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Asker Anonymous Asks:
i know this is a super broad topic - but can you post something about the biology of stress? i find that so fascinating. thank you so much! love this blog!
eosinophillia eosinophillia Said:

Yes of course! I’m sorry I have not been very active lately, but I plan on constantly posting again this week :)

Antibodies And Their Role In the Immune Response

The immune response consists of two complementary systems, the humoral and cellular immune systems. The humoral immune system is focused on bacterial infections and extracellular viruses (those found in body fluids), but can also respond to individual foreign proteins. At the heart of the humoral immune response are soluble globular proteins known as antibodies or immunoglobulins, often abbreviated Ig. Immunoglobulin bind foreign bacteria, viruses, and other large molecules and target them for destruction. They are composed of 20% blood protein, and are produced by B lymphocytes, or plasma B cells, named because they complete their development in the Bone marrow.

Each antibody of the immune system specifically binds to a particular chemical structure which distinguishes it from all others. Humans are capable of producing billions of types of antibodies with unique binding specificities. Therefore, any chemical structure on the surface of a virus or invading cell will most likely be recognized and bound by one or more antibodies. This diversity is derived from genetic recombination mechanisms for a set of immunoglobulin gene segments. Any molecule or pathogen capable of eliciting an immune response is called an antigen. Antigens include viruses, bacterial cell walls, or individual proteins or macromolecules. Antigens are of varying complexity, and can be bound by several different antibodies. An individual antibody binds only a particular molecular structure within the antigen, called its antigenic determinant, or epitope

Immunoglobulin G, or IgG is the major antibody class and one of the most abundant proteins in the blood serum. It is composed of four polypeptide chains: two heavy chains and two light chains, linked by noncovalent and disulfide bonds (yellow bonds above). The heavy chains of an IgG molecule interact at one end, then branch to interact separately with the light chains, forming a Y-shaped molecule. At the “hinges” separating the base of an IgG molecule from its branches, the immunoglobulin can be cleaved with proteases. Cleavage with the protease papain liberates the basal fragment, called Fc because it usually crystallizes readily, and the two branches, called Fab, the antigen binding fragmentEach branch contains a single antigen-binding site. IgG is the major antibody in secondary immune responses, which are initiated by a class of B cells called memory B cells. As part of ongoing immunity to antigens already encountered and dealt with, IgG is the most abundant immunoglobulin in the blood.

IgG is one of five classes of immunoglobulins found in vertebrates. Each class has a characteristic type of heavy chain, denoted by the greek letters alpha, delta, epsilon, gamma, and mu for IgA, IgD, IgE, IgG, and IgM, respectively. 

  • IgG makes up 75% of plasma antibody in adults because they are produced in secondary immune responses. Maternal IgG crosses the placental membrane and gives infants immunity in the first few months of life. IgG also activates the complement system.
  • IgA antibodies are found in external secretions, such as saliva, tears, intestinal and bronchial mucus, and breast milk, where they disable pathogens before they reach the internal environment. 
  • **IgE is associated with allergic responses. When mast cell receptors bind with IgE and antigen, the mast cells degranulate and release chemical mediators, such as histamine. 
  • IgM antibodies are associated with primary immune responses and with the antibodies that react to blood group antigens. IgM also activates the complement system.
  • IgD antibody proteins appear on the surface of B lymphocytes along with IgM, but the physiological role of IgD is unclear. 

Immunoglobulins have several immune mechanisms (denoted by numbers above): 

Making antigens more visible to the immune system:

  1. (2) Acting as opsonins (opsonization) - Soluble antibodies coat antigens to facilitate recognition and phagocytosis by immune cells such as leukocytes (white blood cells).
  2. (3) Agglutination (clumping of antigens) - binding of pathogens causing their immobilization and clumping them together to enhance phagocytosis
  3. (3) Inactivating bacterial toxins - binding and neutralizing toxins produced by bacteria

Enhance inflammation:

  1. (6) Activating the complement system - Antigen-bound antibodies use the Fc end of the antibody molecule to activate complement, part of the innate immune system that involves cleavage of small proteins which release cytokines that amplify the response and activation of cell killing membrane attack complex.
  2. (5) Activating mast cells - Mast cells have IgE antibodies attached to their surface. When antigens or complement proteins bind to IgE, the mast cells degranulate, releasing chemicals that mediate the inflammatory response. Mast cells contain histamine and heparin, and are involved in allergic response. Antihistamines stabilize mast cells and prevent degranulation.

