receptors that can do this.

Answer 15

CTLA-4 and PD-1.

Question 16

Which two pathways are there to activate B cells?

Answer 16

T cell-independent and T cell-dependent B cell activation.

Question 17

What is T cell-independent B cell activation?

Answer 17

Many polysaccharide and lipid antigens have multiple identical antigenic epitopes. Upon recognition of such microbes with repetitive epitopes, the microbe is coated with antibodies. These antibodies can bind with the B cell through cross-linking, through an intracellular cascade this activates the B cell.

Question 18

What is T cell-dependent activation?

Answer 18

Most globular proteins lack a repetition of epitopes and therefore cannot be coated with antibodies. This makes the B cell unable to get activated (because no crosslinking can occur), so it needs the help of CD4+ T cells. Here, the B cell acts as an APC. The B cell ingests the protein antigens, degrades them and displays the peptides bound to class II MHC molecules on the surface, where helper T cells can recognise the antigen. When a helper T cell binds to the antigen, it will express CD40L and activate the B cell.

Question 19

Some of the progeny of the expanded B-cell clones differentiate into antibody-secreting plasma cells. What determines which antibody is secreted by the plasma cells?

Answer 19

The type of antigen (small molecules or bigger molecules).

Question 20

What type of antigen stimulates the secretion of IgM?

Answer 20

Lipids and polysaccharides.

Question 21

What type of antigen stimulates the secretion of other antibodies (IgG, IgA, IgE)?

Answer 21

Protein antigens (through T cell-dependent B cell activation).

Question 22

What is production of functionally different antibodies, all with the same specifity, based on?

Answer 22

On heavy-chain class (isotype) switching. After T cell-dependent B cell activation`isotype switching occurs, where IgG, IgA and IgE are produced.

Question 23

What are typical functions of IgG?

Answer 23

Opsonization and transplacental transfer.

Question 24

IgA mostly resides in what kind of tissue?

Answer 24

Mucosal lumen

Question 25

IgE mostly binds to what kind of cells?

Answer 25

Mast cells

Question 26

What is the process of affinity maturation, which cells help this process?

Answer 26

Helper T cells (specifically follicular helper T (Tfh) cells) stimulate the producion of antibodies with higher affinity for the antigen.

Question 27

What is the location where isotype switching and affinity maturation occurs?

Answer 27

In the follicles of the germinal center.

Question 28

Match antibodies (IgG, IgM, IgA, IgE) with its functions: opsonization, activation of complement system, neutralizing microbes in the lumen of the respiratory and gastrointestinal tracts, protects newborns through transplacental transfer, functions with mast cells and eosinophils to kill parasites.

Answer 28

IgG: opsonization, activation of complement system, protects newborns through transplacental transfer.
IgM: activation of complement system
IgA: neutralizing microbes in the lumen of the respiratory and gastrointestinal tracts
IgE: functions with mast cells and eosinophils to kill parasites.

Question 29

What is the reason that circulating IgG antibodies have half-lifes af about 3 weeks, which is much longer than the half-lives of most blood proteins?

Answer 29

IgG is recycled and it can reduce its own catabolism.

Question 30

Why is the generation of memory cells an important goal of vaccination?

Answer 30

Memory cells are generated upon initial activation of lymphocytes, they may survive for years after infection and can respond much faster and more effectively when reexposed to the antigen in comparison to naïve cells.