FoM_FoNF Flashcards
define aetiology
cause of disease
define pathogenesis
how disease develops
define symptoms
what patients notice and feel
define signs
what the doctors observe
define diagnosis
the identification of the nature of an illness or other problem by the symptoms
define prognosis
the likely course of a medical condition
define natural history
collects health information in order to understand how the medical condition or disease develops and how to treat it
what is pathology
the study of disease
what are the different classifications of disesae
inflammatory disorder of circulation disorder of cell growth degenerative developmental unnatural
what is inflamation
succession of changes occurring in living tissue when it is injured
e.g. meningitis
what is circulatory disturbances
abnormalities of flow, vessel wall, components of the blood
e.g. myocardial infarction
what is disorders of growth
abnormal cell growth: maturation, differentiation, quantity, control
e.g. cervical carcinoma
what id degenerative disorders
heterogeneous group
abnormalities of tissue and organs
e.g. amyloidosis
what is developmental
abnormalities of gametogenesis and embryogenesis
e.g. down syndrom
what can unnatural conditions be
traumatic
iatrogenic
what is traumatic
accidental or deliberate
e.g. fractured bone
what is iatrogenic
treatment related
e.g. immunosuppression in chemotherapy for malignancy
what is general organisation of the body systems
the human body is a complex society of cells, structurally and functionally organised into tissues and organs
the cell is the smallest unit of the body we commonly refer to but it is made up many internal components
these components form machinery that create energy to power the cell and allow it to function
what is the equation of life
nutrients + O2 = energy (ATP) + waste (incl. CO2)
define homeostasis
maintaining an optimum internal environment within the body
how do the major systems maintain health and optimal homeostasis
involves cooperative action of organ systems, coordinated by nervous system and endocrine system (hormones)
why is it important to maintain constancy of the internal environment
in an effort to prevent disturbance and maintain optimum “similar conditions” or, in other words, a relatively constant internal environment in which all processes work optimally
what is negative feedback mechanism
when a condition that is homeostatically regulated is sensed to have shifted from the normal range, a signal is generated that produces a response that corrects the original disturbance
Causes a return to a set point
Negative feedback is the most common type of homeostatic feedback.
It aims to reduce the disturbance of a monitored variable – think about the example of getting dehydrated when working outside on a hot day. The threat to water balance in the body is countered by an increased thirst, driving the individual to seek water
Negative feedback is a key aspect of maintaining homeostasis
cannot prevent the disturbance from happening
what is feed forward systems
more sophisticated than negative
additional receptors permit system to anticipate (predict) change and therefore activate response earlier
the threat to water balance is counteracted by the kidney detecting the increased body fluid concentration and pre-empts a state of dehydration. It responds by producing smaller volumes of urine, and a more concentrated form of urine, thus conserving water
what is positive feedback mechanism
uncommon in homeostasis but does occur and is vitally important when it does
opposite of negative feedback as negative aims to restore disturbed conditions, positive sets off a train of events that lead to an even greater disturbance
amplifies the response
e.g. nerve action potential
what is the daily water balance in man and how does this affect homeostasis
Water makes up 60% body weight so about 42L
Homeostatic maintenance of water is crucial because water affects the concentration of everything else in the body
what are the different body fluid compartments and what is the distribution of water
intracellular fluid and extracellular fluid
intracellular fluid (ICF) is found within the cells
ECF is made up of :
- plasma, the dynamic component of ECF that is contained within blood vessels (it surrounds blood cells)
- interstitial fluid (ISF), the fluid outside blood vessels that surrounds cells other than blood cells.
2/3 of the water is in the intracellular fluid while 1/3 is in the extracellular fluid
intracellular - 28L
interstitial - 11L
plasma - 3L
what is the nature of the barriers which separate the body compartments
the cell membrane separates the ICF and the ECF and has selective permeability
the capillary wall - separates plasma and the ISF and is permeable to everything but plasma protein and blood cells
water has no barriers and moves by osmosis
what is the dilution principle
based on the DILUTION PRINCIPLE, (3 things to remember )
- c = m/v, v = m/c = Dilution Principle
- ONLY plasma can be sampled, only compartments of which plasma is a component can be measured directly (plasma, ECF, TBW).
