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BABS2202 Study (Short Answer Questions)

Immunology
• What is chemotaxis?
Chemotaxis is the movement of phagocytic cells towards the site of infection. When an
infection occurs, C5 proteins attach on to the pathogens causing the infection, and are broken
down into C5a and C5b sub-proteins, which spread outwards. The receptors on the
phagocytic cells, including neutrophils and macrophages, detect this higher concentration of
C5a proteins (complement protein) [i.e. change in chemical concentration] within the body.
Afterwards, these cells move towards the highest concentration of C5a compliment proteins
to kill the pathogen and prevent further spread of infection.

• What is the acute inflammatory response?


The acute inflammatory response is part of innate immunity. As soon as a pathogen passes
through the physical, mechanical, biochemical and cellular defences of the body, the acute
inflammatory response is initiated to fight the infection. White blood cells are required to
fight infection in large masses, whereby the blood vessels are dilated for this pathway and
migration [increased blood flow]. Also, the blood vessels become more permeable to
nutrients that can ease the infection. Overall, this results in redness, swelling and heat.

• Discuss Burnett’s Clonal Selection Theory (primary and secondary response).


Burnett’s Clonal Selection Theory states that every human has all the B cells to fight
infection, but in small amounts. When an antigen (proteins found on the surface of the
pathogen) is present, B cells are produced to mediate and kill the pathogen. After reinfection
of the same antigen, more B cells are produced and the rate of recovery is faster, i.e. greater
immunological memory improves over time. The primary response results in a larger
populous of B cells specific to the antigen, whilst the secondary response results in some B
cells differentiating into plasma cells that produce antibodies, and other B cells becoming
memory B cells that improve immunological memory.

Cell Signalling
• Discuss the basic response pathway of cell-cell signalling or communication and
the types of cell communication. What are different types of extracellular
molecules?
1. Signal – extracellular molecules are produced and secreted from one cell to a receptor
of another or itself
2. Receptor – receives the extracellular molecules
3. Transduction – the signal of the extracellular molecules is TRANSLATED and
AMPLIFIED, so it can be read by another cell
4. Response – the signal is interpreted and acted upon by the ‘target proteins’

The types of communication between cells are either direct, via an ion gated channel, or
indirect, via autocrine, paracrine or endocrine pathways. The autocrine pathway involves one
cell, whereby the extracellular molecules are secreted and receives by a receptor on the same
cell. The paracrine pathway involves two cells, but can only be used in close proximity to one
another as the extracellular molecules are unstable for long distances. In contrast, the
endocrine pathway involves hormones that can travel long distances within the bloodstream.

Transduction is the translation and amplification of the signal transmitted and received by the
cell receptor. Once the cell receptor binds to the extracellular molecule, it is activated and
recruits specialised proteins to bind to it and form the cell signalling cascade that reaches the
target protein, and then a response. Another way of transduction, is where the receptor binds
to the extracellular molecules, gets activated and then activates an effector molecule that
produces 2nd messenger molecules for amplification. These 2nd messenger molecules bind to
specialised proteins and goes through the cell signalling cascade, whereby it finally reaches
produces 2nd messenger molecules for amplification. These 2nd messenger molecules bind to
specialised proteins and goes through the cell signalling cascade, whereby it finally reaches
the target protein and a response.

The different types of extracellular molecules include:


- Amino acids (polar)
- Proteins (polar)
- Gases (polar)
- Hormones (non-polar)

• Discuss the response pathway of steroid hormones


1. Steroid hormones attach to proteins and travel to its target cell (protein acts as a driver
for the hormone)
2. Once it reaches the target cell, the steroid hormone disassociates from the protein and
diffuses through the membrane, due to its non-polar feature.
3. Hormone bind to receptor proteins in the cytoplasm and travel into the nucleus
4. Hormone-receptor complex binds to a specific promoter region on the DNA
5. Hormone is transcribed into mRNA and translated into a protein
6. Once this protein is produced, it initiates the cell signalling cascade that amplifies the
signal and provides a response to the original signal

• Discuss the response


pathway of G protein-coupled receptors
A ligand molecule binds to the receptor protein on the
membrane and activates the G protein-coupled
receptor, whereby the GDP attached to the G protein
initially is converted to GTP, in order for it to be
activated. The beta and gamma subunits also detach
from the G protein, and this leaves the alpha subunit
of the G protein to attach to an effector molecule for
transduction à leads to a response.

In order to deactivate the alpha subunit and GTP from


transmitting a repeated signal, the GTP is hydrolysed
into GDP and Pi, and the alpha subunit binds to the
beta and gamma subunits to form the original G
protein. However, to prevent the G protein to bind to
the receptor protein, arrestin binds to the receptor
protein. Another way to prevent G proteins from
binding to the receptor protein is for PKC and the
presence of Ca2+ (Protein Kinase C) to bind to it, as an
effector molecule.
presence of Ca2+ (Protein Kinase C) to bind to it, as an
effector molecule.

