Midtterm nr 2 Flashcards
Immunology
The what are the different immune organs?
Primary immune organs(Central): - Thymus, - Bursa fabrici (Birds) - Bursa equivalents (mammals) - Embryonic liver - Bone marrow Secondary immune organs (peripheral): - Lymph nodes - Spleen - MALT (mucosa associated lymph tissue) - GALT (Gut assiciated lymph tissue)
Natural Immunology
What are the two different immune systems?
Natural immunity (Innate) Adaptive (acqiured) immune respons
Natural Immunology Natural immunity (innate) - general description
- Not antigen specifick
- Activated by Toll-like receptors
- Immediate immune responce (security guard on a club)
- Has no memmory
Natural Immunology Natural immunity (innate) - Cells
- Neutrophil
- Eosinophil
- Basophil
- Monocytes/Macrophages
- Natural killers (Kills the virus and tumor infected cells)
Natural Immunology
What is a macrophage?
Derives from the monocyte
Different names depending on what tissue you find them
Granules filled with digestive enzymes
Importaint in fighting bacterias
Importaint in ingest damaged cells by phagocytosis
Present antigens to T-cells
Destroys tumor cells and plays role in inflammatory resp.
Natural Immunology
What does the NK cells do?
The parts that kills the virus and tumor infected cells
Does not require a binding to MHC-Ag complex, therefore they kills tumors with low levels of MHC molecules.
Natural Immunology
What are the most important cells in tumor immunology=
CD4 (-)
CH8 (-)
Natural Immunology
What are the main molecular components
Complement factors and their receptors Heat shock proteins Fc receptors Inflammatory cytokines Histamine
Immunology
What is the complement system
- A group of proteins taking part in the activation of the inactive enzymes like blood in coagulation cascade.
- I helps or complements the antibodies and the phagocytic cells to clear the phatiogens from the body.
- Consist out of 3 dif ways
- All the three ways are converted into C3 complement component. The C9 will then make a drill
Immunology - The compliment system
What are the 3 dif ways of the complement system?
- Alternative pathway: A previously unknown antigen appears in the body as a TRIGGER
- Classic pathway: Previously produced specific antibody and the antigen built a complex and innate the process.
Mannose binding lectin: Binds to the oligosacharides of certain virus or infected cells.
Immunology - The component system
How will the 3 kinds of pathways of the complement system kill the virus?
The 3 dif ways will convert into C3 complement component. The C9 will then make a drill.
Activate a membrane drill, that makes the membrane of the virus etc discontinues.
The ENZYME or OSMOTIC SHOCK will kill the virus.
Immunology - The component system
What are the function of the compliment system?
Lyse bacterial membrane
Initiates chemotaxis
Stimulate opsonization
Immunology - Adaptive (acquired) immune response
What are the different antigens?
Auto: From you’re self
Allo: From same species
Xeno: From another species
Immunology - Adaptive (acquired) immune response
The adaptive immune response has two types of specific immune response, what are They?
The Humoral
The Cellular
Immunology - Adaptive (acquired) immune response
The humoral immunity
From the bone marrow Their antibodies are synthesized in secondary lymphatic organs. Cells: B-lymphocytes plasmacells. Immunoglobulins Receptor: BCR
Immunology - Adaptive (acquired) immune response
The Cellularl immunity
Produced in the Thymus
Cells: T-lyphocytes, lymphoblasts
Receptors: TCR
Immunology - Adaptive (acquired) immune response
Active immunity
Inducted when cells get in contact with a non-self antigen. Actively reacts to the antigen.
Immunology - Adaptive (acquired) immune response
Passive immunity
When an individual is made immune by receiving the cells or immunoglobulins of an already immunized individuals: Vaccine
Immunology - Adaptive (acquired) immune response
3 different phases
Afferent phase
Central phase (Activation phase)
Efferent phase
Immunology - Adaptive (acquired) immune response
Afferent phase
Antigens are recognized by foreign bodies and their processing.
