What Factors Affect Antibody Production?

In an effort to reduce the spread and severity of COVID-19, many researchers around the world have investigated what antibodies this disease produces, whether the antibodies have long-term protective effects and how this information can be used to promote the rapid development of a vaccine.

Unfortunately, immune responses differ between every single human being; therefore, it is crucial to understand what factors determine how antibodies are produced to fully evaluate the potential of future COVID-19 treatments.

Natural antibodies are considered to be the first line of defense that a newborn organism has against potential pathogens. As compared to adaptive antibodies, which are specific to certain antigens, natural antibodies arise in germ-free conditions.

While natural antibodies exist in most vertebrates, the common natural antibodies produced in humans include immunoglobulin M (IgM), IgA, including its isotypes IgA1 and IgA2, as well as IgG and its isotypes including IgG1, IgG2, IgG3, and IgG4.

Natural antibodies are most commonly produced by the B1 lymphocytes and marginal zone B cells while humans are still in the fetal and post-fetal period. Some of the most notable properties of natural antibodies include polyreactivity, high avidity levels, autoreactivity, and moderate anti-microbial affinity.

Although natural antibodies constitute about 1% of the immunoglobulins present in the blood, with their numbers decreasing as humans age, they serve important roles in the prevention of various illnesses including autoimmune diseases, atherosclerotic plaque formation, inflammation, and even certain cancers.

If an antigen is presented to the innate immune system and the natural antibodies are unable to control the infection, the adaptive immune response is activated. There are two types of adaptive immune responses, which include the cell-mediated immune response and the humoral immune response.

Whereas the cell-mediated immune response is achieved by the action of T cells, the humoral immune response instead dependents upon the activity of both B cells and adaptive antibodies.

As compared to natural antibodies that are produced before exposure to foreign pathogens, adaptive antibodies are only produced after an antigen binds to the B-cell receptor (BCR) of B2 lymphocytes. The binding of the antigen to a B cell initiates the secretion of specific cytokines that cause rapid proliferation of the B cells.

As the B cells continue to reproduce, antibodies with the same antigen recognition pattern originally found on the BCR will be secreted. Note that the antigens that initiate the adaptive immune response can be produced following direct exposure to pathogens or following vaccine administration.

2. Detecting Brain Disease Using the Eye. By Susha Cheriyedath, M.Sc.

The human eye shares several vascular and neural similarities to the brain, and hence, our eyes have been found to offer a direct window to brain pathology. The unique characteristics of our eyes allow them to be a relatively affordable biomarker for Alzheimer's disease (AD) and other illnesses of the brain.

Currently, the diagnosis of AD is only possible after patients start showing early cognitive loss. A formal diagnosis is made using cognitive or mental state examinations, but the diagnosis can only be confirmed after examining the brain post mortem.

Well-established biomarkers for AD presently used include Aβ-42, T-tau, and p-tau found in the cerebrospinal fluid, and fluorodeoxyglucose and Pittsburg Compound B found in the brain. Although these biomarkers are crucial for AD monitoring, the widespread implementation of these biomarkers is still a challenge.

Visual biomarkers for AD

Alzheimer's patients usually report visual symptoms, and this encouraged scientists to look for potential ocular biomarkers for AD. Studies showed that certain visual symptoms could be an indication of dementia onset as well as the development of senile plaques in the visual regions in the brain.

As more and more details about the sequence of events, as well as the neurodegenerative changes in AD, are discovered, structural retinal biomarkers were found to have the potential to help in the early diagnosis of AD. Commonly reported vascular issues in AD are a blood-brain-barrier compromise, impaired Aβ clearance, vasoconstriction, reduced blood vessel density, and blood flow.

Direct visualization of the hallmarks of AD in the retina can be the most promising AD biomarker because of its specificity for AD. However, ongoing work is necessary to verify that Aβ plaques are present in retinal tissues and that these retinal deposits are predictive of cerebral deposits. In addition, VVAD, a visual variant of AD, has been found to affect relatively younger people. VVAD patients present with visual symptoms in their 50s or 60s and eventually follow the course of cognitive decline typically seen in patients with AD.

Non-retinal biomarkers for AD include pupillary reactions such as pupil size and pupillary response to light. Eye movements also play a crucial role because AD patients have trouble with reading due to suboptimal eye movements said to be linked to memory. AD sufferers have been shown to present with higher latency during voluntary eye movements, and show decreased eye movement speed. They may also fail to fixate on or follow a moving target.

Apart from being crucial and early indicators of brain illness, these visual changes are easy to examine since the eye is very accessible, and retinal imaging is a simple procedure, all of which make ocular biomarkers very attractive.

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