Leukocytes Rolling Adhesion

Blood vessel endothelium at site of infection expresses selectin molecule P-selectin and E-selectin.Leukocytes such as neutrophils express the ligand for selectin in form of s-Lex .The binding of endothelial selectins to s-lex is weak and cannot hold the cell against the flow of blood .instead the cell rolls on the wall of the blood vessel making and breaking many interactions with the selectins

Antigenic Drift

Pathogens such as influenza virus have receptors that enable them to bind host cell surfaces, Antibodies to these viral receptors prevent the virus to binding to and infecting the cells, these are neutralizing antibodies since they neutralize the ability to infect the cell. However some virus have mutation that alter the receptor in the ways to prevent binding of neutralizing antibodies, while leaving the virus able to bind to and infect host cells.


In this way the pattern of antigens expressed by the virus can change over time. This process of accumulation of small changes is called has antigenic drift and contributes our susceptibility to influenza infections.

Germinal Centers

Germinal centers is place were B cells proliferates and undergoes both isotype switching and somatic hyper mutation,B cells are formed within Bcell follicle and lymphoid organs.
Formation of germinal center starts when dendritic cells display antigen on the surface ,which activates Antigen specific CD4 Tcells,which proliferate and mature into affector cells capable of activating Antigen specific B cells.

B cells enter into the follicle and begins to proliferate rapidly ,During this time it also undergoes somatic mutation to introduce new variation in the B cell receptor.
B cell undergoes process of selection after somatic mutation .When the receptors are tested for the ability to bind the antigen.
Those who fail to bind or fail to compete efficiently with other B cell receptors will die.

Lymphocyte Trafficking

Naive T lymphocytes leave blood stream across the specialised endotherlial wall o blood vessel called High endothelial venule(HEV).
The specialized endothelium synthesis number of molecules which are involved in lymphocyte homing in the lymph node.In particlualr homing receptor GLYCAM1 and ICAM-1 and chemokine such as MIP3 beta.
Initial binding of Naive T cells to the vascular endothelium is mediated by L-selectin binding to GLYCAM1 ,subsequently chemokine binding occurs which triggers binding of intergin LFA-1 to its ligand ICAM1.


Lymphocytes are able to migrate across endothelium and into T cell area of lymph node.
Naive T cells can inspect Dendritic Cells in the lymph node for the presence of specific antigens.If T cells didn't recognise antigen,then T cells are not activated and passed out of lymph node to return to the circulation.
T cells that don meet the speciic antigen in the lymph node are activated and begins to proliferate and mature into effector cells.

T Cell Granule Release

Cytotoxic T cells contains number of cytoplasmic organnels,cells like golgi apparatus and micro tubule prganising center are common to all the cells,others like cytotoxic garnaules are formed cD8 T cells and natural killers
During interaction of Cytotoxic T cells with the targets these organnels will become redistributed win cytoplasm of the T cells,So that it can allow T cells to deliver effective function directly on the target cells.

Th LFA1 mediates the initial contact with the potential target cells and binding to it in ICAM-1.If the T cell receptor finds no specific antigen on target cell,then T cell is not activated abd T cells Dis engages itself
If T cell receptor finds the specific antigen on the target cell,it becomes activated.Changes occur is\n cytosol of T cells in which cytoplasmic organelles in the T cells moves to face the target cells.
This Reorganization directs both granules and new protein synthesis into interphase between T cells and target cells.
Cytokines like interleukin 2 and interferon γ released from golgi and directed towards the target cells.

Immunological Synapse

Immunological synapse is the interface between an antigen-presenting cell and a lymphocyte. It was first discovered by Abraham Kupfer at the National Jewish Center in Denver and the term was coined by Michael Dustin at NYU who studied it in further detail. Key molecules in the synapse are the T cell receptor and its counterpart the major histocompatibility complex (MHC). Also important are LFA-1, ICAM-1, CD28, and CD80/CD86. The structure is composed of concentric rings, the C-SMAC, the P-SMAC, and the D-SMAC each containing a peculiar mix of molecules.




