L14 Flashcards

1
Q

What are the 3 properties of the immune system (vertebrates)

A
  1. SPECIFIC recognition of foreign molecules
  2. Ability to DESTORY foreign parasite
  3. MEMORY mechanism, rapid response to second infection
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2
Q

4 examples of antigens

A

Antigens are molecules being recognized

  1. Bacteria
  2. Viruses
  3. Other Parasites
    4, Foreign molecules
    -> Non-self
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3
Q

What are the 2 types of the human immune system? Describe the main components of each

A
  1. Non-specific (Innate)
    a) Barriers
    - (skin, stomach acid etc…)
    b) Inflammation
    - (phagocytes –white blood cells/leukocytes)
  2. Specific (adaptive)
    a) Lymphocytes
    - B-lymphocytes
    Humoral response
    b) T lymphocytes
    - Cellular response - Thelper cells
    - Tcytotoxic cells
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4
Q

Compare the humeral vs. cellular response

A
  1. Humeral (B cells from Bone-marrow))
    - Abs
    - works OUTSIDE the cell
    - causes proteolysis
  2. Cellular (T cells from Thymus)
    - works INSIDE infected cell
    - Tissue rejection
    - Virus infected cells
    - Cancer cells
    - causes proteolysis

Similar immunoglobulin molecules involved

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5
Q

Compare proteins of the humoral and cellular immune response using a diagram

A

Slide 7

  • Common evolutionary origin
  • Gene duplication + diversification of function
  • Soluble IgG, B cell, Killer T cell, MHC class I, MHC class II
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6
Q

Describe and label the immunoglobulin domain structure

A

Slide 8

Each immunoglobulin monomer is made up of 4 polypeptide chains: 2 light chains, (23 KDa), 2 heavy chains (53 KDa), which are bound by disulfide bonds

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7
Q

Draw the following Ig and describe the fxn

A

Slide 9
1. IgM: Early response to microorganisms, Only in bloodstream (pentamer), J- poly peptide

  1. IgG: (g-globulin) most abundant of circulating Ab, transverse blood vessel walls, crosses the placenta
  2. IgA: monomer or dimer, J polypeptide body secretions, lines the surface of cells
  3. IgD: Little is known about its function
  4. IgE: Associated with allergic reactions, Constant regions interact with mast cells.
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8
Q

Draw an IgG, labelling each part. What is the fxn of the constant domains of the heavy chains

A

Slide 10

  1. Signal macrophages to attack particle
  2. Identify Ig type for delivery to diff tissues or secretion
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9
Q

What is the Fc fragment?

A

fragment that crytallizes easily

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10
Q

What is the Fab fragment?

A

fragment with antigen binding

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11
Q

2 reasons why its difficult to work with full length Ab?

A
  1. Abs are very flexible (Flexible linker)

2. Divalent, cause aggregation and precipitation

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12
Q

Describe the attack of a foreign molecule from many angles

A

When a foreign molecule is found in the blood, many different antibodies may bind to it, attacking at different angles. Three different antibodies that bind to the protein lysozyme (in green at the center) are shown here. The crystal structures (PDB entries 1fdl , 3hfl , and 3hfm ) each include only one arm of the antibody (termed “Fab” for “antigen-binding fragment”), which has been separated from the antibody for ease in study. The rest of the antibody is indicated extending from the edges of the illustration. Notice that the antibodies pick entirely different binding sites on the small lysozyme molecule.

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13
Q

IgG mainly has what kind of protein domain

A

Beta sandwich/Beta sheets

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14
Q

Both the constant and variable domains of the light and heavy chains have a similar structure called _____

A

the immunoglobulin fold

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15
Q

What is the immunoglobulin fold?

A
  • Found in many proteins involved in cell recognition

- 2 antiparallel b-sheets packed tightly against each other

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16
Q

Describe the constant domain of Abs. Draw it as a greek key motif and boxing the greek key motif

A
  • Compressed antiparallel “b-barrel”
  • 7 b-strands (4 + 3)
  • Joined by a disulfide bond
  • Short loops
17
Q

Describe the variable domain of Abs.

