but what IS an antibody??
The adaptive immune system in mammals arose about 500 million years ago. A major evolutionary event was the emergence of the recombination-activating gene (RAG) when one type of enzyme gene mutated into another permitting the synthesis of an enzyme that can cut and paste DNA.
These genes and the enzymes they code for, called RAG (Recombinant Activating Genes) edit the VDJ genes by deleting or inverting segments of DNA within the genes. In this way, one gene can code for many many many different antibody proteins.
Acquired Immunity II: Antibody Response
(B cells produce antibodies and memory cells)
hormones exhibit cell receptor specificity
there are soo many examples of how immune response varies among animals. here's one: sharks have a high natural resistance to viruses even though their immune systems are relatively basic. Squalamine is a broad-spectrum steroidal antibiotic that is water soluble and produced in copious quantities by sharks. Squalamine fights bacteria and is also a fungide and kills pathogenic protozoa.
examples of hormonal control
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Innate Immunity:
cytokines
Sequence of Hormone Action:
1.hormone is synthesized, stored then secreted when release is triggered
2.hormone is transported via circulation to target cells
3.hormone is recognized by specific cells membrane receptors of target cells
4.hormone signal is relayed and amplified to the cell interior causing cell response
5.reactions of target cells are recognized by the original hormone-producing
cells leading to a reduction of hormone production in a negative feedback loop.
6. hormone is degraded
...while others are water soluble
T cell maturation
Acquired Immunity I: Cell Mediated Response
(cytotoxic T cells destroy pathogen)
Amine hormonesare synthesized from the amino acids tryptophan or tyrosine. Ex: melatonin is synthesized from tryptophan... when secreted by the pineal gland it helps regulate circadian rhythm. Tyrosine derivatives include thyroid hormones and
catecholamines such as epinephrine, norepinephrine, and dopamine. Epinephrine and norepinephrine are secreted by the adrenal medulla and play a role in the fight-or-flight response, whereas dopamine is secreted by the hypothalamus and inhibits the release of certain anterior pituitary hormones. Some amine hormones are polar while others are not.
1. Hypothalamus - Pituitary - Thyroid
2. Hypothalamus -Pituitary -Gonads
hormones are chemical messengers (ligands) which carry signals via the bloodstream to specific cells/tissues that exhibit receptors specific to the hormone. hormones work slowly, are long lasting, and influence growth, development, metabolism, reproduction and more. hormones are produced by
endocrine glands.
homeostatic mechanisms control hormone secretion
what is meant by autoimmunity?
Interleukin is a type of cytokine that can reset the
thermostat in the hypothalamus increasing body temperature. Monocytes release these and other cytokines in response to pathogenic infection, damage to tissues, or an antigen/antibody reaction.
Psoriasis:
T cells fail to recognize self and attack skin cells setting up an immune response. Inflammation occurs. This triggers an increase in cell division. Newly formed skin cells normally take about a month to reach the skin's surface via cell turnover but with psoriasis it takes only days resulting in thick patches of skin.
Hypothalamus ->
Pituitary ->
Growth Hormone
Pituitary -
stimulating hormone
TSH
acquired immunity I:
cell mediated response:
cytotoxic T cells identify and destroy infected cells displaying antigen on
MHC I complex
Innate Immunity:
inflammation
an example you will recognize with a negative feedback loop...
Growth Hormone
helper T cell
ooops...don't forget
synpatic signaling
some hormones are lipid
soluble...
Pituitary - ACTH
( adrenocorticotropic hormone
and it all comes back to homeostasis...
Adrenal Glands - cortisol
Target gland -
target hormone T3/T4
your spleen, thymus and nodes/nodules
Hypothalamus -
releasing hormone
TRH
Classes of Hormones
insulin
cytotoxic T cell
esialic acid mutation
Steroid Hormones
are hydrophobic so they can diffuse across the plasma membrane of a cell. Once inside, they bind to receptors in either the cytoplasm or nucleus, forming an activated receptor-hormone complex which moves into the nucleus and binds to the DNA. In this way it serves as a transcription factor, regulating gene expression. Examples of steroid hormones include estrogen, progesterone and testosterone.
compared to type 2
Feedback mechanisms:
a signal is sent from the hypothalamus to the pituitary gland in the form of a
"releasing hormone,"
which stimulates the pituitary to secrete a
"stimulating hormone"
into circulation. The stimulating hormone then signals the
target gland to secrete its hormone.
As the level of this hormone rises in the circulation, the hypothalamus and the pituitary gland shut down secretion of the releasing hormone and the stimulating hormone,
which in turn slows the secretion by the target gland.
