Session 3- MHC and adaptive immunity

Question 1

Why can’t hand sanitiser stop spread of C. difficile?

Answer 1

The spores need to be physically washed off the hands

Question 2

What is peritonitis?

Why is the peritoneum a potential space?

Answer 2

Peritonitis is infection of the peritoneal cavity
= the space between the visceral (around organs) and parietal (attached to abdominal wall) peritoneum.

Can fill with fluid, causing ascites

Question 3

What is ascites?

Answer 3

Excess fluid in the peritoneum causing a swollen abdomen

Question 4

What does the peritoneum usually contain?

Answer 4

peritoneal fluid which acts a lubricant for the viscera and contains antibodies to fight infection

Question 5

Dysuria

Answer 5

Painful or difficult urination

Question 6

Why are diabetics at greater risk of lung infections like pneumonia?

Answer 6

Diabetics have an impaired immune system so are more susceptible to infection

Question 7

Difference between phagocytosis and pinocytosis?

Answer 7

Both bring extracellular material inside the cell in a vesicle.

• Phagocytosis is the whole microbe
• Pinocytosis is soluble particles only

Question 8

Name 4 types of antigen presenting cell.

Which T- cells do they present to?

Answer 8

Macrophages- effector
B lymphocytes- both
Dendritic cells - naive
Langerhans cells - naive

Dendritic cells found in mucosal membranes, blood, lymph nodes
Langerhans cells in skin

Question 9

What are HLA genes?

What makes them so diverse and why is this important?

Answer 9

HLA genes encode MHC molecules (present antigens to immune cells).

HLA genes are highly polymorphic (many alleles). This means one infection can’t wipe out the entire population.

Question 10

What does histocompatibility mean?

Answer 10

How similar the HLA alleles are between two tissues

Question 11

Which cells present

• MHC class 1
• MHC class 2

Answer 11

MHC 1 = all nucleated cells
MHC 2 = APC’s only
This means APC’s present both MHC 1 and 2

Question 12

MHC class 1 and 2 present ____ antigen to which T cells?

Answer 12

MHC Class 1:
Intracellular antigen to naive CD8 (cytotoxic) T cells

MHC Class 2:
Extracellular antigen to naive CD4 T cells

Question 13

HLA genes which encode 
MHC class 1
MHC class 2

Answer 13

HLA-A HLA-B HLA-C

HLA-DP HLA-DQ HLA-DR

Question 14

The 2 MHC classes are involved in different types of adaptive immunity.
What are they?

Answer 14

MHC 1 - cell mediated immunity

MHC 2 - humoral immunity

Question 15

How do the MHC classes differ in structure

Answer 15

MHC 1 - single chain

MHC 2 - double chain

Question 16

Can 2 people have the same set of MHC molecules?

Answer 16

Only identical twins because they are genetically determined and do not adapt

Question 17

Why is MHC diversity so great?

Answer 17

• Co-dominant expression of parental MHC molecules (offspring is better protected as they can recognise a greater number of antigens).
• Highly polymorphic HLA genes (lots of alleles)

Question 18

How are extracellular proteins presented to T cells?

Answer 18

• The protein is taken into the cell via phagocytosis/ pinocytosis and contained within an endosome.
• Protein degradation occurs within endosome to produce smaller peptides
• Endosome fuses with a vesicle containing MHC class 2 molecules (from ER) and a complex is formed if they are complementary
• MHC complex inserts into the plasma membrane
• Peptide recognised by CD4+ T cell with complementary TCR

Question 19

How are intracellular proteins presented to T cells?

Answer 19

• Protein presnt in the cytoplasm is labelled for destruction by the E3 Ubiquitin ligase (ubiquitination)
• Degraded into peptides by the proteosome complex
• Peptides transported into the ER by the TAP protein complex (TAP 1 & 2)
• MHC-1 -peptide complex occurs if complementary to each other
• Complex migrates and inserts into plasma membrane
• Peptide recognised by CD8+ T cells

Question 20

What is the TAP protein complex?

Answer 20

Protein complex which transports intracellular antigenic peptides into the ER
Stands for transported associated with antigen processing
2 components; TAP 1 and 2

Question 21

One MHC molecule presents more than one antigen. What is this property? How is this achieved?

Answer 21

Broad specificity
It increases the number of antigens recognised by your set of MHC molecules

MHC molecules have a highly polymorphic peptide binding cleft

Question 22

Link MHC molecules and different susceptibility to infection between individuals

Answer 22

Your fixed set of MHC molecules determines what the body can recognise and present to T cells to initiate an immune response.
Weak/ strong immune response to an infection

Question 23

Viral load?

Relevance to HIV

Answer 23

Number of viruses present in the bloodstream
A higher viral load means your CD4+ count will reduce quicker and you’re more likely to develop AIDS (acquired immune deficiency syndrome)

Question 24

When do you diagnose AIDS?

Answer 24

When the CD4+ count drops below 200 cells/microlitre

Question 25

Elite controllers/ LTNP long term non-progressors?

Answer 25

People with HIV who have a very low viral load and maintain a CD4+ count above 500 cells/ microlitre. Their body controls viral replication

Question 26

Which APC will recognise cellulitis caused by Staphylococcus infection?

Answer 26

Langerhan cells bc they are found in the skin

Question 27

Toll like receptors which recognise - gram positive - gram negative

Answer 27

``` Positive: TLR- 1 (lipoproteins) TLR 2 peptidoglycan Negative: TLR 4 (LPS, lipopolysaccharide) TLR 5 (flagellin) ```

Question 28

Where are APC's found?

Answer 28

lymphoid tissue lymphoid organs (nodes and spleen) Circulation (myeloid and plasmacytoid dendritic cells)

Question 29

MHC molecules in elite controllers of HIV are different to those in normal people. How?

Answer 29

Their MHC's recognise peptides which are vital for the virus to survive- the peptides don't mutate. So they can launch an effective immune response against the virus. MHC molecules in other people recognise peptides which are not necessary for survival and can be mutated. The virus is poorly recognised (due to changing peptides) and poorly attacked as these proteins are relatively unimportant. Viral load rises and CD4+ count falls

Question 30

Clinical problems with MHC molecules

Answer 30

- Allograft rejection | - Association with autoimmune diseases (diabetes and ankylosing spondylitis)

Question 31

How do MHC molecules impact organ transplants?

Answer 31

HLA genes between the donor and host must align. Mismatch causes rejection and/ or graft vs host reaction

Question 32

What associations have been made between HLA molecules and autoimmune diseases?

Answer 32

- Certain HLA molecule present in >90% of patients with ankylosing spondylitis - < 75% of patients with insulin-dependant diabetes mellitus