Week 3: Antigen Presenting? Flashcards

1
Q

What is adaptive immunity?

A

An acquired response to an antigen that allows for responses to a wide variety of antigens encountered over a lifetime

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2
Q

What is an antigen?

A

Any substance recognized by antigen receptors on T and B lymphocytes

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3
Q

What are the components of a pathogen?

A
  1. Protein
  2. Glycoprotein
  3. Polysaccharides
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4
Q

What is antigenic determinant or epitope?

A

Portion of an antigen that is recognized by the antigen receptor

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5
Q

What are the chemical antigens?

A
  1. Nickel
  2. Penicillin
  3. Urushiol
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6
Q

How does the adaptive immune system target pathogens?

A
  1. B and T cells use their antigen receptors to recognize antigens
  2. B cell receptors (antibodies) can recognize and bind to epitopes on free antigen and start the process of eliminating extracellular pathogens or toxins
  3. Neither B cells or antibodies can respond to antigens of pathogens inside cells
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7
Q

How do you respond to intracellular and extracellular pathogens?

A

Major histocompatibility complex (MHC) to show antigens to T cells

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8
Q

What is another name for MHCs?

A

Human Leukocyte Antigen (HLA) complex

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9
Q

What is MHC locus?

A

A cluster of genes that encode MHC molecules

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10
Q

What occurs during transplantation of MHC?

A

MHC setermines whether a particular tissue is a good match between the donor and recipient

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11
Q

What are alleles?

A

Multiple alternative forms of MHC genes

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12
Q

What is the function of MHC alleles?

A

Inherit role in the body’s infection response suspecible to disease and risk of developing autoimmunity

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13
Q

What is the function of MHC?

A

Role in how immune system develops immunity of all types of antigens

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14
Q

What are naive B cells receptors (BCR)?

A
  1. Recognizes a broad range of antigen types
  2. Binds to intact molecules
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15
Q

What are naive T cells receptors (TCR)?

A

Have antigen-binding site but can’t recognize the diversity of antigen types that B cells can

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16
Q

What are the limitations T cell recognition?

A

Short peptides that are produced by antigen processing (8-25aa’s long)

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17
Q

What is antigen presentation?

A

Foreign peptide that binds to a protein in the ER or endoscope and loaded in the MHC and brough to the cell surface where the antigen binds to the T cell receptors

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18
Q

What are the properties of a TCR?

A
  1. Glycoprotein that resembles Fab of IgG antibody
  2. Membrane bound
  3. Antigen receptor only
  4. Germline recombination to generate TCR diversity during thymus development
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19
Q

How is TCR diversity generated?

A

T cell development prior to antigen binding

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20
Q

Describe the structure of TCR?

A
  1. Heterodimeric protein with a a chain and b chain with cytoplasmic tails
  2. Va and Vb variable regions bind antigen and each T cell has a single antigen binding specifiticy
  3. Each V domains has 3 complementary determining region (CDR)
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21
Q

What are CDRs?

A

Contacts with the antigen peptide presented by the MHC

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22
Q

What is CD3 complex?

A

4 invariant membrane proteins that are transported to the cell surface

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23
Q

Can a and b chains leave ER and cell surface alone?

A

no

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24
Q

What is the function of CD3 complex?

A

Transmits signals through the TCR to the cell’s interior after TCR recognizes its antigen

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25
Q

What are the type of T cells?

A

Cytotoxic and helper

26
Q

What do cytotoxic t cells recognize?

A

antigens presented by MHC class 1 and express CD8

27
Q

What do helper t cells recognize?

A

antigens presented by MHC class 2 and express CD4

28
Q

What are CD4 and 8?

A
  1. T cell co-receptors
  2. Associate with TCR in or to recognize peptides antigens complexed with MHC molecules
29
Q

What is a multiple antigenic peptide?

A

Produced from 1 protein

30
Q

What is antigen processing?

A

When an extracellular pathogen is engulfed and degraded within macrophages and DCs into peptide fragments that produce peptide antigens

31
Q

What produces intracellular pathogen peptides?

A

Antigen processing in all infected human cells

32
Q

What occurs after pathogen peptides are formed?

A
  1. Get to the cell surface
  2. MHC bind and escort the peptide antigen to the cell surface
  3. 1 mHC to 1 peptide and moves to cell surfave
33
Q

What is antigen presentation?

A

TCR recognizing the peptide antigen bound to MHC and displayed on the cell surface

34
Q

What is in MHC class I?

A
  1. Present antigens from intracellular pathogens
  2. Peptides are degraded in the cytosol and then join with MHC class I in the ER to move to cell surface.
  3. CD8+ cytotoxic T cells (CTLs) recognize MHC class I molecules
  4. CTLs induce apoptosis of target cells by releasing cytotoxic enzymes from their granules.
35
Q

What is in the MHC class 2?

A
  1. Present antigens from extracellular pathogens
  2. Peptides are degraded in the lysosome and then join with MHC class II in endosome and move to cell surface.
  3. CD4+ helper T cells recognize MHC class II molecules
  4. Help macrophages and B cells respond to the infection.
36
Q

What are the structural characteristics of MHC class 1?