- The NATURE of BARRIERS which separate compartments is crucial in determining the test substance.
describe the use of the dilution principle in the measurement of body fluid compartments
Compartments that can be measured directly using the Dilution Principle:
- Plasma Volume (PV): Since plasma proteins cannot cross the capillary walls, can use dyes or radioactive labels that attach to plasma proteins, e.g. Evans blue or I125albumin.
- Extracellular Volume (ECF): Need something that freely crosses capillary walls, but cannot cross cell membranes, e.g. inulin, sucrose, mannitol, which are all too large to cross cell membrane or 24Na+ , 36Cl-, which are actively extruded from cells.
- Total Body Water (TBW): There is no barrier to water in the body, so can use a loading dose of heavy water/ deuterated water (D2O).
Other compartments (where plasma is not a component) cannot be directly sampled, calculate volume indirectly;
ISF = ECF-PV, ICF = TBW-ECF
which structures are present in all cell types
plasma membrane cytoplasm cytosol ribosomes nucleus (eukaryote) / nucleoid (prokaryote)
what is the role of the nucleus
Contains DNA, nucleoprotein and some RNA
Nucleoli are sites of ribosomal RNA synthesis and ribosomal assembly
The nucleus is enclosed in the nuclear membrane which, like all biological membranes, is a phospholipid bilayer. It is closely associated with the Rough Endoplasmic Reticulum
what is the role of the endoplasmic reticulum
membrane bound
Endoplasmic reticulum comes in rough (RER) and smooth (SER) varieties
RER has ribosomes attached giving it the “rough” appearance
RER modifies proteins
SER has no ribosomes attached and is mainly associated with lipid and steroid hormone production and metabolism of toxins
what is the role of ribosomes
synthesise proteins
what is the role of the golgi apparatus
packages up protein in preparation for transport out of the cell
what is the role of lysosomes
re membrane bound vesicles containing enzymes – they separate enzymes from the rest of the cell
what is the role of mitochondria
also organelles bound by a phospholipid bilayer
Outer membrane contains pores
Inner membrane has cristae (folds)
Matrix contains most of the enzymes required for metabolising food molecules (e.g. Krebs cycle)
They have their own circular DNA
They have their own ribosomes – similar to bacterial ribosomes
They synthesise most of their own proteins
They can self-replicate
what is the structure and function of the eukaryotic plasma membrane
Comprises a double layer of lipid with attached phosphate groups = phospholipid bilayer
Forms a selective barrier, being choosy about what it allows to cross in or out of the cell
Embedded in the membrane are proteins which act as receptors to detect chemical messengers and signalling molecules in the fluid surrounding cells (extracellular fluid)
what is the role of the cytoskeleton and what classes of protein form the cytoskeleton
only found in eukaryotes and is organised into internal compartments
supports and maintains cell shape
holds organelles in position
helps move organelles around the cell
it is composed of one of three forms of protein:
microfilaments
intermediate filaments
microtubules
what is apoptosis
controlled, programmed cell death
It is a normal process and essential for normal function
Apoptosis and cell proliferation are intimately coupled
Loss of balance between apoptosis and proliferation is associated with some cancers
what is necrosis
untimely death of cells in response to injury or infection. It is not a normal process.
what are stem cells
cells that can differentiate into many (multipotent) or any (pluripotent) cell types of the body
what are cilia and fagela
both are made of microtubules
Cilia—short, usually many present, move with stiff power stroke and flexible recovery stroke
Flagella—longer, usually one or two present, movement is snakelike
what are the major elements used to construct human biomolecules
Hydrogen (H) (1)
Oxygen (O) (2)
Nitrogen (N) (3)
Carbon (C) (4)
these make up more than 99% of the mass of most cells
they are the lightest atoms and are able to make bonds (the numbers in the brackets show hoe many bonds they make)
which of the four atoms (H,O,N,C) is the most versatile
carbon
It can form stable
- Single bonds (with H)
- Single and double bonds (with O and N)
- Single, double and sometimes triple bonds with other C atoms
This variety of bonding capability underlies the evolution of all the different combinations of H, O, N and C into biological molecules
what do biomolecular functionality depend on
the presence of particular functional groups and the way in which these are arranged in space define biomolecular function
which biochemical reactions are the 5 chemical reactions of life
Redox reactions
Making and breaking C-C bonds
Internal rearrangements
Group transfers
Condensation and hydrolysis reactions
give an example of a redox reaction
In many biological redox reactions two e-’s (and two protons) are gained or lost
Often 2 hydrogen atoms (protons) are transferred from one molecule to another in dehydrogenation reactions
e.g.