Immunological synapse. (2009, June 3). In Wikipedia, The Free Encyclopedia. Retrieved 03:03, June 3, 2009, from http://en.wikipedia.org/w/index.php?title=Immunological_synapse&oldid=294087337

Dendritic Cell Migration

Dendritic cells (DCs) are immune cells and form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells.
Dendritic cells are key presenting cells in the immune system,The are generated from Bone marrow nd migrate into proliferal tissue through the blood stream,Immature dendritic cell wait for pathogen entry(site of injury).
Dendritic cells express various pattern recognistion receptors that can recognse common features of many bacteria and fungal pathogens.Through this receptor dendritic cells bind and phagocyotsis pathogens,When this receptor bind to the pathogens the activate the dendritic cell which then starts to mature.
In this process dendritic cells migrate to the tissue and changes its behaviour to stop phagocytosis and start expressing immune stimulatory molecules
Activated dendritic cells migrate from tissue to lumphatic vessel,with lymphatic fluid drain to lymph node carrying dendritic cells with it.
T cells migrates through lymph node inspects teh dendritic cells for the presence of specific antigen.T cells which fail to recognize antigens on one dendritic cells carryon to inspect others.
T cells which recognise the specific antigen becomes activated and both proliferated and differntialte into a factor cells.

TCR-APC Interaction

Antigen Presenting cells express both MHC molecules,in this case MHC II molecule co stimulator molecule such as CD80.Stimulation of T cells in this case CD4 tcell by the antigen presenting cell involves the interaction of T cell receptor and co receptor molecule with the MHC peptide complex.As well as the interaction between the  CD80 and CD28.The interaction of antigen presenting cell with T cell causes signals to pass in both direction.Signalling the antigen presenting cell to express additional co-stimulatary molecules such as CD86 and CD40.At the same time signals to T cell receptor and CD28 induce T cell to express CD40L(CD40 ligand).the interaction between CD40L and CD40 As well the additional stimulation through CD28 mediated by interaction with CD86 resolved in full activation of CD4 T cell.


Activation of CD8 T cell also requires multiple receptor ligand interaction ,the same activation siganals induce the antigen presenting cell to express other co-stimulatary molecules such as 4-1BBL ligand (4-1BBL),while initial activation of  CD8 T cells induces the expression of 4-1BB,Binding of 411B ligand to 41BB is thought to required for full activation of CD8 T cells. 

T Cell Killing

Viruses are inter-cellular pathogen that infects the cells of the body. Degradation of virus protein inside the cell allows viral peptide to display on the surface of the cell bound to MHC class 1 protein.CD8 T cells, which recognize MHC peptide complexes, are activated and kill the infected cell. Having killed 1 cell the T cell can move to new target kill that cell and move on again




The killing process is initiated when the T cell receptors and CD8 together bind to MHC class 1 molecule bearing a viral peptide producing the signals that activate the T cell.

Cytotoxic T cell contain membrane vesicle called cytotoxic granules, which package the protein that kills target cells, The most important of these is protein called perforin and set of proteases called granzymes, these proteins are complexed with scaffolding protein called serglycin.

Activation of T cells causes the release content of the vesicles, delivering protein on the surface of the target cells,

Although the exact mechanism is not known the Perforin facilitates the delivery of the granzymes into the cytosol, at this point the target cell are destined for death and the T cell can migrate onward to find new target cells.

The process of cell death initiated by grandzymes uses the same basic cellular machinery that gives rise to apotosis. The granzymes target various cellular proteins that regulate apoptosis such as BID and pro-caspase-3, The granzymes cleaves the BID which in its truncated form causes cytocrome C to release from the mitochondria into the cytosol, simultaneously granzymes activates pro caspase -3 which in turn cleaves ICAD the inhibitor of CAD (caspase activated DNA)

The activated DNA migrates into the nucleus where it degrades the DNA ensuring the death of the cell.

