Download cell is smallest unit of life - life is made out of very complex

Biological background I
What did we learn so far?
- cell is smallest unit of life
- life is made out of very complex molecules, called macromolecules
- cell function is very complicated - lots of things are going on at the same time
in a single cell
I will attempt to give you in the next three lectures an overview of
1) macromolecules,
2) cell structure
3) immune system - how are cells communicating with each other?
My attempt is to give you a mini - mini -mini crash course!
1) Macromolecules
Building blocks of macromolecules
Living organisms also contain a large number of small, simple molecules ranging from
water, metal ions, to sugars and glucose.
Despite the diversity of macromolecules the most common atoms found in living
organisms are carbon (C), oxygen (O), nitrogen (N), hydrogen (H), little amounts of
sulfur (S) and phosphorous (P)
make-up of cell: 59% H, 24% O, 11% C, 4% N, 2% P and S
H = Part of water and all organic molecules
O = Respiration; part of water; and in nearly all organic molecules.
C = Constituent (backbone) of organic molecules
N = Constituent of all proteins and nucleic acids.
P = Constituent of DNA and RNA backbones; high energy bond in ATP
S = Constituent of DNA and RNA backbones; high energy bond in ATP
Living organisms are constructed from 4 great classes of macromolecules. Each of
them performs a different function:
50% protein
15% nucleic acid
15% carbohydrates
10% lipids
10% Other
Now we will discuss the essential structure and function of each of these
macromolecules.
- function
- building bocks
- why do we care in this class?
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1) Nucleic acid
function: serve as information-carrying molecules
Building blocks: Nucleotide
There are five common bases (nucleotides),
adenine (A), guanine (G), cytosine (C), thymine (T), uracil (U)
Larger molecules: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid):
DNA: encodes genetic instructions
has two stands which are twisted together to form a double helix
four nucleotides: adenine (A), guanine (G), cytosine (C), thymine (T)
held together by weak hydrogen bonds (H atom is shared between two atoms)
RNA: assembled like DNA but only has a single strand
four nucleotides: adenine (A), guanine (G), cytosine (C), uracil (U)
How to identify: Contain N in rings, nucleotides made of sugar, phosphate and
nitrogenous base
The human (Homo sapiens) genome is the complete set of human genetic information,
stored as DNA sequences within the 23 chromosome pairs of the cell nucleus and in a
small DNA molecule within the mitochondrion.
Why do we (biophysicists) need to know about DNA structure?
- resistance of DNA to bending and twisting dramatically influences the packaging of the
genome and the expression of the information that lies within.
- The ability of a virus to package, transport, and deliver its genome to a host cell
involves the precise manipulation of DNA throughout the life cycle of the virus.
Understand physical mechanisms responsible for the control that a virus over DNA
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- Dynamic strategies for target-site search by DNA-binding proteins: search by allowing
proteins to slide and hop along DNA. We develop a reaction-diffusion theory of protein
translocation that accounts for transport both on and off the strand and incorporates the
physical conformation of DNA
2) Proteins:
function: Enzymes, structure, receptors, transport, and more
building blocks: amino acids
polypeptides: two or more amino acids joined together by peptide bonds
protein: contains one or more polypeptides
Proteins are long chains of amino acids held together by peptide bonds.
Proteins are made out of 20 distinct amino acids: they can have
- electrically charged side chains (positve, negative)
- hydrophilic (polar)but uncharged side chains
- hydrophobic (non-polar)
How to identify: Contain N and have N-C-C backbone
A little bit more about proteins:
Protein synthesis:
- process by which biological cells generate new proteins.
- In transcription, RNA Polymerase produces (messenger) mRNA.
- In translation, the ribosome uses mRNA and tRNA to produce proteins.
