Immunopathology Practice Questions

Q: Which HLA marker is associated with an increased risk of developing type 1 diabetes mellitus?

HLA-DR4. ***DR 4*** - The **HLA-DR4** allele is strongly associated with increased susceptibility to **type 1 diabetes mellitus** [1]. - It plays a crucial role in the **immune response**, promoting autoimmunity against pancreatic beta cells. *B 7* - HLA-B7 is not specifically linked to **type 1 diabetes**, but is more associated with other **autoimmune diseases** like **ankylosing spondylitis**. - It does not show the same level of genetic correlation with **insulin-dependent diabetes** as DR4 does. *DQ 4* - HLA-DQ4 is not the primary marker for **type 1 diabetes**; instead, HLA-DQ2 and DQ8 are more relevant in conditions like **celiac disease**. - Its presence does not have a significant relationship with the autoimmune destruction of **beta cells** in diabetes. *DQ 3* - HLA-DQ3 is less frequently associated with **type 1 diabetes** compared to HLA-DR4 [1]. - It is more involved with other **autoimmune conditions** and does not reflect the same risk for developing diabetes mellitus. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1113.

Q: Which of the following is a T-cell mediated disease?

Sarcoidosis. ***Sarcoidosis*** - Sarcoidosis is characterized by the formation of **non-caseating granulomas**, primarily driven by **T-cell accumulation** and activation [1]. - The immune response involves **Th1 lymphocytes** releasing cytokines like **IFN-γ** and **TNF-α**, which promote granuloma formation. *Allergic Rhinitis* - This is a **Type I hypersensitivity reaction** mediated primarily by **IgE antibodies** and **mast cell degranulation**. - While T-cells play a role in orchestrating the IgE response, the immediate symptoms are due to **histamine release**, not direct T-cell cytotoxicity or granuloma formation. *Graves' Disease* - Graves' disease is an **autoimmune disorder** primarily mediated by **autoantibodies** (specifically **thyroid-stimulating immunoglobulins**) that bind to and activate the **TSH receptor**. - Although T-cells are involved in breaking tolerance and supporting B-cell activation, the direct tissue damage and functional changes are antibody-driven. *Systemic Lupus Erythematosus (SLE)* - SLE is a classic **autoimmune disease** characterized by the production of numerous **autoantibodies** (e.g., antinuclear antibodies, anti-dsDNA antibodies) that form **immune complexes**. - These immune complexes deposit in various tissues, leading to inflammation and damage, making it primarily a **Type III hypersensitivity** reaction, heavily B-cell and antibody-mediated. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 198-200.

Q: Which type of hypersensitivity reaction is mediated by complement?

Type II hypersensitivity. ***Type -2 hypersensitivity*** [1][2] - This type of hypersensitivity involves **IgG or IgM antibodies** binding to antigens on cell surfaces, activating the **complement system**, and mediating cell lysis [1][2]. - It is associated with conditions like **hemolytic anemia** and **Goodpasture syndrome** due to complement activation [1]. *None* - This option suggests there is no complement-mediated hypersensitivity, which contradicts established immunological classifications [2]. - Complement activation is specifically linked to **Type-2 hypersensitivity reactions**, making this option incorrect [1][2]. *Type -4 hypersensitivity* - This is a **T-cell mediated** hypersensitivity, not involving antibodies or complement, making it inappropriate for the question regarding complement-mediated reactions [2]. - Characteristic conditions include **granulomatous diseases** and **contact dermatitis**, distinguishing it from Type-2 hypersensitivity. *Type -1 hypersensitivity* - Type-1 hypersensitivity is primarily **IgE mediated**, involving mast cells and histamine release, without direct involvement of the complement system [2]. - Conditions like **asthma** and **allergic rhinitis** are examples, further separating it from complement-mediated mechanisms [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 214. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 208-210.

Q: The primary defect in chronic granulomatous disease (CGD) is:

Defective H2O2 production. ***Defective H2O2 production*** - Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the inability of phagocytes (neutrophils, macrophages) to produce **reactive oxygen species**, specifically **superoxide** and its derivatives like H2O2. - This defect is primarily due to mutations in genes encoding components of the **NADPH oxidase enzyme complex**, which is crucial for the **oxidative burst** leading to H2O2 and other antimicrobial agents. *Defective phagocytosis* - Defective phagocytosis refers to an impairment in the engulfment of pathogens, which is not the primary defect in CGD. - In CGD, phagocytes can engulf pathogens, but they cannot effectively kill them intracellularly due to the lack of an **oxidative burst**. *Job's disease* - Job's disease, also known as **hyper-IgE syndrome**, is characterized by high IgE levels, recurrent skin and pulmonary infections, and distinctive facial features. - It is caused by genetic defects in the **STAT3 pathway**, which affects immune cell differentiation and function, and does not involve a primary defect in H2O2 production. *Myeloperoxidase deficiency* - Myeloperoxidase (MPO) deficiency is a condition where neutrophils lack the enzyme **myeloperoxidase**, which contributes to the formation of hypochlorous acid (HOCl) from H2O2 and chloride ions. - While MPO is involved in microbial killing, its deficiency is generally less severe than CGD, as other mechanisms (like H2O2 itself) can still kill pathogens; CGD has a more profound defect in the initial production of ROS.

