Regulation of the Immune Response

Question 1

What is immunological tolerance?

Answer 1

Lack of response to a specific Ag

Question 2

What are the two major mechanisms of tolerance induction?

Answer 2

deletion of reactive cells, inactivation of reactive cells (anergy)

Question 3

What is clonal deletion? Where does it occur?

Answer 3

elimination of autoreactive T cells in thymus caused by tight association of T cell to MHC-presented antigen

Question 4

Why do antigens presented from self-cells induce anergy?

Answer 4

Most self-cells don’t have B7-1 or B7-2 so Ag from them isn’t costimulated, preventing self-Ag recognition.

Question 5

What is functional deletion?

Answer 5

deletion of function of T helper cells, causing loss of cytotoxicity of CTL and B cell antibody formation that require help

Question 6

What are some mechanisms of functional deletion?

Answer 6

deletion of T helper specificity during selection, bias for inappropriate Th1 or Th2 response from production of certain cytokines (i.e. block Th1 cells with IL-10)

Question 7

How does a regulatory T cell bind APCs? How is it activated?

Answer 7

CD4+ T cell binds B7 receptor on APC with CTLA-4, which is activated by the crosslinking of CD28 molecules

Question 8

What are the 5 mechanisms of tolerance n in T cells?

Answer 8

1. clonal deletion
2. clonal anergy
3. functional deletion
4. regulatory T cells
5. blocking of presentation or activation

Question 9

What are the 3 mechanisms of tolerance in B cells?

Answer 9

1. clonal deletion
2. clonal anergy
3. functional deletion

Question 10

How do B cells become anergic?

Answer 10

Immature B cells expressing IgM are capped when exposed to polyclonal IgM or tolerizing Ag and the IgM internalizes. In mature B cells, re-expression occurs within 1-2 days, but immature cells don’t re-express surface Ig

Question 11

How are B cells functionally deleted?

Answer 11

lack of T cell help for T-dependent B cells, presentation of TI-Ag in non-crosslinking form for TI Bcells

Question 12

What affects whether an antigen induces maturity or tolerance?

Answer 12

form, amount or manner of presentation of the antigen

Question 13

Is tolerance easier to induce in mature or immature cells?

Answer 13

Immature cells

Question 14

How does the immunogenicity of an antigen affect induction of tolerance?

Answer 14

The stronger an immunogen the more stringent regime to induce tolerance

Question 15

How does the dose affect immunogenecity of a substance?

Answer 15

need the optimal dose range, higher or lower doses usually induce tolerance

Question 16

What is high dose tolerance?

Answer 16

very large quantity of immunogen can turn off response to it

Question 17

What is more immunogenic: aggregated material or disaggregated material? Why?

Answer 17

aggregated material, clumps and aggregates stimulate APC to phagocytose the antigen

Question 18

Tell whether each of the following routes of administration of antigen favors immune response or tolerance: subcutaneous, oral, IM, IV

Answer 18

immune respone: subcutaneous, IM

tolerance: oral, IV

Question 19

What is cyclophosphamide? What lymphocytes does it work on?

Answer 19

immunosuppressive drug, acts on T and B cells

Question 20

What cells mediate positive selection in the thymus? What is the cell transition at positive selection?

Answer 20

cortical epithelial cells, go from immature CD3- DN thymocytes to immature CD3+ DP thymocytes

Question 21

What cells mediate negative selection in the thymus? What is the cell transition at negative selection?

Answer 21

dendritic cell, immature CD3+ DP thymocytes to mature CD3+ SP thymocytes

Question 22

Why is immune regulation needed?

Answer 22

prevent uncontrolled proliferation of individual B or T cell clones, prevent indefinite response to one challenge to conserve resources for another

Question 23

What is the expression pattern of Tregs?

Answer 23

FoxP3+ , CD25 +, CD4 +

Question 24

What is regulatory tolerance?

Answer 24

T cell specific for self-Ag becomes regulatory, IL-10 and TGFb produced by Treg inhibitsother self-reactive T cells

Question 25

What 6 diseases do Tregs have a role in controlling?

Answer 25

colitis, diabetes, MS, SLE, GVHD, graft rejection

Question 26

What are mechanisms of regulation of Tregs?

Answer 26

direct contact with target cells, cytokine-mediated suppression of T cells

Question 27

What type of immunity do proteins induce?

Answer 27

Humoral and CMI

Question 28

Why can’t polysaccharides and lipids induce CMI?

Answer 28

can’t be presented by MHC molecules to T cells

Question 29

What type of immune response do polysaccharides and lipds induce?

Answer 29

short-lived, IgM and some IgG response to capsule

Question 30

What type of antigen can induce long-lived immunologic memory? How?

Answer 30

proteins/peptides via T cell activation

Question 31

What is antigen blocking?

Answer 31

Ab sequesters Ag which prevents it from being recognized by other Ag-recognizing cells and thus from activating them

Question 32

What does crosslinking of Ig and Fc receptors on the same B cell cause?

Answer 32

paralytic signal to the cell

Question 33

What does crosslinking of two Igs on the same B cell cause?

Answer 33

proliferative signal

Question 34

When do immune complexes augment B cell response? Which Ab type tends to enhance?

Answer 34

when they opsonize APCs, IgM

Question 35

When do immune complexes inhibit B cell response? Which Ab type tends to inhibit?

Answer 35

when they crosslink on same B cell, IgG

Question 36

How is Rh disease prevented?

Answer 36

prevent immune response by using high dose of antiRh Ab to prevent Rh+ from seeing mother’s Rh- and forming immune reponse

Question 37

What is a direct Coomb’s test?

Answer 37

look to see if fetal RBC agglutinate when you add anti-human rabbit Ag–if yes, they are coated in maternal Ab
take maternal serum and add Rh+ RBCs and rabbit Ag—if agglutinates, if Rh+ Ab exist