the pateint Flashcards
what is aerobic metabolism?
Cells require nutrients and oxygen uptake and the removal of carbon dioxide
Distance and dehydration limits of diffusion rate, and therefore size and habitat
There is the development of specialised, internalised respiratory epithelium
what two regions, can we divide the respitory system into
Conducting airways
respiratory airways
What is the conducting zone?
there is no gas exchange here
It’s refers to the air passages that lead to site of respiration so gas exchange can occur
The passages external to the lungs are:
Nasal cavities
Larynx and pharynx
Trachea
Primary bronchi
What is the time in a part of the conducting system?
bronchioles: bronchi within the lungs, branch extensively to form bronchioles
What is the respiratory zone?
it is responsible for gas exchange
It’s refers to the zone that is a part of the respiratory system with gas exchange takes place
This includes:
Respiratory bronchioles
Alveolar ducts
Alveolar sacs
Alveoli
What are the nasal cavities lined with?
sweat glands
Sebaceous glands
Hair follicles
what does the olfactory mucosa do
this is, what’s the nasal cavity is lined with
It’s provides a sense of smell
what is repiratory mucosa
this is what the nasal cavity is also lined with
It secretes an anti-bacterial enzyme and mucus
What is the main purpose of the function of the nasal cavities?
to warm, humidify and filter inhaled air
what are the three sections of the pharynx
nasaopharynx, oropharynx, laryngopharynx
Part of the digestive system and respiratory system
what is the epiglottis
It’s forms an important physical separation
It is a flap that covers the trachea during swallowing, so that food does not enter the lungs
What is the function of the larynx?
it is required for speech
It’s contains to vocal folds, which vibrate with breathing
Laryngeal muscles alter tension, positioning of the folds to create different sounds
What is the structure of the trachea?
The trachea is slightly flattened, connecting the upper and lower airways (nasal and bronchiole Airways)
It’s has C-shaped cartilage rings which allows flexibility and also prevents the trachea collapsing
What is the function of the bronchi?
they help to defended the airways
Goblet cells produce, sticky mucus to trap bacteria
Bronchial epithelial cells produce antimicrobial peptides
Ciliated epithelium cells beat the mucus to the pharynx
what is the mucociliary escalator
sticky mucus made of glycoproteins, traps inhaled particles and bacteria
Celia project into the periciliary fluid and a liquid layer secreted by epithelial cells
The action of the ciliary beating the move, the mucus raft to the back of the throat
what are factors that slow mucociliary transport
cigarette smoke
Dehydration
Positive pressure ventilation
Endotracheal suctioning
High inspired, oxygen concentrations
Hypoxia
Atmospheric pollutants
General anaesthesia
Parasympatholytic drugs
what are the alveolar ducts and sacs
alveolar ducts are tiny ducks, connecting respiratory bronchioles to the alveolar sacs
They are surrounded by smooth muscle, elastin, and collage
Each alveolar sac contains a bunch of alveoli
They are structurally important as a maintains the architecture of the lung to permit gas exchange
Alveolar sacs are collections of alveoli, joined by alveoli docs
what to type of cells are alveoli made up of?
type 1
type 2 (replenish damaged type 1 cells)
pneumocytes
What are alveolar macrophages?
they are in the alveoli
And they patrol at the tissue for defence. Provide protection.
What is the function of type one cells?
They give a thin barrier for gas exchange
What is the function of type two cells?
they secrete a surfactant and defend molecules and repair damage
What is cellular respiration?
Biochemical reactions that produce ATP
What is external respiration (ventilation)
Physiological process for oxygen and carbon dioxide, uptake, transport and elimination
How does external respiration or ventilation occur?
it involves transporting oxygen from the atmosphere to cells
And transport and carbon dioxide from cells to the atmosphere
What are the five important factors in the process of breathing?
