Immunology (Test 1) Chpt 8: Mhcs And Ag Presentation

Front 1

T-cells only recognize processed Ag presented on what?

Back 1

Only processed Ag presented on MHCs.

Front 2

Ag presented on an MHC may also be referred to as what?

Back 2

May be referred to as an HLA complex in humans and H-2 in mice.

Front 3

In what mammalian species are genes that constitute MHCs present in?

Back 3

They are present in EVERY mammalian species.

Front 4

MHCs are implicated in susceptibility to ? and ?.

Back 4

Implicated in susceptibility to disease and autoimmunity.

Front 5

MHCs are important for discrimination between what?

Back 5

Important for discrimination between self and non-self.

Front 6

When were MHCs discovered?

Back 6

They were discovered during studies of rejection to transplanted tissue.

Front 7

MHC encodes how many classes of molecules?

Back 7

MHC encodes 3 major classes of molecules.

Front 8

Name the 3 major classes of molecules that are encoded by MHC.

Back 8

1. Class I MHC genes

2. Class II MHC genes

3. Class III MHC genes

Front 9

Describe class I MHC genes.

Back 9

They encode glycoproteins found on the surface of nucleated cells. It present Ags to Cd8/TC cells.

Front 10

Describe class II MHC genes.

Back 10

It encodes glycoproteins on APCs to present processed Ags to CD4/Th cells.

Front 11

Describe Class III MHC genes.

Back 11

They encode various secreted proteins that have immune functions. (ie, complement and other inflammatory mediators)

Front 12

In both humans and mice how is MHC organized?

Back 12

It is organized into regions.

Front 13

Class I MHC genes and Class II MHC genes have common ? features.

Back 13

They have common STRUCTURAL features.

Front 14

Class III MHC genes are flanked by what? What do class II MHC genes encode?

Back 14

They are flanked by I and II regions. They encode molecules critical to immune function (ie, complement and cytokines)

Front 15

?, ?, and ? arranges in pairs encoding alpha and beta chains.

Back 15

DP, DQ, and DR arrange in pairs encoding alpha and beta chains.

Front 16

MHC gene expression is related to a cluster of genes found where?

Back 16

A cluster of genes found on CHROMOSOME 6.

Front 17

Chromosome 6, as it relates to gene expression, could be described as what? Why?

Back 17

It is polygenic and polymorphic. It has several gene loci. It has many alleles (gene versions)

Front 18

All alleles are not found with ? ? in humans.

Back 18

All alleles are not found with equal frequencies in humans.

Front 19

MHC diversity is a ? ?.

Back 19

It is a population diversity.

Front 20

What is a set of MHC genes inherited from each parent called?

Back 20

It is called a HAPLOTYPE.

Front 21

What is the probability of siblings inheriting identical haplotypes from both parents?

Back 21

Sibling have a 1 in 4 probability of inheriting the same haplotypes.

Front 22

What makes tissue matching between unrelated relative very unlikely?

Back 22

MHC polymorphism makes this very unlikely.

Front 23

Why is MHC polymorphism so powerful?

Back 23

It is powerful because it enable different allelic class I and Class II products to bind an ALMOST infinite array of peptides.

Front 24

A class I molecule has a ? ?, while class II has a ? ?.

Back 24

Class I has a deep socket, II has an open pocket.

Front 25

Class I has an ? chain with ? domains.

Back 25

Class I has an alpha chain with 3 domains.

Front 26

In class I which alpha chain is highly conserved and has a sequence of amino acids that interacts with Tc/CD8.

Back 26

alpha 3

Front 27

Class I has ? microglobulin.

Back 27

It has Beta 2 microglobulin.

Front 28

What is Beta 2 microglobulin required for?

Back 28

It is required for Class I expression.

Front 29

Class II is composed of two ?-? chains.

Back 29

Composed of two non-identical chains.

Front 30

What are the two non-identical chains of class II composed of?

Back 30

They are composed of two alpha domains and two beta domains.

Front 31

It could be said that MHC molecules are what? Explain.

Back 31

They are promiscuous. They do not exhibit the specificity of Abs and TCRs.

Front 32

How many allelic variants of MHC are there in humans?

Back 32

There are several hundred allelic variants in humans.

Front 33

How many class I and class II molecules are expressed by an individual?

Back 33

Every individual only expresses up to 6 different class I molecules and up to 12 different class II molecules.

Front 34

Peptide binding sites are ?.

Back 34

They are POLYMORPHIC.

Front 35

What is an anchor residue?

Back 35

Amino acids that anchor the peptide into the MHC groove. It should be noted that all peptides that binds to Class I molecules contain a carboxyl terminal anchor that are usually hydrophobic (leucine, isoleucine).

Front 36

The peptide binding domain of Class I molecules?

Back 36

Alpha 1/ Alpha 2.

Front 37

The peptide binding domain of class II molecules?

