Advanced Pathophysiology NR 605 Study
Guide: Genetics, Immunity, & Systemic
Disorders
Question 1
A patient presents with a single nucleotide substitution in the HBB gene that
alters a single amino acid in the beta-globin chain, resulting in sickling of red
blood cells under hypoxic conditions. This genetic variant is best classified as a:
• A) Copy number variation (CNV)
• B) Single nucleotide polymorphism (SNP) resulting in a missense mutation
• C) Epigenetic histone modification
• D) Trinucleotide repeat expansion
Correct Answer: B) Single nucleotide polymorphism (SNP) resulting in a
missense mutation
Rationale: A single nucleotide polymorphism (SNP) that changes a single codon
resulting in the substitution of a different amino acid (e.g., valine for glutamic acid in
sickle cell anemia) is a classic missense mutation. CNVs involve larger structural
deletions or duplications.
Question 2
Which epigenetic mechanism involves the direct attachment of methyl groups to
cytosine bases at CpG islands, typically leading to transcriptional silencing of the
affected gene?
• A) Histone acetylation
• B) DNA methylation
• C) MicroRNA post-transcriptional cleavage
• D) Chromatin remodeling via SWI/SNF complexes
Correct Answer: B) DNA methylation
Rationale: DNA methylation (catalyzed by DNA methyltransferases) adds methyl groups
to cytosine residues within CpG islands, condensing chromatin structure and repressing
gene transcription. Histone acetylation, by contrast, relaxes chromatin to promote
transcription.
,Question 3
An autosomal dominant disorder has a recurrence risk of what percentage for
each offspring born to an affected heterozygous parent and an unaffected
parent?
• A) 0%
• B) 25%
• C) 50%
• D) 100%
Correct Answer: C) 50%
Rationale: In autosomal dominant inheritance, a heterozygous affected parent (𝐴𝑎) has
a 50% chance of passing the mutant allele (𝐴) and a 50% chance of passing the normal
allele (𝑎) to each child, regardless of sex.
Question 4
During the vascular phase of acute inflammation, which local chemical mediators
are primarily responsible for immediate arteriolar vasodilation and increased
vascular permeability?
• A) Interleukin-1 and Tumor Necrosis Factor-alpha
• B) Histamine and serotonin
• C) IgG and IgM immune complexes
• D) Complement proteins C3b and C5b
Correct Answer: B) Histamine and serotonin
Rationale: Histamine (released primarily from mast cells) and serotonin are vasoactive
amines stored pre-formed in granules, mediating rapid arteriolar dilation and endothelial
contraction (increased permeability) immediately following tissue injury.
Question 5
Which cellular adhesion molecules are responsible for the initial "tethering" and
rolling of leukocytes along the activated vascular endothelium during the cellular
phase of inflammation?
• A) Integrins (e.g., LFA-1)
• B) Selectins (e.g., E-selectin, P-selectin)
• C) Immunoglobulin supergene family (ICAM-1, VCAM-1)
• D) Cadherins
Correct Answer: B) Selectins (e.g., E-selectin, P-selectin)
,Rationale: Selectins mediate low-affinity, high-on-off-rate interactions that cause
leukocytes to tether and roll along the endothelium. Subsequent firm adhesion is
mediated by integrins binding to ICAM-1 and VCAM-1.
Question 6
A severe, immediate reaction characterized by systemic vasodilation,
bronchospasm, and laryngeal edema occurring within minutes of insect venom
exposure is mediated by which hypersensitivity mechanism?
• A) Type I (IgE-mediated)
• B) Type II (Cytotoxic)
• C) Type III (Immune complex-mediated)
• D) Type IV (Cell-mediated)
Correct Answer: A) Type I (IgE-mediated)
Rationale: Type I hypersensitivity involves allergen cross-linking of cell-bound IgE on
mast cells and basophils, triggering immediate degranulation and release of histamine,
tryptase, and leukotrienes, leading to systemic anaphylaxis.
Question 7
Goodpasture syndrome, characterized by autoantibodies directed against the
non-collagenous domain of type IV collagen in glomerular and alveolar basement
membranes, is an example of which hypersensitivity reaction?
