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Immunology Exam 1 > 4 - Antigen presentation and MHC > Flashcards

4 - Antigen presentation and MHC Flashcards

1
Q

Describe the process of paternity testing

A
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2
Q

What are MHC proteins?

A
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3
Q

What is a MHC haplotype?

A

MHC haplotype

  • The total set of MHC genes on each chromosome
  • You inherit one haplotype from each parent
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4
Q

What does it mean to say that MHC is polygenic?

A

There are multiple different genes within each individual

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5
Q

What does it mean that MHC gene expression is polymorphic?

A

Multiple variants of each gene exist in the population

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6
Q

Are most of the polymorphic genes in humans known or unknown?

A

Known

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7
Q

What is the estimate of the number of MHC alleles with different amino acid sequences? What about on the B locus alone… How many unique alleles exist there?

A

Total: 5,000

B locus alone: 2,500

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8
Q

What is the mode of gene expression for MHC genes?

A

Codominant

  • Alleles on both chromosomes will be expressed simultaneously
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9
Q

What genes encode for Class I MHC proteins?

A

A, B and C genes

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10
Q

What genes encode for class II MHC proteins?

A

D region genes

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11
Q

How many MHC genes does each individual inherit?

A
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12
Q

Why would the number of class II MHC proteins actually be higher than the number of class I MHC proteins in some cases?

A

Some class II MHC alpha and beta proteins can pair up with other class II MHC alpha and beta proteins to produce new alpha/beta chain combinations

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13
Q

What are the chances that two randomly selected individuals will be identical matches for MHC proteins?

A

It is virtually guaranteed that two randomly selected individuals will NOT be identical matches

  • Polygenic, polymorphic and codominant characteristics of the MHC proteins are responsible for this
  • Matching siblings and identical twins are exceptions
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14
Q

What is the role of MHC proteins?

A

T lymphocytes only respond to an antigen when it is expressed on an antigen presenting cell in conjunction with MHC proteins

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15
Q

How are peptides attached to the MHC proteins on cell surfaces?

A

Peptides are non-covalently bound to the MHC proteins on the cell surface

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16
Q

What is the purpose of peptides being bound to the MHC proteins on cell surfaces?

A

Purpose

  • This serves to localize T cell activation to the site of antigen presentation
  • Immunogenic peptides are able to interact with amino acids of the MHC protein
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17
Q

What are two diseases that are associated with particular HLA alleles?

A

This is an association, but not necessarily a cause

  • Narcolepsy - HLA-DR2
    • Affected patients 100%
    • Healthy individuals 22%
  • Ankylosing spondylitis (inflammation of the vertebrae and spinal deformities) - HLA-B27
    • Affected patients 90%
    • Healthy individuals 9&
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18
Q

How is MHC typing used in organ transplantation?

A

Organ transplantation

  • Transplantation of organs between individuals may be rejected since a non-self MHC protein will be recognized as foreign
  • Antisera and molecular techniques are available to type leukocytes as a class I or class II HLA
  • Matching of HLA types plus immunosuppressive drugs are used to dramaticaly increase the success of long term graft survival
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19
Q

How is MHC typing used in paternity testing?

A

Paternity testing

  • Involves HLA typing the mother, child and alleged father
  • Can only EXCLUDE the alleged father, NOT absolutely include!
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20
Q

Where are class I MHC proteins expressed?

A

They are expressed on nearly all nucleated cell bodies

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21
Q

What is the effect of no class I MHC proteins on RBCs?

A

No class I MHC proteins

  • Infections by Plasmodium
  • Undetected by cytotoxic T lymphocytes
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22
Q

What are the regions that exist in two non-covalently-linked polypeptide chains?

A

Regions

  • Peptide-binding
  • Transmemrane
  • Cytoplasmic
23
Q

What is required for cellular expression of the alpha chain when there are two non-covalently-linked polypeptide chains?

A

Beta2 microglobulin

24
Q

What is the role of the peptide binding region?

A

Peptide binding region

  • Holds foreign peptides
  • Allows for recognition by the T cell antigen receptor of CD8 T lymphocytes
25
Q

How large is the cleft of the peptide-binding region?

A

Cleft size

  • The cleft is large enough for a peptide that is 9-11 amino acids long
  • A large antigen must be processed and broken into small fragments for the cleft to be effective
  • Te ends of the cleft are “pinched in”
26
Q

Do all MHC class I alleles bind equally to all peptides?

A

NO!

  • Some MHC class I alleles bind some peptides better than others
27
Q

Why are there polymorphisms among MHC molecules?

A

Polymorphisms

  • To allow different individuals to bind a broad range of antigens thereby conferring a protective advantage on the population
  • No gene recombination occurs, which allows for limited variation to occur simply by inheriting different alleles
28
Q

How are class II MHC proteins expressed?

A

Class II MHC proteins

  • Expressed on “professional antigen presenting cells” or APCs
    • Dendritic cells
    • Macrophages
    • B lymphocytes
29
Q

Why are there polymorphisms among MHC molecules?

A

Polymorphisms

  • To allow different individuals to bind a broad range of antigens thereby conferring a protective advantage on the population
  • No gene recombination occurs, which means that there will be limited variation that can occur by inheriting different alleles
30
Q

What are the regions of two non-covalently-linked polypeptide chains in class II MHC proteins?

A

Regions

  • Peptide-binding
  • Transmembrane
  • Cytoplasmic
31
Q

What else do you need to know about the chains of two non-covalently-linked polypeptide chains in class II MHC proteins?

A

Understand that each chain is encoded by separate MHC genes

32
Q

What is the role of peptide-binding region of a class II MHC protein?