inspiration
Expiration
Compliance
alveolar surface tension
pulmonary surfactant
what is the parietal pleura
lining inside of the throatic cavity
what is the visceral pleura
they cover the long in between the pleural space
Are they contain? pleural fluid which reduces friction
what is negative intrapleural pressure
where interpleural pressure is less than atmospheric pressure
what is a pneumothorax
where damage to the pleural cavity that equalises atmospheric and intrapleural pressure results in a pneumothorax
what happens in a small pneumothorax
air Collects between the lung and the chest wall
what happens in a large pneumothorax
A lot of air collects and pushes on the lung and heart
what is the treatment of a large pneumothorax
Trapped air is removed by using a chest tube
what is pleural effusion
fluid in the pleural cavity
what events occur during inspiration
thoratic cavity lifts upwards and outwards
external inter coastal muscles contract pulling ribs together
internal inter coastal muscles relax
sternocleidomastoids and scale us pulls ribs up
diaphragm contracts and flattens to increase volume
lungs expand
Pulmonary pressure is less than atmospheric pressure which causes air to flow into the lungs
What event occurred during expiration
external intercostal muscles relax. Whereas the internal intercostal muscles contract?
throatic cage lift downwards and inwards
The diaphragm relaxes decreasing its volume and the lungs contract
Pulmonary pressure is greater than atmospheric pressure therefore air is forced out of the lungs
what are the forces during inspiration
outward recoil of chest wall
inward recoil of alveoli
air flows in due to pressure gradient
describe passive expansion of alevoli
alveoli cannot expand by themselves
they respond passively to an increase in pressure across the alveoli wall
Muscles of inspiration contract, which causes intrapleural pressure to become more negative
TPD increases, Alviola pressure decreases, so Alviola volume increases
Air flows into the alveoli
what is TPD
transmural pressure difference
TPD= intrapleural pressure (outside) - alveolar pressure (inside)
what are forces at the end of expiration
no airflow
atmospheric pressure = alveolar pressure
inward elastic recoil of alveoli is balanced by outward recoil of chest wall
normal quiet breathing summary inspiration
diaphragm contracts
chest wall expands
throatic volume increases
intrapleural pressure becomes more negative
alveolar TPD increases
alveoli expand
pressure difference is established
air flows into alveoli until pressures equilibrate
normal quiet breathing summary expiration
inspiratory muscles relax
throatic volume decreases
intrapleural pressure becomes less negative
alveolar TPD decreases
drop in TPD allows alveoli elastic recoil to return to pre inspirstory volume
pressure difference established
air flows out of alveoli
until pressures equilibrate
what is lung compliance
change in volume divided by change in pressure
C=changeV/changeP
L/cm^3
what does a lower compliance suggest
more intrapleural pressure to change the volume
eg in pulmonary fibrosis which has lead to scarring
what does a higher compliance suggest
less pressure is needed
eg in emphysema due to damaged alveoli
what is defined by compliance
the measure of the lungs ability to inflate
what affects compliance
many diseases
how is compliance measured
changes in pressure and colume
how are changes in volume measured
spirometry
how are changes in pressure measured
more difficult but
a balloon for oesophageal pressure
how does emphysema increase compliance
tissue damage
less elastin
easier to inflate
less elastic recoil
how does fibrosis reduce compliance
more collagen
harder to inflate
increases elastic recoil
what is elastance
is the inverse of compliance
stiff lungs have high elastance and low compliance
what is elastin
more compliant
easier to inflate
what is collagen
less compliant
harder to inflate
what is alveolar surface tension
what makes water form droplets
elastic recoil of the lungs is a function of alveolar surface tension
saline filled lungs have a lower elastance than air filled lungs
what are two factors that stabilise alveoli
structural independence of alveoli
pulmonary surfactant
what is alveolar interdependence
alveoli are not bunches of grapes, or even Sephias structurally alveoli are polygons with shared flat walls
Alveoli are held open by the chest wall, pulling on the outer surface of the lung
Alveoli are dependent on each other
a Collapsing Alveoli increases the stress on adjacent alveoli, these would tend to hold it open
What is a pulmonary surfactant?
it is a complex mixture of lipids and proteins that lines, the alveoli in the lungs
It acts to reduce the surface tension of the fluid that lines, the alveoli, making it easier for the lungs to inflate and preventing the collapse of the alveoli during exhalation
what is produces pulmonary surfactant?
type 2 pneumocytes
How does pulmonary surfactant stabilise the lungs?
