IMUNOLOGY

Question 1

What is the primary function of lymph in the immune system?

Answer 1

Lymph is interstitial fluid that drains from tissues and enters the lymphatic system.
Its primary function is to circulate through lymph nodes and activate the immune system in response to pathogens present in tissues.
Lymph eventually drains into the subclavian veins and returns to the venous system.

Question 2

What are the primary and secondary lymphoid organs, and their roles?

Answer 2

1. Primary lymphoid organs: Where lymphocytes form and mature.
   * Bone marrow: Produces B and T cells, maturates B cells.
   * Thymus: Maturation site for T cells.
2. Secondary lymphoid organs: Sites where B and T cells activates and proliferate in response to infections.
   Includes: lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT) (e.g., tonsils, Peyer’s patches in the intestines)

Question 3

What are T-cells and where do they mature?

Answer 3

T-cells are part of the adaptive immune system.
They mature in the thymus.

Question 4

What types of antigens can T-cells recognize?

Answer 4

T-cells recognize only peptide antigens.
Polysaccharides (like in bacterial capsules) cannot be recognized by T-cells.

Question 5

What are MHC Class I and II, and what do they present?

Answer 5

Major Histocompatibility Complex

MHC Class I molecules are found on the surface of all nucleated cells. They present endogenous (intracellular) antigens, such as viral peptides, to CD8+ cytotoxic T cells.
MHC Class II molecules are expressed mainly on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. They present exogenous (extracellular) antigens, derived from pathogens or foreign particles taken up by the cell, to CD4+ helper T cells.

Question 6

What is MHC restriction?

Answer 6

T-cells only react to antigens presented on self-MHC molecules.

Question 7

What is the role of CD3 in T-cell activation?

Answer 7

CD3 complex transmits the signal from the bound T-cell receptor (TCR) into the T-cell, initiating the immune response.

Question 8

What are the two main subsets of T-cells and their functions?

Answer 8

• CD4+ T-cells (helper T-cells) coordinate immune responses:
  1. Stimulate B-cells to produce antibodies and class switch.
  2. Activate CD8 T-cells (cytotoxic T-cells)
  3. Activate macrophages.
• CD8+ T-cells (cytotoxic T-cells) kill virus-infected and tumor cells by recognizing antigens presented by MHC Class I molecules

Question 9

What are Th1 and Th2 cells and their functions?

Answer 9

Th1 and Th2 cells are mature CD4 T-cells

• Th1: Promote cell-mediated immunity (activate CD8+ cells, macrophages). Important for intracellular infections.
• Th2 cells: Promote humoral immunity (activate B-cells). Important for extracellular infections and allergic responses.

Question 10

What cytokines are associated with Th1 and Th2 cells and their roles?

Answer 10

Th1:
Cytokines Th1 differentiation promoters:
* IL12 secreated from APCs
* INF-γ secreated by NK and Th1
Cytokines Th1 response mediators:
* IL-2 –> stimulate T-cells growth, activate B-cells and NK
* INF-γ –> activates macrophages and Th1 response, promotes MHC expression, suppresses TH2 response.

Th2:
Cytokine Th2 differentiation
promoter:
* IL-4 secreated by Th2 and mast cells
Cytokines Th2 response mediators:
* IL-4 –> promotes IgE production, suppresses TH1and activate Th2 response
* IL-5 –> activates eosinpphils and promote IgA production
* IL-10 –> anti-inflammatory, suppresses TH1 response

Question 11

What is co-stimulation in T-cell activation?

Answer 11

CD28 on T-cells must bind to B7 on APCs along with MHC-TCR binding to fully activate T-cells.

Question 12

What are the differences between Th1 and Th2 responses in diseases?

Answer 12

Back:

Th1 response: Key for intracellular infections like TB, granulomatous diseases, listeria.
Th2 response: Key for extracellular infections, allergic responses, and humoral immunity (IgE and IgA).

Question 13

How do CD8+ T-cells kill infected cells?

Answer 13

CD8+ T-cells use perforins, granzymes, and granulysin to induce apoptosis in infected cells.
They also use the Fas-FasL pathway (extrinsic apoptosis pathway).

Question 14

What is the role of regulatory T-cells (Tregs)?

Answer 14

Tregs suppress the immune response to prevent autoimmunity.
They express CD25 and produce anti-inflammatory cytokines like IL-10 and TGF-beta.

Question 15

What are Th17 cells, and why are they important?

Answer 15

Th17 cells produce IL-17 and are essential for mucosal immunity, particularly in the GI tract.
They recruit neutrophils and macrophages and are involved in protection against bacterial infections.

Question 16

What is the function of the thymus in T-cell development?
Back:

Answer 16

The thymus is where T-cells mature, undergoing positive and negative selection to ensure they can bind MHC but do not bind strongly to self-antigens.

Question 17

What is positive and negative selection in the thymus?

Answer 17

Positive selection: T-cells that can bind self-MHC survive.
Negative selection: T-cells that bind too strongly to self-antigens undergo apoptosis.

Question 18

What are AIRE genes, and what happens if they are defective?

Answer 18

AIRE genes help thymus cells express self-antigens for T-cell selection.
Mutations in AIRE genes lead to autoimmune diseases like chronic mucocutaneous candidiasis and endocrine disorders.

Question 19

What are superantigens, and how do they affect T-cells?

Answer 19

Superantigens activate a massive number of T-cells by linking MHC and TCR directly.
This leads to a huge release of cytokines (like IFN-γ and IL-2), causing toxic shock syndrome.

Question 20

Question 1:
A 25-year-old woman receives a tuberculin skin test (PPD) for tuberculosis screening. Forty-eight hours after injection, she develops an indurated and erythematous area at the site of injection. This reaction is primarily due to the activity of which of the following?

A. B-cells producing antibodies against Mycobacterium tuberculosis antigens
B. Neutrophils directly lysing Mycobacterium tuberculosis-infected cells
C. CD8+ T-cells recognizing Mycobacterium tuberculosis antigens on MHC Class I
D. Th1 CD4+ T-cells releasing interferon-gamma and activating macrophages
E. Th2 CD4+ T-cells releasing IL-4 to promote antibody production

Answer 20

Answer: D
Rationale: The PPD test is an example of a delayed-type hypersensitivity reaction (Type IV), which is mediated by Th1 CD4+ T-cells. These T-cells release interferon-gamma to activate macrophages, resulting in local swelling and erythema.

Question 21

A 5-year-old boy presents with recurrent bacterial and viral infections. Genetic testing reveals a defect in the IL-12 receptor on his T-cells. What immune function would be most impaired in this patient?

A. Antibody production by B-cells
B. Activation of CD8+ cytotoxic T-cells by IL-2
C. Activation of Th2 cells and humoral immunity
D. Activation of Th1 cells and macrophage-mediated immunity
E. Differentiation of regulatory T-cells

Answer 21

Answer: D
Rationale: IL-12 is critical for the differentiation of naive CD4+ T-cells into Th1 cells. Th1 cells produce interferon-gamma, which activates macrophages to combat intracellular pathogens. A defect in the IL-12 receptor results in impaired Th1 response and susceptibility to intracellular pathogens like mycobacteria and salmonella.

Question 22

Question 3:
A 30-year-old man is diagnosed with lepromatous leprosy, characterized by diffuse skin lesions and poor immune control of the disease. Biopsy of the skin lesions reveals numerous intracellular Mycobacterium leprae organisms. Which of the following best describes the predominant immune response in this patient?

A. Strong Th1 response with interferon-gamma production
B. Strong Th2 response with IL-4 and IL-10 production
C. Excessive neutrophil recruitment by Th17 cells
D. Excessive Treg cell activity suppressing CD8+ cytotoxicity
E. Deficient Th1 response with lack of IL-2 production

Answer: B
Rationale: Lepromatous leprosy is associated with a predominant Th2 response, which is inadequate for controlling intracellular infections like Mycobacterium leprae. Th2 cells secrete IL-4 and IL-10, promoting humoral immunity but failing to activate macrophages effectively.

Answer 22

Answer: B
Rationale: Lepromatous leprosy is associated with a predominant Th2 response, which is inadequate for controlling intracellular infections like Mycobacterium leprae. Th2 cells secrete IL-4 and IL-10, promoting humoral immunity but failing to activate macrophages effectively.

Question 23

Question 4:
A researcher is studying the role of regulatory T-cells (Tregs) in preventing autoimmunity. Tregs are known to suppress immune responses through the production of which of the following cytokines?

A. IL-2 and interferon-gamma
B. IL-4 and IL-5
C. IL-10 and TGF-beta
D. TNF-alpha and IL-12
E. IL-17 and IL-23

Answer 23

Answer: C
Rationale: Regulatory T-cells (Tregs) suppress the immune response primarily through the production of anti-inflammatory cytokines such as IL-10 and TGF-beta. These cytokines prevent excessive immune activation and help maintain self-tolerance, reducing the risk of autoimmune disease.

Question 24

Question 5:
A 40-year-old man presents with fever and shock after a recent surgery. Blood cultures grow Staphylococcus aureus, and toxic shock syndrome is suspected. The bacterial toxin causing this syndrome acts by stimulating a large number of T-cells. Which of the following mechanisms best explains this phenomenon?

A. The toxin binds to the T-cell receptor and MHC Class I, inducing CD8+ T-cell proliferation
B. The toxin binds directly to the MHC Class II-TCR complex, bypassing antigen processing
C. The toxin induces B-cell class switching to produce IgE
D. The toxin stimulates neutrophil recruitment to the infection site
E. The toxin inhibits regulatory T-cell function, leading to autoimmunity

Answer 24

Answer: B
Rationale: Superantigens like the toxic shock syndrome toxin (TSST-1) produced by Staphylococcus aureus bind directly to the MHC Class II molecule and the T-cell receptor (TCR) outside of the normal antigen-binding groove. This bypasses normal antigen processing and leads to massive, non-specific T-cell activation and cytokine release, resulting in toxic shock.

Question 25

How do lymph nodes contribute to the immune system?

Answer 25

Lymph nodes filter lymphatic fluid and provide a site for immune cells to interact with antigens. They contain B and T cells, and they are sites where immune responses are initiated against pathogens that have entered the lymphatic system.

Question 26

What are the major structural components of a lymph node?

Answer 26

The major structural components of a lymph node include the cortex, paracortex, medulla, afferent lymphatic vessels, efferent lymphatic vessels, and sinuses. The cortex contains follicles with B cells, the paracortex houses T cells, and the medulla contains plasma cells and macrophages.

Question 27

What is the function of the thymus?

Answer 27

Back: The thymus is the site of T-cell maturation and differentiation. It is particularly active during early life, and it shrinks (undergoes involution) as a person ages. T cells learn to distinguish self from non-self in the thymus.

Question 28

What is the role of the bone marrow in the immune system?

Answer 28

Back: The bone marrow is the primary site of hematopoiesis, where all blood cells, including immune cells (B-cells, T-cell precursors, macrophages, etc.), are produced. It is also the site of B-cell maturation

Question 29

What are the main functions of the spleen in immunity?

Answer 29

Back: The spleen filters blood, removes old red blood cells, and is a major site of immune surveillance and response. It houses both red pulp (which filters blood) and white pulp (which contains immune cells like lymphocytes).

Question 30

What is the primary role of the paracortex in lymph nodes?

Answer 30

Back: The paracortex contains mainly T cells and dendritic cells. It is where T cells become activated after encountering antigen-presenting cells (APCs), like dendritic cells. It expands during cell-mediated immune responses (e.g., viral infections).

Question 31

What is found in the medulla of a lymph node, and what is its function?

Answer 31

Back: The medulla contains medullary cords (full of plasma cells secreting antibodies) and medullary sinuses (which contain macrophages). It plays a crucial role in filtering lymph and initiating immune responses through antigen-antibody interactions.

Question 32

What is the function of germinal centers in lymph nodes?

Answer 32

Back: Germinal centers are sites within secondary follicles where B cells proliferate, differentiate, and undergo somatic hypermutation to produce high-affinity antibodies during an immune response. They play a critical role in adaptive immunity.

