Immunology Exam 2

Front 1

Identify the five classes of antibodies.

Back 1

IgG, IgA, IgM, IgD, IgE.

Front 2

General characteristics of IgG

Back 2

Pentamer. used in neutralization, opsonization, sensitization for killing by NK cells, activation of complement system, transport across placenta, and diffusion into extravascular sites.

Front 3

General characteristics of IgM

Back 3

monomer. used some in neutralization, activation of complement system, and transport across epithelium.

Front 4

General characteristics of IgD

Back 4

monomer. is a receptor for antigen found mostly on mature B-lymphocytes.

Front 5

General characteristics of IgE

Back 5

monomer. used in sensitization of mast cells and diffusion into extravascular sites (also fights parasitic infections and is responsible for allergic reactions).

Front 6

General characteristics of IgA

Back 6

Dimer. used in neutralization, activation of complement system, transport across epithelium, and diffusion into extravascular sites.

Front 7

Describe what Bence Jones fragments are and when they can be found.

Back 7

cancerous changes to a B cell results in expansion of a single B cell and its receptor. Multiple myceloma, dimers of k or lamba light chains found in the urine of some multiple myeloma patients. Helped to determine the structure of antibodies.

Front 8

Define the term Framework region (FR)

Back 8

less variable region located between the HV/CDR regions.

Front 9

Define hypervariable region (HV)

Back 9

found on the surface of the binding region. determines the ability to complement a specific antigen. (fold together to form antigen binding pocket).

Front 10

Define complementarity determining region (CDR)

Back 10

regions within antibodies where proteins complement an antigen's shape. Another name for hypervariable region (are made up of hypervariable segments of proteins).

Front 11

Discontinuous vs. continuous epitopes. How does this apply to how the lymphocyte engages the epitope?

Back 11

-Continuous epitope: epitope composed of a single segment of polypeptide chain.
-Discontinuous epitope: epitope composed of amino acids from different parts of the polypeptide chain.
-How that effects lymphocyte receptor engagement: BCR recognizes antigen directly (can be discontinuous epitope). TCR recognizes small peptide fragments in context of MHC (recognizes peptides deep within the native pr- structure).

Front 12

Define Fab fragments

Back 12

variable region fragments that bind antigen (two arms of the antibody)

Front 13

Define Fc fragments

Back 13

constant region found on an antibody molecule that influences effector function (is able to interact with an effector molecule, can crystallize readily).

Front 14

Define Fab2 fragments

Back 14

is when pepsin cuts the carboxy-terminal side of the disulfide bonds resulting in two antigen-binding arms of the antibody molecule that remain linked. Is unable to interact with any effector molecule (can be used in therapy).

Front 15

Isotypic differences

Back 15

different in Fc region

Front 16

Idiotypic differences

Back 16

different in allele region (found in Fc)

Front 17

Allotypic differences

Back 17

different variable regions

Front 18

Define the term hapten as it relates to immunoglobulin binding.

Back 18

Small antigenic molecules that will not stimulate an immune response unless bound to a carrier protein (immunoglobulin)

Front 19

List weak forces used to bind antigen

Back 19

-hydrophobic
-ionic
-Van der Waals
-electrostatic
-hydrogen bonds

Front 20

Describe/define hydrophobic

Back 20

when 2 hydrophobic forces come close into contact and aggregate (away from aqueous environment).

Front 21

Describe/define ionic

Back 21

formed through an electrostatic attraction between two molecules (opposite charge)

Front 22

Describe/define Van der Waals

Back 22

typically describes forces between two dipoles.

Front 23

Describe/define electrostatic

Back 23

based on electronegativity (where one atom has more charge than the other in a pair)

Front 24

Describe/define hydrogen bonds

Back 24

bonds established between hydrogen atoms.

Front 25

Describe the general structure of the T cell receptor and its related co-receptors necessary for proper signal transduction

Back 25

General structure of the T cell receptor includes TCR-α joins with TCR-β to form a heterodimer, the functional TCR. Second less common pair, the ϒ-Ϭ heterodimer as well. Co-receptors necessary include CD4 (recognizes MHC class 2) and CD8 (recognizes MHC class 1).

Front 26

Describe and contrast MHC I versus MHC II in terms of peptide lengths bound, expression patterns, and where the peptides are processed.

Back 26

-MHC 1 detects small peptides, found on most cell with nucleus, expression varies, present peptides from pathogen, particularly viruses. (small peptides transported to ER for processing).
-MHC 2 main function is to activate other effector cells, found on antigen presenting cells, cytokines up-regulate MHC expression in response to infection. (peptides generated in acidified endocytic vessicles).
-Both classes are codominantly expressed.

Front 27

Describe how MHC is able to bind a wide variety of peptides while, in general, peptide binding is a specific process.

Back 27

*Short answer: Highly polymorphic; hundreds of MHC type 1 alleles in the human population.

