Question

4. Multiple sclerosis (MS) is an autoimmune disease in which self-reactive T cells and antibodies attack neurological tissues in the brain. This disease is associated with HLA-DR2 and is ten times more frequent in women than in men.

1. What type of molecule does the HLA-DR2 gene code for?

2. What does it mean that MS is associated with HLA-DR2? Specifically, is this a causal relationship?

3. What does it mean that MS is more frequent in women than in men?

d. In people that develop MS, T cells specific for myelin basic protein (MBP)-derived peptides are present at high levels in the blood and cerebrospinal fluid (CSF). From where do these MBP specific T cells orginate in the body (which organ)? Would you expect that people that do NOT have Multiple Sclerosis have these MBP-specific T cells in their body? Why or why not?

e. Some theories about the onset of MS disease is that it could arise from molecular mimicry following a viral infection of the central nervous system. Explain what this theory means and how it would lead to MS disease.

f. Evidence indicates that Th1 and Th17 cells contribute to MS disease. Based on what you know about how these effector CD4+ T cells work, describe how they contribute to the disease? Specifically, what are the components of the immune response that cause the disease pathology?

Answer 1

A) HLA-DR2 gene is a part of family of Human Leukocyte antigen complex , and it helps the immune system to distinguish b/w the body’s own cells to the proteins made by the foreign antigens The protein produced from the HLA-DRB1 gene, called the beta chain, attaches (binds) to another protein called the alpha chain, which is produced from the HLA –DR gene. Together, they form a functional protein complex called the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.

B) What does it mean that MS is associated with HLA-DR2? Specifically, is this a causal relationship

MS is associated with the this MHC haplotype due to the particular ability of the MHC molecule to bind and present the autoantigen to the T cell , As it linked to be more with the class II genes , which shows the key role in the T-cell autoimmunity .

C) What does it mean that MS is more frequent in women than in men?

The exact reason isn’t identified yet but some research paper indicates that it causes due to the hormones, particularly the estrogen has a variety of effect on the immune system.

D). As normally the T cells originated from the bone marrow and further they got their specific role in the thymus where they undergoes the education where they knows about their self cells and nonself-cells. From here onwards, in course of this the MBP specific T cells originated. In the Thymus they know about this particular cells and they after crossing the Blood Brain Barrier   do their respective function.

the normal people have MBP is responsible for adhesion of the cytosolic surfaces of multilayered compact myelin .The MBP specific T cells originated due to the autoimmune response generated the T-cells start affecting the particular MBP cells due to the wrongly taken as the foreign cells .

E) Some theories about the onset of MS disease is that it could arise from molecular mimicry following a viral infection of the central nervous system. Explain what this theory means and how it would lead to MS disease?

  Molecular mimicry occurs when peptides from pathogens share sequence or structural similarities with self-antigens.. Molecular mimicry may be mediated through human leukocyte antigen class I- and class II-restricted T cells and antibodies, which may explain the diversity in phenotype.

How molecular mimicry lead to the MS disease-?

There is activation of the MBP reactive T cells mainly the Th1 cells by the HSV or say super-antigen (taken as example ) . They binds to the VCAM and its ligand VLA-4. so they crosses the BBB further then they reactivate the T-cells in the CNS several factors like IL-2.IFN gamma ,and TNF alpha etc got upregulated so this causes the B cell-activation and antibody production that damage myelin. (taken from the research paper)

F) Evidence indicates that Th1 and Th17 cells contribute to MS disease. Based on what you know about how these effector CD4+ T cells work, describe how they contribute to the disease? Specifically, what are the components of the immune response that cause the disease pathology?

T helper type 1 (Th1) cells are a lineage of CD4+ effector T cell that promotes cell-mediated immune responses and is required for host defence against intracellular viral and bacterial pathogens Th-17 cells produce IL-17F and IL-17A that induce inflammatory responses.Th-17 cells are differentiated by TGF-beta in the context of IL-6 .Th17 lineage plays a pathogenic role in autoimmune disease and protective role in immuno-surveillance and activates Neutrophils. Therefore, links adaptive with innate immunity. Based upon their respective roles above it can be assume that the T cell populations can cause CNS inflammation and demyelinating lesions.