14. T and B lymphocytes, NK cells and adaptive

Question 1

problem with viruses

Answer 1

they hide within cells using the host cells own machinery to proliferate, so not easily recognised by cells of the innate immune system
t lymphocyte system has evolved to meet this problem

Question 2

T lymphocytes (resting)

Answer 2

medium sized lymphocyte with slightly irregular nucleus that patrols the body, each has a unique T cell receptor (TCR) that when engaged with an abnormal cell (eg a virally infected cell) becomes activated
important it stays in a nonreactive state when not needed

Question 3

the activated cytotoxic T cell

Answer 3

when a T cell encounters its target the TCR sends signals that activate the T cell so it becomes larger, more adherent and motile, begins to make proteins that allow it to attack its target cell
A large cell, often containing granules. These cells develop when a specific antigen is present. Their function is to kill target cells

Question 4

t cells need to be able to

Answer 4

Be able to recognise many different pathogens
To detect those pathogens “hidden” within cells
Eliminate pathogens successfully and safely

Question 5

generating a wide range of receptors

Answer 5

To recognise many different unknown pathogens: we need to generate a wide range of different antigen binding receptors
The T cell evolved to be part of the white cell system relatively late: it could only develop once cells developed the capability to make receptors that could recognise many different targets This happened after an early ancestor organism acquired a new gene that could be rearranged into many new forms to generate a range of different protein products. This provided the basis to generate the highly variable structures that we now see in B-cell or T-cell receptors.

The capability to generate many different receptors patterns allows the T and B cells to recognise toxins, viruses or other pathogens.

Question 6

diversity of t cell receptors

Answer 6

parent gene has variable region,diversity region and joining region
During its development each individual T cell rearranges the T-cell receptor gene into a different structure by breaking and then recombining the 3 different parts of the parent gene in a different way. This means each individual T cell generates a single unique receptor for itself.
Each receptor has two chains the rearranged genes form many different receptor pattern.

This means each T cell can (potentially) recognise a different abnormal target.

Question 7

t cell receptor selection process

Answer 7

The T cell receptor is formed with two chains. A selection process now operates so that only the most effective T cells survive and circulate.

1. If the two chains cannot interact and correctly form a receptor the cell is eliminated
2. If the receptor recognises a “self” i.e. attacks normal tissues it is eliminated
3. Cells that successfully assemble the receptor and do not attack the bodies own tissues enter circulation

The elimination of “self reactive” Y cells takes place in the thymus gland and is referred to as “thymic conditioning”

Question 8

successful T cells

Answer 8

At the end of this process we have “successful T cells” each has a unique receptor that is capable of recognising a different antigen. Importantly these should not react with the bodies own cells.
It is estimated that the T cells in our bodies have around 100 million different receptors to recognise a wide range of abnormal proteins
Each T cell has only has one type of receptor so can only recognise a single abnormal protein.

Question 9

viral infection

Answer 9

Viral proteins are expressed within the cell
Theoretically a virus is hidden from the immune system.
The T cell system has evolved to find these hidden proteins

Question 10

how do we detect pathogens hidden within cells

Answer 10

major histocompatibility molecules (MHC): function is to find hidden proteins
- all proteins made within a cell are also broken down into peptides that are transported to the cell surface where theyre held in a specific peptide binding groove on the MHC molecule. theyre therefore visible to immune cells which can see the proteins made within the cell, including any abnormal (eg viral proteins) being manufactured. detects foreign proteins

Question 11

detect viruses hidden within cellss

Answer 11

things making proteins within a cell include viruses, these are non self proteins
peptides of viral protein displayed on cell surface with MHC molecule
viruses can therefore be seen by the immune system
specific t cell has receptor that recognises displayed peptide as viral protein and recognises non self
Since each T cell has a unique receptor it is very likely that one or more T cells will recognise the MHC/viral peptide as being non-self.

Question 12

responding to pathogens within cells

Answer 12

making more reactive t cells
there is a system of antigen presenting cells in lymph nodes that present antigens from diseased cells to T cells and ensure that those T cells that recognise a particular antigen encouraged to divide and to make many more copies of themselves so that a large number of cytotoxic T cells are formed and able to eliminate the virally infected cells.

Question 13

helper T cells

Answer 13

help the process of making more reactive t cells
are in the lymph node and secrete cytokines that ensure the antigen responsive t cells divide , further helps the proliferation of the reactive cells
occurs in the lymph glands close to the site of infection,

Question 14

killing the infected cells

Answer 14

the cytotoxic t cells formed after interaction with the antigen presenting cell and helper T cells now move into the blood or tissues where theyre able to recognise virally infected cells
cytotoxic t cell identifies a cell displaying viral proteins on its MHC molecules and binds to the target cell using adhesion receptors though the MHC molecules and a range of “accessory” molecules to form a tight specific bond
cell killing responses then initiated

Question 15

how does a cytotoxic T cell kill

Answer 15

cell is given instruction to die

1. 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)
2. 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 16

why apoptosis of infected cells

Answer 16

Programmed cell death (apoptosis) causes cells to activate enzymes that break down all internal components including any virus preventing further spread

Question 17

natural killer cells

Answer 17

Viruses may attempt to evade T cells by reducing MHC expression and therefore becoming invisible to T cells – killing such cells is the function of Natural killer (NK) cells.