• Discuss the response pathway of Receptor Protein-Tyrosine Kinases (RTKs)


1. Ligand molecule binds to receptor
2. Receptors (RTKs) perform dimerization
3. Receptors (RTKs) phosphorylate tyrosine residues on the opposite receptors
4. Proteins with specific domains (SH2 or PTB) to the receptor bind to that receptor
(RTK).
5. Attach to other proteins and then the target protein (Transduction)
6. Response is carried out

Two types of binding – PDGF (Platelet Derived Growth Factor) and EGF (Epidermal Growth
Factor)

Two ways of dimerization:


- PDGF (2 substrates):
o As ligand molecule comes close to one receptor, it induces another
receptor, so it can bind à forms a dimer
o Each receptor phosphorylates the tyrosine residues on the other receptor
- EGF (1 substrate):
o A single ligand molecule binds to a receptor, and induces the other receptor
to bind to another ligand molecule à forms a dimer
o Each receptor phosphorylates the tyrosine residues on the other receptor

Four types of proteins:


- Adaptor proteins (SH2)
- Docking proteins (PTB)
- Transcription factors (SH2)
- Enzymes (SH2)

To deactivate the receptors (RTKs) and prevent further unnecessary signalling and responses
being carried out, the receptor is either; broken down by proteasomes when ubiquitin
molecules are attached to the receptor; degraded by lysosomes; or, recycled.

Ras-MAP Kinase Cascade


So that the Ras protein isn’t constantly turned on, it regulated by the following proteins:
- GAPs [Guanine Activating Proteins] à hydrolyses GTP to GDP, hence deactivates G
protein
- GEFs [Guanine nucleotide Exchange Factors] à dissociates GDP from the G protein
and allows GTP to bind to G protein, hence activates G proteins
- GDIs [Guanine nucleotide Disassociation Inhibitors] à opposite of GEFs

Insulin Receptor
- Insulin Receptors are already present as dimers, unlike the receptors (RTKs)
- Docking proteins are only attached to the receptors

Glucose Receptor
- Since glucose is a large molecule and cannot diffuse through the membrane, it
requires a transporter to cross the membrane and into the cell.
- Once the glucose molecule is in the transporter, the receptor activates protein
kinases that signals the multi-glucose transporter to receive the glucose molecule
and attach it to itself

• Discuss the response pathway of Ion Gated Coupled Receptors


When a ligand molecule binds to the ion gated receptor, it activates the gate and allows
molecules from the extracellular space to pass through into the cytoplasmic side of the
membrane, and vice versa. The three types of ion gated coupled receptors include ligand-
binding, voltage-gated and mechano-gated receptors.
binding, voltage-gated and mechano-gated receptors.

• Name a disease relating to ion gated coupled receptors and describe it.
Cystic fibrosis is a disease relating to the mutated production of chloride ion gated coupled
receptors that increase the amount of sweating and mucous accumulation in the bronchial
tubes of the lungs. This causes the bronchiole tubes in the lungs to be clogged up, resulting in
a lack of effective breathing and lung infections.

Cell-Cell + Cell-ECM Interactions


• Discuss the different types of junctions for cell adhesion
- Tight à proteins attach to the cell membrane and then to the cytoskeleton
- Gap à two cells share resources through connexons, that act like channels
- Adherens à cadherin receptors attach to the catenin proteins on the plasma
membrane, which are connected to the actin filaments of the cytoplasmic
cytoskeleton.
- Desmosomes à identical to adherens, but the site of cell attachment is the
intermediate filament cytoskeleton

• Describe the role of cell adhesion for inflammation


When an infection occurs, neutrophils go to the site of infection through the process of
chemotaxis. As they pass along the exterior walls of the bloodstream, they attach to the E and
P selectin molecules (Cell Adhesion Molecules, or CAMs) and then on the Platelet Acting
Factor (PAF) to firmly grip on the exterior bloodstream walls. Once firmly attached, the
neutrophils slide in between the cells of the bloodstream walls and travel to the site of
infection.

• Explain 3 functions of the Extracellular Matrix (ECM) and what are its
components?
- Elasticity between cells for mechanical and structural support
- Development of organs
- Cell-cell communication

Components include:
- Collagen à a fibrous protein that connects cells within bone and cartilage
(compression)
- Elastin à a fibrous protein that is a component of connective tissues, e.g. epidermal
layer of skin (tension/elasticity)
- Laminin à a fibrous protein that interacts with collagen and allows cells to migrate
to other areas of the Extracellular Matrix for visceral growth and development
- Fibronectin à a fibrous protein that binds with integrins mainly, but also with
collagen and elastin for extra support in cell adhesion.
- Several Glycosaminoglycan (GAGs) molecules form proteoglycans that have a net
negative charge. This charge attracts cations, such as Na+, and therefore attracts
the negative dipole of the oxygen atom in water. Therefore, it keeps the cell
hydrated.

• How do integrins facilitate cell adhesion?


Integrins are a transmembrane protein that interacts with a ligand (e.g. collagens, elastin,
laminin and fibronectin) extracellularly, and alpha-actin fibres in the cytoplasmic region.
Once these components are attached, the integrin receives the signal from the external
environment and sends it to the internal environment, whereby it activates protein kinases for
cell adhesion.

• Explain the role of Ca2+ as an intracellular messenger.


When too much Ca2+ is found in the blood, it can lead to cell death and a stroke. Therefore,
an intracellular messenger for Ca2+ would be vital in regulating the concentration of Ca2+ by
ion gated channels. It also, has the role of allowing PKC to become the effector molecule for
an activated G protein and produce a response that deactivates the function of the G protein
until required.
until required.