Question

Which of the following statements is false? a. In MS plaques perivenular infiltrates contain mainly mononuclear and lymphocytic cells, including CD8+ T-celk, CD4+ T-cells, macrophages, and B-cells. b. In the EAE model, the primary infiltrating cell is the \(\mathrm{CD} 8+\) T-cell. c. Effective MS treatments generally target T-cell responses d. In both EAE and MS, disease susceptibility is influenced by genes that control presentation of antigens to T-cells.

Short answer

a. In MS plaques perivenular infiltrates contain mainly mononuclear and lymphocytic cells, including CD8+ T-cells, CD4+ T-cells, macrophages, and B-cells. b. In the EAE model, the primary infiltrating cell is the CD8+ T-cell. c. Effective MS treatments generally target T-cell responses. d. In both EAE and MS, disease susceptibility is influenced by genes that control presentation of antigens to T-cells. Answer: b. In the EAE model, the primary infiltrating cell is the CD8+ T-cell.

Step-by-step solution

Statement A

In MS plaques perivenular infiltrates contain mainly mononuclear and lymphocytic cells, including CD8+ T-cells, CD4+ T-cells, macrophages, and B-cells. This statement is true, as it correctly describes the composition of inflammatory infiltrates found around inflamed blood vessels (perivenular infiltrates) in multiple sclerosis lesions. These immune cells contribute to the disease's pathogenesis and are involved in the damage to the central nervous system observed in MS patients.

Statement B

In the EAE model, the primary infiltrating cell is the CD8+ T-cell. This statement is false. EAE, as an animal model for studying multiple sclerosis, is predominantly driven by CD4+ T-cells, particularly Th1 and Th17 cells. These cells are responsible for inducing inflammation and, eventually, demyelination in the central nervous system. While CD8+ T-cells can also contribute to the disease process, they are not the primary infiltrating cells in the EAE model.

Statement C

Effective MS treatments generally target T-cell responses. This statement is true. Many multiple sclerosis treatments aim to reduce T-cell responses, as these cells play a significant role in the disease's inflammatory process and demyelination. By targeting T-cell responses, these treatments can help alleviate the symptoms, reduce relapses and slow down disease progression.

Statement D

In both EAE and MS, disease susceptibility is influenced by genes that control presentation of antigens to T-cells. This statement is true. Research has shown that genetic factors that influence antigen presentation to T-cells, such as HLA (human leukocyte antigen) genes, are associated with an increased risk of developing multiple sclerosis. This genetic susceptibility is also observed in the EAE model, where certain MHC (major histocompatibility complex) molecules can determine an individual's vulnerability to EAE induction. In conclusion, the false statement is: "b. In the EAE model, the primary infiltrating cell is the CD8+ T-cell."

Key concepts

Immune Response

The immune response plays a crucial role in the progression of multiple sclerosis (MS), a chronic autoimmune disorder. In MS, the body's immune system mistakenly attacks the central nervous system (CNS), leading to inflammation and damage. Key players in this response include various immune cells such as T-cells, macrophages, and B-cells.

• These immune cells infiltrate the brain and spinal cord, causing lesions characterized by inflammation and myelin damage.
• The lesions primarily occur in areas called MS plaques, where the immune responses are abnormally active.

The excessive immune response in MS can lead to the destruction of oligodendrocytes, the cells responsible for producing the myelin sheath that insulates nerve fibers. This destruction disrupts neural communication, resulting in the varied symptoms associated with MS.

T-cells

T-cells are a type of lymphocyte crucial to the immune system, playing a significant role in multiple sclerosis. They help coordinate immune responses by directly attacking infected cells and assisting other immune cells.

• In MS, CD4+ T-cells, especially Th1 and Th17 subsets, are pivotal in initiating and sustaining inflammation in the CNS.
• CD8+ T-cells can also participate, although they are not the primary cells in some models of MS, like the EAE model.

These T-cells recognize antigens presented by antigen-presenting cells through Major Histocompatibility Complex (MHC) molecules, leading to their activation. This activation results in the production of cytokines and other inflammatory mediators that exacerbate the disease process.

Effective MS therapies often target these T-cell responses to reduce disease activity and progression.

Genetic Susceptibility

Genetic susceptibility is a significant factor in the development of multiple sclerosis, affecting how individuals respond to environmental triggers. Certain genetic markers can predispose individuals to MS, meaning some people are genetically more likely to develop the disease.

• The human leukocyte antigen (HLA) region on chromosome 6 is strongly associated with MS susceptibility.
• Genes in this region are involved in antigen presentation, influencing how immune cells recognize and respond to potential threats.

These genetic influences are mirrored in the EAE model, an experimental framework used to study MS. In this model, the presence of specific MHC molecules can determine the likelihood of developing EAE, reflecting the genetic complexity in human MS.

EAE Model

The experimental autoimmune encephalomyelitis (EAE) model is an invaluable tool for studying multiple sclerosis. It is an animal model, primarily using mice, that mimics many of the pathological features of MS, such as demyelination and inflammation.

• EAE is induced by immunizing animals with myelin proteins, leading to an autoimmune response.
• Unlike MS, where CD8+ T-cells may play a significant role, in EAE, CD4+ T-cells are the main drivers of the disease process.

EAE helps researchers understand the underlying mechanisms of MS and test potential treatments before they proceed to human trials. Insights gained from EAE have greatly contributed to the development of therapies aimed at modulating immune responses in people with MS.