Question 33

What is the role of the sinuses in lymph nodes?

Answer 33

Sinuses (subcapsular, trabecular, and medullary) are spaces that allow lymph to flow through the node. They are lined with macrophages, which trap and process pathogens and debris for presentation to lymphocytes.

Question 34

Postsplenectomy findings: ƒ

Answer 34

- Howell-Jolly bodies (nuclear remnants) - Target cells - Thrombocytosis (loss of sequestration and removal) - Lymphocytosis (loss of sequestration)

Question 35

What are the two main regions of the spleen, and what are their functions?

Answer 35

The spleen consists of two main regions: Red pulp: Responsible for filtering and removing old or damaged red blood cells (RBCs). White pulp: Involved in immune surveillance, containing lymphocytes that respond to blood-borne pathogens.

Question 36

What is the role of the red pulp in the spleen?

Answer 36

The red pulp filters the blood, removes old or damaged red blood cells and platelets, and stores iron from hemoglobin breakdown. It also contains macrophages that help clear pathogens and debris.

Question 37

What immune cells are found in the white pulp, and what is their function?

Answer 37

The white pulp contains B and T lymphocytes. B cells are found in follicles and produce antibodies, while T cells are located in the periarteriolar lymphoid sheath (PALS), where they respond to blood-borne antigens

Question 38

What is the PALS, and what is its function in the spleen?

Answer 38

The periarteriolar lymphoid sheath (PALS) is a region of the white pulp surrounding central arterioles. It contains mainly T cells and is where T-cell activation occurs when they encounter antigens carried in the blood.

Question 39

What is the marginal zone of the spleen, and why is it important?

Answer 39

The marginal zone lies between the red and white pulp and contains specialized macrophages and B cells. It is important for trapping antigens from the bloodstream and initiating an immune response, particularly against encapsulated bacteria.

Question 40

What is the role of splenic macrophages in immunity?

Answer 40

Splenic macrophages, located in the red pulp and marginal zone, are responsible for phagocytosing old red blood cells and pathogens. They also present antigens to lymphocytes to initiate an immune response.

Question 41

Does the spleen store blood? If so, what is stored and why?

Answer 41

Yes, the spleen stores platelets and red blood cells in its red pulp. It acts as a blood reservoir, releasing these cells during times of hemorrhage or increased demand for oxygen, such as during physical activity or trauma.

Question 42

What is the primary function of the thymus?

Answer 42

The thymus is the site of T-cell maturation and differentiation. Immature T cells (thymocytes) migrate from the bone marrow to the thymus, where they undergo positive and negative selection to ensure self-tolerance and proper immune function.

Question 43

What are the two main regions of the thymus, and what are their roles?

Answer 43

The thymus consists of: Cortex: The outer region where immature T cells (thymocytes) undergo positive selection. Medulla: The inner region where thymocytes undergo negative selection to eliminate self-reactive T cells.

Question 44

What is positive selection in the thymus, and where does it occur?

Answer 44

Positive selection occurs in the thymic cortex, where T cells are tested for their ability to recognize self-MHC molecules. Only T cells that can bind to self-MHC molecules with moderate affinity survive, while others undergo apoptosis.

Question 45

What is negative selection in the thymus, and where does it occur?

Answer 45

Back: Negative selection occurs in the thymic medulla. T cells that strongly bind to self-antigens presented by MHC molecules are eliminated through apoptosis to prevent autoimmunity. This process ensures self-tolerance.

Question 46

What happens to thymocytes in the cortex of the thymus?

Answer 46

In the cortex, immature thymocytes undergo positive selection. They are tested for their ability to bind self-MHC molecules, and those that successfully bind with moderate affinity survive and move to the medulla for further development

Question 47

What is the function of the thymic medulla in T-cell maturation?

Answer 47

The thymic medulla is responsible for negative selection, where thymocytes that strongly bind self-antigens are eliminated to prevent autoimmunity. Only T cells with weak or moderate affinity for self-antigens survive and mature.

Question 48

What are Hassall’s corpuscles, and what is their function in the thymus?

Answer 48

Hassall’s corpuscles are structures found in the medulla of the thymus. They consist of epithelial cells and may play a role in the regulation of T-cell maturation and in promoting the development of regulatory T cells (Tregs).

Question 49

What are the stages of T-cell development in the thymus?

Answer 49

T cells develop through several stages: Double-negative (CD4−/CD8−): Immature T cells lack both CD4 and CD8 markers. Double-positive (CD4+/CD8+): T cells express both CD4 and CD8 markers as they undergo positive selection. Single-positive (CD4+ or CD8+): After positive and negative selection, T cells become either CD4+ helper T cells or CD8+ cytotoxic T cells.

Question 50

What is the role of the AIRE gene in the thymus?

Answer 50

The AIRE gene (Autoimmune Regulator) is expressed in the thymic medulla and helps present self-antigens to developing T cells during negative selection. AIRE is crucial for eliminating self-reactive T cells, and mutations in AIRE can lead to autoimmune diseases like autoimmune polyendocrine syndrome type 1 (APS-1).

Question 51

How does DiGeorge syndrome affect the thymus?

Answer 51

DiGeorge syndrome results from a deletion in chromosome 22, leading to thymic hypoplasia or aplasia. This results in T-cell deficiency, causing immunodeficiency and increased susceptibility to infections. It is associated with the absence or underdevelopment of the thymus.

Question 52

Thymoma associations:

Answer 52

Myasthenia gravis Superior vena cava syndrome Pure red cell aplasia Good syndrome

Question 53

What is innate immunity?

Answer 53

Innate immunity is the first line of defense against pathogens. It is non-specific, present at birth, and responds rapidly to infections. It includes physical barriers (e.g., skin, mucosa), cellular defenses (e.g., macrophages, neutrophils), and chemical mediators (e.g., cytokines, complement system).

Question 54

What is the role of macrophages in innate immunity?

Answer 54

Back: Macrophages are phagocytic cells that engulf and destroy pathogens, dead cells, and debris. They also produce cytokines that recruit other immune cells to the site of infection and present antigens to T cells, bridging innate and adaptive immunity.

Question 55

How do neutrophils function in innate immunity?

Answer 55

Neutrophils are the most abundant white blood cells and the first to arrive at sites of infection. They kill pathogens through phagocytosis, release of reactive oxygen species, and secretion of antimicrobial enzymes. They also form neutrophil extracellular traps (NETs) to capture microbes.

Question 56

What is the role of natural killer (NK) cells in innate immunity?

Answer 56

NK cells target and kill virus-infected cells and tumor cells. They do this by recognizing cells that have downregulated MHC I, a common feature of infected or transformed cells, and releasing cytotoxic granules to induce apoptosis.

Question 57

What is the complement system, and how does it function in innate immunity?

Answer 57

The complement system is a series of proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens. It promotes inflammation, opsonization (coating of pathogens for easier phagocytosis), and formation of the membrane attack complex (MAC), which directly lyses pathogens.

Question 58

What are the three pathways of complement activation?

Answer 58

Alternative pathway: Spontaneous conversion of C3 to C3B. Lectin pathway: Mannose-binding lectin binds mannose on pathogens, leading to C3B production, from C2b-C4b (C3 convertase). Classical pathway: Activated by antigen-antibody complexes, leading to C3B formation, from C1- Antibody-antigen complex and C2b-C4b.

Question 59

What is the function of C3B in the complement system?

Answer 59

C3B binds to bacterial surfaces, leading to bacterial cell death and the formation of the membrane attack complex (MAC). It can also act as an opsonin to promote phagocytosis by macrophages.

Question 60

What is the membrane attack complex (MAC)?

Answer 60

The MAC is formed by complement proteins C5 to C9. It pokes holes in the bacterial cell membrane, leading to bacterial lysis and death. C3b cleaves C5 and form C5b that binds to C6-9 = MAC

Question 61

What are anaphylatoxins in the complement system?

Answer 61

C3A and C5A are anaphylatoxins. - Stimulates histamine release and increases vascular permeability, possibly contributing to anaphylaxis. C5A also recruits neutrophils to sites of complement activation (neutrophil chemotaxis).

Question 62

What role does Factor H play in the complement system?

Answer 62

Factor H inhibits the alternative pathway of complement on host cells by accelerating the decay of C3 convertase and inactivating surface-bound C3B, protecting host cells from destruction.

Question 63

What is the function of DAF (CD55) and CD59?

Answer 63

DAF (CD55) disrupts C3B attachment to prevent MAC formation. CD59 directly inhibits the formation of the MAC. Both protect host cells, particularly red blood cells, from complement-mediated lysis.

Question 64

What are de the complement system regulation?

Answer 64

Factor H: inhibits the alternative pathway of complement on host cells by accelerating the decay of C3 convertase and inactivating surface-bound C3B. DAF (CD55): disrupts C3B attachment to prevent MAC formation CD59: directly inhibits the formation of the MAC.

Question 65

What is the mechanism of Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Answer 65

PNH is caused by a deficiency in DAF (CD55) or CD59, leading to complement-mediated lysis of red blood cells. Symptoms include anemia, hemoglobinuria, abdominal pain, erectile dysfunction, and thrombosis.

Question 66

What is hereditary angioedema?

Answer 66

A deficiency in C1 inhibitor (break down bradukinin) protein leads to unregulated bradykinin activity, causing recurrent episodes of swelling (angioedema), especially in the face, throat, and GI tract.

Question 67

What medication should be avoid in patientes with Hereditary Angioedema and why?

Answer 67

ACE inhibitors should be avoided as they exacerbate symptoms by preventing bradykinin breakdown.

Question 68

What are the clinical consequences of C3 deficiency?

Answer 68

Recurrent infections with encapsulated bacteria (e.g., pneumococci and Haemophilus influenzae). Increased susceptibility to autoimmune diseases due to impaired clearance of immune complexes (C3b will not be formed and will not draw macrophage to clear antibody-antigen complexes): - Glomerular nephritis from immune complex deposition in their kidneys - Type III hypersensitivity syndromes

Question 69

What is the significance of terminal complement pathway deficiencies (C5-C9)?

Answer 69

Deficiencies in C5 to C9 impair MAC formation, leading to recurrent Neisseria infections, especially Neisseria meningitidis.

Question 70

What is the role of C1 in the classical complement pathway?

Answer 70

C1 binds to two Fc portions of antibodies close together (e.g., IgM), activating C1R and C1S to cleave C2 and C4, leading to the formation of C3 convertase and subsequent C3B production.

Question 71

Why is IgM a better activator of the classical pathway than IgG?

Answer 71

IgM is a pentamer with multiple Fc regions close together, making it easier to activate C1 (needs two Fc portions bond) and the classical complement pathway, while IgG requires two molecules to be close together to achieve this.

Question 72

What are the two main tests for complement system function?

Answer 72

CH50 test: Assesses the classical pathway by measuring the lysis of sheep red blood cells. C3/C4 levels: Quantifies complement consumption and helps diagnose complement-mediated diseases like lupus nephritis.

Question 73

What is the role of C3 nephritic factor in membranoproliferative glomerulonephritis type II?

Answer 73

C3 nephritic factor is an autoantibody that stabilizes C3 convertase, leading to excessive complement activation, hypocomplementemia, and kidney damage.

Question 74

How does CRP (C-reactive protein) interact with the complement system?

Answer 74

CRP binds to bacterial polysaccharides, activating the early classical pathway and consuming C3 and C4, but it does not activate the terminal complement pathway

Question 75

What is the role of C5B in MAC formation?

Answer 75

C5B binds to C6, C7, C8, and C9 to form the MAC, which pokes holes in bacterial cell membranes, leading to bacterial death.

