Determination of the effector T cell response

T_h1/T_h2 Model for helper T cells. An antigen is ingested and processed by an APC. It presents fragments from it to T cells. The upper, T_h0, is a T helper cell. The fragment is presented to it by MHC2.^[1] IFN-γ, interferon γ; TGF-β, transforming growth factor β; mø, macrophage; IL-2, interleukin 2; IL-4, interleukin 4

	Type 1/ Th1	Type 2/ Th2
Main partner cell type	Macrophage	B-cell
Cytokines produced	interferon-γ and tumor necrosis factor-beta. (Interleukin-2 was classically associated with Th1 cells, but this association may be misleading; IL-2 is produced by all helper T cells early in their activation.)	interleukin-4, interleukin-5, interleukin-6, interleukin-10, interleukin-13
Immune stimulation promoted	Cellular immune system. Maximizes the killing efficacy of the macrophages and the proliferation of cytotoxic CD8+ T cells. Also produces opsonizing antibodies	Humoral immune system. Stimulates B-cells into proliferation, to induce B-cell antibody class switching, and to increase neutralizing antibody production.
Other functions	The Type 1 cytokine IFN-γ increases the production of interleukin-12 by dendritic cells and macrophages, and via positive feedback, IL-12 stimulates the production of IFN-γ in helper T cells, thereby promoting the Th1 profile. IFN-gamma also inhibits the production of cytokines such as interleukin-4, an important cytokine associated with the Type 2 response, and thus it also acts to preserve its own response.	The Type 2 response promotes its own profile using two different cytokines. Interleukin-4 acts on helper T cells to promote the production of Th2 cytokines (including itself; it is auto-regulatory), while interleukin-10 (IL-10) inhibits a variety of cytokines including interleukin-2 and IFN-γ in helper T cells and IL-12 in dendritic cells and macrophages. The combined action of these two cytokines suggests that once the T cell has decided to produce these cytokines, that decision is preserved (and also encourages other T cells to do the same).

CD4

CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells.
Note:Regulatory T cells (T_reg, sometimes known as suppressor T cells)
Function
CD4 is a co-receptor that assists the T cell receptor (TCR) to activate its T cell following an interaction with an antigen-presenting cell. Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II molecules on the surface of the antigen-presenting cell using its extracellular domain

Medical Robotics Bioports to the Human Body

http://www.youtube.com/watch?v=7RKnr6XXPps&feature=channel

IMRI & Positron Emission Tomography: A New Tool for Biomedical Imaging?

http://www.youtube.com/watch?v=jdBvPkJv1YM&feature=related

Phosphodiesterase

PDE substrate specificities by enzyme family. Both means it hydrolyzes both cAMP and cGMP.

Classification and nomenclature

The PDE superfamily of enzymes is classified into 11 families, namely PDE1-PDE11, in mammals. The classification is based on:

• amino acid sequences
• substrate specificities
• regulatory properties
• pharmacological properties
• tissue distribution.

Clinical significance
phosphodiesterase enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. ^[8]
Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their degradation by PDE

http://en.wikipedia.org/wiki/Phosphodiesterase#Clinical_significance

PCR

The polymerase chain reaction (PCR) is a scientific technique in molecular biology to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence
Developed in 1983 by Kary Mullis,^[1] PCR is now a common and often indispensable technique used in medical and biological research labs for a variety of applications.^[2][3] These include DNA cloning for sequencing, DNA-based phylogeny, or functional analysis of genes; the diagnosis of hereditary diseases; the identification of genetic fingerprints (used in forensic sciences and paternity testing); and the detection and diagnosis of infectious diseases. In 1993, Mullis was awarded the Nobel Prize in Chemistry for his work on PCR.^[

Prostagladin

what is the relationship between NSAIDs and Prostagladin (eicosanoids) ?

http://en.wikipedia.org/wiki/Eicosanoid
NSAID is a drug that block COX1 enzyme that convert Arachidonic Acid to Prostaglandin.
Prostaglandin Function:
- PGD2:Promotion of sleep
-PGE2: +Smooth muscle contraction;
             +inducing pain, heat, fever;
             +bronchoconstriction
-PGF2α:Uterine contraction
-PGI2: +Inhibition of platelet aggregation;
           + vasodilation; embryo implantation
http://en.wikipedia.org/wiki/Eicosanoid#Function_and_pharmacology

Ecosanoid

Ecosanoid

Eicosanoids


Origin and metabolism. The eicosanoids,

prostaglandins, thromboxane,

prostacyclin, and leukotrienes, are

formed in the organism from arachidonic

acid, a C20 fatty acid with four

double bonds (eicosatetraenoic acid).

Arachidonic acid is a regular constituent

of cell membrane phospholipids; it is

released by phospholipase A2 and forms

the substrate of cyclooxygenases and

lipoxygenases.

