Midterm II Flashcards

1
Q

What are the primary function of antigen presenting cells?

A

specialized cells that capture and display antigen and activate T lymphocytes

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2
Q

What are the three types of APCs? Most effective?

A

Dendritic cells(most effective because this their only known fxn), macrophages, and B cells.

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3
Q

Why do T cells only recognize short peptides?

A

MHC molecules can bind and display peptides and no other chemical structures.

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4
Q

Why is MHC restriction?

A

T cells can recognize a specific peptide displayed by only of the large number of different MHC molecules that exist

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5
Q

What is the function of a dendritic cell as an APC?

A

Activate naive T cells causing clonal expansion, differentiation into effector T cells

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6
Q

What is the function of a macrophage as an APC?

A

Associated mostly with previously activated T cells to recognize antigens on intact proteins to internalize, and break down. (cell-mediated)

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7
Q

What is the role of the B cell as an APC?

A

Associated mostly with previously activated T cells to initiate a B cell activation and antibody production (humoral)

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8
Q

What is the route of an antigen into the body?

A

Microbes enter through the skin, gastrointestinal tract, and respiratory tract they are then captured by dendritic cells and transported into the lymph nodes. Some antigens are captured by APCs and transported into the blood stream to enter the spleen.

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9
Q

How are APCS able to activate T lymphocytes before arriving to the lymph node?

A

Activated dendritic cells express high levels of MHC molecules with bound peptides and costimulators required for T cell activation.

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10
Q

What is the initial step in the induction of T cell responses to protein antigens?

A

Naive T cells that recirculate through lymph modes encounter these APCs and the T cells that are specific for the displayed peptide-MHC complexes are activated.

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11
Q

What is the role of the lymph node in the antigen route?

A

The lymph node collects antigen from epithelium and connective tissues

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12
Q

What is the spleen in the antigen route?

A

After antigens filter into the spleen from the blood stream the spleen is responsible for blood borne pathogens.

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13
Q

What happens when the lymph enters the lymph node?

A

First the lymph enters the lymph node by the afferent lymphatic vessel, draining into the subcapsular sinus while some lymph enters fibroblast reticular cell conduits. In the subcapsular sinus, antigen are taken up by macrophages and dendritic cells, which carry the antigens into the cortez. If in the fibroblast reticular cells, low weight antigens are extracted by dendritic cells.

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14
Q

How does the MHC gene allow individual to successfully a receive a skin graft?

A

When injected with a transplant consisting the antibodies are recognized by the HLA allowing the antigens to be recognized. The inheritance of a particular HLA allele is a major determinant of graft acceptance or rejection.

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15
Q

Explain the experiment that determined MHC restriction.

A

A mouse was injected with a CD8+ CTLs specific for virus develop in the animal. These CTLs recognize and kill virus-infected cells if the cells express MHC alleles that are expressed in the animal. CTLs and the infected target cell must be derived from mice that share a class I MHC allele. This indicates that CD8+ is restricted by self class I MHC alleles. Also, CD4+ is restricted to MHC class II.

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16
Q

Which molecule recognizes MHC Class II?

A

CD4+

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17
Q

CD8+ recognizes which MHC molecule?

A

MHC Class I

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18
Q

Why are MHC molecules polymorphic?

A

They are polymorphic due to the evolution of microbes to ensure individuals will be able to deal with the diversity of microbes, and populations will be protected from devastating loss of life from emerging infections.

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19
Q

What are the differences between class MHC I and class MHC II molecules?

A

MHC I are expressed on nucleated cells and MHC II are expressed on DCS, macrophages and other types. MHC I are intracellular to capture viruses and any nucleated cell that can harbor a virus. Therefore, MHC class I are important for viral and tumor antigens. MHC class II recognize help naive T cells recognize antigens that are captured and presented by DCs in lymphoid organs. Differentiated CD4s function to activate macrophages that eliminate extracellular microbes and help B cells to make antibodies. MHC class II is specific for extracellular microbes and proteins.

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20
Q

How does class I molecules activate the adaptive immune response?

A

Class I molecules respond to interferons that are produced during the early innate immune response to many viruses. Therefore, the expression of MHC class I is increased to display CD8+.

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21
Q

How are MHC II regulated?

A

These are regulated by IFN-gamma(cytokine) which produced by NK cells during the innate and adaptive immune response. This allows APCS amplification of MHC II molecules.

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22
Q

Describe the class I structure.

A

Class I consist of one heavy light chain(alpha) and one light chain (beta) that are non-covalently linked. The heavy light chain is 45 kDA and the light chain is 12 kDa. Alpha1 and alpha2 consist of 8 antiparallel beta sheets that support the 2 parallel strands of alpha helices forming the peptide binding cleft. Has a beta2 microglobulin. Alpha 1 and 2 are polymorphic causing variations. Bind peptides that are 8-11 residues long.

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23
Q

Why does helper T cells recognize class II while cytotoxic cells recognize class I?

A

The binding sites are different.

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24
Q

Where does the CD8 bind on the MHC molecules?

A

It binds to the alpha 3 domain which has an amino acid sequence conservation

25
Q

Describe the class II structure.