NAD+ being reduced to NADH (as it gains electrons and thus list its positive charge
NADH is the reducing agent (as It donates electrons to pyruvate causing pyruvate to be reduced to lactate. In doing so NADH loses an electron thus gains +ve charge and becomes oxidised to NAD+. )
NADH a reducing agent (which becomes oxidised itself to NAD+ as it reduces other compounds)
NAD+ is an oxidising agent (which becomes reduced itself as it oxidises other compounds)
give an example of making and breaking C-C bonds
e.g. Cleavage of glucose in the glycolysis pathway
give an example of internal rearrangements
e.g. Also in glycolysis, a rearrangement of the conformation of G6P occurs before the sugar is split
give an example of group transfers
e.g. Also in glycolysis…
In an enzyme catalysed reaction, a phosphoryl group (PO32-) is transferred from ATP to F6P
ATP provides energy for cellular reactions
give an example of condensation and hydrolysis
Condensation reactions occur where two smaller molecules combine to form a larger molecule and in doing so release water (or other small molecules e.g. methanol).
Hydrolysis reactions involve adding water to a molecule, and most commonly simultaneously breaking down a large molecule into smaller units.
The sub-units of proteins, polysaccharides and nucleic acids are all joined by condensation and broken by hydrolysis reactions
what is the general structure of nucleic acids
These form the core structure of DNA and RNA
Put simply, they are polymers of nucleotide monomers linked by 3’,5’-phosphodiester bonds
A nucleotide monomer is formed from a base (see below), a sugar molecule and a phosphate group:
There are 2 kinds of base in nucleic acids
Pyrimidines – cytosine (C), thymine (T) (DNA only) and uracil (U) (RNA only)
Purines – adenine (A) and guanine (G)
RNA is formed from “normal” ribose sugars
DNA is formed from deoxyribose sugars, which lack an oxygen atom
what is the general structure of lipids
A family of molecules made up of fatty acids There are three classes of lipids: Triacylglycerides Phospholipids Sterols
what are triacylglycerides
Also called triglycerides
Storage lipids
Non-polar
3 fatty acid chains linked to glycerol
what are phospholipids
Similar to triacylglycerides,
But they have only two fatty acids chains and a phosphate group attached to the ‘head’ of these chains
This makes them polar
They form biological cell membranes – very important!