premature babies without functional surfactant have difficulty in inflating their lungs
there is a tendency for spontaneous alveolar collapse
hypoxia may reduce surfactant production and can lead to acute respiratory distress syndrome
neonates are given exogenous surfactant
how do you use a spirometer
inverted canister in a water filled space
inner space is connected to tubing into which the person breathes
breathing pattern is traced on the rotating drum
what is tidal volume
the amount of air moved in and out the lungs during a normal breath
what is residual volume
it is the air that remains in the lungs after maximal exhalation
what is expiratory reserve volume ERV
is the additional amount of air that can be forcefully exhaled from the lungs after normal exhalation
what is inspiratory reserve volume
the additional amount of air that can be forcefully inhaled into the lungs after normal inhalation
what is functional residual capacity FRC
is the volume of air that remains in the lungs after normal exhalation, when the muscles of respiration are at rest
what is inspiratory capacity IC
is the maximum amount of air that can be inhaled into the lungs after normal exhlation
what is total lung capacity TLC
the maximum amount of air the lungs can hold after maximum inhalation
what is vital capacity VC
is the maximum amount of air that can be exhaled forcefully after maximum inhalation
what is restrictive disease
eg fibrosis
reduced compliance and increased elastic recoil
increased breathing rate
what is obstructive disease
eg emphysema
increased compliance/resistance
decreased elastic recoil
decreased breathing rate
what are limitations of spirometry
it can only measure the king volumes exchanged by a conscious con operative subject
it cannot measure
RV
FRC
TLC
what is nitrogen wash out technique
it is a way of measuring lung volume
Nitrogen watch out technique (you breathe 100% oxygen, and measure how much nitrogen is expelled)
What is the helium dilution technique?
it is another way of measuring lung volume
(Breathe a known volume of helium, and measure the helium left at a steady rate/state)
what is body plethysomography
It’s measures the change in pressure in a closed system
how to calculate TLC
RV+VC=TLC
how to calculate RV
FRC-ERV=RV
what is minute volume
is the volume of air entering and leaving the nose every minute
what is anatomical dead space
refers to the volume of air that occupies the conducting airways of the respiratory system
What is alveolar ventilation?
It’s refers to the volume of air that reaches the alveoli, where the gas exchange occurs per unit of time
what is alveolar dead Space
it refers to the portion of the alveoli volume that is ventilated but not perfused
it occurs when the alveoli are ventilated, but do not receive sufficient blood flow for gas exchange.
what is physiological dead space
anatomical dead space + Alveolar dead space
what does Boyles law state?
The absolute pressure exerted by a given mass of an ideal gas is inversely proportional to the volume it occupies, If the temperature and amount of gas remain unchanged within a close the system.
P1V1=P2V2
What does Boyles law mean?
as you breathe in, the volume of your lungs increases, so the pressure decreases, allowing air to flow into the lungs
what does Dalton’s law of partial pressure state?
The total pressure exerted by the mixture of non-reactive gases is equal to the sum of the partial pressures of individual gases
what does Dalton’s law mean?
Changes in the percentage of gas in the lung create a driving force (pressure differential) to move the gases into and out of the lungs
what is the calculation for Dalton’s law?
P total = P1+P2+P3 exc
What does Henry’s law state?
at a constant temperature, the amount of a given gas that dissolves in a given to type and volume of liquid is directly proportional to the partial pressure of the gas in the equilibrium with that liquid.
What does Henry’s law mean?
That’s the amount of oxygen transported into the blood depends on partial pressure. Oxygen has to be transported in the blood as a dissolved gas
what happens during oxygen exchange?
oxygen is carried physically dissolved in the blood and chemically combined to haemoglobin
Oxygen enters the blood in the lungs down it’s partial pressure gradient
Oxygen leave the blood in the tissues down it’s partial pressure gradient
What happens during carbon dioxide exchange?
carbon dioxide enters the blood in the tissues down. It’s partial pressure gradient
Carbon dioxide, leave the blood in the lungs down its partial pressure gradient
What are factors that affect gas exchange?
The rate of gas exchange will be reduced if:
Partial pressure gradient is reduced
Surface area for exchange is reduced
The distance for transfer is increased
The solubility of gases reduced (temperature dependent)
Why is the diffusion coefficient for carbon dioxide greater than oxygen?
Because carbon dioxide is much more soluble in water than oxygen
Haemoglobin let us transports the oxygen we need tell me more
4 polypeptide chains to our four and two beta subunits
there is one haem group per polypeptide
One iron group per haem
One oxygen molecule per iron
Each molecule of haemoglobin can carry up to 4 molecules of oxygen
This increases oxygen carrying capacity
How do you measure haemoglobin?
using a haematocrit
What is a haematocrit?