• A) Type I
• B) Type II
• C) Type III
• D) Type IV
Correct Answer: B) Type II
Rationale: Type II hypersensitivity reactions involve IgG or IgM antibodies directed
against fixed cellular or extracellular matrix antigens, leading to complement activation,
neutrophil recruitment, and tissue destruction (e.g., Goodpasture syndrome, hemolytic
transfusion reactions).
Question 8
Systemic Lupus Erythematosus (SLE) tissue damage is primarily driven by the
systemic deposition of circulating antigen-antibody complexes that activate the
complement cascade. This represents which type of hypersensitivity?
• A) Type I
, • B) Type II
• C) Type III
• D) Type IV
Correct Answer: C) Type III
Rationale: Type III hypersensitivity is mediated by immune complexes (antigen-antibody
aggregates) that circulate and precipitate out in blood vessels, glomeruli, or joints,
triggering localized complement activation and neutrophil-mediated injury.
Question 9
A positive tuberculin skin test (PPD) read at 48 to 72 hours showing induration
and erythema is classic for which type of immune response?
• A) Type I immediate hypersensitivity
• B) Type II antibody-dependent cell cytotoxicity
• C) Type III immune complex deposition
• D) Type IV delayed-type cell-mediated hypersensitivity
Correct Answer: D) Type IV delayed-type cell-mediated hypersensitivity
Rationale: Type IV hypersensitivity is mediated by sensitized T lymphocytes (CD4+
helper cells releasing cytokines and CD8+ cytotoxic cells) rather than antibodies, taking
48–72 hours to manifest clinically.
Question 10
An infant presents with recurrent severe viral, fungal, and bacterial infections,
severe failure to thrive, and absent thymic shadow on chest radiography. Genetic
testing reveals an interleukin-2 receptor gamma chain mutation. This condition is
diagnosed as:
• A) X-linked agammaglobulinemia (Bruton's)
• B) Severe Combined Immunodeficiency (SCID)
• C) DiGeorge syndrome
• D) Chronic granulomatous disease
Correct Answer: B) Severe Combined Immunodeficiency (SCID)
Rationale: SCID involves profound defects in both humoral (B-cell) and cellular (T-cell)
immunity due to genetic anomalies like the IL-2 receptor gamma chain mutation (X-
linked) or ADA deficiency, presenting with life-threatening opportunistic infections in
infancy.
Question 11
Guide: Genetics, Immunity, & Systemic
Disorders
Question 1
A patient presents with a single nucleotide substitution in the HBB gene that
alters a single amino acid in the beta-globin chain, resulting in sickling of red
blood cells under hypoxic conditions. This genetic variant is best classified as a:
• A) Copy number variation (CNV)
• B) Single nucleotide polymorphism (SNP) resulting in a missense mutation
• C) Epigenetic histone modification
• D) Trinucleotide repeat expansion
Correct Answer: B) Single nucleotide polymorphism (SNP) resulting in a
missense mutation
Rationale: A single nucleotide polymorphism (SNP) that changes a single codon
resulting in the substitution of a different amino acid (e.g., valine for glutamic acid in
sickle cell anemia) is a classic missense mutation. CNVs involve larger structural
deletions or duplications.
Question 2
Which epigenetic mechanism involves the direct attachment of methyl groups to
cytosine bases at CpG islands, typically leading to transcriptional silencing of the
affected gene?
• A) Histone acetylation
• B) DNA methylation
• C) MicroRNA post-transcriptional cleavage
• D) Chromatin remodeling via SWI/SNF complexes
Correct Answer: B) DNA methylation
Rationale: DNA methylation (catalyzed by DNA methyltransferases) adds methyl groups
to cytosine residues within CpG islands, condensing chromatin structure and repressing
gene transcription. Histone acetylation, by contrast, relaxes chromatin to promote
transcription.
,Question 3
An autosomal dominant disorder has a recurrence risk of what percentage for
each offspring born to an affected heterozygous parent and an unaffected
parent?
• A) 0%
• B) 25%
• C) 50%
• D) 100%
Correct Answer: C) 50%
Rationale: In autosomal dominant inheritance, a heterozygous affected parent (𝐴𝑎) has
a 50% chance of passing the mutant allele (𝐴) and a 50% chance of passing the normal
allele (𝑎) to each child, regardless of sex.
Question 4
During the vascular phase of acute inflammation, which local chemical mediators
are primarily responsible for immediate arteriolar vasodilation and increased
vascular permeability?