Q: Which cells are responsible for GVHD?

Immunocompetent T cell donor. ***Immunocompetent T cell donor*** - **Graft-versus-host disease (GVHD)** primarily involves **donor T cells** recognizing the recipient's tissues as foreign. - These donor T cells then mount an immune response against the **host's antigens**, leading to tissue damage. *Immunocompetent B cell recipient* - **B cells** are mostly responsible for **humoral immunity** (antibody production), which is not the primary mechanism of GVHD. - While recipient B cells can contribute to immune responses, they are not the main effector cells in initiating and perpetuating GVHD. *Immunocompetent NK cell recipient* - **Natural killer (NK) cells** are part of the innate immune system and can kill target cells without prior sensitization. - However, recipient NK cells are typically suppressed in the transplant setting and do not mediate GVHD; rather, **donor NK cells** can sometimes have a protective role. *Immunocompetent T cell recipient* - The recipient's immune system, including **recipient T cells**, is usually **immunosuppressed** or ablated before transplantation to prevent graft rejection. - If the recipient's T cells were immunocompetent, they would likely reject the graft, leading to **graft rejection (host-versus-graft reaction)**, which is the opposite of GVHD.

Question 1

In a patient with a history of organ transplantation, which type of hypersensitivity reaction is primarily responsible for graft rejection that occurs days to weeks after transplantation?

Accepted Answer

Type IV hypersensitivity

Answer

Type I hypersensitivity

Answer

Type II hypersensitivity

Answer

Type III hypersensitivity

Question 2

A 28-year-old female presents with a rash after using a new cosmetic product. A skin biopsy reveals lymphocytic infiltration around the blood vessels and basal cell vacuolization. Which type of hypersensitivity reaction is most likely involved?

Accepted Answer

Type IV

Answer

Type I

Answer

Type II

Answer

Type III

Question 3

A patient with chronic granulomatous disease is unable to produce which of the following substances that are necessary for microbial killing?

Accepted Answer

Superoxide anion

Answer

Hydrogen peroxide

Answer

Nitric oxide

Answer

Hypochlorous acid

Question 4

Which HLA marker is associated with an increased risk of developing type 1 diabetes mellitus?

Accepted Answer

HLA-DR4

Answer

HLA-B7

Answer

HLA-DQ3

Answer

HLA-DQ4

Question 5

Which of the following is a T-cell mediated disease?

Accepted Answer

Sarcoidosis

Answer

Allergic Rhinitis

Answer

Graves' Disease

Answer

Systemic Lupus Erythematosus (SLE)

Question 6

Which type of hypersensitivity reaction is mediated by complement?

Accepted Answer

Type II hypersensitivity

Answer

Type I hypersensitivity

Answer

No hypersensitivity reaction

Answer

Type IV hypersensitivity

Question 7

The primary defect in chronic granulomatous disease (CGD) is:

Accepted Answer

Defective H2O2 production

Answer

Job's disease

Answer

Defective phagocytosis

Answer

Myeloperoxidase deficiency

Question 8

What is the purpose of the Direct Coombs' test?

Accepted Answer

Detection of immune components bound to red blood cells (RBCs).

Answer

Detection of immune components in the serum.

Answer

Detection of cell surface antigens on red blood cells (RBCs).

Answer

Detection of antigens circulating in the serum.

Question 9

Which cells are responsible for GVHD?

Accepted Answer

Immunocompetent T cell donor

Answer

Immunocompetent NK cell recipient

Answer

Immunocompetent B cell recipient

Answer

Immunocompetent T cell recipient

Question 10

Which type of hypersensitivity is characteristically associated with atopic conditions?

Accepted Answer

Local type I hypersensitivity (e.g., allergic rhinitis, eczema)

Answer

Local type II hypersensitivity (e.g., Goodpasture syndrome)

Answer

Systemic type II hypersensitivity (e.g., autoimmune hemolytic anemia)

Answer

Systemic type I hypersensitivity (e.g., anaphylaxis)

Immunopathology — MCQs

Immunopathology — MCQs

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