what are steroids
Produced in plants, animals and some micro-organisms
Most important one in humans is cholesterol
Another essential component of cell membranes
Precursor to steroid hormones and fat soluble vitamins (A, D, E)
what does hydrophobic mean
water hating
water repelling
lipophilic
what does hydrophilic mean
water loving
water soluble
lipophobic
e.g. sugars, alcohols, aldehydes, ketones, compounds with N-H groups, charged particles such as ions
what does amphipathic mean
have both water loving (hydrophilic) and repelling (hydrophobic) parts
e.g. most proteins, phospholipids
what does polar mean
charge within the molecule is not evenly distributed
e.g. water, the polarity gives rise to hydrogen bonding, such bonding are not unique to water
what are hydrogen bonds
link groups/molecules in precise pattern in space
H bound to N,O,F
molecules containing what tend to be hydrophobic/hydrophilic
molecules which form hydrogen bonds tend to be water-soluble
O2 and CO2 are non-polar and poorly water-soluble
charged molecules tend to be water soluble
how do non-polar (uncharged) molecules arrange themselves
arrange themselves in water so as to minimise disruption of water-water hydrogen bonding
what is pH
a convenient way of expressing [H+] over a wide range of concentrations
Water has a neutral pH because [H+] and [OH-] are equal
Acidic solutions have a greater [H+] and lower [OH-]
Basic (alkaline) solutions have a lower [H+] and higher [OH-]
Note: 1 pH unit represents a ten-fold increase or decrease in [H+]
what is a buffer
a mixture of a weak acid and its conjugate base
biological aqueous solutions resist pH changes sue to buffers being present
buffers maintain the pH of a solution relatively constant
what does a simple equation relate
pH, the buffering action of a weak acid and the Ka of that acid
which buffers in our body are important in our body
phosphate and bicarbonate
what is the henderson - hasselbalch equation
pH is proportional to the ratio of buffer to H-buffer ([buffer] / [H-buffer])
the more buffer you have the more pH goes up (increases alkalinity) and teh more H-buffer you have, the more pH goes down (increases acidity)
Alternatively, if pH goes down, either buffer has gone down or H-buffer has gone up, and vice versa!
What is the structure of membranes
Phosphate head: hydrophilic
Fatty acid tails: hydrophobic
Proteins
What is the function of the cell membrane
Cell membranes act as selective barriers between ECF and ICF. They provide binding sites for chemical recognition (eg, in development and for hormones and neurotransmitters). Differences in membrane proteins are responsible for the varied characteristics of membranes.
What are the different types of membrane proteins and their function
Integral proteins- span the hydrophobic core of the lipid bilayer
Peripheral proteins- associated only with the phosphate head of the lipid bilayer and do not penetrate the hydrophobic core
Define electrochemical gradient
Because the ions creating the concentration gradients are charged particles there is also a difference in charge across the membrane. This creates an electrical gradient.
The net effect of these two forces create an electrochemical gradient which ultimately drives the direction of passive movement.
Any movement against this gradient requires energy (active transport).
electrochemical gradients sare important in determining the movement of ions across membranes
what are the different mechanisms for movement of particles across the membrane
- Diffusion
- either:
i) protein channels or; ii) protein transporters
- Active Transport
- Osmosis
- Filtration
what is the process of endocytosis
there is invagination of the cell membrane to form a vesicle which eventually disintegrates on the cytoplasmic (inside) surface of the membrane, releasing contents which then migrate within the cell to their destination.
what is the process of exocytosis
involves the reverse process of endocytosis. Many proteins manufactured in cells are released from those cells by the process of exocytosis.
what is meant by diffusion across membranes
Process by which a substance in solution expands to fill all the available volume. molecules spread from regions of high concentration to regions of low concentration, until the concentration is uniform (equal) throughout the volume.
it is the major force acting across the membrane and occurs through the lipid bilayer or via protein channels which may be of a number of different types
what is the difference between passive diffusion and facilitated diffusion
Passive diffusion – substance moves directly through the lipid bilayer
Facilitated diffusion – substance requires assistance from membrane proteins to cross the lipid bilayer.
what is the difference between facilitated diffusion and active transport
facilitated diffusion - movement of molecules through transport proteins is down an electrochemical gradients
active transport - movement of molecules through transport proteins against their electrochemical gradients requires energy (ATP)
what are the different types of membrane proteins and their functions
protein channels
- ligand gated: controlled by binding of signal molecules. when the correct signal molecule binds, the gate opens allowing ions to flow through
- voltage gated: controlled by changes in ion concentration
transporter proteins: bind to the specific substances to be transported and undergo a conformation change to transfer the solute across the membrane. transporters alternate between two conformations so that the binding site for a solute is sequentially exposed on one side of the bilayer, then the other
protein pumps: active transport uses pump proteins that transfer substances across the membrane against their concentration gradient. pump that carry out active transport are transporter proteins couples to an energy source e.g. the sodium potassium pump (Na/K- ATPase
what is meant by carrier mediated transport systems
carrier mediated transport proteins provide a mechanism for transport across the membrane, either down a concentration/electrochemical gradient = facilitated diffusion, or against such gradients = active transport
what is meant by osmosis
the diffusion of water only
water will always move down an osmotic gradient so the volume of a cell at any time is dependent on the number of non-penetrating solutes on the 2 sides of the membrane
what is the difference between osmosis and diffusion
Osmosis: Net movement of H2O from regions of high H2O concentration to regions of low H2O concentration
Where as:
Diffusion: Net movement of solute from regions of high solute concentration to regions of low solute concentration
Water can move freely between cells and the ECF so that the body is in osmotic equilibrium. Not all solutes move freely.