It’s measures the percentage of red blood cells in a total volume of blood
It is also sometimes referred to as a packed cell volume (PCV)
It’s usually lies between 37 and 54%
What are factors affecting oxygen Carriage by haemoglobin?
PH
Partial pressure of carbon dioxide
Temperature
what is the bohr effect
increase in carbon dioxide, concentration, lowest blood pH. Resulting in the ability of haemoglobin to transport oxygen.
The lower pH causes haemoglobin to release more oxygen
A higher pH causes haemoglobin to hold onto more oxygen
Lactic acid is produced, the pH is a reduced, therefore more oxygen is released at the site of muscle activity . The curve shift to the right.
How does increasing the temperature affect oxygen transport by haemoglobin?
A small increase in temperature also shift the curve to the right
Blood temperature is higher than metabolically, active tissues
This affect helps to unload oxygen from haemoglobin
At low blood temperature haemoglobin will not release oxygen, and there is a very high affinity for the binding of oxygen in the lungs
factors effecting O2 carriage by Hb
2.3 diphosphoglycerate
it is produced by red blood cells during normal glycolysis
However, this chemical binds to haemoglobin and reduces the affinity for oxygen
An increase in this chemical will shift the curve to the right
How is fetal haemoglobin structure any different to normal adult haemoglobin?
Fetal haemoglobin has a higher affinity for oxygen
The curve is shifted to the left
Fetal blood can acquire oxygen from maternal, placental blood
What is carboxyhaemoglobin?
haemoglobin has a 240 times higher affinity for carbon monoxide than oxygen
Haemoglobin plus carbon monoxide formed carboxyhaemoglobin
This reaction is less reversible and it’s shift the curve to the left
Carbon monoxide prevents oxygen loading into the lungs and oxygen unloading in the tissues
Smoking/urban pollution can increase carboxyhaemoglobin concentration
What are the three main ways to transports carbon dioxide?
physically dissolved in the blood (10%)
Bound to haemoglobin (30%)
As a HCO3 (60%) bicarbonate
describe the transport of carbon dioxide by the blood
Carbon dioxide combines with water to form carbonic acid than this disassociates to hydrogen ions and bicarbonate ions
Carbonic anhydrase catalyses this reaction. This is an enzyme that is present at high concentration in red blood cells.
What is the chloride shift?
Movement of bicarbonate ions out of the red blood cell creates proton gradient. Chloride ions are taken into the red blood cell.
what is the haldane effect
This allows the blood to load more carbon dioxide at the tissues. Where there is more deoxyhemoglobin and unload more carbon dioxide at the lungs by there is more Oxy haemoglobin.
an increase of oxygen in the blood displaces carbon dioxide from haemoglobin
Therefore, the tendency of haemoglobin to combined with carbon dioxide is decreased. Therefore carbon dioxide is released on return to the alveoli.
This is the opposite of the bohr effect
What is the primary function of the respiratory system?
It is to take oxygen and to remove carbon dioxide in order to maintain normal levels of partial pressure of oxygen and carbon dioxide
What are the three requirements for the respiratory control system?
it must be automatic
It must be adaptable
It must be subject to voluntary control
Why must the respiratory control system be automatic?
maintenance of carbon dioxide and oxygen levels should not depend on levels of consciousness or alertness
Why must the respiratory control system be adaptable?
There must be mechanisms to compensate for changes in oxygen uptake or carbon dioxide production
Why must the respiratory control system be subject to voluntary control?
there must be mechanisms to voluntarily override, the respiratory control mechanisms, at least for brief periods of time
What is the central controller?
The respiratory centre is located in the medulla oblongata. It receives input from the sensors peripheral and central chemoreceptors.
Neural control of respiration is involved with three components what are these?
factors that generate inspiration and an expiration rhythm
Factors that to generate magnitude of breathing (depth and rate)
Factors that modify, respiration for other purposes (speaking and coughing)
What reduces medullary output?
The pneumotaxic centre
the apneustic centre
what is the primary respiratory control centre?