Transcription
Is the process of creating an equivalent RNA copy of a sequence of DNA. Both RNA and
DNA are nucleic acids, which use base pairs of nucleotides as a complementary
language. During transcription, a DNA sequence is read by RNA polymerase, which
produces a complementary, antiparallel RNA strand. Transcription results in an RNA
complement that includes uracil (U) in all instances where thymine (T) would have
occurred in a DNA complement. The result of transcription is messenger RNA (mRNA),
which will then be used to create that protein via the process of translation.
Translation
Is the third stage of protein biosynthesis (part of the overall process of gene expression).
In translation, messenger RNA (mRNA) produced by transcription is decoded by the
ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into
an active protein. Translation occurs in the cell's cytoplasm, where the large and small
subunits of the ribosome are located, and bind to the mRNA. The ribosome facilitates
decoding by inducing the binding of tRNAs with complementary anticodon sequences to
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that of the mRNA. The tRNAs carry specific amino acids that are chained together into a
polypeptide as the mRNA passes through and is "read" by the ribosome in a fashion
reminiscent to that of a stock ticker and ticker tape. In many instances, the entire
ribosome/mRNA complex will bind to the outer membrane of the rough endoplasmic
reticulum and release the nascent protein polypeptide inside for later vesicle transport and
secretion outside of the cell.
Protein structure
- describes the various levels of organization of protein molecules
- four levels of structural organization, primary, secondary, territory and
quaternary
Primary structure:
- sequence of amino acids
- determines the three-dimensional structure and properties of proteins.
Secondary structure:
- long polypeptide chains are folded or coiled in a number of ways.
- most common form of coiling is the right handed alpha helix.
- other β-pleated sheet
Tertiary structure:
- coiling and folding of secondary structure
- way the structure folds has an important bearing on the properties of the
protein.
- folding brings together active amino acids, which are otherwise scattered
along the chain, and may
- Four Forces Driving Protein Structure Formation
(1) van der Waals forces: covalent, rigidity of protein molecule.
(2) Hydrogen bonds: weak but numerous, give stability
(3) Ionic or electrostatic bonds
(4) Hydrophobic bonds: nonpolar side chains of neutral amino
acids associate with one another.
- Protein in water exposes maximal number of its polar groups
Quaternary Structure:
- Two or more polypeptide chains
Why do we (biophysicists) need to know about protein structure?
Why do proteins fold? Thermodynamic stability of proteins: contributions from enthalpy
and entropy
How do they fold? protein folding kinetics
Protein dynamics: • Protein structures fluctuate on many different timescales (10e-9 sidechain motion, 1s protein folding, • They can unfold (and refold), • They can switch to
another conformation Since proteins do things: bind to other molecules (change their
shape) need to understand structure and fluctuations in it!
nanoparticles want them to attach to cells to tell cell to do something - engineer
nanoparticles (coat) so they perform function we want! Do we need flexible nanos?
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3) Carbohydrate
function: Energy storage (starch glycogen), receptors, structure of plant cell wall
(cellulose, chitin)
building blocks:
Monosaccharide: Simplest form of sugar, basic units of carbohydrates
Polysaccharide: Large carbohydrate Formed by many long chains of
monosacchrides
empirical formula Cm(H2O)n with some exceptions
How to identify: Made of C,H, and O; –OH's on all carbons except one
Why do we (biophysicists) need to know about protein structure?
Carbohydrates: one of the main type of nutrients
Carbohydrate bioengineering is a rapidly expanding field with many applications in
medicine and industry.
design and manufacture of tailor-made carbohydrate molecules for the needs of, for
example, the food, textile or pharmaceutical industries
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4) Lipids
function: Membrane structure, energy storage, insulation
building blocks:
Triglycerides: Energy storage
- "frame" of a triple alcohol (that OH is the alcohol part) called glycerol.
- THEN, long chains of fatty acids are added to each OH
Fatty acids: lipid building block
- the fatty tail: non-polar (hydrophobic)
- carboxyl head: polar (hydrophilic)
- Fatty acids can be
- saturated: as many H bonded to their C
- unsaturated: one or more double bonds connecting C ==> less H
phospholipid
- has two fatty acid chains attached to a glycerol molecule.
