Test 2: Immunodeficiencies

Question 1

What is the difference between congenital/primary and acquired/secondary immunodeficiencies??

Answer 1

congenital/primary= genetic defects

acquired/secondary= non-genetic, develops in response to exogenous trauma/factors. ex: malnutrition, chemo tx, infection

Question 2

What are some common immunodeficiencies caused by defects in innate immunity?

Answer 2

• defects in production of reactive oxygen intermediates by phagocytes = gingivitis, recurrent ulceration, prepuberty periodontitis
• deficiency of B2 interns causing defective leukocyte adhesion = severe progressive periodontitis with alveolar bone loss, perio pockets, premature loss of deciduous and permanent dentitions
• deficiency in Leukocyte ligands for E and P selections causing bind to endothelium weak
• deficiency in lysosomal function in neutrophils, macrophages, and DC, and defective granule fxn in NK cells = early onset aggressive periodontitis with extensive loss of alveolar bone leading to tooth exfoliation, severe gingivitis, ulcers on buccal mucosa and tongue and soft palate

Question 3

What do mutations in critical components of early lymphocyte development/maturation paths lead to?

Answer 3

defects in B and T cell maturation

Question 4

T/F: Severe combined immunodeficiencies (SCID) affect only cell-mediated immunity

Answer 4

False!
They effect both humoral (B cell) and cell-mediated (T cell) immunity

Question 5

If you have a defect in common gamma chains and not correct cytokines being produced (lack of IL-7), what will happen?

Answer 5

decreased T cells and reduced serum Ig
-lead to candidiasis, viral infections, ulcerative stomatitis

Question 6

If you have a defect in enzymes that detoxify (ADA/PNP) which leads to accumulation of toxic metabolites in lymphocytes, what will happen?

Answer 6

progressive decrease in T and B cells
-lead to candidiasis, viral infections, ulcerative stomatitis

Question 7

If you have a defect on maturation of T and B cells (specifically in the RAG genes and other genes involved in VDJ recombination), what will happen?

Answer 7

decreased T and B cells; reduced serum Ig
-lead to candidiasis, viral infections, ulcerative stomatitis

Question 8

What would the antibody deficiency, agammaglobulinemias lead to?

Answer 8

• defect in pre-B receptor checkpoint or Bruton tyrosine kinase mutation
  leads to: decreases in all serum Ig isotopes and reduced B cell numbers
• can be X-linked or autosomal recessive forms
• lead to gingivitis, candidiasis, necrotizing stomatitis

Question 9

What would the antibody deficiency, hypogammaglobulinemia lead to?

Answer 9

• defect in selective IgA deficiency which leads to decreased IgA and
  periodontitis, hyper plastic candidal infection
• common variable immunodeficiency: hypogammaglobulinema leads to gingivitis, necrotizing ulcerative periodontitis

Question 10

What would the antibody deficiency, hyper-IgM syndrome lead to?

Answer 10

mutations in CD40 and CD40L lead to defects in T helper cell mediated B cell, macrophage, and DC activation, defects in somatic mutation, class switching, germinal center formation, defective cell mediated immunity
- mucosal ulcerations, increased infections

Question 11

What is Bare lymphocyte syndrome?

Answer 11

• defects in transcription factors regulating MHC class II gene expression

leads to: defective MHC class II expression, deficiency in CD4 T cells, defective cell mediated immunity and T dependent humoral immune responses
- lead to oral herpes

Question 12

What would MHC class I deficiency lead to?

Answer 12

decreased MHC class I levels; reduced CD8 T cells
- lead to oral herpes

Question 13

What is Wiskott-Aldrich syndrome?

Answer 13

• TCR dependent actin cytoskeletal rearrangements leading to defective T cell activation and leukocyte mobility
• lead to gingivitis, periodontitis, bleeding in oral cavity

Question 14

What is DiGeorge syndrome?

Answer 14

• transcription factor mutations which lead to decreased T cells, but normal B cells and reduced serum Ig
• lead to enamel hypo mineralization, caries altered eruption patterns

Question 15

What is the most common immunodeficiencies?

Answer 15

B cell defect
(selective IgA immunodeficiency)

Question 16

Is HIV transmitted through DNA or RNA?

Answer 16

retrovirus= RNA

Question 17

What is the HIV life cycle?

Answer 17

• viral particles in serum bind to CD4 surface and CXCR4 receptor
• virus now integrates into membrane, fuses, and material enters the cell
• inside cell, RNA is reverse transcribed to pro viral DNA and is integrated into host genome via integrase (can remain dormant for years)
• once activation, transcription of HIV genome occurs
• viral RNAse makes proteases and other enzymes to create core structure of HIV
• viral particles leave the cell is infectious

Question 18

What is the progression of HIV?

Answer 18

• infects mucosal tissues and kills T cell
• can be taken by dendritic cells or draw to lymph nodes to establish the infection
• viral particles are now released into circulation and spreads throughout the body
• overtime, anti-HIV bodies are made and cytotoxic T cells are induced
• after initial response, symptoms get worse over time due to more infection, more viral replication, and total destruction of CD4 cells

Question 19

What is the Clinical course of HIV diseased cells?

Answer 19

• increase in viral particles, high CD4 count
• as infection increases, CD4 count decreases
• CD4 start to recover slightly but continue to decrease over years where less than 200 cells per mm is considered onset of AIDS
• cytotoxic T cells and antibodies respond initially but not super protective

Question 19

What is the Clinical course of HIV diseased cells?

Answer 19

• increase in viral particles, high CD4 count
• as infection increases, CD4 count decreases
• CD4 start to recover slightly but continue to decrease over years where less than 200 cells per mm is considered onset of AIDS
• cytotoxic T cells and antibodies respond initially but not super protective

Question 20

What is mechanism of immunodeficiency caused by HIV?

Answer 20

• direct toxic effects on CD4 T cells
• chronic activation of CD4 cells resulting in apoptosis
• infected CD4 cells killed by CD8 cells and antibodies
• interfere with the functioning CD4 cells
• macrophages and dendritic cells aren’t killed by HIV and can act as reservoirs for HIV

Question 21

What are the immune responses to HIV?

Answer 21

• CD8 cells expand and provide some protection
• CD4 cells help the CD8 cells but can be cytotoxic
• initial antibody response not helpful, later antibody response is helpful but it’s too late
• eliminate CD4 cells severely limits immune response over time

Question 22

Why is immune evasion of HIV so strong?

Answer 22

• HIV has high mutation rate
• viral epitopes can be shielded by sugars
• HIV down regulates class I expression (CD8 cells)
• HIV induces Th2 cytokine (anti-inflammatory) and inhibit Th1 (pro-inflammatory)
• impair dendritic cell activity
• induce regulatory T cells to inhibit immune response to HIV

Question 23

What are untreated oral manifestations in AID patients?

Answer 23

• oral hairy leukoplakia (epstein-barr virus, EBV)
• kaposi’s sacroma (HHV-8)
• necrotizing periodontitis
• candidiasis (fungus)

Question 24

What are treated oral manifestations in AID patients?

Answer 24

• HPV
• caries

Question 25

What are the tx mechanisms of HIV/aids?

Answer 25

• reverse transcriptase inhibors (so can’t make proviral DNA)
• protease inhibitors (so can’t make viral capsid and core proteins)
• fusion//entry inhibitors (so can’t bind or enter cell)
• integrase inhibitors (so HIV can’t insert it’s genetic material into cell)
  vaccines under development due to mutations