Immunology - Adaptive (acquired) immune response Central phase (activation phase)
The activation, spreading and differentiation of specific and non-specific immune cells
Immunology - Adaptive (acquired) immune response
Efferent phase
Activate immune cells and eliminates the non self and develop a tolerance against the,
Immunology - Immunoglobulins
What are immunoglobulins?
Antigen recognizing molecules, and binds specificialy to ligands.
Produced by plasma cells
The immunoglobulins (Ig) are heterogenic (do not derive from the body)
Diff in electroforetic mobility (how they react in gel)
Similar in antigen structure
Composed of chains.
What kind of chain? - By the basis of the molecular mass
Immunology - Immunoglobulins
Heavy and light chains
We talk about light chains and heavy chains and they have a variable region and a constant region.
Immunology - Immunoglobulins
Clevage, antigens-bindings, crystalizing factors.
Variabuility
Immunoglobulins can be cleaved by enzymes into antigen-bindings and crystalizable factors.
Immunology - Immunoglobulins
Clevage, antigens-bindings, crystalizing factors.
VARIABUILITY
Isotipia: Variabuility in class Allotipia: Variabuility in individual type Idiotipia: Variabuility in an immunoglobulin type
Immunology - Immunoglobulins
What are the things that differentiate the diff immunoglobulins
The variable domain
Ag-binding site
Antibodies are formed by immunoglobulin domains
Immunology - Immunoglobulins
Immunoglobulins duel function
Monofunctional: Activated before the antigen administration, Fab-fragment antigen binding dependent.
Polyfunction: Activeted after the antigen administration, Fc-fraction crystallizable dependent.
Immunology - Immunoglobulins
IgA
- Produced in the plasma cell in the submucosa
- Secreted into the interstitial fluid
- Binds the polymeric receptors containing the secretory component on the surface of the mucosal cells.
- IgA is transported to the mucosal cell in a secretory vesicle, and separate from the receptors, which enters the cytoplasm.
Immunology - Immunoglobulins
IgM
Remain in the circulation and play a role against the complex pathogens.
Is the biggest antibody.
Because of its big size it is responsible for the hemolysis of the fetal RBC.
Rh incompability
Polymere
Immunology - Humoral immunity, B-lymphocytes and self restriction.
B-lymphocytes
Synthesizes antibodies (immunoglobulins, ang recognize (binds to antigen) and produce antibodies. Antigen binding triggers the cell differentiation which leads to the transformation of the B-lymphocytes into plasma cells that secrete antibodies.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
B-lymphocytes - Maturation/development
The B-lymphocytes go under several phases of immunoglobulin production.
The genes are activated, and the are regulated at numerous levels in these phases.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
B-lymphocytes - Maturation/development
The primary antibody repertoire
Immunoglobulins against about 10^9 different possible antigen determinants.
Each B-cell carry a single Ig(BcR) on its surface.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
B-lymphocytes - Maturation/development
Stages
- First is the preparation so the pre-B-lymphocytes mature and become virgin-b-lymphocytes.
On each virgin is an IgG-molecule. - When this cell gets into the blood, the antigen- dependent phase starts.
- If there is an antigen in which the virgin B-lymphocytes have an immunoglobulin structure the virgin-lymphocyte binds to the antigen and gets activated.
- This activation may be helper-T-lymphocyte-independent or dependent.
- The now active B cells will settle down in the secondary organs, and develop to plasma cells or memory cells.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
Clone selection theory
- The B-lymphocyte that is specific to one antigen is already present before the antigen gets into the body, and reacts when the virus gets into the body.
This means that the body produces immunoglobulins against possible antigens and stores it on the surface of the B-lymphocyte.
There are also genes doing this, because they join each other randomly resulting in almost unlimited regions capable for recognizing millions of different possible antigens produced.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
Isotype swiching
The constant region changes. H-chain (Histones). The original on is IgM. The major switch is the cytokines. If cytokines is present, other immunoglobulins are made like IgG, IgA, ect.
Immunology - Humoral immunity, B-lymphocytes and self restriction.
Self restriction
- After the antigen stimulus the efficiency and potency of the immune response will DECREASE.