Thyroid
Hormone
evolution of the
endocrine system
Ovary - Estrogen
cells of the immune system
Allergies
eRAG evolves
Peptide/Protein Hormones are
are hydrophylic so they cannot freely cross the plasma membrane requiring receptors on the surface of the cell which are typically coupled to internally anchored proteins such as G proteins. The hormone/receptor complex activates a series of intracellular molecules called second messengers which initiate cell activity, a process called signal transduction. Second messengers include cyclic AMP (cAMP), calcium ions (Ca2+), nitric oxide (NO) and protein kinases. Second messengers amplify the signal.
Peptide hormones consist of short chains of amino acids.
Protein hormones are longer polypeptides.
Peptide/Protein hormones include insulin, glucagon, leptin, ADH, oxytocin and GH.
we benefit from both
innate & adaptive immunity
Acquired Immunity
how do hormones function?
Our human genome has +/- 30,000 genes but it is able to generate
millions of different antibodies to attack millions of different antigens on the surfaces of millions of different pathogens.
HOW???
Our immune system generates this diversity of antibodies by shuffling, cutting and recombining a few hundred genes called VDJ genes. In this way, millions of permutations can be created. This is called
VDJ recombination. There are two proteins called RAG-1 & RAG-2 (RAG genes = Recombinant Activating Genes) that are responsible for editing the VDJ genes by deleting or inverting segments on DNA within the genes. This shuffling takes place inside B cells and T cells during their maturation.
Innate Immunity:
complement
Part 1: Immunity
G proteins...how do they work?
Diabetes: Type 1
vs
immunity, circulation
and your lymphatic system
Eczema:
Chronic inflammation is a huge component of eczema or atopic dermatitis. Inflammation associated with eczema is considered a type 2 immune response. There is a protein called Periostin that is present when both eczema and other allergic diseases (like asthma) are present and is used in the clinical diagnosis of other inflammatory skin diseases. This link >
explains new research in eczema autoimmunity.
I Pathogens cause physiological reactions in all living organisms.
Invertebrates exhibit cell surface receptors which are able to differentiate self and bind to foreign antigens. Multicellular animals including sponges, worms, cnidarians, mollusks, crustaceans, insects, and echinoderms possess phagocytes with a macrophage-like function that can recognize pathogens including virus, bacteria, fungi and parasitic protozoans.
Receptor/ligand binding initiates a signal transduction cascade involving cytokines even in early invertebrates.
Innate immunity is also present in the form of antimicrobial molecules. An early vertebrate, the jawless agnatha fish, was the first to add an adaptive response. Our friend the hagfish
possess variable lymphocyte receptors while all higher vertebrates benefit from the major histocompatibility complex, T-cell receptors, and B-cell receptors/immunoglobulins.
3. Hypothalamus - Pituitary - Adrenal glands
Hypothalamus -GnRH
(gonadotropin Releasing Hormone)
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cytokines
what's a hormone?
Cushing's Disease: excess Cortisol
Innate Immunity:
Eeevolution of the immune response
Hormone levels are controlled by one of three
homeostatic mechanisms:
1. Negative feedback by stimulated hormone:
When one hormone stimulates the production of a second,
the second suppresses the production of the first.
Ex.: Follicle stimulating hormone FSH stimulates the release of estrogens from the ovary.
A high level of estrogen, in turn, suppresses the further production of FSH.
2. Antagonistic pair of hormones:
Ex. Insulin causes the level of blood sugar (glucose) to drop when it is too high.
Glucagon causes it to rise when it is too low.
3. Negative Feedback by controlled molecule:
Hormone secretion is increased (or decreased) by the concentration of the controlled molecule.
Ex.: As Ca2+ in the blood rises, it suppresses the production of the Parathyroid hormone (PTH). Low levels of Ca2+ stimulate PTH release.
cortisol =
acquired immunity II:
humoral/antibody response:
antibody production involving B cells identifying foreign antigens activated by helper T cells identifying APC's displaying MHC II complexes withy the same foreign antigen
how/when did hormones evolve?
Hypothalamus -CRH
(Corticotrophin-releasing hormone)
and then there's SCID:
Severe Combined
Immunodeficiency
Part I: evolution of immunity (and lymphatics)
Part 2: evolution of the endocrine system
Diabetes
An Endocrine Disease
occurs when a gland produces too much or too little of an endocrine hormone leading to a hormone imbalance. Causes may be the development of nodules or tumors which may affect hormone levels.
humans suffer from many diseases such as mumps, typhus and cholera that do not cause disease in other mammals or other apes. The pathogens that cause these diseases use sugar molecules called sialic acids to gain access to our cells. Sialic acids cover the cell membrane of every cell in our bodies. Our sialic acids are structurally different from those found on the cells of other species of apes. alterations in our immune cells occurred in our hominid ancestors > 600,000 years ago. our unique sialic acids promote cell-cell interactions during our adaptive immune response.
Pituitary - FSH
(Follicle Stimulating Hormone)
Innate Immunity:
fever
Chemical Signaling