Medullary respiratory centre
What is the dorsal respiratory group (DRG)?
it is mostly inspiratory neurons
fire muscles, contract inspiration
Stop muscles relax passive expiration
what is the ventral respiratory group (VRG)
inspiratory and expiatory neuron’s are in active in normal and quiet breathing
active inspiration/expiration activates
what generates respiratory rhythm
pre-botzinger complex in the medullary respiratory centre
A network of neurons here display a pacemaker activity
The rate of DRG firing is driven by this complex
what does the pneumotaxic centre do
it is where the impulses are sent to the DRG
It’s switches off Inspiratory neuron’s
Its limits inspiration
what does the apneustic centre do
It’s prevents inspiratory neurons stopping
It’s boosts inspiratory drive
what happens when there is no pneumotaxic centre
creates apneustic breathing
There is a prolonged inspiration with brief, expiatory, gasps,
It is associated with some to severe brain damage
Why is cooperation key in the raspatory centres?
they cooperate to regulate the rate and depth of breathing as an involuntary unconsciousness activity
respiratory centre responds to the physiological needs of the body for oxygen and carbon dioxide, exchange and for blood acid-base balance 
What does the PRG control?
Timing of inspiration, speech and sleep
What is the central pattern generator?
there is no single pacemaker in your own responsible for initiating, breathing, groups of neurons generate bursts of activity
Breathing requires a complex interaction of at least six groups of neurons
There is three phases to the respiratory cycle
What are the overall three phases of the respiratory cycle?
inspiratory phase
Post inspiratory phase (expiatory phase 1)
Expiatory phase 2
What happens in inspiratory phase?
neuronal activity: there is a sudden onset by early inspirtory neutrons this is followed by a ramp increase in inspiratory augmenting neurons
Muscular effector function: inspiratory muscle contraction
What happens in post inspiratory phase (expiatory phase 1)
neuronal activity: reduced discharge from inspiratory, augmenting neurons, expiatory, decrementing, active
Muscular effect to function: reduced activity of inspiratory muscles: passive expiration
What happens in expiatory, phase 2
neuronal activity: expiatory, augmenting neurones can be activated
Muscular effector function: inspiratory muscles are silent; expiatory muscle activity increases gradually.
What usually happens in quiet, breathing
Expiration almost completely is passive
What happens in active breathing?
Exploration almost is completely active; there is high activity of expiatory augmenting neurons
What to do chemoreceptors do?
They determine partial pressure of oxygen and carbon dioxide and hydrogen ions and provide feedback to the breathing centres of the brain to modify rate and tidal volume
What are the two types of chemoreceptor?
Central and peripheral
Where are central chemo receptors found?
in the Medulla
What does an increase in partial pressure of carbon dioxide do?
It increases ventilation
What do central chemoreceptors respond to?
Partial pressure of carbon dioxide
Where are peripheral chemo receptors found?
in the neck and thorax
What does the peripheral chemo receptors do?
They detect changes in oxygen and carbon dioxide
They respond to partial pressure of oxygen
What is hypoventilation?
A reduced breathing rate
what does hypo ventilation lead to?
Can produced an increased partial pressure of carbon dioxide and a reduced partial pressure of oxygen
what does hyperventilation lead to?
an decrease in ventilation
What are the five cardinal signs of inflammation?
Redness (rubor)
Swelling (turgor)
Heat (calor)
Pain (dolor)
Loss of function
what is the triple response
A model of neurogenic inflammation
Whitening, wheal, and flare
Under what conditions does inflammation appear
it is a consequence of injury, infection or other disease
What is chronic inflammation
present within weeks/months after insult
Greater tissue destruction
Cellular infiltrate
More fibrous tissue present
What is acute inflammation?
rapid in onset
Duration is day is two weeks
Changes in blood flow
An increase in vascular permeability
Accumulation of protein, rich oedema fluid (white blood cells)
What are the possible outcomes of acute inflammation?
resolution
Abscess formation (suppuration)
Healing (scar)
Chronic inflammation
What is the stereotypical response in acute inflammation?
local changes to their microcirculation
Increased blood flow to the capillaries
Increased permeability
Escape of plasma and plasma proteins to form serous exudate
Escape of white blood cells
What does changes in vasculature blood flow mean?
that is a possible smooth muscle response
Widespread dilation of arterioles, and venules
hyperaemia 10x more blood flow
Construction of veins, leading to the local increase in pressure
Leakage of plasma leads to slowing of blood flow in vessels (stasis) encouraging cell, adhesion and clotting
What does vascular permeability lead to?