Lymph Node Development

Lymph node is an organ consisting of many types of cells, and is a part of the lymphatic system. Lymph nodes are found all through the body, and act as filters or traps for foreign particles. They contain white blood cells. Thus they are important in the proper functioning of the immune system.


Chemokine Signaling

Chemokine receptors associate with G-proteins to transmit cell signals following ligand binding. Activation of G proteins, by chemokine receptors, causes the subsequent activation of an enzyme known as phospholipase C (PLC). PLC cleaves a molecule called phosphatidylinositol (4,5)-bisphosphate (PIP2) into two second messenger molecules known as Inositol triphosphate (IP3) and diacylglycerol (DAG) that trigger intracellular signaling events; DAG activates another enzyme called protein kinase C (PKC), and IP3 triggers the release of calcium from intracellular stores. These events promote many signaling cascades (such as the MAP kinase pathway) that generate responses like chemotaxis, degranulation, release of superoxide anions and changes in the avidity of cell adhesion molecules called integrins within the cell harbouring the chemokine receptor.

DTH Response

Delayed type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses which, depending on the antigen involved, mediate beneficial (resistance to viruses, bacteria, fungi, and tumors) or harmful (allergic dermatitis, autoimmunity) aspects of immune function. Cutaneous DTH reactions are initiated when CD4 memory T cells are activated by Langerhans cells and other antigen-presenting cells in the skin. Upon activation, CD4 T cells release inflammatory mediators which recruit effector cells to the site of antigen administration. While the monocyte/macrophage is thought to be the major effector cell in this model, CD8+ cytolytic T cells, and NK cells are also thought to serve as effector cells in DTH reactions. Activated effector cells mount an inflammatory response which results in the elimination of antigen and the extravasation of plasma accompanied by selling at the site of challenge. The magnitude of the response to the antigen is measured as an increase in swelling at the site of challenge.

Killer T Cell

This video shows the actions of a killer T cell that attacks a fibroblast.

Hemagglutinin

Hemogglutinin is a membrane fusion protein expressed on the surface of influenza virus. By mediating the fusion of viral and cellular membranes during infection it allows the viral genome to enter the cells.During the fusion reaction, hemoggluttinin inserts a hydrophobic fusion peptide into the host cell membrane and it becomes integral membrane protein in the two lipid bilayers



Tran membrane helix that anchors hemoggluttinin in the viral membrane is omitted from the structure.

Fusion reaction is triggered by low ph, which the virus encounters after the up taking endosomes of the host cell. This change in ph leads to massive structural change including the formation of long alpha helix in the core of protein.

Fusion peptide, which are previously tucked away from protein stock are displayed prominently in the tip of helix, ready to slip into host cell membrane.



Fusion peptide had to removed from the protein to be allowed for crystallization.
On the viral surface of hemogglutinin is a complex with 3 identical sub units.
It is likely the considered action of small number of hemogglutinin trimers is required to trigger a membrane fusion effect.

Intracellular Listeria Infection

Listeriosis is an infection caused by the gram-positive motile bacterium Listeria monocytogenes.1,2 Listeriosis is relatively rare and occurs primarily in newborn infants, elderly patients, and patients who are immunocompromised.



Leukocyte Rolling

Leukocytes are white blood cells that help in fighting infection (at site of injury, infection or inflammation). Cytokines are released which stimulate endothelial cells, which lines adjacent blood vessel. Endothelial cells express surface proteins called Selectins.


Selectins binds to carbohydrates in membrane of leukocytes causing it to stick to walls of blood vessel. Binding interaction is insufficient lower affinity that leukocytes can roll on along the vessel wall in search for points to exit.

Leukocytes adhere tightly and squeeze between endothelial cells without disturbing the vessel walls and crawl out of the blood vessel to adjacent connective tissue

Listeria Parasites

Listeria parasites move throughout the cytosol of an infected cell by recruiting host cell actin.