- The lymphocytes will die or be converted to memory cells.
Negative feed back mechanism.
Immunology - Cellular immunity, T-lymphocytes and hte MCH structure of the cells.
Endogenous
Endogenous substances and processes are those that originate from within an organism, tissue or cell.
Immunology - Cellular immunity, T-lymphocytes and hte MCH structure of the cells.
MHC 1
Pressent on the surface of the nucleated cells.
Endogenously produces antigens.
Recognized by the cytotoxic Tc-Ly.
The present fragments of non self to the cytotoxic T cells
Immunology - Cellular immunity, T-lymphocytes and hte MCH structure of the cells.
MHC 2
Pressent on the surface of the antigen presenting cells, like macrophages, dendrite cells, ect.
MHC2 + forreign antigens are recognized by TH-Ly (helper)
Immunology - Cellular immunity, T-lymphocytes and hte MCH structure of the cells.
What is autocrine
Denoting a mode of hormone action in which a hormone binds to receptors on and affects the function of the cell type that produces it.
Immunology - Cellular immunity,
Development (T-lymphocytes)
Phases
The first phase is an antigen independent phase is when the pre-T-lymphocytes became the virgin T-lymphocytes, and on the surface there will be an Ig-like molecule (TCR) app airing against a certain possible antigen structure.
The antigen dependent phase begins when the T-lymphocytes goes into the bloodstream.
If the Ti-cells carriers a CD4 and a TCR, the cell will be able to recognize an antigen,
which is presented by a APC cell and an MHC 2 antigen.
There will be a linkage, the AP ells and the Ti-cells that will result in the primary stimulation.
Then there is a blastic transformation due to the interlaukulin secretion.
If the virgins have a CD8 antigen expressed beside the MHC 1, and after the blastic transformation, a T cytotoxic is created. This kills tumors and virus antigen carrying cells.
Other T-cells is also created.
There are a lot of T-cells that dies under this process, because they do not recognize the MHC.
Molecular aspects of muscle contraction and electromechanical coupling.
General
Contraction
Is caused by sliding of actin and myosin fibers on each other, forming an actin.myosin complex.
Molecular aspects of muscle contraction and electromechanical coupling.
General
Individual movement of cells/extension;
Caused by exchange of microtubular and actin polymerization/depolymerization if presence of ATP
Molecular aspects of muscle contraction and electromechanical coupling.
Sacromeres
- Located between two Z.bands.
- Less refractive isotopic: I, it has only thin fibers.
- Strongly refractible anisotopic: A-band, thick and thin fibers.
- In the middle the myosin fibers are twisted up:
M-zone surrounded by H-zone, only thick fibers. - There are three new proteins in the sarcoma
Molecular aspects of muscle contraction and electromechanical coupling.
Sacromeres
The three new proteins in sacroma
Titin
Nebulin
Alpha actinin-complex
Molecular aspects of muscle contraction and electromechanical coupling.
Sacromeres
The three new proteins in sarcoma
Titin
Titin: The biggest protein in the body contains one spring like protein chain. Z-line myosin bundles Ensure a precise return of actin and myosin bundles to their original position even after extensive stretch.
Molecular aspects of muscle contraction and electromechanical coupling.
Sacromeres
The three new proteins in sarcoma
Nebulin
Determine the direction and placement of actin polymerization during the development of sarcomeres.
Protects the development actin fibers from rearranging effect of other actin-binding proteins.
Molecular aspects of muscle contraction and electromechanical coupling.
Sacromeres
The three new proteins in sarcoma
Alpha-actinin
Creates z-bands
Molecular aspects of muscle contraction and electromechanical coupling.
The actin complex
Figure
The main component is G-actin that form a double helix.
Tropomyopsin is on the surface of the helix
In resting state: Tropomyopsin covers the active site on the surface of the actin molecule.
Masking takes place when two troponin-complex, binds to tropomyosin.
The Tn-I and Tn-T holds the tropomyosin in position, but the Tn-C (calcium binding) is free in resting condition, but when a calcium binds to the Tn-C, following conformations changes it, displaces tropomyosin fibers.
