Immune System 3

Question 1

Describe the development of B lymphocytes.

Answer 1

• Generation of B-cell receptors in the bone marrow
• Negative selection in the bone marrow
• Migration of B cells through the circulatory system to lymphoid organs and B-cell activation
• Antibody secretion and memory cells in bone marrow and lymphoid tissue

Question 2

Describe the activation of B cells leading to antibody production.

Answer 2

• Mature B cells enter a secondary lymphoid tissue
• In absence of its specific antigen B cell leaves the lymph node and recirculate
• Naive B cells encounter an antigen in a secondary lymphoid tissue
• Antigen-specific B cells are further activated by helper T cells
• Some proliferate in the primary follicle and differentiate into plasma cells which secrete IgM antibody and fight infection (primary response)
• Others migrate in a secondary lymphoid follicle where they mature slowly - once completely differentiated they turn into plasma cells secreting high affinity antibodies
• As primary response subsides B cells in the secondary lymphoid follicle also develop into memory B cells
• At a second encounter with the same antigen these memory B cells will rapidly activate and develop a secondary quicker and stronger antibody response

Question 3

Describe the structure of T cell receptor

Answer 3

• Made of 2 polypeptide chains - alpha and beta
• Each chain have a variable and constant region
• Each V chain contains 3 CDRs

Question 4

State the difference between T cell receptors and antibodies.

Answer 4

• T cell receptors always stick on the surface of T cells unlike antibodies
• T cell receptors act in a complex
• TCR can only detect antigens that are located on the surface of MHC molecules (located on our cells)

Question 5

Describe MHC class 1

Answer 5

• Expressed on all nucleated cells
• Binds TCR of CD8+ T cells

Question 6

Describe MHC class 2

Answer 6

• Mainly expressed on APC
• Binds TCR of CD4 T helper cells

Question 7

Describe the process of endogenous antigen presentation to CD8+ T cells.

Answer 7

• Proteins from pathogens are made in the cytoplasm are presented by MHC class 1 molecules
• Proteins must be processed to peptides before binding
• All nucleated cells have MHC class 1 molecules so any cell infected by virus can be killed by cytotoxic CD8 T cells

Question 8

Describe the process of exogenous antigen presentation to CD4 T helper cells.

Answer 8

• Exogenous antigens are internalised and presented by MHC class 2
• Proteins processed to peptides before binding
• APCs activate helper CD4 T cells

Question 9

Describe the similarities between B cell development and T cell development.

Answer 9

• originate from bone marrow stem cells
• rearrange receptor genes
• express pre-T receptor
• elimination of self-reactive T cells (negative selection)

Question 10

State the differences between T cell development and B cell development.

Answer 10

• T cells undergo development in thymus
• alternative lineages: CD4+ OR CD8+ must be able to interact with self MHC
• Positive selection (elimination of non-functioning cells)

Question 11

Describe the development of T cells.

Answer 11

• T cell progenitors develop in the bone marrow and migrate to the thymus
• Positive and negative selection in the thymus
• Mature T cells migrate to the peripheral lymphoid organs
• Activated T cells migrate to sites of infection

Question 12

What can an immature T cell recognise when they leave the bone marrow and migrate into the thymus?

Answer 12

1. can recognise self MHC and respond to a foreign peptide (defence)
2. Recognise and respond to self MHC plus SELF peptide (danger); eliminated by negative selection
3. No recognition of self-MHC (useless); eliminated by positive selection

Question 13

Describe positive selection of T cells.

Answer 13

• select T cells with a TCR that is able to bind to MHC + self peptide
• Occurs when the TCR of double-positive (CD4+ CD8+) T cells recognise MHC molecules expressed on cortical epithelial cells
• These then move to medulla and mature to single positive cells

Question 14

Describe negative selection.

Answer 14

• Removes cells with a TCR binding tightly to self peptides
• Occurs when the TCR of CD4 or CD8 T cells recognise MHC molecules expressed on dendritic cells/macrophages with high affinity
• T cells with moderate binding to MHC-self peptides complexes are allowed to survive

Question 15

How do activated T cells acquire effector functions in the secondary lymphoid tissue?

Answer 15

Must encounter an antigen presented by dendritic cells and interact with co-stimulatory molecules

Question 16

Describe the function of activated T cells.

Answer 16

1. CD8+ T cells acquire cytotoxic activity - kill cells bearing the MHC 1 - peptide complex
2. CD4+ T cells mainly function by secreting cytokines - help other cell types

Question 17

Once TCR has acquired effector functions what happens?

Answer 17

• no longer require co-stimulation
• change of location; no longer enter lymph nodes instead enter tissues via activated endothelial at sites of infection and inflammation

Question 18

Describe the two ways to activate CD8 T cells.

Answer 18

1) CD8+ responses can be directly activated from infected cells presenting MHC 1/peptide complexes
2) Require help from CD4+ T cell to get activated

Question 19

Describe the mechanisms of killing by cytotoxic CD8+ T cells.

Answer 19

1) secretion of cytotoxic granules - perforin, polymerises in membrane and granzymes (proteases) enter cell
2) fas ligand on T cell interacts with fas on target
3) Can also secrete cytokines - secrete gama IFN which inhibits viral replication, up regulates MHC class 1 expression and antigen presentation and increases macrophage phagocytosis of dead cells.

Question 20

State the 4 types of specific CD4+ T helper cells and their functions.

Answer 20

TH1 - active against intracellular bacteria + help macrophages

TH2 - active against extracellular bacteria + help the B cells

TH17 - active against extracellular pathogens + help the neutrophils with phagocytosis

TFH - supporting B cells maturation

Treg - regulatory cells e.g. inhibit antigen presentation to T cells to reduce autoimmunity