Introduction immunology - adaptive immune system - L3 Flashcards

1
Q
  • How do B cells kill pathogens?
  • How do CD8+ T cells kill pathogens?
  • How do CD4+ T cells kill pathogens?
A
  • B cells: mature B cell expresses membrane-bound immunoglobulin of a single antigen specificity, When a foreign antigen binds to this immunoglobulin, the B cell is stimulated to proliferate. Its progeny differentiate into plasma cells that secrete antibodies of the same specificity as the membrane-bound immunoglobulin.
  • CD8+ T cells bind to target cell (e.g. virus-infected cell) and releases cytokines to kill the cell.
  • CD4+ T cells can either bind to antigen presenting cell (APC), which leads to secretion of cytokines that aid in the killing of the pathogen within the APC or a CD4+ T cell can bind to an antigen-bound B cell, which causes the T cell to secrete cytokines that aid in the differentiation of the B cell into an antibody-secreting plasma cell.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does an antigen-presenting cell (APC) present the antigen to other cells such as CD4+ T cells?

A

Through the use of MHC molecules, located in- and outside the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

There are two kinds of MHC classes: MHC class I and MHC class II. What is the difference between them?

A
  • MHC class I is able to interact with CD8+ T cells. MHC class I presents antigens from intracellular pathogens independent of what type of cell the antigen is located in.
  • MHC class II is able to interact with CD4+ T cells. MHC class II presents antigens from extracellular pathogens located on antigen presenting cells such as B cells, macrophages and dendritic cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

MHC molecules are polymorphic. What is meant by this?

A

MHC molecules come in various allelic forms. This means that everybody expresses a different set of MHC class I and II molecules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What makes the adaptive immune system adaptive and specific?

A

That the receptors of B and T cells are variable, meaning that each unique B or T cell recognizes a different (set of) pathogen(s).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

T cells undergo a process called positive selection in the thymus by cortical epithelial cells. Describe this process.

A

T cells with a T-cell receptor (TCR) that binds to a self-MHC class I molecule on thymic cortical epithelial cells, macrophages, and other cells in the thymus are signaled to survive and proceed to negative selection. T cells with a TCR that binds to no self-MHC class I molecules are signaled to die.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the process of negative selection of B and T cells?

A

T or B cells with a receptor that binds too tightly to a self-MHC class I molecule on dendritic cells, macrophages, and other cells in the thymus or bone marrow are signaled to die. T or B cells with a receptor that binds moderately to a self-MHC class I molecule on dendritic cells, macrophages, and other cells in the thymus or bone marrow are signaled to survive, mature, and enter the peripheral circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

There are mechanisms to prevent autoimmunity (besides negative selection). Such as:
* natural regulatory T cells
* induced regulatory T cells

Describe these two mechanisms in the prevention of autoimmunity.

A
  • Natural regulatory T cells: are formed in the thymus and are specific for self-antigens
  • Induced regulatory T cells: are formed in the periphery and are specific for self- or microbiota antigens.

Regulatory T cells express IL-10 and TGF-B, which are suppressive cytokines. These cytokine produced by the Treg cells inhibit other self-reactive T cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

When T cells leave the primary lymphoid organ (i.e. the thymus), they are still in an immature stage. How do T cells get activated so that they can help the immune system?

A

When there is an infection, dendritic cells and macrophages phagocytose the pathogens (innate immunity). With this, the antigens of the pathogen get engulfed and dendritic cells and macrophages can act as antigen-presenting cells (APCs) and get transported to lymph bodes to stimulate the adative immune system by presenting the antigens to T cells for T cell activation. The T cells become effector T cells and travel to the infected tissue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is meant with cross-presentation and cross-priming?

A
  • Cross-presentation: when dendritic cells phagocytose an extracellular pathogen, the antigen is presented on the cell-surface by an MHC class I molecule. Normally, MHC class I molecules present intracellular pathogens to CD8+ T cells. Therefore, this way of presenting the antigen to CD8+ T cells is called cross-presentation.
  • Cross-priming: the immune response that is initiated by cross-presentation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Activation of a naive T cell by dendritic cells consists of three signals. Describe these signals.

A
  • Signal 1: antigen presentation by MHC molecule to T cell receptor.
  • Signal 2: Costimulation enables proliferation and survival.
  • Signal 3: Production of cytokines by antigen presenting cell, i.e. dendritic cell, result in differentiation in specific effector T cell.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is meant with clonal selection of T cells?

A

Clonal selection: the expansion of T cell clones that recognize a specific antigen and the differentiation into effector cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

There are specific subsets of CD4+ T cells, namely: Th1, Th2, Th17, Tfh, and Treg cells. Describe which produced cytokine is characteristic for each T cell type and what their main function is.

A
  • Th1: IFN-y, activates macrophages.
  • Th2: IL-4, activates cellular and antibody response to parasites.
  • Th17: IL-17, enhances neutrophil response.
  • Tfh: IL-21, activates B cells to refine antibody response.
  • Treg: TGF-B and IL-10, suppress other effector T cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

There are five different immunoglobulin isotypes: IgG, IgM, IgD, IgA, and IgE. Which immunoglobulin is expressed by naive B cells that have been generated in the bone marrow?

A

IgM and IgD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens with B and T cells after they have been generated in the bone marrow (i.e. primary lymphoid tissue)?

A

B and T cells migrate from the bone marrow (primary lymphoid tissue) to the spleen and other secondary lymphoid tissues by entering high endothelial venules (HEVs) and then migrate to B and T cell areas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain how naive B and T cells are activated.

A
  • Naive B cells search for specific antigens displayed by follicular dendritic cells (FDCs) in the B cell area. Naive T cells search for specific antigens presented by dendritic cells in the T cell area.
  • Antigen-activated B cells migrate to the boundary region of the secondary lymphoid organs (not completely active at this point). Antigen-activated T cells proliferate and differentiate.
  • Antigen-activated B cells present antigen to effector Tfh cells (T-follicular helper cells), forming cognate interactions and cognate pairs.
17
Q

What is meant with the cognate interaction and pairs between acitvated B and Tfh cells?

A

B and Tfh cells form specific interaction based on antigen recognition. Cognate refers to the specificity of the interaction, as each B and Tfh cell pair recognizes a particular antigen. This primarily happens in the T cell area.

18
Q

How does the cognate interaction between B cells and Tfh cells result in the activation of B cells?

A

The cognate interaction between a B cell and Tfh cell results in the production of specific cytokines by the Tfh cell that stimulate the process of B-cell activation.

19
Q

Which antibody is produced/expressed upon initial B cell activation in the medullary cords (i.e. effector B cells/plasma cells)?

A

IgM

20
Q

What happens to other activated B cells that do not differentiate into IgM-secreting plasma cells?

A

They move to the B cell follicle (B cell area), where they start to proliferate and form a germinal center.

21
Q

There are two processes that occur in the germinal center that are dependent on CD4+ T cell help:

  • Somatic hypermutation
  • Isotype switch

Explain these two processes and what the effect is of these processes.

A
  • Somatic hypermutation: the introduction of random, high rate point mutations in the B-cell receptor gene of B cells. It gives rises to B cells bearing mutant immunoglobulin molecules on their surface, with part of these ‘mutant’ B cells having a higher affinity for certain antigens.
  • Isotype switch: The function of the antibody that is expressed by B cells is dependent on its structure. In order to produce other antibodies than the primary immune response of IgM production after B cell activation, isotype switching is required. Here, DNA recombination enables rearrangement of the structure of the isotype, resulting in the production of other antibodies such as IgG, IgA and IgE.
22
Q

Besides the fact that somatic hypermutation can lead to B cell receptors with a higher affinity for certain antigens, it is also possible that somatic hypermutation results in BCRs with a lower affinity for certain antigens. How is this process controlled?

A

This process is controlled by measuring the extend of affinity:

  • a B cell in the germinal center with a low affinity for a specific antigen cannot crosslink and cannot present its antigen and the B cell is stimulated to undergo apoptosis.
  • a B cell in the germinal center with a high affinity for a specific antigen can crosslink and can present its antigen and the B cell is stimulated to for survival.
23
Q

(Not specifically in lecture)

What determines whether a B cell differentiates into an effector B cell or a memory B cell?

A

The cytokine that is produced after cognate interaction/crosslinking with a Tfh cell:
* Tfh produces IL-10 -> effector B cell
* Tfh produces IL-4 -> memory B cell

24
Q

Explain why the following occurs:

  • IgM amount increases after first immunization and decreases at a later time period, whereas IgG amount slowly increases and is highest at a later time period.
  • IgM affinity stays low, IgG affinity increases throughout time.
A
  • The primary antibody response start with low affinity IgM.
  • Due to isotype switching and affinity maturation high affinity IgG develops, therefore, the secondary immune response is characterized by high affinity IgG.
25
Q

Antibodies have three functions, namely:

  • Opsonisation
  • Neutralisation
  • Complement activation

Explain these functions.

A
  • Opsonisation: pathogens are coated by antibodies and tagged for elimination by phagocytes.
  • Neutralisation: binding of antibodies to pathogen prevents interaction/binding of pathogens with healthy tissue (prevents infection).
  • Complement activation: some antibodies are very efficient at activating the complement system, thus indriectly leading to opsonisation or inflammatory responses.
26
Q

Different antibodies have different functions. Describe functions of each antibody isotype.

A
  • IgG: neutralisation, opsonisation, complement activation, tissue diffusion
  • IgM: complement activation
  • IgA: mucosal immunity, neutralisation
  • IgE: anti-parasitic, allergies, mast cell binding