- a phosphate (PO4) is in place of the third chain attached
- is negatively charged and interacts nicely with water (hydrophilic)
-- the fatty chains are hydrophobic and don't interact with water.
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- Fats: solid lipids at room temp (mostly saturated),
- oils: liquid lipids at room temp (mostly unsaturated),
Why do we (biophysicists) need to know about protein structure?
- we need to make artifical mebranes in our labs
- When we study protein motion in cells membranes we might want to study effects of
mobility ==> want to make different lipid bilayers of different mobility ==> use different
amount of saturated and saturated lipids
How to identify: Made of C,H, and O; lots of C-H bonds; may have some C=C bonds
(unsaturated)
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Biological background II
5) Adenosine-5'-triphosphate (ATP)
function:
-most important as the "molecular currency" of intracellular energy transfer.
- ATP transports chemical energy within cells for metabolism.
building block: nucleotide + phosphate group
Between phophates we have high energy bonds.
Why do we care?
Energy management in the human body
- chemical reactions within body to store, release, absorb and transfer energy to move,
breath, pump blood
- food we eat provides energy: body digests food we make glucose combine with oxygen
to form water, CO2 and energy C6H12O6 + 6O2 ==> 6CO2 +6H2O +Eout
It takes time to breath, transport oxygen, deliver glucose to a muscle cell for
example. If the power we need in a muscle is increased abruptly we need another
form of energy - this is ATP which we can store, ATP does not require oxidation to
make energy.
ATP involved in molecular motors: how they walk on microtubules
binding of ATP to motor's foot results in a conformational change of the protein(foot)
and foot binds. Then ATP gives off a phosphate and becomes ADP (adenosinediphosphate) (energy is released) and foot (protein unbinds)
The conversion of these two molecules (ATP < - > ADP) plays a critical role in
supplying energy for many processes of life. The deletion of one of ATP’s phosphorus
bonds generates approximately 31 kilojoules per Mole of ATP (7.3 kcal).
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2) Cell Structure
Draw parts while presenting - fill in cell structure
Basic components of the cell (give basic description and function of each)
Membranes:
- Double phospholipid layers (Bilayer) forms a barrier with an outside and an inside.
- flexible. This is possible because the phospholipids are not chemically bonded together;
rather they stay together because of the hydrophilic and hydrophobic interactions.
- contains also a high number of proteins which help relay information (signals)
from the outside of the cell to the inside of the cell or visa versa.
nuclear membrane - the membrane that surrounds the nucleus.
nucleus
-
controls protein synthesis
contains DNA (in chromosomes).
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nucleolus - an organelle within the nucleus
- it is where ribosomal RNA is produce
- Some cells have more than one nucleolus.
- transcription of RNA==> tRNA
- early site of protein synthesis
ribosome - small organelles composed of RNA-rich cytoplasmic granules that are sites of
protein synthesis.
- free inside cell or attached to RER outside nucleus
- tRNA translated into proteins
centrosome - (also called the "microtubule organizing center")
- a small body located near the nucleus
- it has radiating tubules.
- The centrosomes is where microtubules are made.
cytoplasm - the jellylike material outside the cell nucleus
- in which the organelles are located.
Golgi body - (Golgi apparatus or golgi complex) Packing organelle like ER
- a flattened, layered, sac-like organelle that looks like a stack of pancakes
- located near the nucleus.
- It produces lysosomes.
- packages proteins and carbohydrates into membrane-bound vesicles for "export"
from the cell
lysosome - (also called cell vesicles)
- round organelles surrounded by a membrane and containing digestive enzymes.
- This is where the digestion of cell nutrients takes place.
mitochondrion - spherical to rod-shaped organelles with a double membrane.
- converts the energy stored in glucose into ATP (adenosine triphosphate) for the
cell.
Endoplasmic reticulum (ER)
- forms an interconnected network of tubules, vesicles, within cells.