Back 37

Alpha 1/ Beta 1

Front 38

The nature of the peptide binding cleft of class I molecules?

Back 38

It is closed at both ends.

Front 39

The nature of the peptide binding cleft of class II molecules?

Back 39

It is open at both ends.

Front 40

The general size of bound peptides of Class I molecules?

Back 40

8-10 amino acids.

Front 41

The general size of bound peptides of Class II molecules?

Back 41

13-18 amino acids.

Front 42

The peptide motifs involved in binding to MHC molecule for class I molecules?

Back 42

Anchor residues at both ends of peptide; generally hydrophobic carboxyl-terminal anchor.

Front 43

The peptide motifs involved in binding to MHC molecule for class II molecules?

Back 43

Anchor residues distributed along the length of the peptide.

Front 44

The nature of the bound peptide for class I molecules?

Back 44

Extended structure in which both ends interact with MHC cleft but middle arches up away from MHC molecule.

Front 45

The nature of the bound peptide for class II molecules?

Back 45

Extended structure that is held at a constant elevation above the floor of MHC cleft.

Front 46

MHC molecules are ? diverse. Explain.

Back 46

They are ENORMOUSLY diverse. This diversity is seen within a species and within an individual.

Front 47

Is MHC diversity for the same reasons that Abs and TCRs are diverse? Explain.

Back 47

No, it is not the same. Abs and TCR are dynamic and changing. MHCs are fixed in the genes and do not change.

Front 48

MHC expression is dependent upon ? type.

Back 48

Dependent upon CELL-TYPE.

Front 49

Where is MHC I found?

Back 49

On all NUCLEATED CELLS.

Front 50

Where is MHC II found?

Back 50

Found only on APCs.

Front 51

Where are the highest levels of MHC I found?

Back 51

The highest levels are found on lymphocytes.

Front 52

Name 4 cell types that express low levels of MHC I?

Back 52

1. Neural cells

2. Fibroblasts

3. Muscle cells

4. Hepatocytes

Front 53

Which cells appear to lack MHC?

Back 53

Neurons and sperm cells (at certain stages) appear to lack MHC.

Front 54

MHC II is found only on APCs. What does expression depend upon? Explain.

Back 54

Expression varies depending on cell differentiation stage. Pre-B-cells lack MHC II. Low levels on monocytes and macrophages until activation by Ag and then level of expression dramatically increases.

Front 55

Is MHC expression regulated.

Back 55

Yes, it is regulated.

Front 56

List 3 things that are involved in the regulation of MHC expression?

Back 56

1. Transcription Factors

2. Various cytokines

3. Viruses

Front 57

How are transcription factors involved in the regulation of MHC expression?

Back 57

MHCs are flanked by 5' promoter sequences. They are mediated both positively and negatively.

Front 58

How are various cytokines involved in the regulation of MHC expression?

Back 58

INFs and TNF increase MHC I expression. IL-4 increases the expression of MHC II on resting B-cells.

Front 59

Name 3 viruses that are involved in the regulation of MHC expression.

Back 59

1. CMV

2. HPV

3. AD12

Front 60

Bare lymphocyte syndrome is the result of what?

Back 60

It is the result of a defect in TRANSCRIPTION.

Front 61

How many MHCs do BLS patients express?

Back 61

Bare lymphocyte syndrome patients express little to no MHCs.

Front 62

BLS patients expression of little to no MHCs leads to an increased susceptibility to what?

Back 62

They have an increased susceptibility to viral and opportunistic infections.

Front 63

What are the symptoms seen in BLS patients?

Back 63

The symptom range from none to SCID (Severe combined immunodeficiency).

Front 64

A defect in what 2 genes is involved in BLS syndrome? Explain.

Back 64

A defect in TAP1 and TAP2 genes. These TAP proteins are required for the loading of peptides.

Front 65

List 5 diseases that compromised MHC leaves you susceptible to?

Back 65

1. Autoimmune disorders

2. Some viral diseases

3. Complement disorders

4. Neurological disorders

5. Some allergies

Front 66

Give an example of an autoimmune disorder that a person with compromised MHC expression is susceptible to?

Back 66

HLA B27 allele (Ankylosing Spondylitis)

Front 67

Give an example of a neurological disorder that a person with compromised MHC expression is susceptible to?

Back 67

HLA-DR2 (Narcolepsy)

Front 68

In the 1970s it was discovered that both ? and ? T-cells could recognize Ag only when couple with a ?-? molecule.

Back 68

Both CD4 and CD8 T-cells could recognize Ag only when coupled with a self-MHC molecule. This is related to self-MHC restriction.

Front 69

T-cells require ? Ag.

Back 69

T-cells require PROCESSED Ag.

Front 70

The target cells involved in Ag processing and presentation display what?

Back 70

They are cells that display peptides associated with MHC I to CD8/Tc cells.

