Immunopathology II

Question 1

what cell regulates both the humoral and cellular components of the immune system?

Answer 1

mature T4 cell

Question 2

what is the cause of X linked agammaglobinemia?

Answer 2

mutation in tyrosine kinase gene responsible for pro/pre B cell signal transduction and continued B cell maturation

Question 3

which antibody crosses the placenta?

Answer 3

IgG

Question 4

patients with agammaglobinemia are susceptible to what types of infections?

Answer 4

enteric viruses and protozoa (no IgA)

Question 5

what is the main feature of common variable immunodeficiency?

Answer 5

hypogammaglobinemia, usually all Ab classes but sometimes isolated to IgG

Question 6

what is the mechanism of common variable immunodeficiency?

Answer 6

1. intrinsic B cell defect 2. abnormal T cell signaling to B cells (increased suppression or decreased helper activity) 3. inability of B cells to mature into plasma cells

Question 7

what is the mechanism for selective IgA deficiency?

Answer 7

IgA and B cells fail to mature

Question 8

what are the symptoms of selective IgA deficiency?

Answer 8

1. recurrent GI, respiratory, GU infections secondary to weakened mucosal defenses 2. increased risk for AI disorders (RA, SLE) 3. 40% have anti-IgA antibody

Question 9

what is the cause of hyper IgM syndrome?

Answer 9

failure of T cells to: 1. induce B cell isotype switching from IgM to IgG/A/E, and 2. activate macrophages to remove intracelullar microbes

Question 10

IgM producing B cells normally activate transcription genes that encode for other Ig isotypes via what signaling process?

Answer 10

signaling between CD40 on B cells and CD40L on Th cells

Question 11

what are the levels of IgM in hyper IgM syndrome?

Answer 11

normal or elevated

Question 12

hyper IgM syndrome has what type of inheritance?

Answer 12

1. X linked 70% 2. autosomal recessive for mutation of CD40 gene or activation induced deaminase enzyme required for switching

Question 13

what are the clinical symptoms of hyper IgM syndrome?

Answer 13

1. recurrent pyogenic infections (no opsonizing IgG) 2. intracellular infections (P. jiroveci, no phagocytosis) 3. AI lysis (anti-RBC IgM reaction) 4. GIT lymphoid hyperplastic accumulations of IgM+ B cells

Question 14

what are the features of DiGeorge syndrome?

Answer 14

T cell defect, hypocalcemia, cardiac abnormalities, cleft palate

Question 15

what are the dysmorphologies of DiGeorge syndrome?

Answer 15

1. facial - low set ears, midline clefts, small mandible 2. cardiac - VSD, right subclavian artery derived from pulmonary artery

Question 16

the x linked pattern of SCID involves what mutation? what is the result?

Answer 16

1. common gamma chain subunit of cytokine receptors 2. impaired lymphocyte development, proliferation, function

Question 17

the autosomal recessive pattern of SCID involves what deficiencies? what are the effects?

Answer 17

1. adenosine deaminase deficiency - metabolites are toxic to lymphocytes 2. failure of MHC II expression - impaired T cell recognition of antigen

Question 18

what are the clinical features of wiskott aldrich syndrome?

Answer 18

immunodeficiency, thrombocytopenia, eczema

Question 19

what is the defect associated with WAS? what is the result?

Answer 19

WAS protein responsible for cytoskeletal maintenance and linkage of membrane receptors to cytoskeleton - progressive depletion of T and B cells

Question 20

what are the clinical manifestations of WAS?

Answer 20

1. antibody levels normal (IgG) or elevated (IgA/E) with exception of IgM (low) 2. No antibody to polysaccharide antigen, poor antibody response to protein antigen 3. T cell deficit secondary to peripheral, progressive depletion in blood and nodal tissue

Question 21

why is immunodeficiency linked to autoimmunity?

Answer 21

persistent infections leads to altered immune response and generation of auto reactive cells

Question 22

what are the mechanisms of T cell loss in HIV infection?

Answer 22

1. viral replication in infected CD4 cells (cytopathic) 2. activation of uninfected CD4 T cells (apoptotic) 3. expression of HIV peptides on infected CD4 T cells (death by CTLs)

Question 23

what are the effects of HIV infection?

Answer 23

1. selective lymphopenia of CD4 T cells with diminished T cell function 2. polyclonal B cell activation with hypergammaglobunemia yet impaired specific B cell response to new antigen 3. altered macrophage function with decreased MHC II expression and antigen presentation

Question 24

what is the pathogenesis of B cell lymphomas following HIV infection?

Answer 24

increase in follicular T cells following HIV infection signals germinal centers to proliferate and become hyperplastic

Question 25

what is the histologic appearance of P. jiroveci in the lungs?

Answer 25

alveoli filled with foamy exudate, thickened interstitium, coffee bean appearance with silver stain

Question 26

what is the histologic appearance of candida?

Answer 26

pseudohyphae and blastoconidia (budding yeast)

Question 27

what is the histologic appearance of pulmonary CMV?

Answer 27

enlarged, infected alveolar cells with a single basophilic nuclear inclusion, a perinuclear halo and multiple indistinct basophilic cytoplasmic inclusions

Question 28

what is the main feature of progressive multifocal leukoencephalopathy?

Answer 28

reduced amount of myelin - loss of oligodendrocytes

Question 29

what type of tumor is Kaposi's sarcoma?

Answer 29

endothelial type tumor, many RBCs, highly vascular

Question 30

what are the two components of amyloid?

Answer 30

1. amyloid protein fibrils - beta pleated sheets bind congo red 2. pentagonal component - glycoprotein

Question 31

what is the composition of amyloid light chain (AL)?

Answer 31

Ig light chains, often gamma, derived from abnormal clones of Ig secreting plasma cells

Question 32

what is the composition of amyloid associated (AA)? when does it occur?

Answer 32

1. related to non-Ig AA protein and its precursor SAA (an acute phase reactant) 2. occurs with inflammatory or infectious states (secondary type)

Question 33

when does the ATTR form of amyloid occur?

Answer 33

autosomal dominant deposition of a mutant form of transthyretin in peripheral nerves - leads to polyneuropathy

Question 34

where is AB 2-microglobulin found?

Answer 34

deposition in synovium, joints, and tendon sheaths (complication for dialysis)