- (sac-like structures) held together by the cytoskeleton
- serves many general functions, including the facilitation of protein folding and
the transport of synthesized proteins in sacs called cisternae.
- cisternae are sent to the Golgi body, or inserted into the cell membrane
rough endoplasmic reticulum - (rough ER)
- covered with ribosomes that give it a rough appearance.
- synthesize proteins
smooth endoplasmic reticulum - (smooth ER)
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-
-
contains enzymes
produces and digests lipids (fats) and membrane proteins
metabolize carbohydrates and steroids
3) Immune System
http://www.nobelprize.org/educational/medicine/immunity//immune-detail.html
How does our immune system work?
How do cells communicate with each other?
- The immune system is one of nature's more fascinating inventions.
- The immune system is very complex.
- It is made up of several types of cells and proteins that have different jobs to do in
fighting foreign invaders.
- When the immune system is fully understood, it will most likely hold the key to ridding
humankind of many of its most feared diseases.
There are two parts to the immune system (IS)
- Recognition and response.
1) Recognition:
- recognizes foreign molecules known as pathogens such as viruses, bacteria,
fungi, and parasites,
- distinguishes between self and non-self.
2) Response: invading molecules are recognized
- effector response: neutralize pathogens by
- effector cells which are activated
These cells don’t do anything until they are activated.
- The immune response makes you sick. You get fewer or aching since the
response releases chemicals which are the symptoms one feels when we get sick.
Autoimmunity: Sometimes the IS fails and it turns against itself, autoimmunity.
The IS is coordinated in two different ways:
1) the innate response and
2) the adaptive response.
We say that this division is artificial since one does not work without the other
1) Innate Response:
- non-specific and works the same for everything (there is no different fewer for
different pathogens).
- has no memory and does not happen faster the second time.
- occurs within hours of infection, lasts about 1 day
2) Adaptive Response:
- specific against specific molecules. For example an influenza response will not
help you against another virus.
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- immune response develops memory
- response is faster and stronger the second time..
- occurs after ~ 1day and lasts multiple days and longer
How Does the Immune System work? A Brief Overview
Plan A: First the IS prevents infection by relying o the barriers to entry like the skin,
mucous membrane (both anatomical barriers) or physiological barrires like body
temperature, or pH (~2 in our stomach which is unpleasant for some pathogens).
If plan A is successful health is maintained.
Plan B:
a) When plan A fails the innate IS is activated to destroy the invaders. We notice
this when we get fewer. If the innate immune response is successful health is
restores and the immune response is terminated.
b) If the innate response is unsuccessful it activates the adaptive immune response
which we hope will destroy the pathogen. If this happens health is restored and
we obtain some memory.
c) If the adaptive immune response fails as well we die. If it was only partially
successful one might develop chronic diseases.
Now I will give a glimpse of the immune system and the intricate ways in which its
various parts interact. Immunity is a fascinating subject that still conceals many secrets.
Important Nomenclature:
Antigen (Ligand):
sometimes a protein
An antigen is anything that is recognized by the body's immune system as foreign.
The antigen binds to a receptor or antibody on the immune cell and stimulates the cell.
The part of the antigen molecule to which the antibody binds is called the epitope.
could be pieces from an invador
A stimulated cell can make new antibodies ==> ANTIbody GENerator.
Antibody:
a protein
An antibody is a protein that is secreted by an immune cell in response to a stimulus.
An antibody is the protein that is produced against a specific antigen.
An antibody binds to that specific antigen only
receptors:
a protein
Molecule that is found on the surface of a cell (embedded in cell membrane)
receives signals from the outside and brings them to the inside of the cell
Numerous receptor types are found in a typical cell
Each type is linked to a specific biochemical pathway
an antibody can bind to a receptor - like IgE
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there are also antigen (Ligand) receptors
Affinity:
Antigen and antibody binds covalently, the reaction is reversible. Some lock on really
strong others less. Antibody affinity refers to the strength of the binding of antibody
to the ligand epitope: high affinity bond is very strong. We also call it on-off rate, how
long the bound holds. The bond can be disrupted by high salt concentrations, extreme pH,
by detergents, and by competition with high concentrations of the pure epitope itself.