  • A peptide-binding region holds foreign peptides
  • This region can be recognize by a CD4 lymphocyte
  • The cleft of this region holds on to the protein fragments
A
33
Q

Which class of MHC proteins (I or II) can hold larger peptides? How long of a protein fragment can a class II hold?

A

Class II MHC proteins can hold larger peptides than class I MHC proteins because the cleft is open at the ends rather than “pinched off”

  • The cleft in class II MHC proteins can hold protein fragments of 10-30 amino acids long
34
Q

Do all alleles bind peptides the same in class II MHC proteins?

A

No!

  • Some MHC class II alleles bind some peptides better than others
35
Q

How does MHC restrict the immune system? Class I? Class II?

A

MHC restriction of immune response

  • CD4 T lymphocytes recognize peptides on self class II MHC proteins
  • CD8 T lymphocytes recognize peptides on self class I MHC proteins
  • REMEMBER: just remember that the multiple of the two numbers together must be equal to 8
    • 4 x 2 = 8 (class II recognizes CD4)
    • 8 x 1 = 8 (class I recognizes CD8)
36
Q

What are T lymphocytes able to recognize?

A
37
Q

Where would you find class I MHC-associated peptide expression?

A

Nearly all nucleated cells

38
Q

Where would you find class II MHC-associated peptide expression?

A

Class II MHC-associated peptide expression

  • Dendritic cells
  • Macrophages
  • B cells
39
Q

What is special about dendritic cells in class II MHC-associated peptide expression?

A

Dendritic cells

  • Most potent APCs
  • Most widely used for stimulating primary immune responses
  • Example: activation of naive T cells
40
Q

Which cells are better at stimulating a secondary response?

A

Macrophages and B cells

41
Q

How are naive T cells activated?

A

Clonal expansion and differentiation into effector T cells

42
Q

What is the response of the effector T cell?

A
  1. Macrophage activation (cell-mediated immunity)
  2. B cell activation and antibody production (humoral immunity)
43
Q

Dendritic cells - Where are they produced? What do they do? Where are they found?

A

Characteristics:

  • Produced by the bone marrow → circulate in the blood → migrate into the tissues as long-lived immature dendritic cells
  • Continuously sample environment through phagocytosis and macropinocytosis
  • Present in nearly every organ of the body
44
Q

How does interferon-γ enhance class II MHC proteins?

A

Here’s what happens…

  • First, APC (antigen presenting cell) activates T lymphocytes
  • Then interferon-γ is released by T cells
  • This induces an increase in the number of class II MHC (major histocompatibility complex) proteins found on the surface of APC

Net result

  • There will be more class II MHC expression on APCs
  • There will be more APCs to present antigens to T lymphocytes
  • The immune response will be more efficient/effective
45
Q

Describe a typical antigen presentation scenario

A

Typical scenario

  • Dendritic cells are constantly “sampling” their environment
  • During an infection, immature dendritic cells take up an antigen
  • This immature dendritic cell then becomes activated and migrates to the nearest lymphoid tissue
  • Once it reaches the lymphoid tissue, the dentritic cells mature
  • This allows them to present the antigen to the T-helper lymphocytes found in the lymphoid tissue
46
Q

Are endogenous antigens processed by the class II MHC pathway?

A

NO - they are processed by a separate and distinct pathway

47
Q

How are endogenous antigens processed?

A

The same way as class II MHC proteins, they are just shuttled down a different pathway

  • Endogenous antigens are processed by a path separate and distinct from the class II MHC pathway
  • Nothing intrinsically different about peptides that bind class I or class II MHC proteins, just shunted down different processing pathways
48
Q

How are peptide-class I MHC complexes formed? What is their purpose?

A

Process

  • Peptide-class I MHC complexes are formed in the ER
  • From there, they are shuttled out to the plasma membrane of the virally-infected cell
  • This allows them to alert T lymphocytes that the cell is infected
  • In uninfected cells, class I MHC proteins bind self peptides
49
Q

Describe the steps of endogenous antigen processing

A
  1. Production of proteins in the cytosol
  2. Proteolytic degradation of proteins
  3. Transport of peptides from cytosol to ER
  4. Assembly of peptide-class I complexes in the ER
  5. Surface expression of peptide-class I complexes
50
Q

How are exogenous antigens processed?

A

Process:

  • Exogenous antigens are internalized by:
    • Phagocytosis,
    • Receptor-mediated endocytosis or
    • Fluid phase pinocytosis
  • Class II MHC proteins are bound by the “MHC class II-associated invariant chain”
  • This prevents the binding of cellular proteins
  • Vesicles then fuse with the plasma membrane
  • In the absence of exogenous antigens, class II MHC binds self-peptides
51
Q

What is the relationship between the effectiveness of MHC binding and the effectiveness of the immune response?

A

Peptides that are more effective at binding MHC proteins are more likely to induce an immune response (immunodominant)

52
Q

For review, what is the process that exogenous antigens partake in?

A

Exogenous antigens → class II MHC proteins → activate T-helper cells → antibody production effective against extracellular pathogens

53
Q

For review, what is the process that endogenous antigens partake in?

A

Endogenous antigens → class I MHC proteins → activate CTL’s effective against virus-infected cells or tumor cells

54
Q

For review, how does antigen processing work?

A

Cross-presentation

  • Some dendritic cells can capture exogenous protein antigens and present peptides on class I MHC to CD8+ cytotoxic T lymphocytes
  • Involves the fusion of phagosomes containing the exogenous antigen with the endoplasmic reticulum, where the proteins are translocated to the cytoplasm for processing down the class I MHC pathway

Immunology Exam 1 (8 decks)

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