The peptide bound is an integral part of the MHC molecule’s structure. When peptides are not bound, the molecules are unstable. MHC class 1 molecules bind short peptides of 8-10 amino acids by both ends by contacts between atoms and invariant sites. MHC class 2 molecules can bind peptides of lengths that are not constrained (no bound ends of peptide) and has a peptide-binding cleft that has shallow and deep pockets allow for more variation in binding.

Front 28

MHC is polymorphic, polygenic, and expressed coordinately. Explain what this means to the immune systems ability to display antigen in a population and individually.

Back 28

This means that there is variability in the binding region (polymorphic) allowing more types of antigen to be bound (also within an individual with regards to how MHC binds to a T cell). That the expressed coordination allows for a large amount of response to a certain stimuli (in the case of class 1) or a differential response to certain stimuli (class 2) leading a variation within the individual, but not necessarily on a population level. Multiple gene inheritance (One from your father and one from your mother) allows for further variation in binding to antigens between individuals in a population (each individual would vary).

Front 29

There are three class MHC I and three MHC II genes with alleles from each parent. How many different MHC I and II molecules are expressed on the surface of a cell capable of such expression?

Back 29

If both parents are heterozygous, then there would be 6 potential molecules expressed on the surface of a cell capable of such expression.

Front 30

Describe the nomenclature of the three MHC I and II genes in general.

Back 30

MHC class 1 genes and molecules are HLA-A, HLA-B, and HLA-C. MHC class 2 genes code for alpha and beta chains: HLA-DP, HLA-DQ, and HLA-DR regions. So if you had HLA-DPA it would code for the alpha chain the HLA-DP molecule which would pair with the beta chain to form the completed dimer.

Front 31

Describe antigen processing for MHC I and II with associated structures and roles included.

Back 31

-MHC 1: proteasome (tube-like structure) cleaves proteins into small peptides to be presented by HLA class 1 molecules. Immunoproteasome stimulated with IFN’s. These peptides are then transported into the E.R. by TAP-1 and TAP-2 (allow for peptide editing). MHC 1 does not leave the E.R. until it is bound to peptide. Calnexin keeps the MHC 1 semi-folded until the peptide is available for loading. Calreticulin binds to the newly formed MHC 1 after beta 2 microglobulin is associated with the alpha heavy chain. Once bound the MHC/Peptide complex can make it sway to the surface via the golgi apparatus.

-MHC 2: Peptides for MHC 2 are generated in acidified endocytic vesicles. Due to being synthesized in the ER, a source of many proteins in various stages of synthesis, a method is needed to keep improper loading restricted. Invariant chains prevent loading of ER proteins. It also delivers MHC to the vesicles.

Front 32

Describe the role of CD1 as a non-classical MHC gene.

Back 32

-CD1 allows for lipids and glycolipids to be presented. (Similar to MHC in that it has a groove to bind antigen, however the groove most likely binds the hydrophobic backbone of the antigen).

Front 33

Describe the process of immunoglobulin gene rearrangement as it applies to formation of B and T cell receptors, including associated enzymes necessary for normal development.

Back 33

- Recombination Signal Sequence (RSS). Conserved regulatory sequences of nucleotides flanking the gene segments allow recognition and rearrangement. Heptamer+spacer (12 or 23 bp)+nonomer. Spacer sequence varies but length is conserved.
- V(D)J Recombinase: the complex of enzymes that carry out the recombination event leading to a lymphocyte receptor. RAG-1 and RAG-2 are recombination-activating genes are the lymphoid specific parts of the complex. Complex includes TdT (terminal deoxynucleotidyl transferase) and exonucleases.

Front 34

Describe the many ways that the immune system increases the diversity of variable region binding in order to create a wide array of antigen binding.

Back 34

-Combinatorial diversity: the pattern of segments joined in light and/or heavy chains.
-Junctional diversity-the addition or subtraction of bases during the recombination process.
-Somatic Hypermutation-upon activation by antigen point mutations occur at a higher rate than other cells.

Front 35

Describe the role of RSS sequences in the formation of IG receptors.

Back 35

-DNA rearrangements are guided by conserved noncoding DNA sequences that are found adjacent to the points at which recombination takes place (RSSs). Conserved regulatory sequences of nucleotides flanking the gene segments allow recognition and rearrangement. Heptamer+spacer (12 or 23 bp)+nonomer.

Front 36

Relate the loss of a step in the formation of an Ig receptor or CD 40/CD 40L to the associated immune system deficit.

Back 36

Loss of any component of the V(D)J recombinase may result in severe combined immunodeficiency. If you lose CD40 (or CD40L), then you can't have class switching.

Front 37

Describe the process of class switching as it applies to B cell development including the terms somatic hypermutation and gene conversion.