Front 71

APCs associated with Ag processing and presentation display what?

Back 71

They display peptides associated wtih MHC II to CD4/Th cells. (However, sometimes APCs can present Ag on MHC I).

Front 72

APCs must express ? ? and deliver a ? signal.

Back 72

APCs must express MHC II and deliver a co-stimulatory signal.

Front 73

List 3 professional antigen presenting cells.

Back 73

1. Dendritic cells (several types)

2. Macrophages

3. B cells

Front 74

What are the most effective professional antigen presenting cells?

Back 74

Dendritic cells

Front 75

What must macrophages be activated by before they become an antigen presenting cell?

Back 75

They must be activated by phagocytosis.

Front 76

B-cells constitutively express ? but require activation before they express ? molecules.

Back 76

They express MHC II but require activation before they express costimulatory molecules.

Front 77

Dendritic cells express MHC II. What else do they have the ability to use?

Back 77

They can also use MHC I.

Front 78

Dendritic cells are ?. Why is this fortunate?

Back 78

They are NUCLEATED. This is fortunate because most viruses infect cells other than APCs. This relates to "altered self-cells".

Front 79

Give 3 examples of altered self-cells that can serve as targets for viruses?

Back 79

Cancer cells, aging body cells or allogenic cells from a graft can serve as targets for dendritic cells that use MHC I.

Front 80

How are intracellular and extracellular Ags trafficked?

Back 80

They are trafficked through separate intracellular compartments.

Front 81

List two intracellular compartments by which intracellular and extracellular Ags may be trafficked through.

Back 81

1. Cytosolic Pathway

2. Endocytic Pathway

Front 82

The cytosolic pathway is responsible for processing which Ags? Where is it presented?

Back 82

Responsible for processing endogenous Ags. (Like viruses replicating within a nuceate host cell). It is presented on membrane with MHC I.

Front 83

The endocytic pathway is responsible for processing which Ags? Where is it presented?

Back 83

Processes exogenous Ags. It is presented on the membrane with MHC II.

Front 84

In eukaryotes, ? levels are regulated.

Back 84

Protein levels are regulated.

Front 85

In the cytosolic pathway for endogenous Ags intracellular proteins are degraded into ? ? by ?.

Back 85

Intracellular proteins are degraded into SHORT PEPTIDES by PROTEOLYSIS (PROTEOSOME).

Front 86

In the cytosolic pathway for endogenous Ags, the protein targeted for proteolysis has what associated with it?

Back 86

It has UBIQUITIN associated with it.

Front 87

List the 5 steps for the pathway of class I MHC-associated antigen presentation.

Back 87

1. Production of proteins in the cytosol.

2. Proteolytic degradation of cytosolic proteins.

3. Transport of peptides from cytosol to ER.

4. Assembly of peptide-class I complexes in ER.

5. Surface expression of peptide-class I complexes.

Front 88

What do chaperone molecules help peptides assemble?

Back 88

They help peptides assemble with MHC-I.

Front 89

What does MHC I require the presence of for stability?

Back 89

MHC-I requires the presence of a PEPTIDE for stability.

Front 90

When peptides are assembled with MHC-I what, at the cell surface, recognizes Ag?

Back 90

At the cell surface CD8/Tc cells recognize Ag.

Front 91

Where are the alpha chain and beta2-microglobulin made? What protein are they associated with?

Back 91

They are made in the RER. They are associated with the ER membrane protein CALNEXIN.

Front 92

In the endocytic pathway for exogenous Ags what happens to the exogenous Ags? What is involved?

Back 92

Exogenous Ags are internalized by APCs and are phagocytosed and processed for presentation with MHC-II. This involves endosome action, MHC transport, and MHC-peptide binding.

Front 93

List the 5 steps of the pathway of class II MHC-associated antigen presentation.

Back 93

1. Uptake of extracellular proteins into vesicular compartments of APC.

2. Processing of internalized proteins in endosomal/lysosomal vesicles.

3. Biosynthesis and transport of class II MHC molecules to endosomes.

4. Association of processed peptides with class II MHC molecules in vesicles.

5. Expression of peptide-MHC complexes on cell surface.

Front 94

What is "cross-presentation" necessary for?

Back 94

It is necessary for immunity against most tumors and viruses that avoided APCs.

Front 95

What does "cross-presentation" play a role in?

Back 95

It plays a role in HPV, Influenza, CMV, EBV, Listeria, Salmonella, and E. Coli. Also seen in tumors of the brain, pancreas, melanoma, and leukemia.

Front 96

Where is the clearest example of "cross-presentation" seen?

Back 96

The clearest example is found on dendritic cells.

Front 97

Describe the mechanism of cross-presentation?

Back 97

The mechanism is not totally clear. It involves transportation by TAP to ER where association with MHC I occurs. The MHC I complex goes to cell surface where it can be detected by CD8/Th cells.