Monoarticular joint pain - Immunology

Question 1

a) What do HLA and MHC stand for
b) Are they the same thing?

Answer 1

a) HLA = Human leukocyte antigen

MHC = Major histocompatibility complex

b) Yes

Question 2

a) Describe the role of MHC/HLA proteins
b) What are the two main classes?

Answer 2

a) They provide a conveyer belt to present peptides, broken down by proteoloysis normal inside the celll (viral) to immune system
b) Class I and class II

Question 3

Describe the role of MHC/HLA genes

Answer 3

• Define a genetic locus that varies between individuals
• They are highly polymorphic and produce proteins that vary greatly between individuls
• They provide populations with diversity in their immune systems so they aren’t wiped out by pathogens

Question 4

What occurs if the peptide or MHC is wrong?

Answer 4

T-cell is activated

Question 5

What do T-cells recognise?

Answer 5

• MHC/HLA
• SELF peptide

Question 6

Describe the role of gene rearrangements (VDJ recombination)

Answer 6

Provides massive diversity in antigen recognition

Question 7

Describe positive and negative selection of T cells

Answer 7

1. Progenitor T-cells enter thymus where adhesion molecules on medullary epithelial cells stimulate
2. Thymic medulla cells use MHC to educate T-cells by presenting self-proteins (peptides) to immature T-cells
3. If immature T-cells have weak binding for MHC self-peptide they survive - know as positive selection. If strong binding, they die - known as negative tolerance

Question 8

Describe the secondary immune system process from phagocytosis to memory B cells

Answer 8

The lymphoid organs concentrate antigens and B and T cells

Pathogen-associated molecular pattern (PAMPs) are recognised by Toll-like receptors and can trigger phagocytosis

Dendritic cells take up antigens by phagocytosis and make lots of MHC class II that binds peptides

1. APC find antigens throughout the body
2. They take up antigen and present peptides on MHC class II
3. They migrate to lymph nodes to find T-cells in concentrated ‘special areas’

Dendrititc cells present antibodies to T-cells, T-cells help B-cells make antibody

Memory B-cells divide in the germinal centre and plasma cells move to efferent lymph and blood to deliver antibody

Question 9

What is tolerance?

Answer 9

Tolerance is a state of unresponsiveness to molecules (self or harmless environmental antigens) that the immune system has the capacity to recognize and attack

Question 10

What are the two type of immunological tolerance?

Answer 10

• Central tolerance
• Peripheral tolerance

Question 11

Describe central tolerance of B and T cells

Answer 11

B-cells

• Self-reactive B-cells are retained in the bone marrow and under go apoptosis so they do not get to lymph nodes

T cells

• Self-reactive T-cells (recognise self peptide + self MHC) and T cells that fail to recognize self MHC (no positive selection) are removed in the thymus by apoptosis or become tregs before they go to lypmh nodes

Question 12

Describe peripheral tolerance of B and T cells

Answer 12

B cells

• Absence of T-cell help (for protein antigens) induces anergy (lack of responsiveness to an antigen despite the presence of antigen-specific lymphocytes)

T cells

• T cells do not circulate through immune-privileged sites (Sites that tolerate the presence of antigen without an immune response)
• Absence of costimulation ( T cells require costimulation to become activated. Costimulation is normally provided by APCs or other cells in the vicinity that respond to the infection) induces anergy
• Repeated or high-doe exposure antigen induces activation-induced cell death