This principle is used by using affinity columns to measure affinity or for antibody
purification.
Avidity:
Describes the ensemble of interactions. The affinity of one interaction might be low but if
you have many of them the avidity might be high. You can think of it that many weak
interactions are actually strong.
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Biological background III
Important Nomenclature continued:
Antigen (more general Ligand):
sometimes a protein
An antigen is anything that is recognized by the body's immune system as foreign.
The antigen binds to a receptor or antibody on the immune cell and stimulates the cell.
The part of the antigen molecule to which the antibody binds is called the epitope.
could be pieces of the invador
A stimulated cell can make new antibodies ==> ANTIbody GENerator.
Antibody:
- a protein known as immunogobulin (for example IgE, IgG, IgA)
- large Y-shape protein produced by B cell in response to a stimulus
- used by the immune system to identify and neutralize foreign objects such as bacteria
and viruses. For example sick cells are marked with specific antibodies so that eater cells
can recognize them easier.
- recognizes a unique part of an antigen ==> binds to that specific antigen only
To understand antibodies, think of a hand that can only grab one specific item. Imagine
that your hands could only pick up apples. You would be a true apple-picking champion but you wouldn't be able to pick up anything else.
- Antibodies: Y-shaped antibodies
- two identical binding sites (light and heavy chains)
are the variable region which is different for every antibody.
Here we bind to antigen
- The constant region does not change for different antibodies
(in reality there are small differences which we ignore at this
point).
- constant region binds to a receptor in the cell membrane
How can we have an infinite number of antibodies?
There are gene segments which can be combined to form different antibodies.
a) light chain:
~ 200 ways.
b) heavy chain: 6000 ways
c) any light and heavy chain can be combined to give the antibody  ~1.2
million. There are more ingredients which increase this number which are
not mentioned here.
receptors:
a protein
Molecule that is found on the surface of a cell (embedded in cell membrane)
receives signals from the outside and brings them to the inside of the cell
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Numerous receptor types are found in a typical cell
Each type is linked to a specific biochemical pathway
an antibody can bind to a receptor - like IgE
there are also antigen receptors: no antibody is needed, receptor binds directly to antigen
Affinity:
Antigen and antibody binds covalently, the reaction is reversible. Some lock on really
strong others less. Antibody affinity refers to the strength of the binding of antibody
to the ligand epitope: high affinity bond is very strong. We also call it on-off rate, how
long the bound holds. The bond can be disrupted by high salt concentrations, extreme pH,
by detergents, and by competition with high concentrations of the pure epitope itself.
This principle is used by using affinity columns to measure affinity or for antibody
purification.
Cells in the immune system
Innate Immunity
Phagocytes:
- cells specialized in finding and "eating" bacteria, viruses, and dead/injured body cells. - three main types, the granulocyte (neutrophils), the macrophage, dendritic cell.
granulocytes just eat for example cells marked by antibodies
macrophages and dendritic: recognize pathogens by means of cell-surface
receptors that can discriminate form self and non-self and help to activate adaptive IS
- each cell type has the same set of receptors. Hence these receptors give rapid responses
which are put into effect without the delay needed for activation in the adaptive immune
response.
Phogocytosis:
cellular process of engulfing solid particles by the cell membrane to from an internal
phagosome.
Phagocytosis in three steps:
1. Unbound phagocyte surface
receptors do not trigger phagocytosis.
2. Binding of receptors causes them
to cluster.
3. Phagocytosis is triggered and the
particle is taken up by the phagocyte
- The phagosome then becomes acidified which kills most pathogens (pH goes down by
pumping protons in the vesicle).