A
  • 9 b-strands
  • C’ and C’’ contains the Hypervariable region CDR2
  • Hypervariable regions on the same side of the barrel
  • Disulfide btwn B and F
  • CDR3 and CDR2: hairpin turns
  • CDR1: crossover turn
  • Loops from the 5 stranded b-sheet contributes more residues to the Ag binding site
  • Another example of the importance
    of loops in protein function
18
Q

The antigen-binding site is formed from close association of the hypervariable regions from ______

A

both heavy and light chains

19
Q

Draw parts of Fab fragment

A

Slide 19

20
Q

Describe packing of the 4-stranded sheets in CONSTANT domains of an Fab fragment (CH1 and CL)

A
  • 4-stranded beta sheets are ~90 degrees (rare in domain-domain interactions)
  • Hydrophobic interactions
21
Q

Another name for hypervariable region

A

CDR (complementarity determining regions)

- CDR1 (~28 AAs), CDR2 (~50 AAs), CD3 (~95 AA’s)

22
Q

Describe the packing of the 5 stranded b-sheets in the variable domains (VH and VL)

A
  1. Variable domains are close to parallel, so HV regions are close. C’’ not involved in the packing
  2. 4 out of the 5 strands pack to form a barrel from the variable domains
23
Q

The hypervariable region join to form an ________

A

extended Ag-binding surface

24
Q

Describe the interaction btwn antigen and Ab

A
  • Complementarities in shape

- INTERmolecular NON-COVALENT bonding

25
Q

What are antigenic determinants/epitopes?

A

Sites on foreign molecules that are recognized by the immune system occur on the surface of molecules (proteins, carbs, lipids)
- Determinant maybe: Far apart in primary structure; But close in tertiary structure

26
Q

How many immunoglobulin folds in

1) TCR
2) Antibody e.g. IgG
3) MHC

A

1) TCR: 4
2) Antibody e.g. IgG: 12
3) MHC: 2

27
Q

Draw slide 32

A

NA

28
Q
  1. What are the 2 types of T cells involved in cellular immune response
  2. What are T cells involved in
  3. What is TCR
  4. What is perforin
A
  1. Cytotoxic T cell and killer T cells
  2. a) killing potential cancer cells
    b) destroying virus infected cells
    c) tissue rejection
  3. What is TCR
    - T cell receptor
    - on the surface of T cells, recognize a viral antigen presented on the surface of a virus infected cell by MHC (major histocompatibility complex)
  4. T cells kill the infected cells by releasing a protein called perforin which forms pores in the membrane of the infected cell
29
Q

Differentiate btwn MHC and TCR

A
MHC = broad specificity
TCR = narrow specificity
30
Q

Describe the role of peptidases in the cellular (T cell) immune system

A

Slide 38

  • Protein goes into proteasome and gets cleaved.
  • Transported into ER by TAP (transporter associated w/Antigen Processing)
  • Forms complex with MHC class I
  • Goes to golgi
  • Displayed on cell surface
  • Recognized by cytotoxic T cell
31
Q

Contrast MHC class I and class III

A
  1. Class I MHC found on the surface of most cells, where it protects us from viral infection.
    - expressed in all cells (nucleated)
  2. Class II MHC, is found in specialized APCs that have the job of picking up proteins around the body and stimulating the immune system when they find a strange peptide to display.
    - expressed in special cells)
32
Q

Compare and contrast and draw MHC I and MHC II

A
  1. MHC I
    - 2 chains (4 domains) = a1, a2, a3, B2m
  • Peptide bound (7-11 AAs)
  • N and C termini BUIRED
  • H bonds at termini
  • Central region exposed (bulging out)
  • Forces peptide into EXTENDED CONFORMATION
  • Differences in MHC I genes (responsible for tissue rejection)
  1. MHC II
    - faces away from membrane surface
    - 2 domains (a1 and b1)
    - 4 antiparallel beta strands followed by helix
    - “floor” (8 stranded sheet; “walls” (2 helices) 18A separation; form the crevice of the antigen binding site
  • peptide bound (>10 AA)
  • ends extend from binding site
  • H bonds ALL along PEPTIDE
  • recognizes more SIDECHAINS
33
Q

Describe the structure of TCR

A
  1. Hypervariable regions: 1, 2, 3
  2. Fab-like structure (Va, Ca, Vb, Cb)
  3. Immunoglobulin domains
  4. Chains linked by disulfide bond
34
Q

Fxn of T-cell receptor

A
  • transmits info across membrane

- t-cells kill infected cell by releasing protein called perforin which forms pores in the membrane of the infected cell

35
Q

Describe the Interaction between Class I MHC-peptide complex and the T-cell receptor

A

TCR recognizes (binds to) both MHC and peptide thru its hypervariable regions on Va and Vb