Immunology Flashcards Preview

I3 Exam 3 > Immunology > Flashcards

Flashcards in Immunology Deck (45):
1

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

allorecognition

2

T cell recognizes unprocessed allogeneic MHC molecule on graft APC

direct allorecognition

3

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

indirect allorecognition

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

hyperacute graft rejection

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

acute graft rejection

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

chronic graft rejection

7

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

graft versus host disease

8

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

graft versus leukemia

9

optimize chance of graft survival
Ab to known panel of HLA antigens are used to probe HLA profile of donor and recipient

serology

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

mixed lymphocyte reaction

11

optimize chance of graft survival
more accurate for identifying genotypes, routine for HLA typing

PCR for HLA gene allotypes

12

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

immunosurveillance

13

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

immune editing

14

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

immune evasion

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

CTLA-4

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

PD-1

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

Transient hypogammaglobulinemia

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)

Severe Combined Immunodeficiency (SCID)

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

X-linked SCID

20

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

JAK3 and IL7 receptor deficiencies

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

Adenosine Deaminase (ADA deficiency)

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)

RAG deficiency
Omenn's syndrome

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

DiGeorge's Syndrome

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

bare lymphocyte syndrome

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

Hyper IgM syndrome

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

Selective immunoglobulin isotype deficiencies

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

Common variable immunodeficiency

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)

Familial hemophagocytic syndrome

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

X-linked lymphoproliferative disease

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

chronic mucocutaneous candidiasis

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)

Hyper IgE syndrome
Job's syndrome

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

Wiskott-Aldrich syndome

33

genetic mutation that affects DNA repair response

In addition to immune defects it is associated with increased incidence of cancer and cerebellar ataxia

Ataxia telangiectasia

34

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

Mediterranean periodic fever syndrome

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

Mutations in IL-12 or IFN-gamma receptor function

36

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

Mutations that affect TLR signaling (MyD88)

37

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

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

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

chronic granulomatous disease

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

Leukocyte adhesion deficiency type 1

40

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

Chediak Higashi

41

complement deficiency
increased risk of Neisseria infection

C5-C9 deficiency

42

complement deficiency
susceptible to bacterial infection

C3 deficiency

43

complement deficiency
linked to defect in immune complex clearance and autoimmunity

C2, C4 deficiency

44

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

defects in DAF and CD59

45

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

deficiency in C1 esterase inhibitor