Question 76

A 3-year-old child presents with recurrent episodes of meningitis caused by Neisseria meningitidis. Laboratory analysis reveals normal levels of C3, but flow cytometry shows a deficiency of the complement proteins C6 through C9. Which of the following is the most likely underlying cause of the patient's susceptibility to these infections? A) Impaired formation of C3 convertase B) Inability to form the membrane attack complex (MAC) C) Impaired opsonization of bacteria D) Defective Factor H production E) Excessive activation of C1 complex

Question 77

A 34-year-old man presents with sudden onset hemoglobinuria in the morning and fatigue. His medical history includes several episodes of thrombosis in unusual locations, such as the portal vein and cerebral veins. Flow cytometry reveals a deficiency of CD55 (DAF) and CD59 on his red blood cells. Which of the following best explains his symptoms? A) Unregulated MAC formation on host cells B) Increased clearance of immune complexes C) Lack of C3 convertase formation D) Increased C5A production causing neutrophil chemotaxis E) Defective C1 inhibitor activity leading to excess bradykinin

Answer 77

Unregulated MAC formation on host cells A) Correct: MAC forms without regulation, causing hemolysis in PNH B) Increased immune complex clearance (not applicable to PNH) C) C3 convertase formation unaffected in PNH D) C5A production is unrelated to hemolysis in PNH E) Bradykinin relates to hereditary angioedema, not PNH

Question 78

A 25-year-old woman with a history of recurrent skin and throat infections presents to the clinic with facial swelling. Her father had similar symptoms. Laboratory testing shows a normal C3 and C4 level, but the C1 inhibitor protein level is undetectable. Which of the following best describes the patient's condition? A) Complement-mediated lysis of red blood cells B) Overactivation of the lectin pathway C) Increased bradykinin leading to recurrent angioedema D) Increased susceptibility to Neisseria infections E) Autoantibody-mediated C3 nephritis

Answer 78

Increased bradykinin leading to recurrent angioedema A) RBC lysis (related to PNH, not applicable here) B) Lectin pathway overactivation (not involved) C) Bradykinin increase (correct) due to C1 inhibitor deficiency D) Neisseria susceptibility (linked to C5-C9, not C1 inhibitor) E) Autoimmune C3 nephritis (related to C3 nephritic factor, not this case)

Question 79

A 4-year-old child presents with a history of recurrent respiratory infections. Blood work shows a low C3 level, and genetic testing reveals a mutation leading to complete deficiency of the C3 protein. Which of the following is most likely impaired in this patient? A) Opsonization of bacteria B) Formation of C5 convertase C) Decay of C3 convertase on host cells D) Activation of mannose-binding lectin E) Activation of the C1 complex

Answer 79

Opsonization of bacteria A) Opsonization of bacteria: Correct. C3b is a key opsonin that enhances phagocytosis of pathogens. B) Formation of C5 convertase: Impaired as C3 is needed to generate C5 convertase. C) Decay of C3 convertase on host cells: Factor H and DAF regulate this, not C3 deficiency. D) Activation of mannose-binding lectin: Part of the lectin pathway, not directly dependent on C3. E) Activation of the C1 complex: Involves the classical pathway, not C3-dependent.

Question 80

A 5-year-old girl presents with recurrent respiratory tract infections and nephritic syndrome. Renal biopsy shows immune complex deposition in the glomeruli. Further testing shows low C3 levels but normal C4 levels. Which of the following is the most likely diagnosis? A) Systemic lupus erythematosus B) Hereditary angioedema C) Membranoproliferative glomerulonephritis type II D) Paroxysmal nocturnal hemoglobinuria E) Classic pathway complement deficiency

Answer 80

Diagnosis: Membranoproliferative glomerulonephritis type II (MPGN II) MPGN II: Low C3, normal C4, immune complex deposition in glomeruli. Other options: SLE: Both C3 and C4 are low. Hereditary angioedema: Linked to C1 inhibitor deficiency (bradykinin-mediated swelling, not nephritis). PNH: Complement-mediated hemolysis, not nephritis.

Question 81

A patient with hereditary angioedema presents to the emergency department with severe swelling of the lips and throat. The patient is immediately treated with epinephrine, but her symptoms do not improve. Which of the following is the best explanation for why epinephrine was ineffective? A) Bradykinin levels are elevated due to C1 inhibitor deficiency B) Histamine is the primary mediator of the patient's condition C) Complement activation is responsible for the swelling D) The alternative pathway of complement activation is hyperactive E) Factor H deficiency leads to excessive complement activation

Answer 81

Reduced form for flashcard back: Answer: A) Bradykinin levels are elevated due to C1 inhibitor deficiency Hereditary angioedema: Caused by C1 inhibitor deficiency → elevated bradykinin. Bradykinin causes swelling; epinephrine is ineffective. Not histamine or complement activation directly. Treatment: C1 inhibitor concentrate or bradykinin-targeted therapies.

Question 82

A 30-year-old woman presents with fatigue and hematuria. Her symptoms have been recurring for several months. She has a family history of glomerulonephritis. Laboratory results show low serum C3 and C4 levels and the presence of an autoantibody stabilizing C3 convertase. Which of the following is the most likely diagnosis? A) C3 nephritic factor-related glomerulonephritis B) Systemic lupus erythematosus C) Hereditary angioedema D) Paroxysmal nocturnal hemoglobinuria E) C5-C9 complement deficiency

Answer 82

Diagnosis: C3 nephritic factor-related glomerulonephritis Key Point: Autoantibody stabilizes C3 convertase, causing low C3/C4. B) SLE: Causes low C3/C4 but no C3 convertase stabilization. C) Hereditary angioedema: Linked to C1 inhibitor deficiency. D) PNH: Causes hemolysis, not glomerulonephritis. E) C5-C9 deficiency: Leads to Neisseria infections, not kidney disease.

Question 83

A 45-year-old man with a history of cirrhosis presents with fever and chills. Blood cultures grow Streptococcus pneumoniae. Further testing reveals impaired opsonization but normal CH50 levels. Which of the following proteins is most likely deficient in this patient? A) C1 B) C3B C) C5 D) C9 E) Mannose-binding lectin

Answer 83

Answer: B) C3B C3B is crucial for opsonization, marking pathogens for phagocytosis. Normal CH50 indicates a functioning classical pathway, but impaired opsonization suggests a C3B deficiency. C1: Would lower CH50. C5: Affects MAC, not opsonization. C9: Lowers CH50, no effect on opsonization. Mannose-binding lectin: Involves lectin pathway, unrelated to opsonization.

Question 84

A 7-year-old boy presents with recurrent episodes of meningitis caused by Neisseria meningitidis. His C3 and C4 levels are normal. Which of the following complement deficiencies is most likely responsible for his infections? A) C2 B) C5 C) C3 D) Factor H E) DAF (CD55)

Answer 84

Answer: B) C5 - Deficiency in C5-C9 leads to impaired MAC formation, increasing susceptibility to Neisseria infections. A) C2 deficiency is linked to immune complex diseases, not Neisseria. C) C3 deficiency causes severe bacterial infections, but C3 levels are normal. D) Factor H affects regulation of complement but isn’t linked to Neisseria. E) DAF deficiency leads to PNH, not recurrent infections.

Question 85

A 28-year-old patient with a history of recurrent infections is found to have low C3 levels and is diagnosed with a deficiency in the alternative pathway of the complement system. Which of the following processes is most likely affected in this patient? A) Spontaneous conversion of C3 to C3B B) Activation of C1 by antigen-antibody complexes C) Cleavage of C4 to C4B D) Formation of the MAC E) Activation of mannose-binding lectin

Answer 85

A) Spontaneous conversion of C3 to C3B - Correct. The alternative pathway relies on the spontaneous conversion of C3 to C3B, essential for pathogen opsonization and complement activation. B) Activation of C1 by antigen-antibody complexes - Classical pathway, not the alternative. C) Cleavage of C4 to C4B - Part of classical and lectin pathways, not the alternative pathway. D) Formation of the MAC - Final step in all pathways, but not specific to the alternative pathway. E) Activation of mannose-binding lectin - Involved in the lectin pathway, unrelated to the alternative pathway.

Question 86

A patient with a history of lupus nephritis presents to the clinic with increasing fatigue. Laboratory studies show low C3 and C4 levels. Which of the following best explains the low complement levels in this patient? A) Deficiency in Factor H B) Increased consumption due to immune complex formation C) Overactivation of the lectin pathway D) Genetic deficiency in the MAC components E) Deficiency of mannose-binding lectin

Answer 86

A) Factor H deficiency: Affects alternative pathway, lowering only C3, not C4. B) Increased immune complex consumption: Correct. Immune complexes in lupus activate the classical pathway, consuming both C3 and C4. C) Overactivation of lectin pathway: Affects innate immunity, not related to lupus nephritis. D) MAC component deficiency: Causes susceptibility to infections, doesn’t reduce C3/C4. E) Mannose-binding lectin deficiency: Impacts lectin pathway, doesn’t explain C3/C4

Question 87

A patient presents with complaints of swelling in his extremities, especially after minor trauma. Genetic testing reveals a deficiency of C1 inhibitor. Which of the following would most likely be elevated in this patient? A) C3 convertase B) C5B C) Bradykinin D) Histamine E) Factor H

Answer 87

Answer: C) Bradykinin Hereditary angioedema is caused by C1 inhibitor deficiency. This leads to elevated bradykinin, causing swelling due to increased vascular permeability. Symptoms: recurrent, non-itchy, non-pitting swelling after trauma or stress. Histamine is not involved, distinguishing this from allergic angioedema.

Question 88

A patient with recurrent pneumococcal infections is found to have low CH50 levels and normal C3 and C4 levels. Which part of the complement pathway is most likely impaired in this patient? A) C1 complex B) Mannose-binding lectin C) Factor H D) C5-C9 (MAC) E) Alternative pathway

Answer 88

Answer: D) C5-C9 (MAC) C1 complex: Would show low C3/C4 levels, not normal. MBL: Affects the lectin pathway, usually with low C3/C4, not isolated pneumococcal infections. Factor H: Affects alternative pathway, causing low C3 levels, not seen here. C5-C9 (MAC): Deficiency causes low CH50 with normal C3/C4, leading to recurrent infections, especially from encapsulated bacteria. Alternative pathway: Would result in low C3 levels, not observed in this patient. Key: Low CH50 + normal C3/C4 = C5-C9 (MAC) deficiency.

Question 89

A patient with lupus is found to have nephritic syndrome and low serum complement levels. Which of the following tests would best assess the function of the classical complement pathway in this patient? A) CH50 B) C3 level C) Factor B assay D) C9 level E) Mannose-binding lectin assay

Answer 89

Answer: A) CH50 Explanation: CH50: Best test for assessing classical complement pathway function (C1, C2, C3, C4), commonly low in lupus nephritis. C3 level: Reflects complement activation but not specific to the classical pathway. Factor B assay: Evaluates alternative pathway, not classical. C9 level: Part of the terminal complement complex, not specific to classical pathway. MBL assay: Tests the lectin pathway, irrelevant to classical pathway function.

Question 90

What mediates Type I hypersensitivity reactions?

Answer 90

IgE antibodies bound to mast cells leading to immediate allergic reactions.

Question 91

Which cytokine promotes IgE class switching in Type I hypersensitivity?

Answer 91

Interleukin-4 (IL-4).

Question 92

Give examples of Type I hypersensitivity reactions.

Answer 92

Asthma, allergic rhinitis, anaphylaxis, food allergies (peanuts, shellfish).

Question 93

Describe the early and late phases of Type I hypersensitivity reactions.

Answer 93

Early phase occurs within minutes (histamine release); late phase occurs hours later (cytokines and inflammatory cells).

Question 94

What are the key mediators released in Type I hypersensitivity?

Answer 94

A: Histamine, leukotrienes, prostaglandins, cytokines.

Question 95

Define atopy.

Answer 95

A genetic predisposition to develop Type I hypersensitivity reactions.

Question 96

What is the treatment for anaphylaxis?

Answer 96

Immediate administration of epinephrine.

Question 97

What mediates Type II hypersensitivity reactions?

Answer 97

A: IgG and IgM antibodies directed against self-antigens on cells or tissues.

Question 98

List examples of Type II hypersensitivity disorders.

Answer 98

A: Rheumatic fever, autoimmune hemolytic anemia, Goodpasture's syndrome, myasthenia gravis.

Question 99

What mechanisms cause cell damage in Type II hypersensitivity?

Answer 99

Phagocytosis, complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC).