• A) Interleukin-1 and Tumor Necrosis Factor-alpha
• B) Histamine and serotonin
• C) IgG and IgM immune complexes
• D) Complement proteins C3b and C5b
Correct Answer: B) Histamine and serotonin
Rationale: Histamine (released primarily from mast cells) and serotonin are vasoactive
amines stored pre-formed in granules, mediating rapid arteriolar dilation and endothelial
contraction (increased permeability) immediately following tissue injury.
Question 5
Which cellular adhesion molecules are responsible for the initial "tethering" and
rolling of leukocytes along the activated vascular endothelium during the cellular
phase of inflammation?
• A) Integrins (e.g., LFA-1)
• B) Selectins (e.g., E-selectin, P-selectin)
• C) Immunoglobulin supergene family (ICAM-1, VCAM-1)
• D) Cadherins
Correct Answer: B) Selectins (e.g., E-selectin, P-selectin)
,Rationale: Selectins mediate low-affinity, high-on-off-rate interactions that cause
leukocytes to tether and roll along the endothelium. Subsequent firm adhesion is
mediated by integrins binding to ICAM-1 and VCAM-1.
Question 6
A severe, immediate reaction characterized by systemic vasodilation,
bronchospasm, and laryngeal edema occurring within minutes of insect venom
exposure is mediated by which hypersensitivity mechanism?
• A) Type I (IgE-mediated)
• B) Type II (Cytotoxic)
• C) Type III (Immune complex-mediated)
• D) Type IV (Cell-mediated)
Correct Answer: A) Type I (IgE-mediated)
Rationale: Type I hypersensitivity involves allergen cross-linking of cell-bound IgE on
mast cells and basophils, triggering immediate degranulation and release of histamine,
tryptase, and leukotrienes, leading to systemic anaphylaxis.
Question 7
Goodpasture syndrome, characterized by autoantibodies directed against the
non-collagenous domain of type IV collagen in glomerular and alveolar basement
membranes, is an example of which hypersensitivity reaction?
• A) Type I
• B) Type II
• C) Type III
• D) Type IV
Correct Answer: B) Type II
Rationale: Type II hypersensitivity reactions involve IgG or IgM antibodies directed
against fixed cellular or extracellular matrix antigens, leading to complement activation,
neutrophil recruitment, and tissue destruction (e.g., Goodpasture syndrome, hemolytic
transfusion reactions).
Question 8
Systemic Lupus Erythematosus (SLE) tissue damage is primarily driven by the
systemic deposition of circulating antigen-antibody complexes that activate the
complement cascade. This represents which type of hypersensitivity?
• A) Type I
, • B) Type II
• C) Type III
• D) Type IV
Correct Answer: C) Type III
Rationale: Type III hypersensitivity is mediated by immune complexes (antigen-antibody
aggregates) that circulate and precipitate out in blood vessels, glomeruli, or joints,
triggering localized complement activation and neutrophil-mediated injury.
Question 9
A positive tuberculin skin test (PPD) read at 48 to 72 hours showing induration
and erythema is classic for which type of immune response?
• A) Type I immediate hypersensitivity
• B) Type II antibody-dependent cell cytotoxicity
• C) Type III immune complex deposition
• D) Type IV delayed-type cell-mediated hypersensitivity
Correct Answer: D) Type IV delayed-type cell-mediated hypersensitivity
Rationale: Type IV hypersensitivity is mediated by sensitized T lymphocytes (CD4+
helper cells releasing cytokines and CD8+ cytotoxic cells) rather than antibodies, taking
48–72 hours to manifest clinically.
Question 10
An infant presents with recurrent severe viral, fungal, and bacterial infections,
severe failure to thrive, and absent thymic shadow on chest radiography. Genetic
testing reveals an interleukin-2 receptor gamma chain mutation. This condition is
diagnosed as:
• A) X-linked agammaglobulinemia (Bruton's)
• B) Severe Combined Immunodeficiency (SCID)
• C) DiGeorge syndrome
• D) Chronic granulomatous disease
Correct Answer: B) Severe Combined Immunodeficiency (SCID)
Rationale: SCID involves profound defects in both humoral (B-cell) and cellular (T-cell)
immunity due to genetic anomalies like the IL-2 receptor gamma chain mutation (X-
linked) or ADA deficiency, presenting with life-threatening opportunistic infections in
infancy.
Question 11