Plant Cell Division

Video on plant cell Division

Mitotic Spindles Video

This video demonstrates the process of division in the mitotic spindles of a fly embryo

Sea Urchin Fertilization

Video on Sea Urchin Fertilization

Microtubule and ER Dynamics

Cell Compartments

Video on Cell compartment

Endosome Fusion

Endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the Golgi and either continue to lysosomes or recycle back to the Golgi. Furthermore, molecules can be directed into vesicles that bud from the perimeter membrane into the endosome lumen. Therefore, endosomes represent a major sorting compartment of the endomembrane system in cells.[1] Endosomes are approximately 500 nm in diameter when fully mature.

Intermediate Filaments

Animation on Intermediate Filaments,its structure andits function

Microtubule Dynamics IN VIVO

Neurite Outgrowth

A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete.

Neuronal Pathfinding

Tomogram of a Mitochondrion

Embryonic development of Tadpole

Keratocytes

The fibroblastic stromal cell of the cornea. Keratocytes produce keratan-sulfate proteoglycans (KSPG), lumican and keratocan to form and sustain proper collagen interfibrillar spacing and fibril diameter of the cornea.

Fluidity of the Lipid Bilayer

Video on Fuluidity of Lipid Bilayer

Red blood cell treated with Detergent

When detergent is added to red blood cell the membrane ruptures and cytosol spills out

Red Blood Cell Membrane

Animation is about Red blood cells membrane,it talks about different functions of red blood cell membrane .

Hair cells

  • The sound sensitive cells in our ear is called hair cells, Each has a tough spiky extensions called Stereocilia on its upper surface and each sends signal to auditory nerve fibers through its basal surface.
  • Hair cells are embedded in a layer supporting cells and are sandwiched between two sheaths extra cellular matrix, the tectorial membrane and basilar membrane.



  • Sound vibrations cause the basilar membrane to vibrate, and this motion pushes the Stereocilia against the tectoral membrane.
  • Stereocilia tilt, triggering an electrical response in the hair cells, the activated hair cell in turn activates the auditory nerve cells.
  • Hair cell membrane contains stretch activated ion channels; these channels are closed when Stereocilia is not tilted.
  • However, when the steroecilia tilt a linking the filament from one Stereocilium to the channel neighboring stereocilium pulls at the channel opening it. Positive charged ions flow into the cell and depolarizing the membrane

Synaptic Signaling

Neurons transmits chemical signal across synapses. The synapse converts the electrical signal of the action potential in the pre synaptic cell into a chemical signal.

When the action potential reaches then nerve terminal it opens voltage-gated calcium channels in the plasma membrane allowing calcium ions to flow into the terminal.


Increased calcium in the nerve terminal stimulates synaptic vesicle to fuse with the plasma membrane releasing the neural transmitter cargo into the synaptic cleft.

Released neuro transmitters diffuse across the synaptic cleft where the bind to and open transmitter gated ion channels in plasma membrane of postsynaptic cell.

Resulting ion flows depolarize the plasma membrane of the postsynaptic cell, thereby converting neurotransmitters chemical signal back into an electrical one that can be propagated as a new action potential.

Enzymes that destroy it or reuptake into nerve terminals or neighboring cells remove neural transmitter quickly from synaptic cleft.

Animal Cell Division

Animation on Animal Cell Division

Wound Healing animation

This Animation shows how cell react to wound and how healing takes place

Enzyme Catalysis

Enzyme catalysis is the catalysis of chemical reactions by specialized proteins known as enzymes. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions.

The mechanism of enzyme catalysis is similar in principle to other types of chemical catalysis. By providing an alternative reaction route and by stabilizing intermediates the enzyme reduces the energy required to reach the highest energy transition state of the reaction. The reduction of activation energy (Ea) increases the number of reactant molecules with enough energy to reach the activation energy and form the product.