Question 18

structure of natural killer cells

Answer 18

Plentiful pale cytoplasm that often seems to flow to surrounding cells
Nucleus is square and bland in the inactive state
Course blue granules

Question 19

natural killer cells action

Answer 19

NK cells recognise reduced or absent MHC antigens on cells.

Any cell with reduced MHC is considered abnormal and therefore destroyed.
When non-self is recognised:

“Secretory lysosome” perforates target cells contains granzyme and perforin that induce apoptosis and death of target cells (similar to T cells)

Question 20

b lymphocytes role and function

Answer 20

small round cell with a dense nucleus
function is to make antibodies
most B lymphocytes circulate in resting state until activation when they recognise a foreign protein by the B cell receptor BCR
b cell then enters lymph nodes, proliferates, then differentitates into an antibody producing plasma cell

Question 21

plasma cell

Answer 21

the mature antibody-secreting form of the B Lymphocyte.
Plasma cells are usually formed in bone marrow and do not circulate. The antibodies are produced in large amounts. 
function – to make a single type of antibody that will recognise a foreign molecule (antigen).

Question 22

basic antibody structure

Answer 22

Y antigen binding site, light chains at top and heavy chains
ANTIBODIES: This is the simplest (IgG form) – there are a number of different forms, but all share similar principles
In essence it has a Y shape with the upper part binding the foreign protein (antigen) and the lower part allowing its killing functions

Question 23

why do we need antibodies

Answer 23

The purpose of antibodies is to do things that other immune cells cannot – to recognise small antigens such as toxins or components of viriuses or bacteria.
to recognise soluble or surface antigens

Question 24

diversity of antibodies

Answer 24

Antibodies are even more diverse than T cell receptors!
The initial formation is similar to the T cell receptor – VDJ recombination generates around 15, 000 000 distinct antibodies
The range of potential targets is huge so each different B cell is able to form a unique antibody using genetic recombination
variable diversity and joining regions
this allows the initial response to antigen to occur, although the optimal antibody is not yet formed

Question 25

how does antibody differ from the t cell receptor

Answer 25

has a second wave of variability occurs after a b cell encounters antigen (somatic hypermutation). allows billion of different antibody types to be generated ie rearrangegd gene has further mutation that creates even more variability in the gene The best of the newly mutated antibodies are selected (affinity maturation). This causes a secondary response producing antibodies of very high affinity

Question 26

how can b cells recognise antigens better than T cells

Answer 26

– after a B cell recognises and antigen, the parent cell divides to make many more B cells each with able to form a slightly different antibody – the very best are selected and eventually produce the most effective antibodies to bind any given antigen. This process, that generates increasingly good 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 27

b cell system

Answer 27

This process is also controlled by antigen presenting cells and T helper cells which encourage the proliferation of cells that have the most effective antibodies B cell development is assisted by antigen presenting cells and T-helper cells.

Question 28

methods of destruction

Answer 28

1. Neutralisation Simply binding antigens can effectively render them harmless – this is the principle of inactivating toxins 2. Opsinisation The antigen is “tagged” as foreign for destruction by cells of the innate system – particularly by phagocytes like monocytes and macrophages 3. Complement activation The complement system is a series of proteins that can be activated by antibody – this generates an “attack complex” that destroys the target. enzymes from the blood are bound to the antibody and activated these then destroy any molecule or cell that the antibody is bound to.

Question 29

immunological memory to pathogens

Answer 29

Once an immune response is completed then cells that responded to the original initiating antigen are retained as “memory cells” these allow a rapid response if the antigen is encountered again. adaptive immune system – those B (or T cells) that recognise an antigen persist to provide memory of the antigen they recognise in case it is ever encountered again – this allows a much more rapid response to be set in place through “immunological memory”. This is the principle used in vaccination.

Question 30

b or t cell deficiency

Answer 30

Deficiency of B or T cells leaves the body entirely defenceless against viruses and some other infections – children without an effective B or T cell immune system must be protected from viral infection – ultimately the only possibility for survival is to have a bone marrow transplant that replaces their defective immune system with a functioning one.

Question 31

autoimmune disease

Answer 31

As shown before this image shows the hands of an individual affected by rheumatoid disease – the joint damage is caused by the granules released by neutrophils, but the disorder itself is initiated by the immune system – affected individuals develop an incorrect immune response in which joint or other tissues are targeted by the immune cells, leading to later recruitment of cells of the innate immune system which cause the damage.

Question 32

vaccination

Answer 32

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