Cellular Immunity and Histocompatibility

Question 1

What is cellular immunity? (L.O 1)

Answer 1

Cellular immunity refers to cells that detect infected cells by the flag. These flags are molecules (MHC) designed to pick up and present bits of virus to the immune system. This would occur in infected cells by viruses (intracellular pathogens, they live INSIDE the cell).
Not only that, cellular immunity checks abnormal changes in cancer cells.

Question 2

What is the thymus and its role? (L. O 2)

Answer 2

The thymus is a primary lymphoid organ largest at birth then shrinks with age. It sits at the top of
the pericardium just above the heart. It controls the T development.

Question 3

Where do original T cells come from?

Answer 3

Haemopoietic lymphoid precursors migrate from the bone
marrow to the thymus where they mature into T
lymphocytes (T = thymus) T cells are only T cells when they are in the thymus.

Question 4

When is the thymus the most active?

Answer 4

Before and after birth, but not during adulthood. This is because it develops the T cell repertoire.

Question 5

What are most of the T cells doing in the thymus?

Answer 5

Most of them are dying as they are learning Thymic education (difference between non-self and self, learning not to react to your own cells). Only the few that survive end up making it into the lymphoid organs and blood.

Question 6

What is thymic education?

Answer 6

When T cells either become other T cells or die.

Question 7

What does thymic education lead to?

Answer 7

Leads to the first step of immune tolerance (tolerance is the mechanism which keeps your T cells from destroying your own tissue).

Question 8

What is the disease called when you break tolerance?

Answer 8

Autoimmune disease

Question 9

What are the two cells that differentiate from T cells in the thymus?

Answer 9

CDR + (helper) AND CD8+ (cytotoxic)

Question 10

What are immature thymocytes called?

Answer 10

CD4+CD8+

Question 11

What are the further subsets of the CD4+ helper cell.

Answer 11

Treg
Th1
Th2
Th17

Question 12

What is the difference between Major Histocompatibility Complex (MHC) & human Leukocyte Antigens (HLA)?

Answer 12

MHC refers to the genetic complex that codes for these proteins whilst HLA refers to the protein on the surface of the cells.

Question 13

What are MHC molecules?

Answer 13

T cells rely on an important set of MHC molecules to “flag” whether a cell is “normal” or “abnormal” and also what type of immune response is required.

Question 14

What are the 2 key feature of MHC?

Answer 14

1. Highly polymorphic ( genes that code for these molecules are different between every body).
2. T cells do not recognise antigen unless it is presented within MHC molecules

Question 15

What is the consequence of your MHC being Highly polymorphic?

Answer 15

Tissue transplantation

Question 16

What is tissue transplantation?

Answer 16

Because the MHC molecules are important for the body’s way to understand the difference between self and non-self, this becomes important for tissue transplantation. When a tissue is implanted, the MHC molecules from the donor are recognised as forgein molecules from the T cells, and so it rejects it which is called graft rejection.

Question 17

How do the T cell know that the donor’s MHC molecules are different and non-self?

Answer 17

It’s because the T cells have been trained through thymic education to recognise their own MHC molecules.

Question 18

What is tissue typing?

Answer 18

This is why transplanting an organ from one person
to another is impossible unless you first carefully
match the MHC genes between donor and recipient.

Question 19

The ability of your T cells to recognise these differences in MHC molecules are governed by what?

Answer 19

Tissue transplantation, viral
immunity and cancer immunotherapy

Question 20

What does the Keytruda (pembrolizumab) do?

Answer 20

This drug is an antibody that regulates your T cells so that your T cells can better understand where there is a cancer cell present. It is an
immunotherapy drug now used to
treat melanoma

Question 21

What is MHC polymorphism?

Answer 21

When the DNA sequence of the MHC molecules are different in individuals.

Question 22

How many MHC main molecules are there?

Answer 22

6 main molecules exist but both your maternal and paternal genes exist so 12 MHC molecules in every person’s cell.

Question 23

What is the peptide binding cleft?

Answer 23

The region of amino acid variation in the MHC molecule.

Question 24

What is MHC restriction?

Answer 24

This refers to the discovery of why we have MHC in the first place. VIRAL IMMUNITY REQUIRES THE IMMUNE SYSTEM TO
RECOGNIZE TWO ANTIGENIC COMPONENTS
SELF
Antigen(s) encoded by MHC
NON-SELF
Antigen(s) encoded by the virus.

Question 25

What are the molecules present in the MHC restriction?

Answer 25

1. T cell receptors made through gene arrangement (like antibodies) that are membrane bound on the T cell. They recognise those antigens are presented on MHC molecules. TCR undergo gene arrangement which gives it diversity like antibodies. 2.The antigen binding site of a TCR is formed the same way as an antibody yet tightly restricted to MHC molecules. This restriction occurs during thymic education. 3. Highly polymorphic HLA molecules are expressed on most cells and present peptide antigens to T cells meaning HLA present antigens.

Question 26

Describe the main difference between antibodies and T cells.

Answer 26

Antibodies can recognise free floating antigens whilst TCRs on recognise antigens that are presented on MHC molecules.

Question 27

What happens at the peptide binding groove?

Answer 27

And all the amino acid differences that constitute that polymorphism occur up around this surface area here that we refer to as the peptide binding group.

Question 28

Function of co receptors.

Answer 28

Found on T cells that help bind the T cell to the MHC molecule. There are CD4 and CD8, and there are class 1 molecule and type 2 molecule.

Question 29

What does CD4 and CD8 bind to?

Answer 29

CD8 = Cytotoxic T cells recognise peptides in MHC class I. * CD4 = Helper T cells recognise peptides in MHC class II

Question 30

What is so important of CD4 and CD8?

Answer 30

They have intracellular tyrosine kinases that connect to their cytoplasmic tail that signal through phosphorylation. They are crucial to the first activation step of the cascade that leads to your immune response and steering it in the right direction.

Question 31

How does the CD4+ Helper T cell function?

Answer 31

First, the MHC Class II molecules (on antigen-presenting cells like Bacteria or virus or cancer peptide) bind and present a processed antigen (peptide). Then The CD4+ T cell receptor (TCR) recognizes and binds specifically to that peptide-MHC Class II complex. It does this by recognising the antigen presenting cells (APC). It then gets activated and proliferates (multiples) which direct immune response. When it proliferates, it creates subsets of T cells produce lots of different cytokines (which are signaling molecules.

Question 32

What is caused by the loss of CD4 helper T cells that are killed by the HIV virus.

Answer 32

AIDS

Question 33

What is the CD8+ Cytotoxic cell function?

Answer 33

CD8+ CTL recognises peptides presented by MHC Class I. Produces granzyme and perforins that punch holes in the target cell membrane and destroy cell viability. Also kills by direct apoptosis.

Question 34

What type of pathogens do MHC class 1 and 2 both encounter?

Answer 34

MHC class one encounters intracellular pathogens such as virus or cancer cells. MHC class two encounters extracellular pathogens such as bacteria.

Question 35

Why has MHC evolved such polymorphism?

Answer 35

Answer: 1. 2. To be able to bind as many peptides as possible to diversify a population’s response and survival to emerging pathogens. Unique HLA haplotypes are found in populations that have faced natural selection from regional pathogens. This ensures that in a population, some individuals will be better equipped to survive the next pathogen.

Question 36

2 important consequences of MHC polymorphism