ALL H2O movements in the body are passive, (via aquaporins, protein water channels).
H2O concentration is inversely related to the concentration of solute, ie the more solute particles there are in solution, the more they will displace H2O molecules lowering the concentration of H2O.
what is the difference between osmolarity and tonicity
Osmolarity describes total number of particles in solution
Tonicity describes the number of non-penetrating particles in solution
definitions of isoosmotic, hypo-osmotic and hyper-osmotic
Osmolarity describes the TOTAL number of solute particles.
An isosmotic solution has the same total number of solute particles as normal ECF (plasma). (300 mosmol/l)
Solutions with fewer total solute particles are hypo-osmotic.(less than 300 mosmol/l)
Solutions with greater number of total solute particles are hyper-osmotic (more than 300 mosmol/l)
definitions of isotonic, hypotonic, hypertonic
Tonicity describes the total number of non-penetrating solute particles e.g. ions
An isotonic solution has the same number of non-penetrating solute particles as normal ECF (plasma). (300 mosmol/l)
Solutions with fewer non-penetrating solute particles are hypotonic. (less than 300 mosmol/l)
Solutions with greater number of non-penetrating solute particles are hypertonic. (more than 300 mosmol/l)
what happens to the cell if it is placed in a hypotonic or a hypertonic solution
Cells in hypotonic solutions swell – because water enters down a chemical gradient
Cells in hypertonic solutions shrink – because water leaves down a chemical gradient
only changes in tonicity cause changes in cell volume, osmolarity has no affect
what are the major determinants of ECF tonicity
Na+ (and Cl-)
what is the most sensitive organ to changes in tonicity
the brain
what are the major determinants of ICF tonicity
K+
what is the average circulating volume of blood in a typical 70kg adult male
5L:
- 1L in lungs
- 3L in systemic venous circulation
- 1L in heart and arterial circulation
what are the functions of blood
- Carriage of physiologically active compounds (plasma)
- Clotting (platelets)
- Defence (white blood cells)
- Carriage of gas (red blood cells)
- Thermoregulation
- Maintenance of ECF pH
what is blood made of
plasma
red blood cells
white blood cells
platelets
what is plasma made of
4% body weight
95% water
what are the plasma proteins
albumin
globulin - subdivided into α, ß, γ globulins
fibrinogen and other clotting factors
what is (colloid) oncotic pressure and how is it generated
Net direction of movement is determined by balance between colloid oncotic pressure (favours movement into capillary) and capillary hydrostatic pressure (blood pressure) which favours movement out of capillary.
Result: concentration of fluid remains unchanged, volume of plasma and interstitial fluid alters
Interstitial fluid acts as fluid reservoir (volume approx. 3-4 times greater than plasma)
what is the lifespan of red blood cells
120 days
what is the lifespan of platelets
10 days
what is the function of red blood cells
- Carriage of physiologically active compounds (plasma)
- Clotting (platelets)
- Defence (white blood cells)
- Carriage of gas (red blood cells)
- Thermoregulation
- Maintenance of ECF pH
what is the function of erythropoietin
erythropoiesis is controlled and accelerated by the hormone erythropoietin
erythropoietin stimulates the progression of Pluripotent Stem cells into becoming immature erythroblasts
where is erythropoietin synthesised
85% is synthesised in the kidney
15 % is synthesised in the liver
which factors increase the secretion of erythropoietin
Secretion is enhanced when oxygen delivery to kidneys is reduced (hypoxia)
situations that increase secretion of erythropoietin include:
- haemorrhage
- anemia
- cardiac dysfunction
- lung disease
what are the 5 types of white blood cells
granulocytes: - neutrophils (most abundant = 86%) - eosinophils (about 1%) - basophils (least abundant = <1%) agranulocytes: - monocytes (5%) - lymphocytes (25%)
what is the difference between monocytes and macrophages
macrophages after 72 hours migrate to connective tissue where they become macrophages and live for 3 months
which factors control white blood cell formation
leukopoiesis
more complex than erythropoiesis because there are many different types of wbc’s
Controlled by a cocktail of cytokines (proteins/peptides released from one cell type which act on another).
