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L2 – Innate Immune Responses
As previously discussed, there are many cells of the innate immune response
such as macrophages, which are derived from monocytes, the closely related
basophils and mast cells, dendritic cells, neutrophils and eosinophils
...
Erythrocytes are also responsible for carrying
oxygen around the body and platelets are involved in blood clotting
...
Both have long membrane projections known
as dendrites, characteristic of nerve cells
...
They bridge the gap
between innate and adaptive immune responses as two independent
responses
...
1 and B7
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Activation of a naive T-cell
1
...

2
...
When DCs travel through the
lymphatics, they change their morphology and are referred to as veiled
cells
...


3
...
The peptide then binds within a cleft of the MHC class II
molecule, which is upregulated in order to facilitate presentation of the
peptides, and is presented on the surface of the dendritic cell to T-cell
receptors (TCR) on the surface of T-cells
...

4
...
The expression of B7 family proteins is controlled by NFκB,
which is activated downstream of many PRRs
...

5
...
For example, IL-12 production by DCs favours
the development of Th1 cells
...
In addition to activating T-cells, DCs can also inactivate T-cells
...
In the absence of microbial danger
signals, the CD80 and CD86 costimulatory molecules are not
expressed at significant levels
...

Activation of B-cells
1
...

2
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3
...

4
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The low affinity B-cells however would die via apoptosis and are
phagocytosed by macrophages
...
They can recognise upregulated selfproteins on infected or tumour cells, as well as cells that lack the normal
expression of MHC class I molecules on their surface and can also recognise
antibody-coated cells
...
The
effect of a signal sent from one receptor is counterbalanced by the signal sent
from the other in a normal cell
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•
•

The inhibitory receptors of either family have cytoplasmic tails that
contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs)
The activating receptors associate with accessory proteins such as
DAP-12, which contain immunoreceptor tyrosine-based activating
motifs (ITIMs) within their cytoplasmic tails
...

On encounter with a normal cell, the NK cell will bind to the activator molecule
and MHC class I molecule on the cell via its activating and inhibitory receptor
respectively
...

There are two situations in which cells sometimes abnormally lack MHC I, in
certain tumours such as some lymphomas or melanomas and cells infected
with certain viruses such as adenovirus, cytomegalovirus and herpes simplex
virus
...
In this case, phosphorylation of the ITAMs within the accessory
protein results in NK cell activation, but because there is no counteracting
inhibitory signal to override the activating signal, the end result would be the
death of the target cell
...
Killing by NK cells is the result of induction
of apoptosis in the target cell either by the perforin granzymes pathway or by
the Fas-ligand pathway
...
NK cells also produce a number of chemotactic
cytokines or chemokines
...
Therefore, the NK cells can bind to antibodies
that are bound to viral antigens present on the surface of infected cells,
following which cytoplasmic granules are released that will destroy the
infected cell
...
It uses both intracellular, cell-surface and soluble or secreted
pattern recognition receptors (PRR), which recognise pathogen-associated

molecular patterns (PAMP)
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Acute phase proteins
• Certain pro-inflammatory cytokines, such as IL-1, IL-6 and Tumour
Necrosis Factor (TNF) released by macrophages in response to
activation of PRRs act on the liver to increase secretion of a group of
molecules that are collectively referred to as the acute phase proteins
(APP)
...
The former two bind to carbohydrates on the
bacterial surface and fix complement so opsonizing the microbe for
facilitated phagocytosis by covalently coating the surface with
abundant C3b
...

• This is a very rapid response of the body to either infection or tissue
damage
...
Plasma
concentration of APPs may increase 1000-fold during infection
...
It
minimises tissue injury and promotes resolution and repair of
inflammatory lesion
...

• They are small cationic antimicrobial peptides around 3
...
They have
anti-microbial and anti-fungal properties
...

• α-defensins are constitutively expressed, whereas β-defensins
although some are expressed all the time, others are only produced in
response to an infection
...

• Because of the polar topology of defensins, they are able to insert
themselves into microbial membranes
...
This results in the
formation of voltage-dependent channels or pores that lead to the loss
of small-molecule gradients and therefore, leads to the death of the
pathogen

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