Session 3- MHC and adaptive immunity Flashcards
Why can’t hand sanitiser stop spread of C. difficile?
The spores need to be physically washed off the hands
What is peritonitis?
Why is the peritoneum a potential space?
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
What is ascites?
Excess fluid in the peritoneum causing a swollen abdomen
What does the peritoneum usually contain?
peritoneal fluid which acts a lubricant for the viscera and contains antibodies to fight infection
Dysuria
Painful or difficult urination
Why are diabetics at greater risk of lung infections like pneumonia?
Diabetics have an impaired immune system so are more susceptible to infection
Difference between phagocytosis and pinocytosis?
Both bring extracellular material inside the cell in a vesicle.
- Phagocytosis is the whole microbe
- Pinocytosis is soluble particles only
Name 4 types of antigen presenting cell.
Which T- cells do they present to?
Macrophages- effector
B lymphocytes- both
Dendritic cells - naive
Langerhans cells - naive
Dendritic cells found in mucosal membranes, blood, lymph nodes
Langerhans cells in skin
What are HLA genes?
What makes them so diverse and why is this important?
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.
What does histocompatibility mean?
How similar the HLA alleles are between two tissues
Which cells present
- MHC class 1
- MHC class 2
MHC 1 = all nucleated cells
MHC 2 = APC’s only
This means APC’s present both MHC 1 and 2
MHC class 1 and 2 present ____ antigen to which T cells?
MHC Class 1:
Intracellular antigen to naive CD8 (cytotoxic) T cells
MHC Class 2:
Extracellular antigen to naive CD4 T cells
HLA genes which encode MHC class 1 MHC class 2
HLA-A HLA-B HLA-C
HLA-DP HLA-DQ HLA-DR
The 2 MHC classes are involved in different types of adaptive immunity.
What are they?
MHC 1 - cell mediated immunity
MHC 2 - humoral immunity
How do the MHC classes differ in structure
MHC 1 - single chain
MHC 2 - double chain
Can 2 people have the same set of MHC molecules?
Only identical twins because they are genetically determined and do not adapt
Why is MHC diversity so great?
- 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)
How are extracellular proteins presented to T cells?
- 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
How are intracellular proteins presented to T cells?
- 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
What is the TAP protein complex?
Protein complex which transports intracellular antigenic peptides into the ER
Stands for transported associated with antigen processing
2 components; TAP 1 and 2
One MHC molecule presents more than one antigen. What is this property? How is this achieved?
Broad specificity
It increases the number of antigens recognised by your set of MHC molecules
MHC molecules have a highly polymorphic peptide binding cleft
Link MHC molecules and different susceptibility to infection between individuals
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
Viral load?
Relevance to HIV
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)
When do you diagnose AIDS?
When the CD4+ count drops below 200 cells/microlitre
Elite controllers/ LTNP long term non-progressors?
People with HIV who have a very low viral load and maintain a CD4+ count above 500 cells/ microlitre.
Their body controls viral replication
Which APC will recognise cellulitis caused by Staphylococcus infection?
Langerhan cells bc they are found in the skin
Toll like receptors which recognise
- gram positive
- gram negative
Positive: TLR- 1 (lipoproteins) TLR 2 peptidoglycan Negative: TLR 4 (LPS, lipopolysaccharide) TLR 5 (flagellin)
Where are APC’s found?
lymphoid tissue
lymphoid organs (nodes and spleen)
Circulation (myeloid and plasmacytoid dendritic cells)
MHC molecules in elite controllers of HIV are different to those in normal people. How?
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
Clinical problems with MHC molecules
- Allograft rejection
- Association with autoimmune diseases (diabetes and ankylosing spondylitis)
How do MHC molecules impact organ transplants?
HLA genes between the donor and host must align. Mismatch causes rejection and/ or graft vs host reaction
What associations have been made between HLA molecules and autoimmune diseases?
- Certain HLA molecule present in >90% of patients with ankylosing spondylitis
- < 75% of patients with insulin-dependant diabetes mellitus