A

Heterodimer of and alpha and beta chain which are similar in size. The alpha and beta form the peptide binding cleft. The beta chain is polymorphic. Trimeric complex of an alpha, beta, and antigenic peptide. Both the`alpha and beta contribute the cavity of the CD4 protein. Bind peptides that 10-30 peptides long.

26
Q

True or false each class I or class II MHC molecule has a single peptide-binding cleft that binds one peptide at a time, but each MHC molecule can bind many different peptides.

A

True

27
Q

Since, MHC molecules can not distinguish between self and foreign antigens why aren’t autoimmune diseases induced?

A

T cells specific for such complexes are killed or inactivated. Therefore, T cells cannot normally respond to self antigens.

28
Q

How do peptides bind to class I MHC?

A

Protein antigens are proteolytically cleaved in APCs to generate peptides that will be bound and displayed by MHC molecules. Once bound, peptides depending on N terminus and C terminus by electrostatic interactions. A hydrophobic pocket recognizes hydrophobic amino acids. anchor residue proteins contribute most of the favorbale interactions of binding. Form a loop due to closed ends of the peptide binding cleft.

29
Q

How do peptides bind to class II MHC?

A

Peptide binding by forming hydrogen or charge interactions. Accommodate larger peptides that extend on the outside of the cleft like a hotdog.

30
Q

What is the structural basis for the fxn of a MHC gene as an immune response gene?

A

Only individuals that express MHC alleles that can bind a particular peptide and display it to T cells can respond to that peptide.

31
Q

Why are peptides transported in the ER binding to class I instead of class II MHC?

A

Class I molecules are attached to luminal aspect of the TAP complex and capture peptides rapidly as the peptides are transported into the ER by TAP. Class II molecules are blocked by the invariant chain.

32
Q

If a protein antigen is produce in the cytoplasm of APCs as the product of a transfected gene which class molecule is presented and which cell recognizes it?

A

MHC class I and CD8+

33
Q

Give an example in which class I MHC would use a CD4+ for recognition?

A

if a protein is added in soluble form to APC and endocytosed into the vesicles of the APCs.

34
Q

What is cross-presentation?

A

DCs can capture and ingest virus infected or tumor cells and present the viral or tumor antigens to naive CD8+ cells.

35
Q

What else is required for recognition of an antigen?

A

APC antigen presentation, adhesion molecules, coreceptors, and costimulators

36
Q

What is an adhesion molecule?

A

stabilize the interaction of the T cells with APCs

37
Q

What are coreceptors?

A

deliver biochemical signals that work in concert with signals from the TCR complex

38
Q

What are costimulators?

A

second signal for T cell activation. Fxn with antigens to stimulate T cells

39
Q

What occurs if an antigen binding lacks costimulation?

A

the cell undergoes apoptosis.

40
Q

Describe the phenomenon of licensing T cells?

A

By the CD40 receptor( b cells and macrophages) and CD40 ligand by activating T cells to become more powerful stimulator of immune responses. Amplifying t cell responses. CANNOT solely be a costimulator.

41
Q

What is an IL-2?

A

An IL-2 is a growth, survival, and differentiation factor for T cells.

42
Q

Where are IL-2 expressed?

A

effector and naive t cells, high affinity of t regulatory cells therefore they cannot be replaced on Tregs.

43
Q

How are IL-2 secreted?

A

Mostly in the synapse between T cell and APC.

44
Q

What does IL-2 promote?

A

Promotes survival of cells by preventing apoptosis and stimulating CDKs by degrading p27. Also, increases IFN-gamma and IL-4 by T cells.

45
Q

How is IL-2 required for regulatory T cells?

A

Suppresses immune responses against self and other and other antigens

46
Q

What aids in induction of clonal expansion?

A

IL-2, costimulators, coreceptors, autocrine growth factors

47
Q

What is the function of B7 molecules?

A

These are ligands found on APCs they can bind CD28 or CTL-4. They have a higher affinity to CTL4. CD28 activates native T cells by stimulating their growth by allowing PI3-kinase to bind it its tail to prevent apoptosis. CTL-4 in an inhibitory response by blocking CD28 access of B7 and possibly recruiting inhibitory signals.

48
Q

What is the function of PD molecules?

A

inhibits the ligand of effector T cells.

49
Q

What are the functions of IFN gamma?

A

IgG B class switching, activating B7, and activating macrophages

50
Q

What are the functions of IL4?

A

activate eosinophils, IgE class switching and mucosal secretion

51
Q

What are the functions of IL17and IL21?

A

B cell activation and induce inflammatory responses.

52
Q

What are subsets of effector T cells?

A

Th1, Th2, Th17, and T regs

53
Q

What do Th1 fight against?

A

intracellular microbes

54
Q

what do Th2 fight against?

A

helmniths and allergies

55
Q

what do th17 fight against?

A

extracellular bacteria and fungi

56
Q

Which stat and transcription factor does TH1 stimulate?

A

Stat 1 and t bet and stat 4 by il-12

57
Q

Which stat and transcription factor does TH2 stimulate?

A

Stat 6 and GATA 3

58
Q

Which stat and transcription factor does TH17 stimulate?

A

STAT 3 and ROR gamma t