- The vesicles fuse with lysosomes that contain enzymes, proteins and peptides that can
attack the microbe.
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- If fusion of lysosomes and vesicles is prevented  adaptive immune response has to
kick in.
- phagocyte displays an antigen fragment from the invader on its own surface, a process
called antigen presentation.
Antigen Presenting Cell APC:
- is an important player in the innate immune response.
- macrophage or dendritic cell, which has eaten an invader, travels to the nearest lymph
node to present information about the captured pathogen .
- can also be B cells
- These cells process antigens (by phagacytosis) and present them to T-cells.
- displays foreign antigen complexes with major histocompatibility complex (MHC) on
their surfaces. T-cells may recognize these complexes using their T-cell receptors
(TCRs).
Complement System:
- The complement system helps or “complements” the ability of antibodies and
phagocytic cells to clear pathogens from an organism.
- consists of a number of small proteins found in the blood, generally synthesized by the
liver, and normally circulating as inactive precursors (pro-proteins).
- Over 25 proteins and protein fragments make up the complement system
- can be activated directly by pathogens or indirectly by pathogen-bound antibodies,
leading to a cascade of reactions that occurs on the surface of pathogens and generates
active components with various effector functions.
-Involves a large number of proteins which are inactive and can give big problems when
activated if the should not be.
Effector functions of complement:
1) Formation of membrane attack complex: The membrane attack complex has a
hypophobic binding site and attaches to the membrane of the host cell/invador. It
pokes a hole in the membrane and causes the lysis of the cell membrane. This
effector function ise very effective on Gram-negative bacteria since the membrane
is very thin. It kills the pathogen by destroying the proton gradient across the
pathogen cell membrane.
2) enhances phagacytosis
3) Promotes Inflammation
4) Chemotaxis of white blood cells: Chemotaxis is the phenomenon in which
bodily cells, bacteria, and other single-cell or multicellular organisms direct their
movements according to certain chemical gradients in their environment.
Adaptive Immunity
Lymphocytes
- white blood cells: two main types: T cells and B cells
- originate in the bone marrow
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- migrate to parts of the lymphatic system such as the lymph nodes, spleen, and thymus
where that wait to mature and be activated
On the surface of each lymphatic cell are receptors or receptors+antibody that enable
them to recognize foreign substances. These receptors are very specialized - each can
match only one specific antigen.
T cells:
- T cells come in two different types, helper cells and killer cells.
- They are named T cells after the thymus, an organ situated under the breastbone. T cells
are produced in the bone marrow and later move to the thymus where they mature.
Helper T cells:
- main regulators of the immune defense
- primary task is to activate B cells and killer T cells
Activation of helper T cells:
When a macrophage or dendritic cell,
which has eaten an invader, travels to
the nearest lymph node to present
information about the captured
pathogen. The phagocyte displays an
antigen fragment from the invader on its
own surface, a process called antigen
presentation. When the receptor of a
helper T cell recognizes the antigen, the
T cell is activated. Once activated,
helper T cells start to divide and to
produce proteins that activate B and T
cells as well as other immune cells.
Helper T cell: They can activate B cells which than mature into Plasma cells and turn on
the Humerol immunity. They can also activate Cytotoxic T cells which can recognize
and kill cells which activates the cell mediated immunity. Both processes belong to the
adaptive immune response.
APC
Helper
T cell
B cell
Cytotoxic
T cell
Humoral Immunity
Cell mediated
Immunity
Humoral Immunity: How does it work?
- The key lymphocyte is the B-cell on its surface antigen-receptors (100,000s),
- B-cell activation: Two things have to happen:
1) The B-cell has to bind its antigen
2) and get stimulated by the proper T-cell.
