I10: A

Question 1

What is the fundamental underlying mechanism of autoimmune disease Options A. Excessive production of neutrophils in the bone marrow B. Defective elimination and or control of self-reactive lymphocytes C. Acute infection by a single pathogen D. Overactive innate physical barriers

Answer 1

B. Defective elimination and or control of self-reactive lymphocytes

Question 2

Autoimmune disease is caused by an imbalance between ______ and ______ immune responses.

Answer 2

effector; regulatory

Question 3

Which of the following are reasons why autoimmune diseases are considered a significant clinical problem Options A. Their chronic nature B. High prevalence in people during prime working and reproductive years C. Associated high healthcare costs D. They only affect the central nervous system

Answer 3

A B C

Question 4

Describe the phases of autoimmune disease progression and how they might manifest clinically over time.

Answer 4

Autoimmune disease develops in three phases initiation propagation and resolution. Clinically it often shows a relapsing-remitting pattern with phases of inactivity remission and exacerbation symptomatic flares.

Question 5

Which factor contributes to autoimmunity by decreasing the efficiency of thymic selection and the function of Regulatory T cells Tregs Options A. Stress B. Aging C. Pesticides D. Structural modification of antigens

Answer 5

B. Aging

Question 6

The release of hidden auto-antigens from privileged sites such as the ______ or ______ during trauma can trigger an autoimmune response.

Answer 6

CNS Central Nervous System; lens or spermatozoa

Question 7

Based on the incidence chart provided in the sources which of the following diseases show a significantly higher incidence in females than males Options A. Sjögren’s Syndrome B. SLE Lupus C. Myocarditis D. Type 1 Diabetes Mellitus

Answer 7

A B

Question 8

Which HLA type is strongly associated with Ankylosing Spondylitis Options A. DRB103 B. DQB102 08 C. B27 D. C06:02

Answer 8

C. B*27

Question 9

Coeliac disease is strongly associated with the HLA types ______ and ______.

Answer 9

DQB102; DQB108

Question 10

Which HLA alleles are associated with Type 1 Diabetes Options A. DRB103 B. DRB104 C. B27 D. C06:02

Answer 10

A B

Question 11

Explain the role of genetic factors and environmental exposure in the development of autoimmunity.

Answer 11

Genetic susceptibility polymorphisms in immune-regulating genes creates a failure of self-tolerance leading to the presence of self-reactive lymphocytes. Environmental stimuli infection tissue injury UV then activate tissue APCs which in turn activate those self-reactive lymphocytes leading to tissue injury and autoimmune disease.

Question 12

Where does central tolerance for T cells primarily occur Options A. Bone marrow B. Spleen C. Thymus D. Lymph nodes

Answer 12

C. Thymus

Question 13

During T cell development in the thymus the elimination of self-reactive T cells is known as ______ ______.

Answer 13

negative selection or clonal deletion

Question 14

Which of the following are mechanisms of peripheral tolerance Options A. Positive selection in the thymus B. Clonal anergy C. Deletion via apoptosis D. Suppression via Regulatory T cells Tregs

Answer 14

B C D

Question 15

Define Epitope Spreading and explain its clinical significance.

Answer 15

Epitope spreading occurs when tissue damage and alterations in self-proteins create new antigenic epitopes. These new epitopes activate more lymphocytes and recruit more immune cells leading to more tissue damage and creating a vicious circle of spreading autoimmunity.

Question 16

What happens to a thymocyte immature T cell that recognizes self-MHC but interacts too strongly with a self-peptide during development Options A. It is signaled for survival Positive selection B. It is released into the circulation C. It undergoes negative selection Signaled death Apoptosis D. It becomes a B cell

Answer 16

C. It undergoes negative selection Signaled death Apoptosis

Question 17

B cell central tolerance occurs in the ______ ______.

Answer 17

bone marrow

Question 18

In the germinal center activated B cells undergo ______ ______ to improve their antibody affinity which may inadvertently create new self-reactivity Options A. Clonal anergy B. Somatic hypermutation C. Positive selection D. Epitope spreading

Answer 18

B. Somatic hypermutation

Question 19

What factors help maintain peripheral tolerance in circulating T-lymphocytes Options A. Lack of HLA class II expression by normal tissue cells B. Inability of tissue cells to express co-stimulatory molecules C. High levels of TNF-alpha D. Suppression by Regulatory T cells Treg cells

Answer 19

A B D

Question 20

How does the body control a hypermutated B cell that acquires affinity for a self-antigen in the germinal center.

Answer 20

If a hypermutated self-reactive B cell encounters strong cross-linking of its B-cell receptor BCR by a self-antigen in the germinal center it is induced to undergo apoptosis to prevent its release as an auto-reactive cell.

Question 21

What is the key transcription factor marker for Regulatory T cells Tregs Options A. T-bet B. FOXP3 C. GATA3 D. NF-kappaB

Answer 21

B. FOXP3

Question 22

______ Tregs develop in the thymus while ______ Tregs arise in the periphery from naive CD4+ T cells.

Answer 22

Natural nTregs; Induced iTregs

Question 23

Which of the following are mechanisms used by Tregs to suppress immune responses Options A. Secretion of IL-10 and TGF-beta B. Expression of CTLA-4 to inhibit co-stimulation C. Secretion of TNF-alpha D. Metabolic disruption or direct killing of effector cells

Answer 23

A B D

Question 24

Describe the clinical relevance of Treg dysfunction.