Tropomyocin then slides into the groove of the two striated actin helix and the myosin-binding amino acid sequences become uncovered on the surface of actin.
Molecular aspects of muscle contraction and electromechanical coupling.
Myosin
Consist of 6 elementary myosin molecules
- Two heavy chains of an elongated alpha helix
- And a globular part (binding site)
- Two light chains, connected to the head region of the alpha helix.
- The head region can bend max 45* and it is responsible for the ATP binding and splitting.
- 3 types of ATPase and this determine the speed of the ATPase activity, aka the efficiency of the entire sarcomere.
Molecular aspects of muscle contraction and electromechanical coupling.
Myocytes
The sarcolemma (plasmalemma) of the myocytes has a several regions of discs and the transverse tubular system (T-tubules).
The T-tubules permit the conduction of electrical impulses.
The sarcoplasmic reticulum regulates the intercellular calcium intake.
Triad: Comprised of two SR and a T-tubule in between.
Molecular aspects of muscle contraction and electromechanical coupling.
The slide filament mechanism
Sliding of myosin microfilaments and actin on each other.
The myosin shift 45* which occurs after the development of connections between myosin head and actin microfilaments.
Calcium ions binds to the TnCs. Tropomyosin will move. Actin and Myosin microfilaments will bind to each other..
ATPase is activated. Sliding and contraction released.
Myosin head binds ATP. If Ca2+ is present, everything starts over again.
Molecular aspects of muscle contraction and electromechanical coupling.
Cross bridge cycle
Development of the calcium signal.
Calsium is released from the sarcoplasmic reticulum after neutral action potential is transmitted to the muscles.
At the same time:
Rising of Ca2+ levels trigger a number of calcium repumping.
Results in calcium level going down. = Calcium trancient
Molecular aspects of muscle contraction and electromechanical coupling.
Calcium transient
Calcium ionsactin-myosin connection is formed
No more ATP = Myosin cannot dissociate from actin and the muscles are in a contractive state: Rigor moris
The individual myosin head needs to work asynchronously, to make the whole muscle contract.
Molecular aspects of muscle contraction and electromechanical coupling.
The L-type
The voltage gated in the Ca2+ - channels in the T tubule.
When the action potential reaches the L-type it open.
- Ca release through the function of the triad
- Activation of muscle proteins
- Muscle contractions
- Relaxation
We also need to remove the calcium from the intracellular fluid = The myoplasmic calcium removal mechanism.
Most importaint: Na ion/ Ca ion anti porter between the myolemma and the EC space removing calcium with a secondary active transport.
There are no active calcium pumps that uses ATP
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
Muscle tissue contains….
Mainly water: 75%
Proteins: 20%
Majority either contractile or passive structure proteins.
Less dominant: Albumun and enzymes
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
What is macroscopic elements
They have a great significance in execution of locomotion.
The direction of shortening is not in line with the macroscopic of the muscle.
Only the component of the total work done is manifested in physical work which is in line with the direction of macroscopic contraction.
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
The red muscle (tonic) fibers
Thin muscle fibers, large amount of myoglobin, most prominent muscles in individuals that need a long muscle capacity, etc. long distance runners.
They have slow contraction, no accumulation of lactic a cidm oxidative condition. short muscle fibers.
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
The white muscle (phasic) fibers
Fast contraction,
work under anaerobic conditions.
Thick muscle fibers
Lactick acid accumulates by glycolysis
If we innervate the red muscles with the neurons of the neighboring white muscle, the red muscles will after a long regeneration period, become white inn ann the features.
Gens may also have some impact because the occurrence of myosin fibers may considerably vary during selection.
The slow LC-3 chains, may substitute the very fast LC-2.
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
Mucle hypertrophy
An increase in size of skeletal muscles through a growth in size of its component cell.
There are two factors that contribute to hypertrophy.
- The mass of individual fibers are increased
- Increase in actin and myosin filaments and increase of energy producing enzymes.
Types of striated muscles, energy sources of muscle functioning, oxygen debet.