Synthesis of prostaglandins (PG),

prostacyclin, and thromboxane proceeds

via intermediary cyclic endoperoxides.

In the case of PG, a cyclopentane

ring forms in the acyl chain. The letters

following PG (D, E, F, G, H, or I) indicate

differences in substitution with hydroxyl

or keto groups; the number subscripts

refer to the number of double

bonds, and the Greek letter designates

the position of the hydroxyl group at C9

(the substance shown is PGF2!). PG are

primarily inactivated by the enzyme 15-

hydroxyprostaglandindehydrogenase.

Inactivation in plasma is very rapid;

during one passage through the lung,

90% of PG circulating in plasma are degraded.

PG are local mediators that attain

biologically effective concentrations

only at their site of formation.

Biological effects. The individual

PG (PGE, PGF, PGI = prostacyclin) possess

different biological effects.

Nociceptors. PG increase sensitivity

of sensory nerve fibers towards ordinary

pain stimuli (p. 194), i.e., at a given

stimulus strength there is an increased

rate of evoked action potentials.

Thermoregulation. PG raise the set

point of hypothalamic (preoptic) thermoregulatory

neurons; body temperature

increases (fever).

Vascular smooth muscle. PGE2

and PGI2 produce arteriolar vasodilation;

PGF2!, venoconstriction.

Gastric secretion. PG promote the

production of gastric mucus and reduce

the formation of gastric acid (p. 160).

Menstruation. PGF2! is believed to

be responsible for the ischemic necrosis

G-Protein Pathway

Receptor-Mediated Endocytosis

Schematic representation of the endocytic pathway and membrane trafficking. Ligands, such as hormones and growth factors, bind to specific surface receptors and are internalized in pinocytotic vesicles coated with clathrin and other proteins. After the liberation of the coating molecules, the pinocytotic vesicles fuse with the endosomal compartment, where the low pH causes the separation of the ligands from their receptors. Membrane with receptors is returned to the cell surface to be reused. The ligands typically are transferred to lysosomes. The cytoskeleton with motor proteins is responsible for all vesicle movements described.

Receptor-Mediated Endocytosis

Internalization of low-density lipoproteins (LDL) is important to keep the concentration of LDL in body fluids low. LDL, which is rich in cholesterol, binds with high affinity to its receptors in the cell membranes. This binding activates the formation of pinocytotic vesicles from coated pits. The vesicles soon lose their coating, which is returned to the inner surface of the plasmalemma: the uncoated vesicles fuse with endosomes. In the next step, the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell.

A 76-year-old man presents to the emergency department (ED) complaining of a sudden onset of abdominal pain.

A 76-year-old man presents to the emergency department (ED) complaining of a sudden onset of abdominal pain. The pain started about 4 hours before presentation to the ED and has been persistent; it is present in the upper abdomen and is centered in the epigastrium. He describes the pain as deep and burning. There is no associated nausea or vomiting. He does not report any changes in his bowel habits and has not experienced any recent fevers. The review of systems is also negative for any recent unintended weight loss or trauma. The patient also reports having had "indigestion" in the past that caused pain similar to what he is currently experiencing, though much less in intensity. His past medical history is significant for coronary artery disease and hypertension. He takes two medications, both for his high blood pressure, but does not drink excessively and does not smoke.
http://cme.medscape.com/viewarticle/727247?src=emed_case_nl_0&uac=149212BX

X-Ray of pneumopertoneum

Numerous signs are described for diagnosing pneumoperitoneum on plain radiographs. One of the best known, the Rigler sign (also known as the double-wall or bas-relief sign), is a visualization of the outer surface of a bowel loop wall resulting from free air in the peritoneal cavity. The intraluminal gas provides negative contrast and outlines the internal wall. The cupola sign, typically seen on supine radiographs, is an inverted cup-shaped arcuate lucency overlying the lower thoracic spine and projecting caudally to the heart. This sign is formed as air accumulates anteriorly in the median subphrenic space under the central leaf of the diaphragm. The umbilical ligaments, the urachus, and particularly the falciform ligament are sometimes identified as linear radiopaque structures in the presence of free air.[1,3,5,7]

cAMP dependent pathway Mechanism

http://en.m.wikipedia.org/wiki/Redox

Pancreatic artery

Adenylate cyclase regulation

Adenylate cyclase is dually regulated by G proteins (Gs stimulating activity and Gi inhibiting it), and by forskolin, as well as other class-specific substrates:

cAMP-dependent pathway, ASA the adenylyl cyclase pathway Mechanism

Mechanism of cAMP-dependent signaling. In this figure, the neurotransmitter epinephrine (adrenaline) and its receptor (pink) is used as an example. The activated receptor releases the Gs alpha protein (tan) from the beta amd gamma subunits (blue and green) in the heterotrimeric G-protein complex. The activated Gs alpha protein in turn activates adenylyl cyclase (purple), which converts ATP into the second messenger cAMP