Activating immune cells:

  1. (1) Activating immune cells - Phagocytic and some cytotoxic cells have membrane receptors that attract the Fc region of antigen-bound antibodies. The presence of a single Fc receptor eliminates the need to have millions of different receptors to recognize different antigens. Instead, with one type of receptor the immune cells are activated by any antibody-bound antigen. If the immune cell is a phagocyte, Fc binding initiates phagocytosis (3). If the immune cell is cytotoxic (eosinophils and natural killer cells), Fc binding initiates respones that kill the antibody-bound cell (4). In the case of B lymphocytes, the antibodies are already an integral part of the lymphocyte (1). In this case, antigen binding plus cytokines from other immune cells activate the cell to produce memory and plasma B cells. 

**IgE plays an important role in the allergic response, interacting with basophils (phagocytic white blood cells) in the blood and with histamine-secreting cells called mast cells, which are widely distributed in tissues. This antibody binds through its Fc region, to special Fc receptors on the basophils or mast cells. In this form, IgE serves as a receptor for antigen. If antigen is bound, the cells are induced to secrete histamine and other biologically active amines that cause dilation and increased permeability of blood vessels. These effects on the blood vessels facilitate the movement of immune system ells and proteins to sites of inflammation. They also produce the symptoms associated with allergies. Pollen or other allergens are recognized as foreign, triggering an immune response normally reserved for pathogens. Specifically, IgE plays a large role in Type 1 hypersensitivity, which involves several diseases such as allergic asthma, allergic rhinitis (inflammation of nasal passages), food allergies, anaphylaxis, and eosiniophilia. 

References:

Lehninger’s Principles of BIochemistry, 5th edition, David Nelson, Michael Cox

Human Physiology, An Integrated Approach, 5th edition, Dee Silverthorn

what is responsible for the heavy feeling in ones eyes when one hasn't gotten enough sleep?
eosinophillia eosinophillia Said:

The most obvious answer would be that your eyelids/eye muscles are still fatigued after working so hard for such a long time. Also, the accumulation of waste products and metabolites, such as lactic acid or phosphates can build up in your eyes, causing them to feel heavy. Lactic acid is known to build up in muscles because the conversion of pyruvate to lactate occurs at a much faster rate than removal of lactate and other metabolites.

Additionally, as your body prepares to go to sleep, your nervous system releases several sleep-inducing factors: peptides, cytokines and neurotransmitters. These play a role in enhancing the immune response, as well as conserving energy, allowing the body to repair itself, and processing memories. The hypothalamus and the parasympathetic nervous system take over this role in sleep onset, which leads to contraction of the various muscles in your eyes, which shuts them involuntarily. During the NREM (non rapid eye movement) cycles of sleep, your body shuts off neurotransmitters and receptors and allows them to rest. Sleep deprivation or waking up during this period means they are probably still partially activated, meaning the effects of sleep onset factors may still be occurring, i.e. eye muscle contractions.

Your sleep cycles are also important. Your NREM cycle is divided into 3 stages. The 3rd stage is known as “deep sleep”. Most people who wake up during this stage tend to be much less awake and tired. If one wakes up in the first 2 stages, they usually feel much more awake, but the effects of sleep deprivation will be felt later in the day. This is why short naps are effective in temporarily resting the body. 

I’m not sure if I answered your question, but these are some things to keep in mind!

Rhodopsin’s role in Visual Signalling and Transduction

In the human eye, light enters through the pupil and is focused on a highly structured collection of light-sensitive neurons in the retina. These specialized neurons are of two types: rod cells, which sense lesser intensities of light (dim light) but cannot discriminate colors, and cone cells, which sense brighter light and are responsible for color vision. Both of these cells synapse with retinal bipolar cells, which transmit electrical signals to ganglion neurons, which integrate the output of many rods and cones and send the resulting signal through the optic nerve to the visual cortex (on the occipital lobe) of the brain.

Delving deeper, on the outer segments of rod cells are many thousands of molecules of rhodopsin. Rhodopsin is an integral protein with seven membrane spanning α helices. This is characteristic of G-protein coupled receptors„ which are responsible for several signal transduction pathways including autocrine, paracrine, and endocrine processes. Rhodopsin in rod cells transduce dim light, while cone cells contain photopsin, which generate color vision.

Rhodopsin consists of a protein moiety, opsin, and a reversibly bound chromophore, retinal. The chromophore (light-absorbing pigment) 11-cis retinal is covalently attached to opsin, the protein component of rhodopsin, through a Schiff base to a Lys residue:

When a photon is absorbed by the retinal component of rhodopsin, the energy causes a photochemical change, causing 11-cis retinal to be “photoisomerized” to all-trans retinal (The R group of retinal in the above image can be seen attached to the carbon-nitrogen double bond below):

This isomerization induces a conformational change in opsin, converting it to metarhodopsin II, which leads to activation of the G protein transducin. GTP bound transducin initiates phosphodiesterase, which hydrolyzes cGMP to GMP. This second messenger cascade results in a decrease of cGMP concentration, leading to closure of cation channels (usually sodium) on the outer membrane. This ultimately leads to hyperpolarization of photoreceptor cells, which controls their rate of neurotransmitter release.

