Here is the narration exactly as it is in the video:
Unfortunately, some genetic factors, bacterial or viral infection or smoking can induce mutation in the collagen II.
This mutation results in replacement of arginine amino acid with citrulline amino acid.
This little change has devastating lifelong sequences on the affected people.
The antigen presenting cells APCs such as dendritic cells which patrol our tissues recognize this new mutated collagen.
These antigen presenting cells have specific detecting molecules on their outer cell membranes called HLA molecules.
Specific types of these HLA molecules which are HLA DR1 and HLA DR4 become confused and deal with the new collagen as foreign body.
“phagocyte them now, phagocyte them now”
As a result, the antigen presenting cells phagocyte this mutated collagen.
After digesting the citrullinated collagens the APCs present some parts of the protein on their outer surface as foreign bodies
On the other hand, T helper cells in our body work as security detectors who search all antigen presenting cells for any suspicious foreign molecules.
Once T helper CD4+ cells meet HLA molecules connected to citrullinated collagen they become activated.
This activation results in production and release of cytokines IL-2 which have autocrine effects as they come back to bind and activate their releasing T helper cells.
IL-2 induces T helper cell proliferation into 2 new cellular lines, T helper 1 abbreviated as Th1 and T helper 2 cells abbreviated as Th2.
The Th2 stimulate the production of various antibodies
whereas Th1 are directed toward cell mediated immunity and later production of interferon gamma and IL-17.
Now we will focus on antibody production
Once Th2 binds to B cell it activates it.
This activation results in sequence of B cell proliferations ended up with 2 new cell lines, Plasma cells and memory cells.
Plasma cells produce various types of antibodies.
Whereas memory cells keep records of all foreign antigens in our bodies and provide long lasting immunological memory.
Now we will focus on the antibodies
The first type of antibodies are the IgG antibodies with attack the cyclic citrullinated peptides abbreviated as CCP.
The anti CCP antibodies are specific markers for diagnosis of rheumatoid arthritis.
The second type of antibodies are the IgM antibodies which attack our IgG antibodies.
So, they are antibodies against our antibodies.
They are called rheumatoid factor and they are very common in the serum of patients with rheumatoid arthritis.
Now both types of antibodies travel through blood to the joints, and even to other tissues.
Remember rheumatoid arthritis is joint disease with systematic manifestations.
Now let’s focus on joints, where antibody complexes accumulation activates phagocytes and complement system.
The activated phagocytes will release inflammatory cytokines such as TNF alpha which play important role in mediating the inflammatory damage to the joints.
They also secrete IL-1, IL-6.
We have also IL-17 and interferon gamma produced by T cells.
Additionally, complement enzymes activate the neutrophils in the joint synovial fluids.
Cytokines stimulate synovial membrane proliferation and swelling which is a remarkable pathological sign of rheumatoid arthritis.
Additionally, they activate osteoclast cells which induce bone erosions.
Angiogenesis also stimulated by cytokines.
Together cytokines released by activated macrophages and activated neutrophils induce the production of protease and collagenase enzymes which progressively erode and destroy the cartilage layer of the joints.
Happy reading (or enjoy your reading, it is up to you Carla)
Narration reading Carla Tordoff Gibson
Pharmacology and Therapeutic department
Kings College London KCL University