MHC Class I Processing

Folding assembly of MHC class 1 molecule takes place in the lumen of ER.Initially folding of Class1 alpha chain is aided by calnexin chaperone.
Partially folded chain is transferred to second chaperone calrecticulam,which further  aids   folding  the chain and association with beta 2-Microglobulin.
Other proteins Frp57 and tapasin associate with it.
Class I molecule binds with the TAP Transporter to form peptide Loading complex.
The peptides that bind to MHC class 1 proteins are geneated by Proteosomes.
In cytoplasm Proteasome generates peptide fragments which will bind to MHC class 1 Protein.
The proteasome degrades protein into shorter fragments within cytosol and transports it to ER by TAP transporter.
By the process of Peptide ending ,non-binding and unstable peptides are released from ER.
Peptides with stable affinity binds with MHC molecule form stable complex.
Final phase of folding MHC class 1 molecule takes place.
Disassociation of Peptide Holding Complex takes place.
Peptide loaded with MHC class 1 molecule exits from ER and Moves to Cell surface with help of Golgi apparatus.where its recognized by by Antigen Receptors of CD8 Tcells.

MHC Class 1 Protein

MHC class I proteins display short peptides, or antigens, derived from normal cell proteins. Peptide-loaded MHC proteins are located on the cell surface where they can be examined by passing T cells of the immune system. The MHC complex has two subunits. The smaller subunit, b2 microglobulin, resembles an immunoglobulin domain.

The larger a subunit also has an immunoglobulin-like domain which is linked to a head domain containing the antigen-binding groove. The antigen-binding groove in the MHC head domain is built from two walls composed of long alpha helices that rest on a floor composed of an eight stranded beta sheet. The peptide on display fits snugly between the helices in the groove.The peptide backbone is bound at both ends by highly conserved regions of the MHC protein. Some peptide side chains extend downwards into specific binding pockets in the groove, while other peptide side chains project upwards where they can be recognized by T cells. MHC class I proteins display their bound peptides on the cell surface for immune surveillance. Immune cells, called cytotoxic or killer T cells, for example, express T-cell receptors that bind to the MHC head domain and the bound peptide. If the cell expressing the MHC protein displays a peptide foreign to the immune system, the T cell is activated by this receptor-MHC interaction. The activated T cell then proceeds to destroy the abnormal cell. Cut-away views of this peptide-bound MHC protein complexed with a T-cell receptor reveal the exquisite precision with which the interacting surfaces fit together.

HCV infection and Immune Response Video

This Animation shows how HCV infection and Replication

This animation shows The cells Response To HCV

These two Animation shows TCell response to HCV
T cell response to MHC II


Proliferation of T cell by IL-10

Anatomy and Diseases of the Basal Ganglia

Basal ganglia (or basal nuclei) are a group of nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem. Mammalian basal ganglia are associated with a variety of functions: motor control, cognition, emotions, and learning. In modern use the term 'ganglia' is in this instance considered a misnomer; 'ganglion' refers to concentrations of neural nuclei in the periphery only (for example those of the autonomic nervous system), and the term 'basal nuclei' is preferred.




The five individual nuclei that make up the primate basal ganglia, along with their major subdivisions, are:
rostral
the striatum, which consists of
putamen
caudate nucleus
external segment of the globus pallidus (GPe)
internal segment of the globus pallidus (GPi)
caudal
subthalamic nucleus (STN)
substantia nigra (SN)
substantia nigra pars compacta (SNc)
substantia nigra pars reticulata (SNr)
substantia nigra pars lateralis (SNl)
There are 2 sets of basal ganglia in the mammalian brain, mirrored in the left and right hemispheres.
Two coronal sections are used to show the basal ganglia; the STN and substantia nigra lie deeper back in the brain (more caudal). Images show two schematic coronal cross-sections of the human brain with nuclei of the basal ganglia labeled on the right side.
Functionally, the basal ganglia consist of a series of circuits, such as skeletomotor, limbic and occulomotor circuits. Each circuit projects to specific nuclei within the basal ganglia and its projections e.g. the skeletomotor circuit projects to the ventral lateral, lateral ventral anterior and centromedian thalamic nuclei.