*The precursor for retinal, is retinol (more specifically, all-trans retinol, or Vitamin A). Vitamin A is produced from β-carotene, which is found in carrots, sweet potatoes, and other orange/yellow vegetables. Vitamin A cannot be produced by humans, which is why it is essential in your diet. Dietary deficiency in Vitamin A leads to night blindness, which makes it impossible to see in low light levels. 

Sources and other readings:

Mechanisms of Opsin Activation

Lehninger, Principles of Biochemistry, Fifth Edition

Rhodopsin and the Eye

Asker toluicacid Asks:
What is that in your picture?
eosinophillia eosinophillia Said:

HIV infecting a CD4 T lymphocyte :)

Asker bichemistry Asks:
A few posts back, you said that when ingested chlorophyll cleanses the body. Could you elaborate on this? Cleanses the body of what? Oxidants? Thanks!
eosinophillia eosinophillia Said:

I apologize for the late reply. As mentioned in the post, the heme group (porphyrin ring) of hemoglobin and the chlorin ring of chlorophyll are almost exactly identical with the exception of the central atom. As a result, when chlorophyll is ingested, it complements the role of hemoglobin by increasing red blood cell count, meaning more oxygen can be carried through the body, and more waste products such as urea and lactic acid can be removed from the body. Additionally, chlorophyll rids the body of heavy metals by binding to them, and also stimulates bowel movements, which cleanses the colon. 

Mitochondrial DNA Mutations in Human Disease

The mitochondria is responsible for producing the energy of the cell and regulating cellular metabolism. Although most of the cell’s DNA is in the nucleus, the mitochondria is unique in being the only other organelle in the cell with an independent genome. As a result, a significant number of human diseases have been attributed to mutations in mitochondrial genes that reduce the cell’s capacity to make ATP. Some cells and tissues, specifically high energy use such as neurons, skeletal and cardiac muscle cells, and beta cells of the pancreas, are less tolerant to lowered ATP production and are therefore more affected by mutations in mitochondrial proteins. 

The inheritance of genetically encoded traits for mitochondria is not the same as that of single gene/Mendelian inheritance. Autosomal inheritance comes from a gene located on one of the 22 pairs of autosomes (non-sex determining chromosomes) and X-linked inheritance comes from a gene located on the X-chromosome (sex determining). Mitochondrial inheritance is transmitted only through the female egg, hence only females can transmit the trait (top left: oocyte (egg cell) division and how it transmits mitochondrial traits; top right: basic mitochondrial inheritance through the mother).

A group of genetic diseases known as mitochondrial encephalomyopathies affect primarily the brain and skeletal muscle. These diseases are therefore inherited from the mother, since the embryo derives all its mitochondria from the egg.

 Leber’s hereditary optic neuropathy (LHON, bottom left) affects the central nervous system, including the optic nerves, causing bilateral loss of vision in early adulthood. A single base change in the mitochondrial gene ND4 changes an Arginine residue to a Histidine residue, resulting in a mitochondria partially defective in electron transfer and therefore leading to insufficient ATP production. 

Myoclonic epilepsy and ragged-red fiber disease (MERRF syndrome, bottom right) is caused by a mutation in the mitochondrial gene that encodes a tRNA specific for the amino acid Lysine. This disease, characterized by uncontrollable muscular jerking, apparently results from defective production of several of the proteins that require mitochondrial tRNAs for their synthesis. Skeletal muscle fibers of individuals affected by MERRF have abnormally shaped mitochondria. Other mutations in mitochondrial genes are believed to be responsible for the progressive muscular weakness that characterizes mitochondrial myopathy and for enlargement and deterioration of the heart muscle in hypertrophic cardiomyopathy. 

Lehninger’s Principles of Biochemistry, 5th edition, Section 19.5

Figure 9-15: The cerebral cortex is specialized into functional areas (Human Physiology: An Integrated Approach, 5th Edition)

The cerebral cortex makes up the outer covering of gray matter over the hemispheres of the cerebrum. It is divided into four pairs of lobes, each responsible for specific functions:

  • Frontal Lobe: controls voluntary movement, complex reasoning skills, problem solving, and conscious thought
  • Parietal Lobes: general sensations such as touch, temperature, vibration, as well as taste. Some parts of the lobe are involved with visual perception.
  • Temporal Lobes: auditory (hearing) and olfactory (smelling) sensations and short-term memory. Processing complex stimuli such as faces and scenes
  • Occipital Lobes: contains the primary visual cortex, visual processing center of the brain

Specialized metabolic functions of mammalian tissues

Lehninger’s Principles of Biochemistry, 5th edition