Question 100

How does Type III hypersensitivity differ from Type II?

Answer 100

A: Type III involves immune complex deposition in tissues; Type II involves direct antibody binding to cells/tissues.

Question 101

Provide examples of Type III hypersensitivity reactions.

Answer 101

A: Serum sickness, Arthus reaction, lupus, post-streptococcal glomerulonephritis.

Question 102

What is serum sickness?

Answer 102

A: A systemic Type III reaction due to circulating immune complexes causing fever, rash, arthralgia.

Question 103

Define an Arthus reaction.

Answer 103

A: A localized Type III reaction where immune complexes form in tissues after antigen injection

Question 104

What mediates Type IV hypersensitivity reactions?

Answer 104

A: Sensitized T cells (Th1 and CD8+ T cells); cell-mediated immunity.

Question 105

Give examples of Type IV hypersensitivity reactions.

Answer 105

A: Contact dermatitis (poison ivy), PPD test for TB, multiple sclerosis.

Question 106

What is the typical timeframe for Type IV hypersensitivity reactions?

Answer 106

A: Symptoms appear 24–72 hours after exposure.

Question 107

Which cytokines are involved in Type IV hypersensitivity?

Answer 107

A: Interferon-gamma (activates macrophages), IL-12 (stimulates Th1 cells).

Question 108

A 25-year-old woman presents with itchy, red, and watery eyes, nasal congestion, and sneezing during spring. She has similar symptoms every year. Skin prick testing shows a positive reaction to grass pollen. Which cytokine is most responsible for promoting the class switching that leads to her symptoms? A) Interleukin-1 (IL-1) B) Interleukin-2 (IL-2) C) Interleukin-4 (IL-4) D) Interleukin-5 (IL-5) E) Interferon-gamma

Answer 108

Correct Answer: C) Interleukin-4 (IL-4) Option A: IL-1 is involved in fever and inflammation but not in IgE class switching. Option B: IL-2 stimulates T-cell proliferation but doesn't promote IgE production. **Option C: IL-4 induces B-cell class switching to IgE, central to Type I hypersensitivity reactions like seasonal allergies. Option D: IL-5 activates eosinophils but doesn't induce IgE class switching. Option E: Interferon-gamma is associated with Th1 responses and inhibits IgE production.

Question 109

A 30-year-old man develops hematuria and hemoptysis. Renal biopsy reveals linear deposition of IgG along the glomerular basement membrane. Which mechanism underlies his condition? A) Immune complex deposition (Type III hypersensitivity) B) Antibody-mediated cell destruction (Type II hypersensitivity) C) IgE-mediated mast cell degranulation (Type I hypersensitivity) D) T-cell mediated delayed hypersensitivity (Type IV hypersensitivity) E) Complement deficiency leading to impaired opsonization

Answer 109

Correct Answer: B) Antibody-mediated cell destruction (Type II hypersensitivity) Option A: Type III shows granular, not linear, deposition due to immune complexes. Option B: Type II involves antibodies (IgG, IgM) targeting basement membranes, as in Goodpasture's syndrome. Option C: IgE-mediated reactions don't cause linear IgG deposition. Option D: Type IV is cell-mediated without antibody deposition. Option E: Complement deficiency isn't associated with these findings.

Question 110

A patient receives antivenom serum after a snake bite. Ten days later, he develops fever, rash, joint pain, and urticaria. Lab tests show low complement levels. Which hypersensitivity reaction is occurring? A) Type I (Immediate hypersensitivity) B) Type II (Antibody-mediated cytotoxicity) C) Type III (Immune complex-mediated hypersensitivity) D) Type IV (Delayed-type hypersensitivity) E) Arthus reaction

Answer 110

Correct Answer: C) Type III (Immune complex-mediated hypersensitivity) Option A: Type I occurs within minutes to hours, not days. Option B: Type II involves antibodies against cell surface antigens. Option C: Type III reactions involve immune complex deposition causing serum sickness-like symptoms. Option D: Type IV is mediated by T cells, not immune complexes. Option E: Arthus reaction is localized, not systemic.

Question 111

A 35-year-old woman develops an itchy, blistering rash 24 hours after hiking in the woods. She recalls contact with plants but has no known allergies. Which immune cells are primarily responsible for her symptoms? A) B cells producing IgE antibodies B) Neutrophils releasing reactive oxygen species C) CD8+ T lymphocytes inducing cell-mediated cytotoxicity D) Mast cells releasing histamine E) Eosinophils releasing major basic protein

Answer 111

Correct Answer: C) CD8+ T lymphocytes inducing cell-mediated cytotoxicity Option A: IgE-mediated responses are immediate (Type I), not delayed. Option B: Neutrophils are not the main players in delayed hypersensitivity. Option C: Contact dermatitis is a Type IV reaction mediated by CD8+ T cells attacking skin cells. Option D: Mast cells are involved in immediate hypersensitivity. Option E: Eosinophils are associated with allergic reactions but not primary in Type IV reactions.

Question 112

A patient with a history of multiple blood transfusions develops fever and chills during a transfusion. Lab tests detect anti-leukocyte antibodies. Which hypersensitivity mechanism is responsible? A) Type I hypersensitivity mediated by IgE B) Type II hypersensitivity involving complement-mediated lysis C) Type III hypersensitivity due to immune complex deposition D) Type IV hypersensitivity mediated by T cells E) Arthus reaction in transfused tissues

Answer 112

Correct Answer: B) Type II hypersensitivity involving complement-mediated lysis Option A: Type I reactions are IgE-mediated and immediate. Option B: Type II reactions involve antibodies against donor leukocytes, activating complement and causing cell lysis. Option C: Type III involves soluble immune complexes, not cells. Option D: Type IV is cell-mediated and delayed. Option E: Arthus reactions are localized and not related to transfusions.

Question 113

Which T-helper cell subtype is involved in promoting IgE production in Type I hypersensitivity?

Answer 113

Th2 cells; they produce cytokines like IL-4 that stimulate B-cell class switching to IgE.

Question 114

What is the role of eosinophils in Type I hypersensitivity reactions?

Answer 114

A: Eosinophils release inflammatory mediators that amplify allergic responses and are recruited by IL-5.

Question 115

Define the Arthus reaction and its type of hypersensitivity.

Answer 115

A: A localized Type III hypersensitivity reaction where immune complexes form in the skin after antigen injection

Question 116

How do Type II and Type III hypersensitivity reactions differ in immune complex formation?

Answer 116

A: Type II involves antibodies binding directly to cell surfaces; Type III involves soluble immune complexes depositing in tissues

Question 117

What is the mechanism of tissue injury in Type III hypersensitivity reactions?

Answer 117

A: Immune complexes activate complement, attracting neutrophils that release enzymes causing inflammation and tissue damage.

Question 118

How does the PPD test utilize Type IV hypersensitivity?

Answer 118

A: It detects a delayed-type hypersensitivity reaction mediated by Th1 cells in individuals exposed to tuberculosis.

Question 119

Which type of hypersensitivity reaction does not involve antibodies?

Answer 119

A: Type IV hypersensitivity; it is mediated by T cells without antibody involvement.

Question 120

What are haptens, and how do they trigger hypersensitivity reactions?

Answer 120

A: Haptens are small molecules that become immunogenic when bound to proteins, triggering immune responses like in Type II hypersensitivity.

Question 121

Which hypersensitivity reaction is responsible for hyperacute transplant rejection?

Answer 121

A: Type II hypersensitivity due to preformed antibodies against donor antigens causing immediate graft destruction.

Question 122

Describe the role of natural killer (NK) cells in antibody-dependent cellular cytotoxicity (ADCC).

Answer 122

A: NK cells bind to the Fc region of antibodies on target cells and induce apoptosis, contributing to Type II hypersensitivity.

Question 123

Which hypersensitivity reaction is associated with granuloma formation?

Answer 123

A: Type IV hypersensitivity; chronic T-cell activation leads to granuloma formation as seen in tuberculosis.

Question 124

What laboratory finding is characteristic of serum sickness?

Answer 124

A: Decreased complement levels (hypocomplementemia) due to consumption during immune complex formation.

Question 125

How does desensitization (allergen immunotherapy) alter the immune response in allergies?

Answer 125

A: It induces the production of blocking IgG antibodies and shifts the response away from IgE-mediated reactions.

Question 126

Explain the mechanism behind autoimmune diseases like Graves' disease and myasthenia gravis.

Answer 126

A: Type II hypersensitivity reactions where antibodies target specific receptors, altering their function.

Question 127

Which cytokines are produced by Th1 and Th2 cells, respectively?

Answer 127

A: Th1 cells produce IFN-γ and IL-2; Th2 cells produce IL-4, IL-5, IL-10, and IL-13.

Question 128

What is the purpose of the Coombs test in immunohematology?

Answer 128

A: To detect antibodies (direct Coombs) or complement (indirect Coombs) on red blood cells, indicating Type II hypersensitivity.

Question 129

What role does IL-5 play in allergic reactions?

Answer 129

A: IL-5 promotes the growth and activation of eosinophils, enhancing allergic inflammation.

Question 130

How does epinephrine counteract the effects of anaphylaxis?

Answer 130

A: It causes vasoconstriction, bronchodilation, and reduces vascular permeability, reversing anaphylactic symptoms.

Question 131

What is the Shwartzman reaction?

Answer 131

A: A rare, severe Type III hypersensitivity reaction causing widespread thrombosis and tissue necrosis after endotoxin exposure.

Question 132

Which hypersensitivity reaction is responsible for contact dermatitis from nickel or latex?

Answer 132

A: Type IV hypersensitivity, mediated by T-cell responses to environmental antigens.

Question 133

Differentiate between Type I hypersensitivity and anaphylactoid reactions.

Answer 133

A: Type I is IgE-mediated, while anaphylactoid reactions are non-IgE mediated but have similar clinical presentations.

Question 134

Explain how Farmer's Lung involves both Type III and Type IV hypersensitivity mechanisms.

Answer 134

A: Early phases involve immune complex deposition (Type III); chronic exposure leads to T-cell mediated inflammation (Type IV).

Question 135

A 45-year-old woman presents with muscle weakness that improves with rest. Antibodies against the acetylcholine receptor are detected. Which type of hypersensitivity reaction is involved? A) Type I B) Type II C) Type III D) Type IV E) Anaphylactoid reaction

Answer 135

Answer and Explanation: Correct Answer: B) Type II Explanation: Myasthenia gravis is a Type II hypersensitivity reaction where antibodies target the acetylcholine receptor, leading to muscle weakness.

Question 136

A patient develops acute hemolysis after receiving penicillin. Which test would confirm the involvement of antibodies against red blood cells? A) Indirect Coombs test B) Direct Coombs test C) Hemoglobin electrophoresis D) Complement assay E) Skin prick test

Answer 136

Answer and Explanation: Correct Answer: B) Direct Coombs test Explanation: The direct Coombs test detects antibodies attached to red blood cells, confirming a Type II hypersensitivity reaction causing hemolysis.

Question 137

Which cytokine is primarily responsible for activating macrophages in a Type IV hypersensitivity reaction? A) Interleukin-4 B) Interleukin-5 C) Interferon-gamma D) Interleukin-10 E) Tumor necrosis factor-alpha

Answer 137

Correct Answer: C) Interferon-gamma Explanation: Interferon-gamma, produced by Th1 cells, activates macrophages in cell-mediated immune responses typical of Type IV hypersensitivity.

Question 138

A 50-year-old man with a history of Hepatitis B develops systemic vasculitis affecting medium-sized arteries. Which type of hypersensitivity reaction is most likely involved? A) Type I B) Type II C) Type III D) Type IV E) Type V

Answer 138

Answer and Explanation: Correct Answer: C) Type III Explanation: Polyarteritis nodosa associated with Hepatitis B involves immune complex deposition (Type III hypersensitivity) causing vasculitis.

Question 139

A patient exhibits a positive Nikolsky sign and is diagnosed with pemphigus vulgaris. Which type of hypersensitivity reaction mediates this condition? A) Type I B) Type II C) Type III D) Type IV E) Type V

Answer 139

Answer and Explanation: Correct Answer: B) Type II Explanation: Pemphigus vulgaris is mediated by antibodies against desmoglein (desmosomes) in skin cells, a Type II hypersensitivity reaction.

Question 140

A 35-year-old woman presents with progressive muscle weakness, particularly in her proximal muscles. She also notices difficulty in swallowing and occasional double vision. Edrophonium (a short-acting acetylcholinesterase inhibitor) administration transiently improves her symptoms. Laboratory testing reveals antibodies directed against nicotinic acetylcholine receptors at the neuromuscular junction. Which of the following best describes the hypersensitivity reaction involved in this patient's condition? A) Type I hypersensitivity involving IgE-mediated mast cell degranulation B) Type II hypersensitivity mediated by antibodies against cell surface receptors C) Type III hypersensitivity due to immune complex deposition D) Type IV hypersensitivity involving T-cell mediated delayed response E) Type V hypersensitivity involving stimulating antibodies

Question 141

A patient receives a kidney transplant and initially does well. However, three weeks post-transplant, he develops signs of renal failure. A biopsy of the transplanted kidney shows mononuclear infiltrates consisting predominantly of lymphocytes, along with signs of vascular endothelial damage. Which of the following mechanisms is most likely responsible for the rejection of the transplanted organ? A) Hyperacute rejection due to preformed antibodies (Type II hypersensitivity) B) Acute rejection mediated by host T lymphocytes (Type IV hypersensitivity) C) Chronic rejection involving immune complex deposition (Type III hypersensitivity) D) Graft-versus-host disease from donor immune cells attacking host tissues E) Anaphylactic reaction mediated by IgE antibodies (Type I hypersensitivity)

Question 142

A 45-year-old man presents with shortness of breath, coughing, and hemoptysis. Laboratory tests show elevated serum creatinine, and urinalysis reveals hematuria with red blood cell casts. A renal biopsy demonstrates a linear deposition of IgG along the glomerular basement membrane on immunofluorescence. Which of the following additional findings is most likely present in this patient? A) Antineutrophil cytoplasmic antibodies (ANCAs) in the serum B) Granulomatous inflammation with necrosis in the upper respiratory tract C) Antibodies against type IV collagen causing alveolar basement membrane damage D) Deposition of immune complexes in the mesangium and subendothelial space E) Presence of anti-dsDNA antibodies causing systemic lupus erythematosus

Question 143

A 23-year-old medical student participates in a clinical trial involving intradermal injections of an experimental antigen. After the fourth injection, she develops a localized area of redness, swelling, and induration at the injection site approximately 8 hours post-injection. A biopsy of the affected skin reveals immune complex deposition and complement activation. Which of the following best describes the hypersensitivity reaction observed in this student? A) Type I hypersensitivity mediated by IgE and mast cells B) Type II hypersensitivity involving antibody-mediated cytotoxicity C) Type III hypersensitivity resulting in an Arthus reaction D) Type IV hypersensitivity mediated by delayed T-cell response E) Serum sickness-type reaction due to systemic immune complexes

Question 144

A 28-year-old man develops a skin rash characterized by erythematous, pruritic vesicles on his forearms and legs two days after hiking in the woods. He recalls brushing against some plants during the hike. Which of the following best explains the mechanism underlying his skin findings? A) IgE-mediated degranulation of mast cells causing immediate hypersensitivity B) Formation of antigen-antibody complexes depositing in the skin C) Antibody-dependent cellular cytotoxicity against skin cells D) Sensitized T lymphocytes mediating a delayed hypersensitivity reaction E) Complement-mediated lysis of keratinocytes due to autoantibodies

Question 145

A 60-year-old man with a history of chronic hepatitis B infection presents with hypertension, abdominal pain, and renal impairment. Biopsy of affected vessels shows transmural inflammation of arterial walls with fibrinoid necrosis. No granulomas are observed. Immunofluorescence reveals deposits of immune complexes in the vessel walls. Which hypersensitivity mechanism is most likely responsible for his condition? A) Type I hypersensitivity involving IgE antibodies B) Type II hypersensitivity with antibodies against vessel wall components C) Type III hypersensitivity due to circulating immune complexes D) Type IV hypersensitivity mediated by T-cell responses E) Antibody-independent, non-immune-mediated vascular injury

Question 146

A child with recurrent bacterial infections is found to have markedly low levels of all immunoglobulin isotypes. Flow cytometry reveals normal numbers of B and T cells. Complement levels are within normal limits. A deficiency in which of the following is most likely responsible for this patient's condition? A) Adenosine deaminase deficiency leading to severe combined immunodeficiency B) Defective CD40 ligand on helper T cells affecting class switching C) Bruton tyrosine kinase mutation causing X-linked agammaglobulinemia D) Deficiency of C3 complement component affecting opsonization E) Mutation in the common gamma chain of cytokine receptors affecting T cells

Question 147

A 30-year-old woman presents with fatigue, joint pain, and a facial rash that worsens with sun exposure. Laboratory tests reveal anemia, thrombocytopenia, and positive anti-dsDNA antibodies. A renal biopsy shows a granular pattern of immune complex deposition in the glomeruli. Which of the following best describes the hypersensitivity reaction involved in her renal pathology? A) Type I hypersensitivity mediated by IgE antibodies B) Type II hypersensitivity with antibodies against basement membrane C) Type III hypersensitivity due to immune complex deposition D) Type IV hypersensitivity involving delayed T-cell response E) Type V hypersensitivity with stimulatory autoantibodies

Question 148

A patient develops a sudden drop in blood pressure, difficulty breathing, and widespread urticaria shortly after being stung by a bee. Which of the following preformed mediators is primarily responsible for his immediate symptoms? A) Leukotriene C4 causing bronchoconstriction B) Prostaglandin D2 causing vasodilation C) Histamine causing increased vascular permeability and bronchospasm D) Interleukin-4 promoting IgE synthesis E) Platelet-activating factor inducing platelet aggregation

Question 149

A 25-year-old woman undergoes tuberculin skin testing as part of a pre-employment health evaluation. Forty-eight hours later, she develops a 15 mm area of induration at the injection site. Which immune components are primarily responsible for this reaction? A) Preformed IgE antibodies and mast cells B) IgG antibodies forming immune complexes C) Sensitized Th1 lymphocytes and macrophages D) Cytotoxic CD8+ T lymphocytes directly killing cells E) B lymphocytes producing antibodies against tuberculin

Question 150

What is the genetic defect and inheritance pattern of X-linked agammaglobulinemia (Bruton's agammaglobulinemia)?

Answer 150

Mutation in the Bruton tyrosine kinase (BTK) gene; X-linked recessive inheritance.

Question 151

BTK gene mutation:

Answer 151

Bruton's agammaglobulinemia

Question 152

What laboratory findings are characteristic of X-linked agammaglobulinemia?

Answer 152

Absence of B cells (CD19+, CD20+), low levels of all immunoglobulins, underdeveloped germinal centers.

Question 153

Absence of B cells and low levels of all immunoglobulins:

Answer 153

Bruton's agammaglobulinemia

Question 154

Immunodeficiencies B-cells disorders

Answer 154

- Bruton's agammaglobulinemia - IgA Deficiency - Common variable immunodeficiency

Question 155

What immunodeficiency is associated with delayed separation of the umbilical cord?

Answer 155

Leukocyte adhesion deficiency (LAD) type I.

Question 156

A 6-month-old male infant presents with recurrent otitis media, pneumonia, and diarrhea. Physical examination reveals absent tonsils and lymph nodes are not palpable. Laboratory tests show absent CD19+ B cells, low levels of all immunoglobulin classes, and normal T cell counts. Question: What is the most likely diagnosis? What is the underlying genetic defect and its inheritance pattern? Why do symptoms appear around 6 months of age?

Answer 156

Diagnosis: X-linked agammaglobulinemia (Bruton's agammaglobulinemia). Underlying Defect and Inheritance: Mutation in the Bruton tyrosine kinase (BTK) gene. X-linked recessive inheritance. Reason for Onset at 6 Months: Maternal IgG antibodies, which provide passive immunity, wane around 6 months. The infant's inability to produce immunoglobulins becomes apparent, leading to increased susceptibility to infections.

Question 157

A 23-year-old woman reports a history of recurrent sinus infections and pneumonia. She also mentions chronic diarrhea and was recently diagnosed with pernicious anemia. Laboratory findings reveal low levels of IgG and IgA, with normal IgM levels. B cell counts are normal, but there is poor response to vaccines. Question: What is the most likely diagnosis? What complications is she at increased risk for? How does this condition differ from X-linked agammaglobulinemia?

Answer 157

Diagnosis: Common variable immunodeficiency (CVID). Increased Risk of Complications: Autoimmune diseases (e.g., pernicious anemia, rheumatoid arthritis). Increased risk of lymphomas and other malignancies. Differences from X-linked Agammaglobulinemia: CVID affects both males and females; X-linked agammaglobulinemia is X-linked recessive (affects males). CVID presents in adolescence or adulthood; X-linked agammaglobulinemia presents in infancy. CVID has normal B cell counts with impaired differentiation; X-linked agammaglobulinemia has absent mature B cells.

Question 158

A 5-year-old boy has recurrent staphylococcal skin abscesses that are cold to touch and lack signs of inflammation. He has coarse facial features, a prominent forehead, and a broad nasal bridge. Dental examination reveals two rows of teeth due to retained primary teeth. Laboratory tests show markedly elevated IgE levels and eosinophilia. Question: What is the most likely diagnosis? What is the underlying immunological defect? Which cytokine pathway is affected?

Answer 158

Answer: Diagnosis: Hyper-IgE syndrome (Job's syndrome). Underlying Immunological Defect: Mutation in the STAT3 gene leading to defective Th17 cell differentiation. Impaired neutrophil chemotaxis. Affected Cytokine Pathway: Decreased production of IL-17 due to defective Th17 cells.

Question 159

A 2-year-old girl presents with recurrent thrush, diaper rash, and chronic Candida skin infections. She also shows signs of hypocalcemia, including muscle spasms. Laboratory findings reveal hypoparathyroidism and adrenal insufficiency. Question: What is the most likely diagnosis? Which gene is mutated, and what is its normal role? How does this mutation lead to her symptoms?

Answer 159

Answer: Diagnosis: Chronic mucocutaneous candidiasis associated with autoimmune polyendocrine syndrome type 1. Gene Mutated: AIRE gene (Autoimmune Regulator gene). Pathogenesis: Normal Role of AIRE: Facilitates expression of peripheral tissue antigens in the thymus for negative selection of self-reactive T cells. Mutation Consequences: Defective negative selection leads to survival of autoreactive T cells. Autoimmunity against endocrine organs (hypoparathyroidism, adrenal insufficiency). Impaired T cell response to Candida antigens.

Question 160

An infant presents with recurrent severe infections, including pneumonia, oral thrush, and chronic diarrhea. Physical examination reveals failure to thrive and absence of lymphoid tissues. Chest X-ray shows no thymic shadow. Laboratory tests indicate very low T cell and B cell counts, and low immunoglobulin levels. Question: What is the most likely diagnosis? Name two genetic defects that can cause this condition. What is the definitive treatment?

Answer 160

Answer: Diagnosis: Severe combined immunodeficiency (SCID). Genetic Defects: X-linked SCID: Mutation in the IL-2R gamma chain gene. Autosomal recessive SCID: Adenosine deaminase (ADA) deficiency. Definitive Treatment: Bone marrow transplantation (hematopoietic stem cell transplantation).

Question 161

A 4-year-old boy presents with progressive difficulty walking, frequent falls, and slurred speech. Physical examination reveals telangiectasias on the conjunctiva and skin. Laboratory tests show elevated alpha-fetoprotein (AFP), decreased IgA and IgG levels, and lymphopenia. There is increased sensitivity to ionizing radiation. Question: What is the most likely diagnosis? Which gene is mutated, and what is its normal function? Explain why these patients are at increased risk of malignancies.

Answer 161

Answer: Diagnosis: Ataxia-telangiectasia. Gene Mutated: ATM gene (Ataxia Telangiectasia Mutated gene). Normal Function: Involved in DNA double-strand break repair through nonhomologous end joining. Activates cell cycle checkpoints following DNA damage. Increased Risk of Malignancies: Accumulation of DNA damage due to defective repair mechanisms. Leads to genomic instability and increased risk of cancers, especially lymphomas and leukemias.

Question 162

A male infant has recurrent bacterial infections with Pneumocystis jirovecii, Cryptosporidium parvum, and CMV. Laboratory tests reveal high levels of IgM and markedly decreased levels of IgG, IgA, and IgE. Flow cytometry shows normal B and T cell numbers. There is a defect in class switching. Question: What is the most likely diagnosis? What is the underlying immunological defect? Which interaction between immune cells is impaired?

Answer 162

Answer: Diagnosis: Hyper-IgM syndrome. Underlying Immunological Defect: Defective CD40 ligand (CD40L) on helper T cells. Impaired Interaction: The CD40L-CD40 interaction between helper T cells and B cells is impaired. This prevents class switching from IgM to other immunoglobulin classes.

Question 163

A 3-month-old male infant presents with severe eczema, petechiae, and recurrent infections with encapsulated bacteria. Laboratory findings include thrombocytopenia with small platelets, elevated IgA and IgE levels, and decreased IgM levels. Question: What is the most likely diagnosis? Which gene is mutated, and how does it affect cells? What is the mnemonic to remember the key features of this syndrome?

Answer 163

Answer: Diagnosis: Wiskott-Aldrich syndrome. Gene Mutated: WAS gene (Wiskott-Aldrich Syndrome gene). Affects the actin cytoskeleton in leukocytes and platelets. Leads to defective immune synapse formation and platelet abnormalities. Mnemonic: WATER: Wiskott-Aldrich Thrombocytopenia Eczema Recurrent infections

Question 164

A newborn fails to shed the umbilical cord stump even after 6 weeks. The area around the stump shows signs of infection but lacks pus formation. Laboratory tests reveal marked neutrophilia but absence of CD18 integrin expression on leukocytes. Question: What is the most likely diagnosis? Explain the pathophysiology leading to the symptoms. What are common infections seen in this condition?

Answer 164

Answer: Diagnosis: Leukocyte adhesion deficiency (LAD) type I. Pathophysiology: Deficiency of CD18 integrin subunit impairs formation of β2 integrins. Neutrophils cannot adhere to endothelial surfaces and migrate to sites of infection. Leads to delayed wound healing, absence of pus, and high neutrophil counts in blood. Common Infections: Recurrent bacterial infections, especially of skin and mucosal surfaces. Omphalitis (infection of the umbilical stump).

Question 165

A child with pale skin, silvery hair, and nystagmus presents with recurrent pyogenic infections. Peripheral blood smear shows giant granules in neutrophils and platelets. Neurological examination reveals peripheral neuropathy. Question: What is the most likely diagnosis? What is the underlying genetic defect? Why do these patients exhibit partial albinism?

Answer 165

Answer: Diagnosis: Chediak-Higashi syndrome. Underlying Genetic Defect: Mutation in the LYST gene (lysosomal trafficking regulator gene). Leads to defective lysosomal trafficking and microtubule dysfunction. Partial Albinism Explanation: Defective melanin granule transport within melanocytes due to microtubule dysfunction. Results in hypopigmentation of skin, hair, and eyes.

Question 166

A 3-year-old boy suffers from recurrent infections with catalase-positive organisms such as Staphylococcus aureus and Serratia marcescens. Nitroblue tetrazolium test is negative (does not turn blue). Dihydrorhodamine flow cytometry shows decreased green fluorescence. Question: What is the most likely diagnosis? What is the underlying enzymatic defect? Explain why catalase-positive organisms are particularly problematic in this condition.

Answer 166

Answer: Diagnosis: Chronic granulomatous disease (CGD). Underlying Enzymatic Defect: Deficiency of NADPH oxidase. Impaired production of reactive oxygen species (superoxide) in phagocytes. Catalase-Positive Organisms Issue: Catalase-positive bacteria neutralize their own hydrogen peroxide. Phagocytes cannot use bacterial H₂O₂ to compensate for defective NADPH oxidase. Leads to inability to kill these organisms effectively.

Question 167

Chediak-Higashi Syndrome: 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Answer 167

1. Autosomal recessive mutation in LYST gene -- affecting lysossomal trafficking and microtuble function. 2. Recurrent pyogenic infections Partial albinism Peripheral neurophaty 3. Clinical features + Blood smear showing giant granules in neutrophils and platelets 4. Bone marrow transplantation

Question 168

Leukocyte Adhesion Deficiency (Type I) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Answer 168

1. Autosomal recessive defect in CD18 - abnormal integrins β2 - impairment of leukocytes adhesion 2. Delayed separation of the umbilical cord (>30d) Recurrent bacterial infections without pus formation Poor wound healing 3. Clinical features + Neutrophilia + Flow citometry showing absence of CD18 4. Antibiotic Bone marrow transplantation

Question 169

Chronic Granulomatous Disease (CGD) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 170

Wiskott-Aldrich Syndrome 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 171

Hyper-IgM Syndrome 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 172

Ataxia-Telangiectasia 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 173

Severe Combined Immunodeficiency (SCID) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 174

Chronic Mucocutaneous Candidiasis 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 175

Hyper-IgE Syndrome (Job's Syndrome) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 176

Thymic Aplasia (DiGeorge Syndrome) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 177

Common Variable Immunodeficiency (CVID) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 178

Selective IgA Deficiency 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 179

X-linked Agammaglobulinemia (Bruton's Agammaglobulinemia) 1. Etiology 2. Clinical Features 3. Diagnosis 4. Treatment

Question 180

Immunodeficiencies T-cells disorders

Answer 180

- Thymic aplasia (Di George Syndrome) - Hyper- IgE Syndrome (Job's Syndrome) - Chronic Mucocutaneous Candidiasis

Question 181

Immunodeficiencies combined B and T-cells disorders

Answer 181

- Severe combined Immunodeficiency - Ataxia-Telangectasia - Hyper-IgM Syndrome - Wiskott-Aldrich Syndrome

Question 182

Immunodeficiencies phsgocyte disorders (Innate Immunity)

Answer 182

- Leukocyte Adhesion Deficiency (LAD) - Chediak-Higashi Syndrome - Chronic Granulomatous Disease

Question 183

What type of hypersensitivity reaction is primarily associated with SLE?

Answer 183

Type III hypersensitivity reaction due to immune complex deposition.

Question 184

Which two antibodies are highly specific for SLE?

Answer 184

Anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies.

Question 185

Which antibody in SLE is associated with disease activity and renal involvement?

Answer 185

A: Anti-dsDNA antibody, levels of which can rise during disease flares and are linked to lupus nephritis.

Question 186

What are common renal complications in SLE?

Answer 186

A: Lupus nephritis, including diffuse proliferative glomerulonephritis (nephritic syndrome) and membranous glomerulonephritis (nephrotic syndrome).

Question 187

What is the major cardiac manifestation seen in SLE?

Answer 187

A: Libman-Sacks endocarditis, a form of nonbacterial endocarditis affecting both sides of the mitral or aortic valve.

Question 188

What is antiphospholipid syndrome, and how is it related to SLE?

Answer 188

A: A syndrome associated with antiphospholipid antibodies, leading to increased risk of blood clots, miscarriages, and can coexist with SLE.

Question 189

Which antibody is responsible for the false-positive syphilis test in SLE patients?

Answer 189

A: Anti-cardiolipin antibody, part of the antiphospholipid antibody profile.

Question 190

Name the antibodies associated with drug-induced lupus.

Answer 190

A: Anti-histone antibodies are commonly elevated in drug-induced lupus.

Question 191

Which drugs are most commonly implicated in drug-induced lupus?

Answer 191

A: Isoniazid, hydralazine, and procainamide.

Question 192

What is the treatment for acute lupus flares?

Answer 192

A: Corticosteroids are commonly used to manage acute flares, with additional immunosuppressants for long-term control.

Question 193

What are the main causes of death in SLE patients?

Answer 193

A: Renal failure, infections (due to immunosuppression), and cardiovascular disease.

Question 194

What is neonatal lupus, and what is its major complication?

Answer 194

A: Neonatal lupus occurs in infants due to maternal autoantibodies (e.g., SSA/Ro) and can lead to congenital heart block.

Question 195

Question 1 A 27-year-old woman presents with fatigue, joint pain, and a facial rash that worsens with sun exposure. Physical examination reveals a malar rash and tenderness in multiple joints, but no swelling. Laboratory findings are as follows: ANA: Positive Anti-dsDNA: Positive C3 and C4: Low Which of the following best explains the mechanism of joint damage in this patient? A. Cytotoxic T-cell-mediated destruction B. Formation of immune complexes C. Direct antibody attack on chondrocytes D. Type IV hypersensitivity reaction E. Eosinophil infiltration

Answer 195

Formation of immune complexes Explanation: SLE is a type III hypersensitivity reaction, where immune complexes (antibody-antigen complexes) deposit in tissues, causing inflammation in various organs, including the joints.

Question 196

A 34-year-old woman with a history of SLE presents with new-onset hypertension, edema, and proteinuria. Laboratory results reveal an elevated creatinine level. A renal biopsy shows diffuse thickening of the glomerular capillary walls with immune complex deposition. Which of the following is the most likely diagnosis? A. Membranous nephropathy B. Minimal change disease C. Diffuse proliferative glomerulonephritis D. Focal segmental glomerulosclerosis E. IgA nephropathy

Answer 196

C. Diffuse proliferative glomerulonephritis Explanation: Diffuse proliferative glomerulonephritis (DPGN) is the most common and severe form of lupus nephritis and is associated with nephritic syndrome and renal impairment in SLE patients.

Question 197

A 25-year-old woman is diagnosed with SLE. Laboratory studies reveal the presence of anticardiolipin antibodies. She reports a history of two miscarriages in the first trimester. Which of the following conditions is she at greatest risk for developing? A. Myocardial infarction B. Deep vein thrombosis C. Bacterial endocarditis D. Acute tubular necrosis E. Polyarteritis nodosa

Answer 197

B. Deep vein thrombosis Explanation: Anticardiolipin antibodies are part of antiphospholipid syndrome, which increases the risk of venous and arterial thromboses, including DVT, and is associated with recurrent miscarriages.

Question 198

A 32-year-old woman with SLE presents with confusion, headache, and a recent seizure. Physical exam reveals a malar rash, and her lab results show anemia and leukopenia. An MRI of the brain shows multiple small ischemic lesions. Which of the following antibodies is most likely associated with her central nervous system involvement? A. Anti-Ro (SSA) B. Anti-Sm C. Anti-dsDNA D. Anti-cardiolipin E. Anti-histone

Answer 198

D. Anti-cardiolipin Explanation: Anti-cardiolipin antibodies are associated with antiphospholipid syndrome, which can cause thromboses, including CNS involvement, leading to ischemic strokes and neurologic symptoms in SLE.

Question 199

A 40-year-old woman being treated for SLE presents with fevers, pleuritic chest pain, and hemoptysis. Laboratory testing shows low C3 and C4 levels, positive ANA, and elevated anti-dsDNA antibodies. A chest CT reveals bilateral pleural effusions. Which of the following mechanisms is most likely responsible for her symptoms? A. Antibody-mediated cytotoxicity against pulmonary alveoli B. Immune complex deposition and complement activation C. Direct infection of lung tissue D. T-cell-mediated pulmonary inflammation E. Autoantibody destruction of pleural cells

Answer 199

B. Immune complex deposition and complement activation Explanation: In SLE, immune complex deposition in tissues such as the lungs leads to inflammation and pleuritic symptoms. Low complement levels indicate ongoing consumption due to immune complex-mediated inflammation.