Types of Muscle hypertrophy
Sacroplasmic hypertrophy:
Increase muscle glycogen storage
Myofibrillar hypertrophy:
Focuses on increased myofibril size
Types of striated muscles, energy sources of muscle functioning, oxygen debt.
Remoddeling of slow muscles
Nutrient and energy supply increased.
Myoglobin content of fiber, mitochondria etc. increased
Types of striated muscles, energy sources of muscle functioning, oxygen debt.
Energy source
Is one ATP and 1 creatinin-phosphate.
If we use more ATP than we have, it leads to oxygen debt.
Glycogen is the main energy source for fast movement, and glucose is the main energy for long term contraction.
During heavy physical activity, energy source is always anaerobe glycolysis.
After the hard physical work the muscles will try to consume more oxygen, so the oxygen consumption will go up, because the re-synthesize is going under aerobic conditions.
The stores used up by anaerobic mechanism are re-synthesized during rest by oxygen consumption.
Macroscopic events of muscle contraction
What are the elements of muscle contractions
The elements of the contraction are the sacromer.
Macroscopic events of muscle contraction
Types of contraction
Isotonic contraction
Isometric contraction
Macroscopic events of muscle contraction
Auxotonic
Working against increasing tension
Macroscopic events of muscle contraction
Preload
The muscles adjusted with preload and then the isotonic contraction
Macroscopic events of muscle contraction
Afterload
The contraction starts as an isotonic contraction, but is then blocked off by something, isometric contraction.
When the correct stimulus is applied, the muscles answers with contraction. During the contraction of the contraction component : 1. the serial elastic components will reach equilibrium with the load and followed by shortening with constant tension.
Macroscopic events of muscle contraction
Summation
Addition of skeletal muscles contraction forms caused by different reasons.
The ALL or NON law only apply to single muscle fibers.
If there is not enough stimulus, no contraction.
Macroscopic events of muscle contraction
Quantal summation
In a muscle when more and more fibers contract due to the increasing in action potential.
Macroscopic events of muscle contraction
Contraction summation
Representive stimuli there will be additional Ca release before the end of Ca transient
Macroscopic events of muscle contraction
Stircase effect
If the new stimuli arrive immediately after the end of the twitch the new contraction have increasing amplitudes.
Due to increase efficiency of ion gates.
Macroscopic events of muscle contraction
Tetanus
Additive effect of all the summation forms.
Two forms:
- Incompleete
- Compleete
Length - tension diagram: working range and power of the muscle: Heat production and muscle fatigue.
Each skeletal muscle is under a certain degree of strength.
Length X tension = work.
The length tension curve can be obtained when one stimulated muscles which are passively stretches with varying loads.
Macroscopic events of muscle contraction
Isotonic maximum curve
If we passively stretch muscle A, B, C distance above resting length and in these positions we stimulate the muscle with maximal signal stimuli, 2um is the optimal resting length for smooth muscles.
Macroscopic events of muscle contraction
Isometric condition
No shortening is possible here so we can only measure the extent of tension.
In skeletal muscle, length measured under maximum power is identical to the normal working range of the muscle.
Macroscopic events of muscle contraction
Velocity/tension relationships
The less the tension is the higher the velocity becomes velocity*tension=power.
Unloaded and Overloded muscles
Macroscopic events of muscle contraction
Velocity/tension relationships
Unloaded muscles
Muscle contract with maximal velocity.
Macroscopic events of muscle contraction
Velocity/tension relationships
Overloaded muscles
Contract with zero velocity. It gives us an idea about the power of the muscle. Under intermediate load the muscle contraction can be optimal fast.
Intermediate tension and intermediate velocity - result in MAXIMAL POWER
Macroscopic events of muscle contraction
Heat production
During contraction ATP breakdown while after contraction synthetic process create heat
Macroscopic events of muscle contraction
Phasic fibers
Produce more heat during restitution. Because of the huge O2 debt created during contraction and the restitution creates heat.
Macroscopic events of muscle contraction
Tonic fibers
Heat production mostly occurs during contraction.
Activation heat: Cam release + Myosin activation.