colony stimulating factors
interleukins (meaning between wbc’s)
what is the function of platelets
Adhere to damaged vessel walls and exposed connective tissue to mediate blood clotting
DO NOT adhere to healthy intact endothelium.
what is the role of thrombopoietin in platelet formation
Formation of platelets is governed by Thrombopoietin
what is meant by haematocrit
blood is made up of many components
the haematocrit is the measurement of the percentage red blood cells to whole blood
what is the normal value for haematocrit
40-50%
when may the haematocrit change
in dehydration- that number will increase
will increase under the influence of erythropoietin (illegally)
what is blood viscosity
How thick/sticky blood is compared to water.
Plasma - x 1.8 thicker than water
Whole blood - x 3-4 thicker than water
when may viscosity of blood change
Viscosity is not an absolute value, depends on:
haematocrit - 50% increase in haematocrit increases viscosity approx. 100%
temperature - increase in temp decreases viscosity and vice versa. 1oC changes viscosity by around 2%
flow rate - decreased flow rate increases viscosity and vice versa.
what is the main role of the immune system
the body’s ability to resist or eliminate potentially harmful foreign material
provides immunity/protection from infectious diseases
what is the difference between innate and adaptive immunity
innate:
Non-specific
Distinguishes between human cells and pathogens, but not between different types of pathogen
Fast and immediate: first to come into play
No memory: will produce the same response
adaptive:
Highly specific
Distinguishes between different pathogens based on shapes on the surface – called antigens
Slower: Can take few days to develop
Immunological memory: memory cells remember
which cells are involved in the innate immune response system
cellular: phagocytes eosinophils, mast cells basophils humoral: complement cytokines
what are phagocytes
are the cells of the immune system that track down, engulf and destroy bacteria, other pathogens as well as own damaged or dead cells.
common phagocytes are neutrophils and monocytes
what are neutrophils
Most abundant White Blood Cells (WBCs) (8x106/ml~50-60%)
Track down, engulf and destroy pathogens,
They contain granules that are filled with many destructive enzymes such peroxidases, alkaline and acid phosphates which are responsible for kill and destroy bacteria and other pathogens
what are monocytes
Monocytes (macrophages):
~5% of WBCs, larger than neutrophils
Can engulf much more
Macrophages (big eaters):
Break down pathogens, process specific components of these pathogens called antigens and present these processed antigens to the cells of the adaptive immunity to produce specific immune response in the form of antibody and cytotoxic T cells
Antigen Presenting Cells (APCs)
what is the porocess of phagosytosis
Movement of the phagocyte toward the microbe
Attachment of microbes to phagocyte surface
Endocytosis of microbe and formation of phagosome
Fusion of phagosome with lysosome
Killing of microbe through digestion by enzymes
Discharge of waste materials
what is eosinophil
Help combat parasitic infections.
Involved in allergy and asthma.
Granules contain many enzymes.
what are mast cells
a type of white blood cells and they have granules that contain substances that are toxic to parasites and host tissues. They have on their surfaces, receptors that are specific to IgE antibodies (IgE Abs) and can bind to them, this class of Abs are usually produced against some parasites and some allergens. When these antibodies that are bound to mast cells interact and bind with these substances which are called allergen, mast cells release their granules` content which includes many chemicals mainly histamines. this leads to local effects like runny rose, watery eyes, itching, which are characteristic to allergic diseases such hay fever, but if the amount of histamine released is larger, then this might lead to constriction of airway which might cause breathing difficulties, the main symptom of Asthma, or dilation of blood vessels which cause low blood pressures and sometimes death.
what are basophils
Least abundant of WBCs (less than 1%)
Contain large cytoplasmic granules with inflammatory mediators.
