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Immunology > MHC > Flashcards

MHC Flashcards

1
Q

What does MHC stand for?

A

Major histocompatibility complex

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2
Q

What is MHC?

A

Complex of genes that defines a genetic locus
Highly polymorphic (causes diversity)

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3
Q

Where is MHC class I expressed and what is it recognised by?

A

Expressed on most cells except neurones
Recognised by cytotoxic T-cells expressing CD8 +

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4
Q

How does the MHC conveyor belt work?

A

MHC conveyor belt loads self proteins that can be degraded in the cell - these proteins are identified by T-cells
If the T-cell identifies MHC + self peptides it ignores the cell
But if T-cell recognises non-self peptides ie will respond:
- CD8+ cytotoxic T-cell binds to MHC I peptide and kills infected cells
- CD4+ helper t-cells bind to MHC class II on APC (antigen presenting cell) and help B cells

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5
Q

Where are T-cells educated?

A

Thymus

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6
Q

Describe the role of MHC in immune tolerance?

A

Immature T cells (before leaving thymus) are presented to thymus epithelial cells (MHC I) and thymus dendritic cells (MHC II)
thymus uses these cells to present self proteins (peptides) to T-cell receptor by immature T cells
These T-cells have CD4 and CD8 - called double positive immature T-cells
Positive selection - when immature T-cells have weak binding to MHC self protein it survives
Negative Selection - when immature T-cells have strong binding to MHC self protein it dies

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7
Q

What is negative selection?

A

When immature T-cell has strong binding to MHC self protein it dies

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8
Q

What is positive selection?

A

When T-cell has weak binding to MHC self protein it survives

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9
Q

What causes autoimmune diseases?

A

Some helper T-cells arable to leave thymus, despite having strong biding to self MHC proteins
These T-cells help B-cells produce antibodies against some self proteins
These are called autoantibodies

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10
Q

What is HLA?

A

Human leukocyte antigens
Same as MHC but in humans not mice

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11
Q

What is a HLA gene? And why is it important?

A

Defines a genetic locus that varies by individuals
Important in understanding increasing risk of autoimmune diseases and understanding the immune response of a population to a vaccine

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12
Q

What is the action of MHC I?

A

Kills infected cells

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13
Q

What is MHC II expressed by and recognised by?

A

Expressed by APCs
Recognised by T-helper cells via CD4+

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14
Q

What is the action of MHC II ?

A

T-helper cells bind to MHC II on APCs and provide help to B-cells

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15
Q

What is the function of T-helper 1 cells?

A

Aid effector functions of antibodies by allowing isotope switching to make different classes of antibodies

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16
Q

What is the function of T helper 2 cells?

A

Aid B-cell differentiation
Aid plasma cell generation - secretes antibodies
Important during vaccination - TH2 stimulated in good vaccination

17
Q

How is a single gene able to generate a vast number of antigen biding specificities?

A

Ig gene rearrangement
A whole range of variable, diversity and joining regions can be spliced together to generate Ig’s with different antigen binding regions

18
Q

How do B and T cells find each other to agree on antigens?

A

Lymph nodes act as a funnel to concentrate antigens and immune cells
Antigens get to the lymph node via dendritic cells which take up antigens by phagocytosis, dendritic cells make lots of MHC I which binds peptides

19
Q

What are adaptions of dendritic cells ?

A

Massive surface area for engulfing pathogens
Make large quantities of MHC I to bind peptides
Express lots of peptides on their plasma membrane

20
Q

What is the action of dendritic cells?

A
  1. PAMPs recognised by TLRs in innate immunity - triggers phagocytosis, triggers delivery of pathogen to lysosomes for degradation, enhances uptake into dendritic cells
  2. Dendritic cells take up antigens at sites of infection and present peptides on MHC II
  3. Change the expression of cell adhesion molecules allowing them to migrate through lymphatics to find T-cells
    4.Dendritic cells present antigen to helper T-cells, which divide if see non-self peptide
  4. T-cells help B cells to make antibodies
21
Q

How do B and T cells fins the vaccine antigen when it is injected into the arm?

A
  1. Vaccines contain adjuvants that activate TLRs and increase phagocytosis by APCs
    - Adjuvants contain: PAMPs, precipitate antigens to increase phagocytosis, encapsulate antigens in nano materials, to: activate TLRs, increase phagocytosis by APCs
22
Q

What are two mechanism of tolerance?

A

Central tolerance
Peripheral tolerance

23
Q

What are the 4 major peripheral tolerance mechanisms? And how do they work?

A

1.T regulatory cells - inhibit response of all other immune cells be expressing CTLA-4 receptors, which inhibit co-stimulatory B7 on APCs
2. Colonial anergy - occurs due to lack of co-stimulation, decreased expression and availability of B7 in presence of self-antigens
3. Peripheral depletion - cells are induced to die by up regulation of cell surface marker FAS
4. Peripheral tolerance in B cells - via anergy due to lack of activating stimulus

24
Q

What are steps of recombination of B cells?

A
  1. Recombination first occurs for the heavy chain in pro-B cells
  2. If the heavy chain is ok the pro-B cell becomes a pre-B cell and rearranges the light chain (if not the cell dies)
  3. If the heavy and light chains assemble properly the B-cell becomes an immature B-cell with a B-cell receptor
  4. If B-cells make a self-reactive B-cel. Receptor that binds to self-proteins, B-cell cannot leave bone marrow and dies
25
Q

Describe the steps of T cell maturation/education

A
  1. T cell pre-cursors from bone marrow and liver have not rearranged genes
  2. T cells migrate to thymus
  3. VDJ recombination occurs in the thymus before the T cells get to the lymph nodes
  4. Self reactive T-cells are removes in the thymus
  5. Early progenitor T cells arriving from bone marrow to thymus encounter adhesion molecules that stimulate the proliferation of immature T cell and stimulate the TCR gene rearrangement
  6. Thymic medulla cells use MHC to educate T cells by presenting self proteins to immature T cells and their newly rearranged receptors
  7. CD4 and CD8 determine thee type of T cell emerging from thymus
26
Q

What is the limitation of self-reactive T cells in the thymus called?

A

Central I cell tolerance

Immunology (7 decks)

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