Contraction heat:
Sliding filaments mach and Ca re-pumping during relaxation.
Macroscopic events of muscle contraction
Fatigue of muscles
Depend on the ratio of phasic and tonic fibers.
IN VITRO FATIGUE:
Lack of O2 and lack of transmitters.
IN VIVO FATIGUE:
Peripheral- decrease of energy sources and increase in metabolic products
Central fatigue- exhausting of motor units.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Endocytosis
A form of active transport in which a cell transports molecules (such as proteins) into the cell (endo+cytosis) by engulfing them in an energy-using process.
Opposite: Exocytosis
The regulation of muscle work and muscle-nerve connection: The motor unit.
Regulation of muscle function
Synthesis of vesicles in the golgi of motoneuronflow of vesicles toward the knobthe synthesis of the acetylcholine in the cytosolthe action potential tuning through. The axon opens voltage gated Ca channels and the Ca influx from the EC increase the Ca-concentration and initiate the acethylcholinge containing vesicles
The regulation of muscle work and muscle-nerve connection: The motor unit.
Regulation of muscle function
Exocytosis
Exocytosis:
Acetylcholine gets into the synaptic space,
Some disappears
Most is bound to receptors
Small amount of end plate potential is produced, but there is not enough to create a action potential.
Extensive exocytosis result in the lack of vesicle and will be refilled with acetylcholine.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Regulation of muscle function
Endocytosis
Endocytosis: Stimulated by clathrin. Traps a section of the membrane and carries into the cell. Fine movement 1:1 ratio of nerve fibers Other skeletal muscles: 1:100
The regulation of muscle work and muscle-nerve connection: The motor unit.
Muscle type
Acetylcholine: Inactivetivated, open, closed
Nicotinc Acetylcholine:
Two alpha and two delta subunits, blocks the effect of certain competitive blocks.
Increase in EC magnesium concentration antagonize acethylcholine receptors and blocks function of the sarcomere.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Motor unit
The action potential is generated and runs to the myoneural junction,
The acetylcholine containing vesicle open up at the synaptic knobs Ach to Ach-R of sacrolemma.
The Ach channels opens up
Na+ enters through the channels and the end potential + action potential is generated.
The action potential activated the sarcoplasmic reticulum through the t system.
The Ca is released in the sacrolemma, and the contraction starts.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Fusimotor system:
There are modified fibers that play a role in the stretch-detection and the fine tuning of muscle cells.
We can find receptors in the Golgi tendon receptors.
We have: Static fibers Dynamic fibers Efferent fibers Afferent fibers aplha-efferent gamma-efferent co-activation system
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Static fibers
Static fibers:
Sensitive to length change of tension
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Dynamic fibers
Sensitive to length and velocity of tension
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Efferent fibers
From the central nerve system.
The longer away from the CN, the thinner the fibers
It uses the greek alphabet.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Afferent fibers
From the periphery
The large alpha-motor neurons innervate the phasic muscle.
Small alpha-motorneurons innervated the tonic muscles. Small adjustments.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Alpha-efferent
Makes the big contractions.
Servomechanism:
Without the influence from the cerebral motor center.
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Gamma-efferent
Fine adjustments
The regulation of muscle work and muscle-nerve connection: The motor unit.
Fusimotor system
Co-activation system
Co activation mechanism:
Both alpha and gamma-efferent.
Rapidly corrects any error in motor command execution.
Characheristics of Smooth muscle
General
The myosin and the action are less organized and the muscle contraction are not voluntary.
Characheristics of Smooth muscle
Units
Multiunit:
The individual fibers are not connected with gap junction
Single fibers or small groups are under direct neural control.
Capable for fine movements.
Single units:
Hundreds of units connected with a gap junction.
The nerves only innervate the cells on the surface.
Characheristics of Smooth muscle
Contraction
The sliding activated by myosin light chain kinase.
The contraction is continuous until there is another enzyme
The SM is not based on ALL or NOTHING law
They are usaly in weak contraction all the time.
No transverse tubular system.
The action potential occurs only in single units.