Question 200

A 28-year-old woman with a history of photosensitivity and joint pain presents with a facial rash after sun exposure. Her lab results are significant for a positive ANA titer of 1:320, positive anti-dsDNA, and low complement levels. Which of the following additional findings is most likely to be present? A. Elevated haptoglobin B. High erythropoietin level C. Hemolytic anemia D. Hypokalemia E. Hypercalcemia

Answer 200

C. Hemolytic anemia Explanation: Hemolytic anemia can occur in SLE due to autoimmune destruction of red blood cells, often presenting with anemia and low haptoglobin levels due to intravascular hemolysis.

Question 201

A 30-year-old woman with SLE is found to have proteinuria on routine screening. A renal biopsy reveals findings consistent with membranous glomerulonephritis. Which of the following clinical syndromes is most likely associated with this renal pathology? A. Nephritic syndrome B. Nephrotic syndrome C. Rapidly progressive glomerulonephritis D. Alport syndrome E. Focal segmental glomerulosclerosis

Answer 201

B. Nephrotic syndrome Explanation: Membranous glomerulonephritis in SLE patients typically presents with nephrotic syndrome, characterized by heavy proteinuria, hypoalbuminemia, and edema.

Question 202

A 24-year-old woman with SLE presents with Raynaud's phenomenon and a malar rash. She reports joint pain and fatigue, especially in the morning. Laboratory tests reveal a positive ANA and anti-Smith antibodies. Which of the following tests would best support the diagnosis of SLE if present? A. Elevated C3 and C4 B. Positive anti-histone antibody C. Low complement levels (C3, C4) D. Positive anti-mitochondrial antibody E. Positive anti-RNP antibody

Answer 202

C. Low complement levels (C3, C4) Explanation: Low levels of complement proteins (C3, C4) are common in active SLE due to complement activation from immune complex formation and are a supportive finding for SLE diagnosis.

Question 203

Describe the pathophysiology of RA.

Answer 203

A: Inflammation of the synovium leads to pannus formation, which erodes cartilage and bone, causing joint destruction. It is a Type III hypersensitivity reaction.

Question 204

What are the main inflammatory mediators in RA?

Answer 204

A: TNF-alpha and IL-6.

Question 205

List three extra-articular manifestations of RA.

Answer 205

A: Serositis (pleuritis, pericarditis), subcutaneous (rheumatoid) nodules, and ocular involvement (episcleritis, scleritis, uveitis).

Question 206

Which laboratory test is more specific for RA, RF or anti-CCP antibodies?

Answer 206

A: Anti-CCP antibodies are more specific for RA.

Question 207

Which HLA serotype is strongly associated with RA?

Answer 207

A: HLA-DR4.

Question 208

What is Felty syndrome?

Answer 208

A: A triad of RA, splenomegaly, and neutropenia, seen in severe, long-standing RA cases.

Question 209

What are the risks associated with RA in terms of bone health?

Answer 209

A: RA accelerates osteoporosis, increasing fracture risk, especially with long-term steroid use.

Question 210

A 52-year-old woman presents with a 6-month history of progressive joint pain in her hands and wrists, particularly in the morning, lasting for about two hours. Physical examination reveals swelling and tenderness in her metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints bilaterally, but her distal interphalangeal (DIP) joints are spared. Lab results show elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as positive rheumatoid factor (RF) and anti-citrullinated protein antibodies (anti-CCP). Which of the following statements about her disease is most likely correct? A) The disease typically starts with asymmetric joint involvement. B) Joint stiffness in this disease worsens with activity. C) The presence of anti-CCP antibodies is highly specific for her condition. D) The DIP joints are commonly involved in this disease.

Answer 210

Answer: C Explanation: Anti-CCP antibodies are highly specific for rheumatoid arthritis, while DIP involvement is typically absent in RA and asymmetric joint involvement is more common in osteoarthritis.

Question 211

A 40-year-old woman is newly diagnosed with rheumatoid arthritis. She reports having had some joint swelling and tenderness in her fingers over the last several weeks. She is prescribed methotrexate as part of her treatment regimen. Which of the following is the primary reason for using methotrexate in rheumatoid arthritis? A) To provide immediate pain relief. B) To suppress acute inflammatory response only. C) To act as a disease-modifying agent and prevent joint destruction. D) To block specific cytokines, such as TNF-alpha.

Answer 211

Answer: C Explanation: Methotrexate is a disease-modifying antirheumatic drug (DMARD) that helps prevent joint destruction and progression of rheumatoid arthritis, making it a cornerstone of RA treatment.

Question 212

A 58-year-old man with rheumatoid arthritis presents with pain and swelling at the back of his knee. He reports that the pain worsened over the past two days and radiates down his calf. Physical examination reveals a palpable mass in the popliteal fossa. Duplex ultrasound reveals no evidence of deep vein thrombosis. Which of the following is the most likely cause of his symptoms? A) Ruptured Baker’s cyst B) Popliteal artery aneurysm C) Cellulitis D) Septic arthritis

Answer 212

Answer: A Explanation: A Baker’s cyst, also known as a popliteal cyst, is common in patients with RA and can rupture, causing pain that mimics DVT. A negative ultrasound helps rule out DVT.

Question 213

A 36-year-old woman presents with persistent dry eyes and dry mouth. She has a history of rheumatoid arthritis. Physical examination reveals bilateral parotid gland enlargement. Which of the following is the most likely diagnosis? A) Primary Sjogren’s syndrome B) Secondary Sjogren’s syndrome C) Systemic lupus erythematosus D) Scleroderma

Answer 213

Answer: B Explanation: Secondary Sjogren’s syndrome is often associated with other autoimmune diseases like RA, leading to symptoms such as dry eyes and dry mouth due to lacrimal and salivary gland involvement.

Question 214

A 60-year-old woman with long-standing rheumatoid arthritis presents with worsening fatigue, weight loss, and nephrotic syndrome. A renal biopsy reveals deposits with apple-green birefringence under polarized light after Congo red staining. Which of the following best explains the findings? A) Primary amyloidosis due to plasma cell dyscrasia B) Secondary amyloidosis related to chronic inflammation from RA C) Drug-induced nephrotoxicity from long-term methotrexate use D) Anti-GBM disease secondary to immune complex deposition

Answer 214

Answer: B Explanation: Secondary amyloidosis (AA amyloidosis) is a known complication of chronic inflammatory conditions like RA. The apple-green birefringence seen on Congo red staining is characteristic of amyloid deposits.

Question 215

A 48-year-old woman with rheumatoid arthritis has been started on infliximab, a TNF-alpha inhibitor. Two months later, she develops a cough, night sweats, and fever. A chest X-ray reveals a cavitary lesion in the right upper lobe. Which of the following is the most likely underlying cause? A) Reactivation of latent tuberculosis B) Bacterial pneumonia C) Lung abscess due to anaerobic infection D) Fungal infection

Answer 215

Answer: A Explanation: TNF-alpha inhibitors, like infliximab, can reactivate latent tuberculosis, which often presents with cavitary lesions in the upper lung lobes.

Question 216

A 52-year-old woman with rheumatoid arthritis presents with severe pain in the PIP and MCP joints. She is found to be positive for RF and anti-CCP antibodies. Which HLA serotype is most commonly associated with her condition? A) HLA-B27 B) HLA-DR3 C) HLA-DR4 D) HLA-DQ2

Answer 216

Answer: C Explanation: HLA-DR4 is the most commonly associated HLA serotype with rheumatoid arthritis, especially in cases with seropositivity for RF and anti-CCP antibodies.

Question 217

A 62-year-old woman with a long history of rheumatoid arthritis is found to have splenomegaly and neutropenia during her routine exam. She has deformed joints and multiple subcutaneous nodules. Which of the following best describes her condition? A) Sjogren’s syndrome B) Felty syndrome C) Lupus D) Secondary amyloidosis

Answer 217

Answer: B Explanation: Felty syndrome is characterized by rheumatoid arthritis with splenomegaly and neutropenia, typically in patients with long-standing, severe RA.

Question 218

What is the characteristic pathologic finding in scleroderma?

Answer 218

A: Excessive collagen deposition leading to tissue sclerosis.

Question 219

What does CREST stand for in limited scleroderma?

Answer 219

A: Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias.

Question 220

What is a hallmark feature of Raynaud’s phenomenon?

Answer 220

A: Vasospasm in the fingers, leading to white or blue fingertips, especially in response to cold.

Question 221

Which organ complications are common in diffuse scleroderma?

Answer 221

A: Renal (renal crisis), GI (dysmotility), cardiac (pericarditis, myocarditis), pulmonary (hypertension, interstitial lung disease).

Question 222

Which antibody is associated with diffuse scleroderma?

Answer 222

A: Anti-topoisomerase I (Anti-SCL70).

Question 223

Which antibody is associated with limited scleroderma (CREST syndrome)?

Answer 223

A: Anti-centromere antibody.

Question 224

Which antibody is associated with rapid skin progression and increased risk of renal crisis in diffuse scleroderma?

Answer 224

A: Anti-RNA polymerase III.

Question 225

What is the treatment of choice for scleroderma renal crisis?

Answer 225

A: ACE inhibitors.

Question 226

What is the main treatment approach for scleroderma?

Answer 226

A: Organ-specific management (e.g., calcium channel blockers for Raynaud’s, PPIs for esophageal reflux).

Question 227

Which antibody test is common but non-specific in scleroderma?

Answer 227

A: Anti-nuclear antibody (ANA).

Question 228

Which pulmonary complications are the leading cause of death in scleroderma?

Answer 228

A: Pulmonary hypertension and interstitial lung disease.

Question 229

What is sclerodactyly, and what is its clinical significance in scleroderma?

Answer 229

A: Sclerosis of the skin on the fingers, leading to claw-like hands in severe cases; a key feature in CREST syndrome.

Question 230

Which autoimmune conditions are associated with scleroderma?

Answer 230

A: Primary biliary cirrhosis, Sjogren's syndrome, lupus, rheumatoid arthritis, Hashimoto’s thyroiditis.

Question 231

How does esophageal dysmotility present in scleroderma, and what is the underlying cause?

Answer 231

A: Presents with difficulty swallowing and reflux due to collagen deposition and hypotonia of the lower esophageal sphincter..

Question 232

A 45-year-old woman presents with progressive tightening of the skin on her hands and face. She reports difficulty swallowing and frequent episodes of acid reflux. Physical examination reveals telangiectasias on her cheeks and sclerodactyly. Which antibody is most likely to be positive in this patient? A) Anti-centromere antibody B) Anti-SCL70 (anti-topoisomerase I) C) Anti-dsDNA antibody D) Anti-RNA polymerase III

Answer 232

Answer: A) Anti-centromere antibody Explanation: The clinical presentation suggests limited scleroderma (CREST syndrome), which is associated with anti-centromere antibodies.

Question 233

A 50-year-old woman with a 5-year history of Raynaud's phenomenon presents with sudden-onset severe hypertension and acute kidney injury. Her physical examination reveals diffuse skin thickening. Which of the following is the most appropriate initial treatment? A) Beta-blockers B) Calcium channel blockers C) ACE inhibitors D) High-dose corticosteroids

Answer 233

Answer: C) ACE inhibitors Explanation: Scleroderma renal crisis is managed with ACE inhibitors, as they reduce hypertension and protect renal function in this setting.

Question 234

A patient with diffuse systemic sclerosis presents with progressive dyspnea on exertion and fatigue. Physical examination shows elevated jugular venous pressure and lower extremity edema. Which of the following is the most likely underlying cause of these symptoms? A) Left ventricular failure B) Pulmonary hypertension C) Acute pericarditis D) Primary pulmonary edema

Answer 234

Answer: B) Pulmonary hypertension Explanation: Pulmonary hypertension is a common and severe complication in diffuse systemic sclerosis and can lead to symptoms of right heart failure.

Question 235

A 37-year-old woman with limited scleroderma presents with complaints of white discoloration of her fingertips when exposed to cold. She is diagnosed with Raynaud's phenomenon. Which of the following is the first-line pharmacologic treatment for this condition? A) Beta-blockers B) Calcium channel blockers C) ACE inhibitors D) Corticosteroids

Answer 235

Answer: B) Calcium channel blockers Explanation: Calcium channel blockers are the first-line treatment for Raynaud’s phenomenon in scleroderma to prevent vasospasm and improve blood flow.

