Immunology

Question 1

the ability of T cells to recognize non-self MHC alleles

Answer 1

allorecognition

Question 2

T cell recognizes unprocessed allogeneic MHC molecule on graft APC

Answer 2

direct allorecognition

Question 3

presentation of processed peptide of allogeneic MHC molecule bound to self-MHC

Answer 3

indirect allorecognition

Question 4

minutes to hours after transplant
preformed anti-graft Ab
primarily Ab-mediated indicating prior exposure to donor antigens; complement involved in immune complex formation that causes tissue damage
rapid, irreversible damage

Answer 4

hyperacute graft rejection

Question 5

1-2 weeks after transplant
primarily T cell mediate in response to non-self MHC
requires T cell priming, clonal expansion, differentiation
monitor graft function and use immunosuppressants at earliest sign of rejection; reversible/controllable
repeat episode are common

Answer 5

acute graft rejection

Question 6

months after the transplant
cell mediated and Ab mediated immunity
fibrosis and scarring associated with tissue remodeling, loss of graft function (slow infiltration of immune cells)
targets recipient and donor vessels causing tissue damage
difficult to manage and immunosuppression is often ineffective

Answer 6

chronic graft rejection

Question 7

immune response that results from T cells in the donor bone marrow mounting an immune response to recipient tissue

Answer 7

graft versus host disease

Question 8

immune response that results from allogeneic bone marrow transplant in which donor T cells attack host leukemia cells

Answer 8

graft versus leukemia

Question 9

optimize chance of graft survival

Ab to known panel of HLA antigens are used to probe HLA profile of donor and recipient

Answer 9

serology

Question 10

optimize chance of graft survival
proliferation test of donor and recipient lymphocytes in tissue culture; proliferation in response to allogeneic cell exposure is measured with radioactive thymidine that is incorporated into DNA

Answer 10

mixed lymphocyte reaction

Question 11

optimize chance of graft survival

more accurate for identifying genotypes, routine for HLA typing

Answer 11

PCR for HLA gene allotypes

Question 12

the immune system surveys self-tissues for malignant cells and decreases cancer development

Answer 12

immunosurveillance

Question 13

selective pressure may result in development of tumors that are less immunogenic over time

Answer 13

immune editing

Question 14

because of immune editing, tumors that ultimately develop have evolved mechanisms to evade an effective immune response

Answer 14

immune evasion

Question 15

negative co-stimmulatory molecule expressed on T cells after activation and on T reg cells which can interfere with T cell activation
interacts with B7 with higher affinity than CD28
therapeutic targeting to promote T cell activation is associated with autoimmune inflammatory complications

Answer 15

CTLA-4

Question 16

negative co-stimulatory molecule expressed on T cells after activation
induces signaling events that inhibit TCR stimulation
therapeutic blockage promotes tumor specific immune response

Answer 16

PD-1

Question 17

normal immunodeficient in newborns

decreased Ig levels during the window between decrease in maternal Ab (IgG via placenta) and when infant begins to produce Ab
Decreased/altered T cell immunity in newborns may also affect humoral response

Answer 17

Transient hypogammaglobulinemia

Question 18

severe defect in immune function resulting in increased susceptibility to bacteria, viruses, fungi, and protozoa including opportunistic infections
always associated with a defect in T cell function but may also involve B cells and NK cells
prenatal screening is being widely instituted (look for DNA fragment byproduct of somatic recombination = TCR excision circles = TREC)

Answer 18

Severe Combined Immunodeficiency (SCID)

Question 19

mutation of the gene encoding the common gamma chain which is an important part of type 1 cytokine receptors (IL-2, IL-4, IL-7, IL-15 receptors)

common SCID

IL-7 receptor is critical for T cell growth and survival during development
NK cells require IL-15 for survival
B cells may develop normally in BM but have defects in humoral response due to lack of T cell help

Answer 19

X-linked SCID

Question 20

SCID

phenotypically identical to X-linked SCID due to the defect in IL-7 dependent responses

Answer 20

JAK3 and IL7 receptor deficiencies

Question 21

autosomal recessive form of SCID due to a defect in purine metabolism and toxicity to developing T and B cells

Severe deficiency in mature T and B cells

Second most common SCID

Answer 21

Adenosine Deaminase (ADA deficiency)

Question 22

defect in RAG protein resulting in defective somatic recombination and deficiency in T and B cell development

Complete loss of RAG results in complete defect in recombination and lymphocyte development

Hypomorphic mutation leaves some residual RAG activity resulting in a diminished number of T and B cells, associated with restricted antigen receptor repertoire and Th2 effector function (atopic dermatitis)

Answer 22

RAG deficiency

Omenn’s syndrome

Question 23

embryonic defect due to deletion of region of chromosome 22; usually involves defect in development of cardiac aortic arch, parathyroid gland, and thymic epithelium (defect in 3rd and 4th pharyngeal pouches)

Relatively common (1/4000 births) but defect is variable resulting in variable severity of T cell defect

Defect improves with age and is not severe
In a minority of cases complete T cell deficiency is more severe and similar to SCID

Not associated with a lymphocyte intrinsic defect, treatment with hematopoietic stem cell is not effective – treated with thymus epithelium transplant

