Lecture 12 - The adaptive immune system

Question 1

Resting T-cells: what are they and what do they do?

Answer 1

The “resting” T lymphocyte is a medium-sized lymphocyte with a slightly irregular nucleus that patrols the body – each has a unique T-cell receptor (TCR) and if that receptor engages an abnormal cell (e.g. a virally infected cell) it becomes activated

Detect virally infected cells

Question 2

Activated T-cells: what are they and what do they do?

Answer 2

A large cell, often containing granules - These cells develop when a specific antigen that is recognised by their “T-cell receptor” (TCR) is detected. The function of these cells is to kill target cells that contain that antigen

When a T cell encounters its target the TCR send signals that activated the T cell: it becomes larger, more adherent and motile and begins to make proteins that allow it to attack it’s target cell.

Question 3

What are the T-cell’s three main roles and how do they complete them?

Answer 3

• There must be a range of T cells with different receptors that allow to them recognise many different pathogens -
• There must be a mechanism for them to detect those pathogens even when they are “hidden” within cells -
• They must be able to eliminate pathogens successfully and safely -

Question 4

How did different T-cell receptors get added during evolution?

Answer 4

In early prehistoric times, a new gene was acquired by living organisms, likely from a virus, which could be rearranged into many new forms to generate a range of different protein products - using a variable, diversity, and joining regions

This provided the basis to generate the highly variable ‘antigen receptors’ that we now see in B-cells or T-cells

Question 5

What type of receptors are not presented in the T-cell?

Answer 5

Receptors with their two chains not interacting correctly

Receptors detecting ‘self’

Question 6

How do T-cells detect virally infected cells?

Answer 6

Major histocompatibility molecules (MHC)

Showing ‘hidden’ intracellular proteins is the function of the MHC system: All proteins made within a cell are also broken down into peptides that are transported to the cell surface where they are held in a specific peptide binding groove on the MHC molecule

Question 7

Making more reactive T cells

Answer 7

T cells that recognise the antigen are further activated and caused to proliferate through specialist “antigen-presenting cells”. These cells receive antigens from diseased cells brought to the lymph node and present the antigen highly effectively to the T cells.

This process is helped by “helper T cells” in the lymph node that secrete cytokines that ensure the antigen-responsive T cells divide - The second part of the process is the helper T cells which secrete cytokines such as IL-2 that further help the proliferation of the reactive cells

Question 8

Killing infected cells

Answer 8

The cytotoxic T cell specifically binds to infected cells to form a tight specific bond – cell-killing responses are then initiated.

The mechanism of cell killing is important – apoptosis causes the degradation of intracellular proteins including the virus

Question 9

What are two ways that t-cells are killed?

Answer 9

Perforin is released that causes small pores to form in the target cell – through these pores enters granzyme and granulysin – these enzymes cause the target cell to undergo programmed cell death (apoptosis)

FAS – this signalling protein on T cells can bind to FAS ligand on target cells setting up signals that instruct the cell to enter apoptosis.

Question 10

Three other T cell functions

Answer 10

Support of antibody formation CD4+ helper T cells also promote antibody formation linking T cells to the control of B cells (see next lecture)

Interaction with the innate immune system: DAMPS and PAMPS activate antigen presenting cells causing T cell activation – this interaction can promote the adaptive immune response. Conversely, the activated CD4+ T cells may regulate innate immunity

Negative regulation of immune responses: regulatory CD4+ T cells contribute to the down-regulation of immune cell activity

Question 11

B lymphocytes

Answer 11

Small round cell with a dense nucleus

Y-shaped with heavy chains, light chains, and an antigen binding site

If the B-cell recognises a foreign protein it enters lymph nodes, proliferates, and then differentiates into an antibody-producing plasma cell

Question 12

How is antibody diversity formed?

Answer 12

Recombined genes - 15,000,000 potential combinations

Question 13

Affinity mutation: how well can b cells recognise antigens, how are the best antigens produced, and what is affinity mutation?

Answer 13

B cells are able to recognise antigens even better than T cells – after a B cell recognises an antigen, the parent cell divides to make many more B cells each able to form a slightly different antibody – the very best are selected in the lymph nodes and eventually produce the most effective antibodies to bind any given antigen, often supported by helper T cells

This process, which generates increasingly better antibodies as the immune response develops is called “affinity maturation”. Effectively it means the body can generate billions of different antibody structures until the very best are found, selected and become plasma cells

Question 14

What three ways are targets destroyed by plasma cells?

Question 15

Neutralisation

Answer 15

Binding antigens can effectively render them harmless if it binds to a functionally important part – this is the principle of inactivating toxins

Question 16

Opsonisation

Answer 16

The antigen is “tagged” for destruction by cells of the innate system – particularly monocytes and macrophages

Question 17

Complement activation

Answer 17

The complement system is a series of proteins from the blood plasma that can be activated by antibodies – this generates an “attack complex” that destroys the target

Question 18

B/T-Cell deficiency: what happens, how fatal is it, and how can it be remedied?

Answer 18

Leaves the body entirely defenceless against viruses and some other infections – ultimately the only possibility for survival is to have a bone marrow transplant that replaces their defective immune system with a functioning one

Question 19

B/T-Cell deficiency: what clinical situations do they arise in and how do they manifest in?

Answer 19

• HIV/AIDS infection
• Immunosuppressive therapy following organ transplant
• Immunosuppression to treat autoimmune disease

Repeated severe or persistent viral infection
Increase in malignant disorders

Question 20

Rheumatoid arthritis: what is it, what occurs in those who suffer from it, does it

Answer 20

One of the best-known autoimmune disorders where an uncontrolled immune response is provoked against joints

This initially involves autoantibodies where neutrophils release granules causing joint damage and then severe reactions involving the innate system will destroy joints

Modern immune-suppressive treatments now greatly reduce the severity of these reactions

Question 21

Vaccination: what is it, what is the process, what are the examples of its effectiveness, and what is its effectiveness rate?

Answer 21

The use of immunological memory – by introducing a dead virus (or similar preparation), the immune system can be made to mount a response followed by an “immunological memory” which can respond rapidly to a real infection by the same virus with these memory cells.

There are many effective examples e.g. the eradication of smallpox and the major control of polio

Immune systems are different some individuals do not generate an adequate response - most vaccines are highly effective e.g. the MMR vaccine and polio vaccines are each >99% effective after three doses