Back 37

Class switching is irreversible nonhomologous DNA recombination leading to switches in classes of antibodies (immunoglobulins). It is stimulated in the course of an immune response by external signals such as cytokines released by T cells or mitogenic signal delivered by pathogens. When AID (activation-induced cytidine deaminase) is initiated it converts cytidine to uracil which: leads to transition mutations, leads to transversion mutations, APE1 causes a single strand ‘nick’ in the DNA by removing the rest of the residue. AID is only expressed upon B cell activation and only affects B cells. The single strand nick may result in gene conversion or double-strand break that is used for class switch recombination. Somatic hypermutation is also dependent upon AID. AID requires the DNA to be single strand to be effective, thus only actively transcribed genes are targeted in B cells. By introducing mutations, some antigen binding regions improve binding to the antigen and are saved via T cell signaling (affinity maturation). Non-productive mutations result in B cell death.

Front 38

Explain MHC restriction as it relates to the T cell receptor

Back 38

antigen must be coupled with MHC molecule (specifically of that person)

Front 39

Where is the c region relating to the b cell receptor?

Back 39

embedded in the plasma membrane

Front 40

What can bind antigen directly? What does this result in?

Back 40

B cell receptor. Leads to activation and clonal expansion of the B cell.

Front 41

How does each antibody isotype vary?

Back 41

in its constant region and thus the effector mechanism it involves in the immune process.

Front 42

How many types can heavy chains consist of? Light chains? Be able to recognize each (reference notes-ppt 1 for the greek symbols)

Back 42

5. 2.

Front 43

What is an epitope?

Back 43

the antigenic determinant of a particular substance or protein

Front 44

What is papain, what does it do? What does this result in?

Back 44

an enzyme. capable of cutting the antibody molecule at the hinge region. Fab fragment.

Front 45

What is pepsin, what does it do? what does this result in?

Back 45

an enzyme that digests below the hinge joint result in the F(ab')2 fragment.

Front 46

What makes up the B cell receptor?

Back 46

immunoglobulins

Front 47

What joins to form a heterodimer? What is this structure similar to?

Back 47

TCR-alpha with TCR-beta. antibody.

Front 48

What does TCR recognize?

Back 48

peptides deep within the native protein structure.

Front 49

T cells have two major classes. Name them.

Back 49

CD4 and CD8.

Front 50

What does CD4 recognize? CD8?

Back 50

MHC class 2. MHC class 1.

Front 51

Characteristics of MHC Class 1

Back 51

found on most cells; all that have a nucleus. level of expression varies. present peptides from pathogens, especially viruses.

Front 52

Characteristics of MHC Class 2

Back 52

main function is to activate other effector cells. Found in cells that participate in IR, but not other tissues.

Front 53

What can up-regulate MHC expression in response to infection?

Back 53

IFN-y

Front 54

What are the functions of MHC?

Back 54

critical in the maturation of T cells. Critical in antigen presentation to T cells. MHC restriction. present in all vertebrates, but most is known about humans and mice.

Front 55

Which chromosome does MHC complex map to in humans?

Back 55

chromosome #6

Front 56

What are the differing versions of HLA genes referred to as?

Back 56

Alleles, which can fill the two spots at a given locus.

Front 57

The advent of what has allowed for more accurate serotyping?

Back 57

PCR

Front 58

Define Homozygous

Back 58

both alleles are the same

Front 59

Define heterozygous

Back 59

two different alleles at that locus

Front 60

Define codominant

Back 60

both alleles are expressed equally

Front 61

Define haplotype

Back 61

the set of class 1 and class 2 genes expressed on an individual chromosome (one half of your diploid set)

Front 62

How is HLA nomenclature set up? (hint: __/___/__)

Back 62

locus/allele group/subtype (i.e.DRB1/07/01)

Front 63

Describe the effects of MHC Polymorphism

Back 63

MHC binding to the T cell may be effected. Peptide binding properties are also affected. preferentially binds peptides by anchor residues that share a common motif. homozygous MHC genes limit the variety of antigen the MHC can present

Front 64

What is the role of TAP? Tapasin?

Back 64

Tapasin helps include the formation of TAP as well as facilitate loading of high affinity peptides from the cytosol to the ER. The complex between them allows peptide editing. once bound, the MHC/peptide complex goes to surface via golgi apparatus.

Front 65

What are two theories of receptor development?

Back 65

Germline and somatic diversification.

Front 66

Where does gene rearrangement occur? what does it do?

Back 66

in lymphocytes. greatly enhances variability of certain parts of their receptors.

Front 67

What do V gene segments do?

Back 67

encode most of the variable region of the lymphocyte receptor

Front 68

What do J gene segments do?

Back 68

complete the final functional variable region gene.

Front 69

Explain heavy chain somatic recombination

Back 69

heavy chain made from 3 separate gene segments combined to form the functional gene.

Front 70

What can result in severe combined immunodeficiency?

Back 70

loss of any component of the V(D)J recombinase.

Front 71

What does AID increase the need for?

Back 71

DNA repair complexes. Leads to increased mutation rates.

Front 72

What prevents B cell class switching?

Back 72

Loss of AID or the DNA repair complexes

Front 73

Does affinity maturation get stronger or weaker binding over time?

Back 73

stronger.