an increase in pressure which causes increased
exudate carrying foreign matter carried to lymph glands, where immune response is initiated
What does white blood cell recruitment entail?
expression of adhesion molecules
emigration of neutrophils
Directed to the site of injury/infection by chemo, taxis
Neutrophils are predominant in the first 24 hours
What is the role of neutrophils?
they live for 3 to 4 days
They die at the inflammatory site
The phagocytose and engulf and remove agent
Microbial killing is achieved by lysosomal enzymes and free radicals generated in the respiratory burst
what are morphological features
Cardinal signs
Severe skin injury (blisters)
Epithelial injury
Boil (collection of neutrophils and debris is pus)
What are the advantages of the effects of acute inflammation?
Dilution of toxins
plasma protein, release (antibodies)
Fibrin formation
cell nutrition
plasma mediator system, activated
Promotes immunity
What are the harmful effects of acute inflammation?
swelling (obstruction of breathing)
Interference with blood flow (meningitis)
Inappropriate inflammation
What are the resolutions of acute inflammation?
removal of stimulus
No permanent loss of function
Associated with healing
Excessive scarring
What happens in chronic inflammation
main white blood cell is macro phage
Healing and repair coexists with inflammation
Fibrosis is main cause of loss of function
what are eicosanoids
they are a group of signalling molecules that are derived from poly unsaturated fatty acids
They are produced locally in response to stimuli, such as injury or infection
They are 20 carbon fatty acids from membrane phospholipids, which are oxygenated and poly unsaturated
what is PGE2 in inflammation?
It’s causes pain
It enhances bone turnover and cartilage degradation in arthritis
It acts on called sensitive neurons in the hypothalamus (fever)
what does LTB4 do
Neutrophil activation
what does LTC4 and LTD4 do
They increase vasodilation
what does LTC4, D4 and E4 do
The increase mucus secretion (asthma)
What is histamine?
it is an amine that has many actions in both the periphery, and in the central nervous system
It is released in type, one hypersensitivity. Common in allergies and allergens, including contact, dermatitis, eczema, hayfever, food allergy
Tell me more about histamine
it is a basic amine
It is actively taken up by platelets
It is found in mast cells and other white blood cells, some nerves and specialised cells in the gut
H1 is involved in inflammation
H2 is released in the acid in the stomach
H1-H3 are GPCR receptors
describe the pathophysiology of the H1 Receptor
It’s causes muscle contraction and increases post capillaries venule permeability
It’s a decrease in blood pressure, mainly by receptors on the arterioles, but constrict blood blood vessels
H1 receptors on nerve endings cause itch
They have a role in allergy and hayfever due to an increase in vascular permeability
what is the bradykinin cascade
tissue injury and collagen exposure
Leads to activation of clotting cascade
kallikrein and kinases
Activation of sensory nerve endings an increase in vascular permeability
what is substance P
it has 11 amino acid nuclear found in sensory nerves
a member of the neurons in family of peptides
pain transmitter in the spinal cord
releases histamine and other inflammatory mediators
mediator of neurogenic inflammation
opioid peptides
endorphins and enkaphalins
block pain transmission at the spinal cord
stimulate pathways in the brain to block pain transmission and perception
what are similarities between T and B cells
they are lymphocytes
they develop in the bone marrow
they have diverse AG receptors on their surface
why are T cells unlike B cells
they mature in the thymus
exert their functions by interacting with other cells of the immune system
they recognise different Ag (peptides, processed, presented with MHC)
they never release a soluble Ag receptor
their receptor doesn’t change on Ag recognition
what does the Fc region of an antibody do
talks to the rest of the immune system
what does the Fab region of the antibody do
binds to Ag
what is the TCR
the T cell receptor
antigen receptor of T cells
resembles a membrane associated Fab fragment of immunoglobulin
describe the structure of the TCR
membrane bound glycoprotein
(heterodimer)
one Ag binding site
Ag binding at the top surface
two transmembrane domains per chain
short cytoplasmic tail
what does the one Ag binding site in the TCR
consist of
one alpha chain TCR alpha
one beta chain TCR beta
what are the hyper variable regions on a TCR molecule
Complimentary determining regions (CDRs)
On loops at tip
how does TCR diversity effect gene arrangement