A
  1. Composed of 1 polypeptide chain: a chain consisting of 3 extracellular domains
  2. a chain has 1 transmembrane domain
  3. b2-microglobulin-not part of the MHC (non-covalently complexed)
  4. Peptide binding site is made up of a1 and a2
  5. a3 domain interacts with CD8 on CTL
  6. Only a domains are encoded by MHC gene.
37
Q

What are the structural characteristics of MHC class 2?

A
  1. Consists of 2 polypeptide chains: a and b
  2. 2 external domains (a1 and a2, b1 and b2)
  3. a2 and b2 make up the two transmembrane domains
  4. a1 and b1 make up the peptide binding site
38
Q

What do MHC class 1 bind to?

A

8-10aa in length

39
Q

What do MHC class 2 bind to?

A

12-25 aa in length

40
Q

Describe MHC binging?

A
  1. Deep peptide binding groove on the MHC molecule is where the peptide antigen is held by noncovalent interactions
  2. Each molecule has peptide size constraints within the grooves due to structure
  3. Both have promiscuous binding affinity because they can bind a large number of different peptides of varying amino acid sequences
41
Q

Describe MHC class 1 antigens processing?

A
  1. Processes and presents endogenous antigens
  2. Presents self peptides from improperly folded or made or damaged proteins in the cytosol
  3. Present viral peptides
  4. Cytosolic proteins are broken down by proteasome
  5. Proteasome degrades the cytosolic proteins into small peptides
  6. Peptides are transported to the ER where they are modified to be 8-10 aa long and then non-covalently bind in peptide binding groove of MHC class I.
    7.Loaded MHC class I travels to the cell surface in a vesicle released from the Golgi.
42
Q

Describe MHC class 2 antigens processing?

A
  1. Processes and presents exogenous antigens
  2. Proteins from extracellular bacteria or extracellular virus particles as well as soluble protein antigens are taken into the cell by phagocytosis.
  3. Antigen is taken up into a endocytic vesicle (phagolysosome) where it is degraded by proteases into peptide fragments.
  4. Vesicle containing peptide fragments merges with vesicles containing MHC class II molecules from the Golgi.
  5. A peptide that is 12-25 aa long binds in the peptide binding groove of MHC class II and is taken by vesicle to the surface of the cell.
43
Q

How do T cells see antigens?

A

Antigen specific or MHC restricted

Once antigen is processed and presented, a T cell bearing the appropriate receptor can bind to it and being activation

44
Q

Describe the presentation of MHC C1 to CD8?

A
  1. Recognition of antigen by T cells requires cell-to-cell contact
  2. MHC antigen complex is recognized by corresponding TCR
  3. CD8 binds to a site on the MHC class 1 molecule that does not overlap with the site recognized by the TCR
45
Q

Describe the presentation of MHC C1 to CD4?

A
  1. Recognition of antigen by T cells requires cell-to-cell contact
  2. MHC antigen complex is recognized by corresponding TCR
  3. CD4 binds to a site on the MHC class ii molecule that does not overlap with the site recognized by the TCR
46
Q

What is MHC restriction rule of 8?

A

CD4 (Helper T cells) x MHC II = 8
CD8 (Cytotoxic T cells) x MHC I = 8

47
Q

How are MHC molecules distributed?

A
  1. T cells responses are guided by the differential expression of the 2 MHC classes
  2. All cells are suspecible to infection therefore all nucleated cells express MHC class 1 molecules
  3. MHC CLASS 2 MOLECULES ARE EXPRESSED ON ANTIGEN PRESENTING CELLS that specialize in the uptake, processing, and presentation of extracellular antigen
48
Q

What are antigen presenting cells?

A

Cells that present peptide antigens loaded in the MHC 2 molecules to T cells

49
Q

What are examples and function of antigen presernting cells?

A
  1. DCs and macrophages specialize in taking up antigens from their enzironement
  2. B cells also internalize antigens that bound to their BCR
50
Q

Describe the T cell function when contacting other cells?

A
51
Q

What causes inherited diversity of MHC?

A
  1. Gene families
  2. Genetic polymorphism
  3. Allotypes
  4. MHC 1 and 2 arise from the combination of multiple genes and multiple alleles
52
Q

What are gene families?

A

set of genes encoding proteins of similar structure

53
Q

What is genetic polymorphism?

A

Alternative form of a given gene (allele)

54
Q

What are allotropes?

A

The different protein products from different alleles

55
Q

What are A,B, and C HLAs?

A

Polymorphic that have genes that have many alleles

56
Q

What are oligomorphic?

A

Few alleles

57
Q

What is polymorphism?

A

Genetic diversity ultimately affects the variety of peptides that bind to the mHC molecule

58
Q

What is the most polymorphic genetic complex known?

A

MHC
5-10% different DNA sequencing
Each individual differs from others in some if not all MHC alleles

59
Q

What are the advantages of polymorphism?

A

If a novel disease should arise, at least part of the population should be able to present antigen and defend themselves against pathogen

60
Q

What is the disadvantage of polymorphism?

A

Greatly complicates transplantation