Immunology 4 - lectures 13-15

Question 1

What does autologous mean?

Answer 1

from self

Question 2

What does allogeneic mean?

Answer 2

from a genetically different individual of same species.

Question 3

What does xenogeneic mean?

Answer 3

from a different species

Question 4

What does syngeneic mean?

Answer 4

from a genetically identical individual (identical twin)

Question 5

What is an immune correlate of protection?

Answer 5

immune response to a vaccine closely associated with protection against infection or disease.

Question 6

What is a neutralizing antibody?

Answer 6

antibody that binds to a virus to prevent attachment or viral replication in a cell.

Question 7

How are neutralizing antibodies maintained?

Answer 7

1) circulating antibodies
2) long-lived plasma cells (that go primarily to the bone marrow)
3) memory B cells.

Question 8

What are the three types of memory T cells and how are they distinguished?

Answer 8

1) Centra-memory T cell. Expresses lymph node homing receptor.
2) Effector-memory T cell. Travel all over (blood and tissue) do not express the homing receptor for the lymph nodes.
3) Tissue-resident memory. Don’t circulate, adopt features of resident memory cells.

Question 9

How are memory cells able to be activated much more quickly than Naive T cells?

Answer 9

Memory T cells do not require costimulation, so can be activated by any APC (DCs, B cells, endothelial cells, macrophages). Produce cytokines more quickly.

Question 10

How do you attenuate a virus?

Answer 10

Pass the virus through cells of another species; virus mutates to spread in that species, but when doesn’t grow as well in human cells, can be introduced to generate antibodies.

Question 11

What are the four major considerations for vaccine design?

Answer 11

1) nature of pathogen (bacteria, virus, etc.)
2) mechanism of clearance (antibody vs. T cell)
3) Tissue sight of infection and pathogenesis.
4) safety - protection vs. immunopathology.

Question 12

What are the major surface structures of influenza targeted by vaccines and what is their function?

Answer 12

1) hemaglutinin (HA) - binds sialyc acid to get in the cell.
2) neuraminidase (NA) - important to assemble inside the cell.
Both proteins have highly conserved and highly variable regions.

Question 13

How does one treat RSV?

Answer 13

Give palivizumab - monoclonal anti-F protein Ab. Vaccine against RSV in the 1960s caused too strong an immune response.

Question 14

What are the four types of allograft rejection, when do they occur (temporal relative to transplant date), and what mediates their occurrence?

Answer 14

1) hyper acute rejection: most rapid rejection, occurs due to antibodies already being present against HLA or blood type, antibodies attach to graft, complement cascade, immediate rejection.
2) acute vascular: same mechanism as 1) but initial level of antibodies is low, but quick activation of B cells, more antibodies, similar rapid complement cascade and rejection.
3) cellular: largely T-cell mediated, though some innate contribution due to DAMPs during the transplant process. Due to HLA mismatch.
4) chronic

Question 15

How do anti-HLA antibodies develop?

Answer 15

pregnancy, blood transfusion (with some leukocytes getting through), previous transplants, natural antibodies against xenografts.

Question 16

What is difference between direct and indirect allorecognition?

Answer 16

in direct recognition, donor DCs are acting as the APCs, while in indirect recognition, the host DCs act as the APCs.

Question 17

What are the three major types of immunosuppression typically used?

Answer 17

1) corticosteroids.
2) cytotoxic agents
3) calcinurin inhibitors.

Question 18

What do calcinurin inhibitors do to T cells?

Answer 18

Reduce IL-2 expression (no T cell proliferation) and suppress exocytosis of cytotoxic granules.

Question 19

What tissue is primarily affected in graft-versus-host disease?

Answer 19

epithelial tissues - skin, intestinal system, liver.

Question 20

What is erysipelas?

Answer 20

Common post-surgical complication characterized by fiery red skin, fever/chills, malaise. Due to Strep pyogenes, typically self-limited and rarely fatal.

Question 21

What types of cells to chemotherapy agents target?

Answer 21

proliferating cells, including gametes, hair follicles, hematopoietic and GI cells.

Question 22

What are ‘differentiation antigens?’ Provide some examples.

Answer 22

antigens produced in a tissue-specific manner.
CD20 for B cells
Tyrosinase for melanocytes
Prostatic acid phosphatase

Question 23

What medication is used as immunotherapy against B-cell lymphomas and what is the target for the medication?

Answer 23

Ritaximab - targets CD20 proteins found on B-cell surface (but not plasma cells, so immune damage is acceptable).

Question 24

Where are the following proteins expressed, and how must immunotherapeutic agents target them?

1) CD20
2) tyrosinase
3) prostatic acid phophatase

Answer 24

1) cell surface
2) cytoplasm
3) cytoplasm

Question 25

What is a 'tumor dysregulated antigen?' Provide some examples.

Answer 25

protein that is over-expressed in tumor cells, but that exists at a basal level in normal, healthy tissue. Her2/neu receptor overexpressed in 30% of breast cancers. Perception prevents Her2 from dimerizing, decreasing proliferation. MUC-1 over-expressed with unnatural glycocylation pattern in many tumors, indicating invasive behavior. MUC-16 or CA-125 morally over-expressed in 90% of ovarian cancers.

Question 26

What are oncofetal proteins?

Answer 26

proteins expressed during development, but only found after birth in some chronic inflammatory diseases and in cancer.

Question 27

What are cancer/testis antigens?

Answer 27

Normally in testis and trophoblastic tissues, but turned on in many cancers.

Question 28

Why are antigens expressed exclusively within the spermatozoa invisible to effector CD8 cytotoxic T cells?

Answer 28

They do not express MHC1.

Question 29

Defects in what genes are often associated with organ-specific autoimmune diseases?

Answer 29

``` Defects in AIRE (inadequate expression of self-peptides in thymus) and FOXP3 (defect in Tregs). ```

Question 30

What is the major determinant of systemic autoimmune disease?

Answer 30

MHC alleles.

Question 31

What immune cell plays the dominant role in MHC I associated diseases? Give 3 examples of diseases.

Answer 31

CD8 T cell plays the dominant role: ankylosing spondylitis psoriatic arthritis psoriasis.

Question 32

What immune cell plays the dominant role in MHC II associated diseases? Give 3 examples of diseases.

Answer 32

autoantibodies or CD4 T cells: T1DM systemic lupus erythematosus MS

Question 33

What is 'citrullination' and why is it important?

Answer 33

post-translational modification of a peptide involving the loss of an immune group on arginine. Allows for modified self peptide to bind MHC molecule and may be responsible for rheumatoid arthritis.

Question 34

What are the three currently used vaccine strategies and what are examples of each?

Answer 34

1) killed bacteria: Typhus fever. 2) live-attenuated viruses: influenza 3) subunit vaccines: pertussis, tetanus, diptheria toxin.

Question 35

What is alum do when added to vaccines?

Answer 35

Adjuvant that stimulates Th2 response, activates inflammasome.

Question 36

Are TLR agonists used in humans?

Answer 36

No - too risky, can cause huge immune rxn. Trying to improve it.