Answer 24

Dysfunction of Regulatory T cells leads to a loss of tolerance and the development of autoimmunity. Conversely therapies involving Tregs are being investigated for treating autoimmune diseases and improving transplant tolerance.

Question 25

Which monogenic autoimmune disease is caused by a defect in the FOXP3 gene Options A. APS-1 B. ALPS C. IPEX D. Infantile enterocolitis

Answer 25

C. IPEX

Question 26

Mutations in the AIRE gene lead to ______ ______ syndrome APS-1 due to defective negative selection in the thymus.

Answer 26

autoimmune polyglandular

Question 27

Which genes are associated with Systemic Lupus Erythematosus SLE according to the genetically complex table Options A. C2 and C4 complement proteins B. FCGRIIB Fc-gamma receptor C. NOD2 D. CTLA4

Answer 27

A B

Question 28

Defective apoptosis of self-reactive T and B cells in the periphery is the mechanism for which Mendelian disease Options A. IPEX B. ALPS Autoimmune lymphoproliferative syndrome C. APS-1 D. RA

Answer 28

B. ALPS Autoimmune lymphoproliferative syndrome

Question 29

The theoretical possibility that sequence similarities between foreign and self-peptides result in cross-activation of autoreactive cells is called ______ ______.

Answer 29

molecular mimicry

Question 30

Which environmental factors are listed as potential predisposing triggers for autoimmunity Options A. UV radiation B. Vitamin D deficiency C. Chemicals such as smoking and pesticides D. Drug-induced reactions

Answer 30

A B C D

Question 31

How does UV radiation contribute to the initiation of autoimmune diseases like SLE.

Answer 31

UV radiation induces apoptosis in many cells. This increases the burden of nuclear antigens like DNA and chromatin that are not normally exposed to the immune system providing targets for autoantibodies.

Question 32

Which virus is associated with Rheumatoid Arthritis RA Autoimmune Hepatitis AIH and Thyroid disease Options A. Parvovirus B. Epstein-Barr virus EBV C. Coxsackie virus D. HCV

Answer 32

B. Epstein-Barr virus EBV

Question 33

The bacterium ______ ______ is strongly linked to the development of Rheumatoid Arthritis RA.

Answer 33

Porphyromonas gingivalis or Campylobacter jejuni

Question 34

Which of the following bacteria are listed in the sources as triggers for Rheumatoid Arthritis Options A. Streptococcus pyogenes B. Chlamydia C. Borrelia burgdorferi D. Salmonella typhi

Answer 34

A B C D

Question 35

Describe the propagation phase of autoimmune disease progression.

Answer 35

During propagation physical symptoms become evident. This phase is characterized by a cytokine storm elevated inflammatory markers like ESR and CRP and a significant imbalance between T effector cells and Tregs. Stress or other illnesses can exacerbate this phase.

Question 36

What is the mechanism of Graves Disease Options A. Autoreactive T cells against joint synovium B. Autoantibodies against the thyroid-stimulating-hormone TSH receptor C. Destruction of myelin sheaths by T cells D. Destruction of pancreatic islet beta cells

Answer 36

B. Autoantibodies against the thyroid-stimulating-hormone TSH receptor

Question 37

Hashimoto’s thyroiditis results in ______ because of the destruction of thyroid tissue leading to underproduction of thyroid hormones.

Answer 37

hypothyroidism

Question 38

Which autoimmune diseases primarily involve autoreactive T cells as the main mechanism of tissue destruction Options A. Type 1 Diabetes B. Multiple Sclerosis C. Graves Disease D. Rheumatoid Arthritis

Answer 38

A B D

Question 39

Systemic Lupus Erythematosus SLE involves autoantibodies and T cells against which antigens Options A. Thyroid hormones B. Joint synovium C. DNA chromatin and ribonucleoprotein D. Myelin

Answer 39

C. DNA chromatin and ribonucleoprotein

Question 40

Sjögren’s syndrome is characterized by lymphocyte infiltration of exocrine glands leading most commonly to ______ ______ and or ______.

Answer 40

dry eyes; mouth

Question 41

Why is it often difficult to pinpoint the exact factors responsible for the initiation of an autoimmune disease.

Answer 41

This is because patients usually only develop physical symptoms long after the abnormal immune reaction has already begun subclinically making the original triggering event hard to identify in retrospect.

Question 42

What is a major limitation of most current autoimmune therapies Options A. They are too expensive for most patients B. They target the terminal phase of inflammation rather than the cause of the disease C. They only work in males D. They require monthly blood transfusions

Answer 42

B. They target the terminal phase of inflammation rather than the cause of the disease

Question 43

Continuous lifelong therapy for autoimmunity can result in an increase in ______ and ______ complications.

Answer 43

malignant; infectious

Question 44

Which of the following are listed as treatment options for autoimmune diseases Options A. Steroids for general inflammation suppression B. Cytokine antagonists like TNF-alpha blockers C. Monoclonal antibody therapy D. Antibiotics to cure the underlying cause

Answer 44

A B C

Question 45

Summarize the step-wise approach to treatment for autoimmune diseases.

Answer 45

Treatment is a step-wise process that should be reassessed at every stage. It generally moves from general inflammation suppression steroids to more targeted therapies like cytokine antagonists or monoclonal antibodies often requiring lifelong management.