No proven function
Found in parasitic infection
what are cytokines
Small proteins – secreted by both immune and some nonimmune cells in response to stimulus.
They communicate with other cells
bind to specific receptors on these cells producing a signalling molecules that lead to many biological effects in these cells
Key players in innate and acquired immunity
Differentiation
Activation
Chemotaxis
Enhancing cytotoxicity
what are the components of the lymphatic system
lymphatic vessels
lymphatic organs
- primary lymphatic organs (bone marrow & thymus)
- secondary lymphatic organs (lymoh nodes, spleed, tonsil…)
what is the function of the lymphatic system
Drainage of tissue
Absorption and transport of fatty acids and fats
Immunity
what is the function of the primary lymphoid organs
Places where blood cells are produced and receive their ‘early training’
(acquire ability to interact with antigens)
Bone Marrow (production of T cells & B cells, maturation (training) of B cells)
Thymus
what is the function of the secondary lymphoid organs
Sites of Lymphocyte activation by antigens
The development of adaptive immune response to Antigens by T and B cells
Lymph nodes
Spleen
Mucosal Immune system (Peyer`s Patches)
Tonsils
where are t cells produced, matured and activated
production: bone marrow
maturation: thymus
activation: any of the secondary lymphoid organs
where are b cells produced, matured and activated
production: bone marrow
maturation: bone marrow
activation: any of the secondary lymphoid organs
what are t lymphocytes
T cells are responsible for cell mediated immunity and assisting B cells
About 1012 in a human body
what is CD8+
Cytotoxic T cells:
T lymphocytes with CD8+ receptors (Cell surface receptor is the T Cell Receptor (TCR) which only recognises antigens when bound to MHC I) - Killing
what is CD4+
Helper T cells
T lymphocytes with CD4+ receptors (Cell surface receptor is the T Cell Receptor (TCR) which only recognises antigens when bound to MHC II)
- Stimulate B Cells to produce antibody
what are T helper cells (Th)
Cannot kill infected cells or pathogens
Activate and direct other immune cells
what is the function of Th1, Th2 and Th17
Th1: for example, activate macrophages.
Th2: activate Eosinophil, mast cells.
Th17: activate neutrophil particularly in their phagocytic activity.
what is the function of natural killer cells
provide first line of defense against many viruses. As they can distinguish between infected and uninfected host cells they are able to target and kill infected cells.
what is the role of b cells in immunity
B cells Involved in humoral immunity
Main function is the production of antibodies
Antibodies directed against antigens
B cells produced and mature in the bone marrow
B cells express B Cell Receptor (BCR)
On activation, they are differentiated into Plasma cells (responsible for Abs production), with the help of T helper cells
what are antibodies
proteins that are produced as an immune response against antigens
Different antigens induce the production of different antibodies
what is the structure of antibodies
can be divided into two regions
Upper region is called antigen binding region, the specific part of the antibody that recognises and interacts with antigen.
The lower region is called Fc region .
what are the three mechanisms by which Antibodies can prevent infections with microbes
neutralisation
Opsonization or facilitating phagocytosis
Complement activation through the classical pathway
what is the complement system
Complement system consists of more than 30 proteins/factors that are found in the plasma, present in an inactive form
They are activated in a cascade –like format
activation of the complement in fact takes place on the surface of the target cells
what are the three functions of the complement system
Direct lysis of target cells.
enhance the immune response
enhance phagocytosis
what is the final product of complement activation and what is its effect on microbes
The final result of C activation in any of these pathways leads to the production of membrane attack complex (MAC ) which basically makes a hole in the target cells and eventually leads to direct lysis and destruction of these targets.