Question 236

A 60-year-old woman with systemic sclerosis presents with difficulty swallowing and frequent heartburn. Esophageal manometry reveals hypotonicity of the lower esophageal sphincter. Which of the following is the underlying cause of her esophageal symptoms? A) Vasospasm of esophageal arteries B) Fibrosis of the esophageal muscles C) Hypertonicity of the upper esophageal sphincter D) Gastric acid hypersecretion

Answer 236

Answer: B) Fibrosis of the esophageal muscles Explanation: Collagen deposition leads to fibrosis and hypotonia of the lower esophageal sphincter, resulting in dysmotility and reflux.

Question 237

Which of the following complications is associated with the presence of anti-RNA polymerase III antibodies in a patient with scleroderma? A) Limited skin involvement B) Increased risk of renal crisis C) Decreased likelihood of pulmonary hypertension D) Lower likelihood of esophageal involvement

Answer 237

Answer: B) Increased risk of renal crisis Explanation: Anti-RNA polymerase III antibodies are associated with a higher risk of renal crisis and rapid skin progression in diffuse scleroderma.

Question 238

A 35-year-old woman is diagnosed with scleroderma and primary biliary cirrhosis (PBC). Which of the following laboratory abnormalities is most likely to be present? A) Elevated anti-Smith antibody B) Increased anti-mitochondrial antibody (AMA) C) Elevated serum creatinine D) Positive rheumatoid factor

Answer 238

Answer: B) Increased anti-mitochondrial antibody (AMA) Explanation: Anti-mitochondrial antibodies are commonly elevated in primary biliary cirrhosis, which is associated with scleroderma.

Question 239

A patient with CREST syndrome has recurrent heartburn and regurgitation. What would be the best diagnostic test to evaluate her esophageal motility? A) Upper endoscopy B) Barium swallow C) Esophageal manometry D) 24-hour pH monitoring

Answer 239

Answer: C) Esophageal manometry Explanation: Esophageal manometry is used to measure esophageal motility and lower esophageal sphincter tone, which are often reduced in scleroderma due to fibrosis.

Question 240

A 42-year-old woman with scleroderma presents with fatigue, weight loss, and jaundice. Laboratory tests show elevated bilirubin and alkaline phosphatase. Which associated autoimmune condition should be suspected? A) Lupus B) Sjogren’s syndrome C) Primary biliary cirrhosis D) Hashimoto’s thyroiditis

Answer 240

Answer: C) Primary biliary cirrhosis Explanation: Primary biliary cirrhosis (PBC) is associated with scleroderma and presents with elevated bilirubin and alkaline phosphatase.

Question 241

A patient with systemic sclerosis presents with digital ulcers and pain in her fingers that worsens with cold exposure. Which of the following describes the pathophysiology of this finding? A) Inflammation of joint capsules B) Vasospasm of small arteries C) Nerve compression in carpal tunnel D) Increased collagen deposition in tendons

Answer 241

Answer: B) Vasospasm of small arteries Explanation: Raynaud’s phenomenon, seen in scleroderma, results from vasospasm of small arteries, leading to ischemia and ulcers in the digits.

Question 242

What is keratoconjunctivitis sicca?

Answer 242

A: Dryness of the eye's surface due to lacrimal gland damage, common in Sjogren’s Syndrome.

Question 243

What is lymphocytic sialadenitis?

Answer 243

A: Lymphocyte infiltration of salivary glands, characteristic of Sjogren's Syndrome and a diagnostic biopsy finding.

Question 244

What antibodies are associated with Sjogren’s Syndrome?

Answer 244

A: Anti-SSA (Ro) and Anti-SSB (La) antibodies, ANA, and often Rheumatoid Factor.

Question 245

Which test measures tear production in Sjogren's Syndrome?

Answer 245

A: The Schirmer Test.

Question 246

What is Schirmer test?

Answer 246

Measures tear production in Sjogren's Syndrome

Question 247

Salivary glands biopsy find in Sjogren's:

Answer 247

Lymphocytic sialadenitis

Question 248

What is the primary treatment for oral dryness in Sjogren’s Syndrome?

Answer 248

A: Oral hygiene, artificial saliva, and muscarinic agonists like pilocarpine.

Question 249

What serious complication is associated with Sjogren’s Syndrome due to chronic inflammation?

Answer 249

A: Increased risk of B-cell lymphoma.

Question 250

What is neonatal lupus, and how is it connected to Sjogren's Syndrome?

Answer 250

A: A condition affecting infants born to mothers with anti-SSA/SSB antibodies, which can cause congenital heart block and skin rash.

Question 251

Which hypersensitivity type is Sjogren's Syndrome classified as?

Answer 251

A: Type IV hypersensitivity, involving T-cell mediated tissue destruction

Question 252

What other autoimmune diseases is Sjogren’s often secondary to?

Answer 252

A: Rheumatoid arthritis, lupus, and primary biliary cirrhosis.

Question 253

What is the common first symptom reported by patients with Sjogren's Syndrome?

Answer 253

A: Difficulty chewing dry foods like crackers due to reduced saliva.

Question 254

A 45-year-old woman presents with complaints of dry mouth and dry eyes for the past few months. She also reports joint pain and intermittent episodes of fingertip discoloration in cold weather. Physical examination reveals dental caries and cracked lips. Laboratory studies show positive anti-SSA and anti-SSB antibodies. Which of the following tests would most likely confirm the suspected diagnosis? A. ESR and CRP levels B. Schirmer test C. Serum uric acid level D. Creatinine clearance E. Serum calcium levels

Answer 254

Answer: B. Schirmer test Explanation: The patient’s symptoms and antibody profile are consistent with Sjogren’s Syndrome. The Schirmer test measures tear production and is often used to confirm decreased lacrimal gland function in suspected cases.

Question 255

A 50-year-old woman with a known history of Sjogren's Syndrome is being evaluated for persistent unilateral swelling of her parotid gland. She notes that the swelling is larger than previous episodes and does not resolve. Which of the following is the most concerning potential complication in this patient? A. Sialadenitis B. B-cell lymphoma C. Systemic sclerosis D. Rheumatoid arthritis E. Parotid gland cyst

Answer 255

Answer: B. B-cell lymphoma Explanation: Patients with Sjogren’s Syndrome have an increased risk of developing B-cell lymphoma, which may present as persistent, unilateral swelling of a salivary gland.

Question 256

A 32-year-old pregnant woman with a history of Sjogren's Syndrome is concerned about the risk of complications for her baby. She has positive anti-SSA and anti-SSB antibodies. Which of the following conditions should the healthcare provider monitor for in her newborn? A. Patent ductus arteriosus B. Complete heart block C. Tetralogy of Fallot D. Atrial septal defect E. Ventricular septal defect

Answer 256

Answer: B. Complete heart block Explanation: Anti-SSA and anti-SSB antibodies can cross the placenta and may lead to neonatal lupus, which includes congenital complete heart block as a significant complication.

Question 257

A 60-year-old woman presents with complaints of dry mouth, dry eyes, and difficulty swallowing. A biopsy of her salivary glands shows lymphocytic infiltration. She has positive rheumatoid factor and ANA antibodies. Which of the following mechanisms is primarily responsible for the glandular destruction observed in this patient? A. Immune complex deposition B. T-cell mediated cytotoxicity C. Complement activation D. Neutrophil infiltration E. Eosinophil degranulation

Answer 257

Answer: B. T-cell mediated cytotoxicity Explanation: Sjogren’s Syndrome is classified as a type IV hypersensitivity reaction, with T-cell-mediated destruction of the salivary and lacrimal glands, leading to lymphocytic sialadenitis.

Question 258

A patient with Sjogren’s Syndrome undergoes salivary gland scintigraphy as part of her evaluation. The results show significantly reduced radiotracer uptake. Which of the following additional tests is most likely to help confirm decreased salivary production in this patient? A. ESR and CRP B. Schirmer test C. Sialometry D. Anti-double-stranded DNA antibodies E. Thyroid function tests

Answer 258

Answer: C. Sialometry Explanation: Sialometry, which involves collecting and weighing saliva, is a direct measurement of salivary production and can confirm decreased function in Sjogren’s Syndrome.

Question 259

A 45-year-old woman is diagnosed with primary Sjogren’s Syndrome. Which of the following statements about her condition is most accurate? A. Treatment primarily involves NSAIDs for joint pain B. Anti-inflammatory drugs are the mainstay for glandular symptoms C. Pilocarpine may be used to stimulate saliva production D. Immunosuppressive therapy is essential for all cases E. She is not at risk of developing lymphoma

Answer 259

Answer: C. Pilocarpine may be used to stimulate saliva production Explanation: Pilocarpine, a muscarinic agonist, is often prescribed to increase saliva and tear production in Sjogren’s Syndrome. Immunosuppressants and anti-inflammatory drugs are typically limited to cases with severe extraglandular symptoms.

Question 260

A patient with known Sjogren’s Syndrome has developed a rash consisting of multiple red circular lesions on her face. She is also diagnosed with complete heart block shortly after birth. The mother of this newborn likely has which of the following antibody elevations? A. Anti-dsDNA B. Anti-RNP C. Anti-Smith D. Anti-SSA/SSB E. Anti-histone

Answer 260

Answer: D. Anti-SSA/SSB Explanation: Anti-SSA and anti-SSB antibodies can cross the placenta and cause neonatal lupus, which may present as a facial rash and congenital complete heart block in newborns of mothers with autoimmune conditions like Sjogren’s or lupus.

Question 261

Immunodeficiency with Partial albinism

Answer 261

Chediak-Higashi Syndrome - Autosomal recessive mutation in LYST gene affecting lysosomal trafficking and microtubule function

Question 262

Immunodeficiency with neutrophilia

Answer 262

Leukocyte Adhesion Deficiency (Type I) - Autosomal recessive defect in CD18 (β2 integrin subunit) affecting leukocyte adhesion

Question 263

Immunodeficiency with thrombocytopenia and eczema

Answer 263

Wiskott-Aldrich Syndrome - X-linked recessive mutation in WAS gene affecting cytoskeletal function in leukocytes and platelets

Question 264

Immunodeficiency with opportunistic infections

Answer 264

Hyper-IgM Syndrome - X-linked defect in CD40 ligand on Th cells

Question 265

Immunodeficiency with gait problems and veins on face and conjunctiva

Answer 265

Ataxia-Telangiectasia - Autosomal recessive mutation in ATM gene (chromosome 11) affecting DNA repair

Question 266

Immunodeficiency with elevated AFP

Answer 266

Ataxia-Telangiectasia - Autosomal recessive mutation in ATM gene (chromosome 11) affecting DNA repair

Question 267

Immunodeficiency with low TRECs, failure to thrive, recurrent infections (bacterial, viral, fungal, protozoal) without face and heart deformations

Answer 267

Severe Combined Immunodeficiency (SCID) - X-linked SCID: Mutation in IL-2R γ chain - Autosomal recessive SCID: Adenosine deaminase (ADA)

Question 268

Immunodeficiency with thrush, esophagitis, diaper rash and endocrine disorders

Answer 268

Chronic Mucocutaneous Candidiasis - T cell dysfunction due to defects in AIRE genes

Question 269

Immunodeficiency with retained primary teeth

Answer 269

Hyper-IgE Syndrome (Job's Syndrome) - Autosomal dominant mutation in STAT3 gene → defective Th17 cell differentiation

Question 270

Immunodeficiency with recurrent viral, fungal, protozoal infections and facial abnormalities

Answer 270

Thymic Aplasia (DiGeorge Syndrome) - 22q11.2 deletion → failure of 3rd and 4th pharyngeal pouches development

Question 271

Immunodeficiency with hypocalcemia

Answer 271

Thymic Aplasia (DiGeorge Syndrome) - 22q11.2 deletion → failure of 3rd and 4th pharyngeal pouches development

Question 272

Immunodeficiency with giant intracellular granules

Answer 272

Chediak-Higashi Syndrome - Autosomal recessive mutation in LYST gene affecting lysosomal trafficking and microtubule function