Answer 23

DiGeorge’s Syndrome

Question 24

class I and II MHC deficiencies or a TAP deficiency

MHC I deficiency results in no CD8 T cells
MHC II deficiency results in no CD4 T cells

Answer 24

bare lymphocyte syndrome

Question 25

most commonly caused by mutation in CD40 ligand gene, other causes include CD40 and AID mutations Results in defective Ig isotype switching and germinal center reaction since CD40/CD40L interaction is critical for T cell help Infectious disease susceptibility similar to other B cell defects (capsular bacteria) Defective cell mediated immunity due to CD40/CD40L role in macrophage activation

Answer 25

Hyper IgM syndrome

Question 26

IgA is most common, often clinically silent because IgM can compensate and is also transported across the mucosal epithelium, associated with autoimmunity (and celiac disease), and infections at mucosal surfaces IgG deficiencies associated with IgA deficiency result in significant clinical impact Molecular defect is unknown in most cases

Answer 26

Selective immunoglobulin isotype deficiencies

Question 27

relatively common but difficult to diagnose because the heterogeneous molecular basis is often unknown Associated with poor antibody production, bacterial infection susceptibility, and autoimmunity Unclear is defect is specific to B cell or is indirect due to lack of T cell help

Answer 27

Common variable immunodeficiency

Question 28

associated with defects in cytotoxic effector function dependent on granule exocytosis most commonly due to a perforin deficiency T cells are activated but incapable of killing target cells Hyperactive CTLs increase cytokine production and cause increased macrophage activation which causes phagocytosis and destruction of other blood cells (RBCs and platelets)

Answer 28

Familial hemophagocytic syndrome

Question 29

caused by SAP deficiency SAP is an adapter protein important for lymphocyte activation involving cell-cell interaction Defects in NK cell and CTL killing of virally infected cells Defects in T/B cell interaction Patients are hypogammaglobulinemic and susceptible to viral infection Associated with severe hyperproliferative (hyperactivated T cell) response to EBV infection Similar phenotype to hematophagocytic syndrome

Answer 29

X-linked lymphoproliferative disease

Question 30

associated with susceptibility to candidal infections Defect in Th17 effector responses due to defects in IL-17 or IL-17R, or to STAT1 protein mutations that lead to inhibition of Th17 cell development

Answer 30

chronic mucocutaneous candidiasis

Question 31

most commonly associated with STAT3 mutations that affects IL-17 development as well as IL-10 signaling Also affects keratinocyte-associated barrier function Clinically characterized by elevated IgE, atopic dermatitis, and chronic skin infections (staph abscesses)

Answer 31

Hyper IgE syndrome | Job's syndrome

Question 32

genetic mutation in the WASP protein that regulates actin cytoskeleton and causes defects in lymphocyte activation and development Increased incidence of autoimmunity due to defects in T reg function and FAS signaling

Answer 32

Wiskott-Aldrich syndome

Question 33

genetic mutation that affects DNA repair response In addition to immune defects it is associated with increased incidence of cancer and cerebellar ataxia

Answer 33

Ataxia telangiectasia

Question 34

defect in innate immunity | pyrin mutation results in constitutive activation of NALP inflammasome

Answer 34

Mediterranean periodic fever syndrome

Question 35

affect both innate and adaptive responses Defect in Th1 development and associated immune function (macrophage activation and clearance of phagocytosed pathogens) Increased susceptibility to mycobacterial infections

Answer 35

Mutations in IL-12 or IFN-gamma receptor function

Question 36

result in an increase in gram positive bacterial infections with decreased inflammatory reaction, no wide spread susceptibility to other microbes

Answer 36

Mutations that affect TLR signaling (MyD88)

Question 37

clinically associated with herpes simplex encephalitis, no wide spread susceptibility to other viruses

Answer 37

Mutations that affect immune responses to viruses (IFNalpha-dependent signaling, TLR3)

Question 38

results from mutations affecting the expression of proteins that are part of NADPH oxidase that cause defective generation of ROS intermediates that mediate microbicidal activity against phagocytosed microbes Increased susceptibility to fungal and extracellular bacterial infections

Answer 38

chronic granulomatous disease

Question 39

results from a mutation involving beta-2 integrins (CD18 is the beta chain that is common to the family that includes LFA-1) Defect adhering to blood vessels and marginating to sites of peripheral inflammation Leukocytosis, difficulty wound healing (healing of umbilical stump) and increased susceptibility to bacterial and fungal infections

Answer 39

Leukocyte adhesion deficiency type 1

Question 40

defect in development of lysosomal granules that results in defective neutrophil function

Answer 40

Chediak Higashi

Question 41

complement deficiency | increased risk of Neisseria infection

Answer 41

C5-C9 deficiency

Question 42

complement deficiency | susceptible to bacterial infection

Answer 42

C3 deficiency

Question 43

complement deficiency | linked to defect in immune complex clearance and autoimmunity

Answer 43

C2, C4 deficiency

Question 44

molecules important in downregulating spontaneous activation of MAC defects are associated with paroxysmal noctural hemoglobinuria

Answer 44

defects in DAF and CD59

Question 45

associated with excess hereditary angioneurotic edema that causes an increase in circulating C2a which has anaphylotoxin activity and causes severe vasodilation

Answer 45

deficiency in C1 esterase inhibitor