what are the different classes of amino acids
aliphatic amino acids - ‘R’ group consisting of hydrocarbon chains
aromatic amino acids - ‘R’ group consisting of hydrocarbon ring
sulfur containing amino acids (disulphide bridges)
basic amino acids (contain NH2)
acidic amino acids (contain COO)
polar amino acids (contain OH)
what is the primary structure
The sequence in which amino acid monomers are
synthesised and bonded together to form a polypeptide chain
what is the secondary structure
hydrogen bonding along the backbone of the protein strand results in regions of secondary structure
these structures are:
alpha helices
parallel or antiparallel beta pleated sheets
turns
what is the tertiary structure
the polypeptide folds into a tertiary structure
this conformation is stabilised by interactions between R groups such as:
hydrophobic interactions ionic bonds london dispersion forces hydrogen bonds disulfide bridges - covalent bonds between R groups containing sulfur
what is the quaternary structure
quaternary structure exists in proteins with two or more connected polypeptide subunits
it describes the spatial arrangement of the subunits
The oxygen-carrier haemoglobin is an example of a
globular protein with quaternary structure
what is the function of proteins
structural proteins enzymatic proteins receptor proteins hormonal proteins transport proteins storage proteins defensive proteins contractile proteins
Protein functions usually involve interactions (often specific) with other biomolecules. Proteins have diverse functions, but all have the same general structure, an unbranched linear polymer of L-amino-acid residues, linked by peptide bonds (a polypeptide). There are twenty genetically-coded amino-acids.
what are globular protein
Storage Enzymes Hormones Transporters Structural
what are fibrous proteins
Muscle fibres
Connective tissue
what are membranous proteins
Membrane transporter
Membrane enzymes
Cell adhesion molecules
what is an enzyme
A protein molecule that catalyzes chemical reactions without itself being destroyed or altered
Biological catalyst that differs from a chemical catalyst:
- Catalyses very high reaction rates
- Shows great reaction specificity
- Work in mild temperature/pH conditions
- Can be regulated
Very important – nearly all biochemical reactions involve them
catalyse reactions by lowering activation energy of reactions
how will the rate of the reaction vary when enzyme concentration is changed
increasing the enzyme concentration will speed up the reaction so long as there is substrate available
how will the rate of the reaction vary when enzyme concentration is changed
the more substrate that’s available the quicker the enzymes collide and bind with them
what are V, V0, Vmax, [S], Km, in Michaelis-Menten
V = velocity aka rate
V0 = initial reaction velocity
Vmax = maximum reaction velocity
[S] = substrate concentration
Km = the substrate concentration when the reaction is at ½ the maximum velocity (Vmax)
what do Km and Vmax tell us
Km – how specific the enzyme is for the substrate
- Low value = good fit
- High value = poor fit i.e. takes a lot of substrate to get to ½ Vmax
Vmax – how fast a reaction is proceeding when the enzyme is saturated with substrate
what is a competitive inhibitor
an inihibitor binds to the active site of the enzyme and prevents the substrate from binding
how does a competitive inhibitor affect Vmax and Km
Vmax unchanged
Km increases because it takes more substrate to overcome the inhibition
what is a non-competitive inhibitor
an inhibitor binds to a secondary site on the enzyme. this changes the shape of the active site and prevents the substrate from binding
how does non-competitive inhibition affect Vmax and Km
Vmax decreased
Km remains the same
why is enzyme activity measured in a clinical setting
Tissue damage
Determine origin of affected tissue
Diseases related to enzyme defects
What factors determine enzyme activities in serum/plasma?
The release of enzymes from cells may be triggered by a number of processes:
Hypoxia – loss of oxygen supply due to occlusion, or inadequate oxygenation, or loss of oxygen carrying capacity
Cellular damage due to chemicals, drugs
Physical damage due to trauma, surgery, burns, radiation etc.
Immune disorders – anaphylaxis, autoimmune disease etc
Microbiological agents – bacteria, viruses, fungi, protozoa, helminths
Genetic defects – many, e.g. Duchenne’s Muscular Dystrophy
Nutritional disorders – protein-calorie, vitamin, mineral deficiency
what are problems with enzyme measurement
Not specific i.e. can be found in more than one tissue in the body.
Particular requirements – temperature, pH etc.
Assays must be optimised