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Then B cell divides and proliferates (5-6 days) until they turn into to different cell types
a) Plasma cell: These effector cells don’t have membrane bound antibodies and
their job is to discrete antibody in the serum. They are alive for a few days and
release up to 2000 antibodies/s. Which means that the cytoplasm is full of
endoplasmic reticulums (ER).
b) Memory B-cell: Has antibodies bound. It got activated once and depending on
the type can survive a few weeks up to the whole lifetime. They can turn into
Plasma cells very quickly and since one has very many of them the response at
the second exposure to the same pathogen occurs very quickly.
In the Figure below we see that the induction period lasts about 5-6 days which is the
time it takes for the B-cells to divide and produce plasma cells. After the primary
response the induction time of the secondary response only takes 1-2 days and it is a lot
stronger. Memory and vaccination works the same.
Cell Mediated Immunity: How does it work?
- whatever is invading our body is attacked and either phagocytosed or lysed by.
- How does a macrophage know what is harmful (and should be ingested through
phagocytosis) and what is not?
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- How can our bodies get rid of cancerous cells that are too large to phagocytose?
- T-cells are the key players.
T-Cell Receptor (TCR): T-cells have TCRs in the membrane.
They are heterodimers (they are different) and consist of a
two heavy and light chains. The difference between T-cells and
B-cells is how they recognize pathogens. T-cells only recognize
their antigen if they are presented by MHC molecule
(major histocompatibility complex) which
present a pathogen’s epitope. There are two types of MHC
classes:
Every cell in our bodies has a specific marker on its membrane, called MHC (major
histocompatibility complex), that serves as an ID marker that it belongs in our bodies.
MHCs of Class I are on every cell, while MHCs of Class II are only on APCs and
lymphocytes (T cells and B cells).
If a T cell is running around and encounters MHC Class I on every cell it bumps into, it
recognizes every cell as belonging in the body, and no immune response will occur.
However, if a T cell runs into a cell that doesn't display an MHC, the T cell will
immediately know that that cell doesn't belong in our bodies; the cell-mediated immune
response will then begin, and the foreign cell will be destroyed.
a) MHC-I: can be produced by any nucleated cell in the body. It presents
endogenous antigen (Ag) to Cytotoxic (Tc) T-cells. The presenting cell then
gets killed by the Tc-cell which makes small holes in the membrane of
effected cells through which it releases chemicals which lyse the cell.
Endogenous means that the peptide was produced inside the cell such as a
virus/bacteria which got inside the cell and produces stuff inside the cell.
Hence MHC-I molecules display “altered self”.
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b) MHC-II: This class I soley displayed by ACP such as dendritic cells,
macrophages, and B-cells (antigen binds to Ig and gets internalized and
broken appart). They present exogenous Ag (peptides produced outside cell)
to T helper cells. ACPs take pathogen up and break them into pieces inside the
cell, select different pathogen peptides and present them to the outside world.
Signal transduction
occurs when an extracellular signaling molecule activates a cell surface receptor. In turn,
this receptor alters intracellular molecules creating a response. There are two stages in
this process:
1) A signaling molecule activates a specific receptor protein on the cell membrane.
2) A second messenger transmits the signal into the cell, eliciting a physiological
response.
In either step, the signal can be amplified. Thus, one signaling molecule can cause many
responses. A signal transduction functions much like a switch.[
Common features in ALL signal transduction cascades:
1) Receptor binds to ligand: here we are interested in surface receptors which bind to
ligand extracellularly only. After ligand binding the receptor can change in two
ways:
i)
Allosteric change (conformational change) of receptor where its shape
depends on its
activity. i.e. G-protein receptors, after receptor’s
change in shape G-protein can bind on.
ii)
Receptor clustering: crosslinking of receptor
2) Generation of 2nd messenger
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3) Involvement of kinases and phosphatases: Kinase adds phosphate 
phosphorylation, and phosphatase takes off phosphate  inactivation of cascade.
4) Result in Cascade: changes receptor activation. Initially 1-2 receptors get
activated which activate more proteins in downstream signaling. Very small
initial effects get amplified through the cascade.
5) At default pathway is always “off”: cascade does not turn on without the
appropriate ligand binding to the receptor.
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