Test source

Basal ganglia. (2009, May 19). In Wikipedia, The Free Encyclopedia. Retrieved 22:08, May 19, 2009, from http://en.wikipedia.org/w/index.php?title=Basal_ganglia&oldid=291041764

What causes neuronal death in Alzheimer's disease.

Pathophysiology of Schizophrenia


Lipoproteins that Circulate in the Blood Collecting Fat

High-density lipoproteins (HDL), often referred to as the "Good Cholesterol", circulates in the blood stream collecting fat and cholesterol from arteries and transporting them to the liver for removal. The movie shows how these lipoproteins (in blue and green) can gather the fat molecules (in white and brown) into small particles allowing them to flow through blood vessels.



SDS-PAGE

SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis, is a technique widely used in biochemistry, forensics, genetics and molecular biology to separate proteins according to their electrophoretic mobility (a function of length of polypeptide chain or molecular weight). SDS gel electrophoresis of samples having identical charge per unit mass due to binding of SDS results in fractionation by size and is probably the world's most widely used biochemical method.

Muscle contractile protiens

Myofibrils (obsolete term: sarcostyles) are cylindrical organelles. They are found within muscle cells. They are bundles of actomyosin filaments that run from one end of the cell to the other and are attached to the cell surface membrane at each end.

Actomyosin motors are important in muscle contraction (relying in this case on "classical myosins") as well as other processes like retraction of membrane blebs, filiopod retraction, and uropodium advancement (relying in this case on "nonclassical myosins").

Structure

The filaments of myofibrils, myofilaments, consist of two types, thick and thin.

* Thin filaments consist primarily of the protein actin, coiled with nebulin filaments.
* Thick filaments consist primarily of the protein myosin, held in place by titin filaments.

The protein complex composed of actin and myosin is sometimes referred to as "actomyosin."

In striated muscle, such as skeletal and cardiac muscle, the actin and myosin filaments each have a specific and constant length on the order of a few micrometers, far less than the length of the elongated muscle cell (a few millimeters in the case of human skeletal muscle cells). The filaments are organized into repeated subunits along the length of the myofibril. These subunits are called sarcomeres. The muscle cell is nearly filled with myofibrils running parallel to each other on the long axis of the cell. The sarcomeric subunits of one myofibril are in nearly perfect alignment with those of the myofibrils next to it. This alignment gives rise to certain optical properties which cause the cell to appear striped or striated. In smooth muscle cells, this alignment is absent, hence there are no apparent striations and the cells are called smooth.
Myofibril. (2009, June 13). In Wikipedia, The Free Encyclopedia. Retrieved 00:09, June 13, 2009, from http://en.wikipedia.org/w/index.php?title=Myofibril&oldid=296076817

Ion Channel Coupled Receptors

Animation describing the role of ion channel coupled receptors in neurotransmission

Low Back Pain Lecture

Dr. John Chardos Department of Medicine (VA) on the cause, treatment and prevention of low back pain. Most people have experienced low back pain at one time or another, so it is no surprise that it is one of the most common problems in primary care. Although it is so common, it is not clear how to best treat back pain. John Chardos, MD presents information to better understand back pain and what can be done to manage it


Male Physiology

Spermatogenesis is the process by which male spermatogonia develop into mature spermatozoa. Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is the male version of gametogenesis. In mammals it occurs in the male testes and epididymis in a stepwise fashion, and for humans takes approximately 64 days.permatogenesis is highly dependent upon optimal conditions for the process to occur correctly, and is essential for sexual reproduction. It starts at puberty and usually continues uninterrupted until death, although a slight decrease can be discerned in the quantity of produced sperm with increase in age. The entire process can be broken up into several distinct stages, each corresponding to a particular type of cell: