Lecture 16 The Gastrointestinal System PT3 - Immune response

Question 1

How are CD8 cytotoxic T cells (CTLs) activated during infection?

Answer 1

CD8 cytotoxic T cells are activated when:

Their T cell receptor (TCR) recognizes antigenic peptides presented by MHC class I molecules on the surface of infected cells.
Costimulatory signals from antigen-presenting cells (APCs), such as CD80/CD86 binding to CD28 on the T cell.
Cytokines like IL-2 promote the proliferation and activation of CTLs.

Question 2

What mechanisms do CTLs and NK cells use to eradicate infected cells?

Answer 2

CTLs and NK cells use the following mechanisms to eradicate infected cells:

Perforin and Granzyme: Perforin forms pores in the target cell membrane, allowing Granzyme to enter and induce apoptosis.
Fas-FasL pathway: CTLs express FasL, which binds to Fas on target cells, triggering apoptosis.
NK cells can also recognize and kill cells lacking MHC class I via activating receptors.

Question 3

What are the key differences and similarities between T cell receptors (TCRs) and B cell receptors (BCRs)?

Answer 3

TCRs recognize peptides presented by MHC molecules on other cells, while BCRs recognize free antigens in their native form.
TCRs are membrane-bound and do not get secreted, whereas BCRs can be secreted as antibodies.
Both TCRs and BCRs are highly specific and undergo recombination to generate diversity.
Both signal through associated complexes (CD3 for TCRs, Iga/Igß for BCRs).

Question 4

Describe the composition and functions of BCRs and antibodies.

Answer 4

BCR composition: A membrane-bound immunoglobulin with two heavy chains and two light chains. It has an antigen-binding site and is associated with Iga/Igß for signaling.
Antibody functions: Secreted form of BCR that neutralizes pathogens, opsonizes microbes for phagocytosis, and activates the complement system.

Question 5

How does diversity in BCRs arise?

Answer 5

BCR diversity arises through:

V(D)J recombination: Random recombination of variable (V), diversity (D), and joining (J) gene segments.
Junctional diversity: Addition or deletion of nucleotides at gene segment junctions.
Somatic hypermutation: Occurs in activated B cells, introducing mutations in the variable region to increase affinity.
Class switching: Changes the constant region to produce different antibody isotypes without altering antigen specificity.

Question 6

What are the steps in the maturation of B cells?

Answer 6

Pro-B cell: Rearrangement of heavy chain genes.
Pre-B cell: Expression of the rearranged heavy chain along with a surrogate light chain.
Immature B cell: Surface expression of a complete BCR with light and heavy chains.
Mature B cell: Expression of both IgM and IgD BCRs on the surface, ready to respond to antigens.
Activation: Upon encountering an antigen, mature B cells can differentiate into plasma cells or memory B cells.

Question 7

How do CTLs (Cytotoxic T Lymphocytes) work?

Answer 7

CTLs are a type of CD8+ T cell that play a crucial role in killing virus-infected and tumor cells.

Mechanism of Action:
CTLs recognize and bind to infected or abnormal cells via their T Cell Receptor (TCR), which interacts with MHC class I molecules presenting viral peptides on the surface of infected cells.
Once activated, CTLs release perforin and granzyme:
Perforin forms pores in the membrane of the target cell.
Granzyme enters through these pores and induces apoptosis (programmed cell death).
CTLs can also trigger cell death via the Fas-FasL pathway, where the FasL on the CTL binds to the Fas receptor on the target cell, initiating apoptosis.

Question 8

How do we activate B cells?

Answer 8

B cells are activated through a series of interactions with antigens and helper T cells.

Activation Process:
Antigen Binding: A B cell receptor (BCR) binds to a specific antigen on the surface of a pathogen or soluble antigen.
T Cell Help:
In most cases, B cells also require assistance from helper T cells (CD4+ T cells) to become fully activated.
The B cell presents the processed antigen on MHC class II molecules to the helper T cell.
The T cell then releases cytokines (such as IL-4, IL-5, and IL-21) that help drive B cell activation, proliferation, and differentiation.
Clonal Expansion: Once activated, B cells undergo clonal expansion and differentiate into:
Plasma cells: These cells produce and secrete large amounts of antibodies.
Memory B cells: These cells persist and provide a rapid response upon subsequent exposure to the same antigen.

Question 9

How are antibodies made?

Answer 9

Antibodies are produced by plasma cells, which are the differentiated form of activated B cells.

Production Process:
After B cells are activated and interact with T helper cells, they differentiate into plasma cells.
Plasma cells are specialized for secreting large quantities of antibodies (also called immunoglobulins) into circulation to neutralize pathogens.
The class of antibody produced (IgG, IgA, IgM, etc.) is influenced by class-switch recombination, which is driven by cytokines and signals from helper T cells.

Question 10

What do the different types of antibodies do?

Answer 10

Antibodies (immunoglobulins) have different classes, each with unique functions in the immune response:

IgM:

The first antibody produced during an immune response.
Effective at activating the complement system.
Found mainly in the bloodstream.
IgG:

The most abundant antibody in blood and extracellular fluid.
Crosses the placenta to provide passive immunity to the fetus.
Plays a major role in opsonization, neutralization of toxins, and activation of complement.
IgA:

Found in mucosal areas (like the gut, respiratory tract, and urogenital tract) and in secretions (saliva, tears, breast milk).
Protects mucosal surfaces by preventing the attachment of pathogens.
IgE:

Involved in allergic reactions by binding to mast cells and basophils.
Plays a role in defense against parasitic infections.
IgD:

Functions primarily as a receptor on naive B cells and plays a role in the initiation of B cell activation.

Question 11

How do CTLs (Cytotoxic T Lymphocytes) work?

Answer 11

Cytotoxic T lymphocytes (CTLs) play a critical role in the immune system by targeting and killing infected or abnormal cells.

Mechanism:
CTLs recognize and bind to infected cells via T-cell receptors (TCRs), which interact with MHC class I molecules presenting viral peptides.
Once bound, CTLs release perforins and granzymes:
Perforins form pores in the infected cell’s membrane.
Granzymes enter through these pores and trigger apoptosis (programmed cell death).
CTLs can also use the Fas-FasL pathway to induce apoptosis by engaging Fas receptors on the target cell.

Question 12

How are B cells activated?

Answer 12

B cells require two signals for full activation:

Signal 1: Antigen Binding: B cells encounter their specific antigen and bind it through their B-cell receptor (BCR).
Signal 2: T-Helper Cells: In most cases, B cells require help from T-helper cells (CD4+ cells), which provide a secondary signal by recognizing antigen fragments presented on MHC class II molecules on the B cell. The helper T cell secretes cytokines such as IL-4 and IL-5, promoting B-cell activation.
Activated B cells proliferate and differentiate into:
Plasma cells: Secrete large quantities of antibodies.
Memory B cells: Provide long-term immunity

Question 13

How are antibodies made?

Answer 13

Once B cells are activated and differentiated into plasma cells, they begin secreting antibodies.

Antibodies (immunoglobulins) are Y-shaped proteins that recognize and bind specific antigens.
The process involves:
B cells capture an antigen.
Present the antigen to helper T cells.
Once activated, B cells undergo class switching and affinity maturation to optimize the antibody response.
The result is the production of high-affinity antibodies.

Question 14

What do the different types of antibodies do?

Answer 14

IgM:
First antibody produced in an immune response.
Effective at activating the complement system.
IgG:
Most abundant antibody in circulation.
Crosses the placenta to protect the fetus.
Neutralizes pathogens, opsonizes antigens for phagocytosis, and activates complement.
IgA:
Found in mucosal areas and body secretions (saliva, tears, breast milk).
Protects mucosal surfaces.
IgE:
Involved in allergic reactions.
Activates mast cells and basophils to release histamine.
IgD:
Functions as a BCR on naive B cells and is involved in the activation of B cells.

Question 15

How does poliovirus enter and spread within the body + immune respsonse?

Answer 15

Back:

Entry via fecal-oral route.
Replicates in the gastrointestinal tract (GI), particularly in the Peyer’s patches.
Primary viremia circulates the virus through the body.
Secondary viremia targets tissues such as the brain and meninges, potentially causing encephalitis and paralysis.
Immune response includes:
Innate immune defenses: IFN and NK cells.
T cells clear infected cells.
Antibodies prevent viremia and reinfection

Question 16

What are the steps for activating CD8+ cytotoxic T cells (CTLs)?

Answer 16

Back:

Viruses are intracellular pathogens.
Viral proteins synthesized by the host are degraded by the proteasome.
MHC-I molecules display viral peptides.
CD8+ T cells recognize these MHC-peptide complexes and become effector CTLs.
Naive T cells require two signals:
Antigen-MHC I recognition.
Co-stimulation by APCs (CD28 and cytokines).
Effector CTLs kill infected cells by releasing perforin and granzyme

Question 17

How is diversity in naive T cells generated?

Answer 17

Back:

Naive T cells undergo V(D)J recombination, creating a large diversity of T-cell receptors (TCRs).
Weak TCRs that bind MHC-self peptides survive through positive selection.
Negative selection eliminates T cells with strong affinity for MHC-self peptide complexes.
Some T cells with specific TCRs that recognize MHC-viral peptide complexes proliferate and differentiate during infection.

Question 18

What is cross-presentation, and why is it important?

Answer 18

Back:

Dendritic cells (DCs) phagocytose extracellular antigens and present them on MHC-I molecules (normally used for intracellular antigens).
This process is called cross-presentation.
It allows dendritic cells to activate CD8+ T cells, even when the DCs themselves are not infected by the virus.
Important for generating CTLs against viruses that do not infect antigen-presenting cells (APCs) directly

Question 19

How do CD4+ T cells assist CD8+ T cells in gaining effector functions?

Answer 19

Back:

Th1 CD4+ T cells help by secreting IFN-γ and expressing CD40L, which:
Increases MHC-I and MHC-II expression.
Enhances costimulatory molecules on APCs.
IL-2 is secreted to stimulate clonal expansion of CD8+ T cells.

Question 20

Describe the Fas-FasL pathway in CTL-mediated killing.

Answer 20

Back:

CTLs express FasL (Fas ligand) on their surface.
FasL binds to Fas receptors on target cells, triggering apoptosis.
This pathway requires MHC-viral peptide recognition and allows CTLs to kill infected cells via apoptosis.

Question 21

What are the two main mechanisms used by CTLs to kill infected cells?

Answer 21

Back:

Perforin-Granzyme pathway:
Perforin creates pores in the target cell membrane.
Granzymes enter and activate caspases, leading to apoptosis.
Fas-FasL pathway:
CTLs express FasL, which binds to Fas on target cells, initiating apoptosis.

Question 22

How do memory CTLs respond to a viral reinfection?

Answer 22

Back:

During the first viral encounter, effector CTLs proliferate and differentiate.
Memory CTLs are formed after the initial infection.
Upon reinfection, memory CTLs rapidly respond, limiting viral replication more efficiently than during the primary infection.

Question 23

Outline the lifecycle of cytotoxic T lymphocytes (CTLs).

Answer 23

Back:

Activation of naive CD8+ T cells into CTLs via MHC-I peptide presentation and co-stimulation.
Clonal expansion and differentiation into effector and memory CTLs.
Killing of infected cells via perforin-granzyme or Fas-FasL.
Contraction of effector population post-infection.
Memory CTLs remain for faster response upon re-exposure.

Question 24

How are CD8 Cytotoxic T Cells (CTLs) activated during infection?

Answer 24

Answer: Viral proteins are processed and presented on MHC-I molecules by APCs. CD8+ T cells recognize these complexes, requiring additional co-stimulation from APCs and cytokines for full activation.

Question 25

How do CTLs and NK cells eradicate infected cells?

Answer 25

Answer: CTLs kill infected cells by releasing perforins and granzymes, leading to apoptosis. NK cells detect missing or altered MHC-I molecules and similarly release perforins and granzymes to kill target cells.

Question 26

Compare and contrast T-cell receptors (TCR) and B-cell receptors (BCR).

Answer 26

Answer:
TCR: Recognizes processed antigen peptides presented by MHC molecules. Restricted to protein antigens.
BCR: Can recognize a broad range of molecules (proteins, polysaccharides, lipids) directly without MHC presentation.

Question 27

What is the composition of BCRs and antibodies?

Answer 27

Answer: BCRs are membrane-bound antibodies with variable (V) and constant (C) regions. Antibodies are secreted forms of BCRs, with five isotypes: IgM, IgG, IgA, IgD, and IgE.

Question 28

What are the steps in B cell maturation?

Answer 28

Answer: B cells mature in the bone marrow. Heavy chain rearranges first, followed by light chain recombination. Immature B cells express IgM and undergo positive and negative selection before maturing and expressing IgD.

Question 29

What immune responses are involved in fighting poliovirus?

Answer 29

Answer: The immune system uses innate defenses like IFN and NK cells, T cells to clear infected cells, and antibodies to prevent viremia and reinfection.

Question 30

What is cross-presentation, and why is it important?

Answer 30

Answer: Cross-presentation occurs when dendritic cells present extracellular antigens on MHC-I molecules, critical for activating CD8 T cells when DCs are not directly infected.

Question 31

What mechanisms do CTLs use to kill infected cells?

Answer 31

Answer: CTLs release perforins to form pores in the target cell membrane, allowing granzymes to enter and induce apoptosis. CTLs also produce IFN-γ to enhance immune responses.

Question 32

What do B cell receptors (BCRs) recognize?

Answer 32

Answer: BCRs recognize proteins, polysaccharides, lipids, and nucleic acids, either as free-floating antigens or surface-bound. They have highly specific antigen-BCR interactions.