happens pre-antigen
gene segment recombine for each chain (DNA rearrangement)
Essentially, using the same mechanisms as for B cells
what is different with TCR and B cells
in B cells, after Ag binding, heavy chain, constant regions could change (class, switching of Ab)
This doesn’t ever happen with the TCR
what consists of the alpha chain
V&J regions
only 1C region
what consists of the beta chain
V,D and J regions
2C regions but there is no functional difference
what do alpha chains like
light chain (V-J)
what do beta chains like
heavy chains
(D-J) then (V-DJ)
why is RAG important (RAG1 and RAG2)
recombination activating gene
what is RSS
Recombination signal sequences
what is SCID
severe combined immunodeficiency
Happens when there is a lack of functional B and T cells
opportunistic infections
lethal during infancy unless treated or BM transplant
various mutations can cause this including RAG defects
list ways in which there could be TCR diversity
rearrangement of the gene segment (DNA)
Transcription (RNA)
Splicing (mRNA)
Translation (rough endoplasmic reticulum)
Endoplasmic reticulum (Association of alpha and beta chains, transport to T cell serface)
explain how extra proteins are needed for TCR expression
TCR complex is required for exit from ER
4 invariant chains are required
held together with strong electrostatic interactions
Signalling components of TCR
Defects here lead to immuno deficiency
what are the two classes of T cell population
a chain & b chain
y chain and sigma chain 1-5%
less frequent
Less studied
Less variable
how do T cells recognise Ag
though TCR
what is the TCR complex required for
Required for trafficking and signalling
why are there two different classes of MHC and T cell
to deal with different pathogens (intracellular/extracellular)
To interact with different T cells
How do T cells help?
defined to an antigen on either a macro phage or B cell (MHC)
Cytokines, then destroy this antigen
Correct antibodies are now formed from the plasma cell, or there is an activated macro phage
CD4
how do T cells kill
CD8 T cell binds to a virus, infected cell
There is a cell contact
Lysozymes are released and a dead virus infected cell is produced
what does MHC do
allows CD4/CD8 to bind
what does the MHC bind to
CD8/CD4 and TCR + (co-receptor)
what are the 2 major compartments of a cell
cytosol
vesicular system
what is the cytosol
peptides from intracellular pathogens
what is the vesicular system
peptides from extracellular pathogens
What is the class one pathway?
cytosolic proteins are degraded
This generates peptides
Which are transported into the endoplasmic reticulum lumen
TAP (transporter of antigenic, peptides), transport class, one type, peptides
chaperone holds MHC1 til it binds
Peptide loading complex is formed
TAP delivers the peptide
The complex disassociates, and it is loaded to the surface
MHC1 is loaded with a peptide that is too long at the N-terminus
ERAP removes terminal amino acids to give a peptide of 8 to 10 residues
MHC class 1 molecule travels to the cell surface
what can class 1 not do
leave the ER without a peptide
what happens in Bare lymphocyte syndrome
non functional TAP
peptides cannot enter the endoplasmic reticulum
That is very low levels of surface MHC class 1
That is a low cytotoxic, T cell response (CD8)
Chronic respiratory infections, poor response to viruses
what else do MHC class 1 do
display self antigens too
displays peptides derived from normal self proteins
there is no immune response to these, unless self reactive T cells have been allowed to leave the thymus (autoimmunity)
what is the MHC class 11 (2) pathway
phagocytosis
Phagosome
Lysosome function
Peptide formation
Vesicular fusion
Peptide loading
binding of peptides to MHC class 11 molecules in the ER
in vesicles invariant chain is cleaved leaving the CLIP fragment bound
CLIP blocks binding of peptides to MHC class 11 in vesicles
HLA-DM facilitate the release of CLIP
Allowing peptides to bind
MHC 1 expression profile
most human cells
MHC class 11 expression profiles
professional (APC)
thymic epithelium for T cell testing
what are MHC molecules
polygenic
enclosed by different gene families
different classes
clustered in chromosomal region MHC
are polymorphic
another word for different variants
isotypes
another word for different alleles
allotypes
how many MHC class 1 does each human cell contain
3 class 1 from each parent
6 class 1 per cell
how does MHC prevent a population being susceptible to a single infection?
Permits lots of different peptide presentations
what is MHC a primary reason for
it is the major reason for transplant rejection, so a perfect match is needed (twins or clones)
