Lecture 36 - clonal selection and memory (immune disorders) Flashcards
What cells are missing in SCID?
T and B cells
SCID full name
Severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency, SCID, is a rare genetic (X linked) disorder that is characterised by the disturbed development of functional T cells and B cells
Do not have functional T or B cells because of the various mutations and this means that from the moment you are born you are susceptible to every microbe
Central and peripheral tolerance
Occasionally B cells edit their specificity and no longer become ‘self’ reactive
Some CD4 T cells differentiate into regulatory cells
Central tolerance, also known as negative selection, is the process of eliminating any developing T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides.
Peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease.
Rheumatoid arthritis
Rheumatoid arthritis (RA) is a autoimmune disorder that primarily affects joints - it is a good example of what happens when our immune cells attack self tissue
Results in crippling and joints become immobile. Infection can occur, bone erosion, inflamed tendon, thinning of cartilage etc.
Disease where central and peripheral tolerance fails and T and B cells that shouldn’t be let out, do go out and go toward tissues that they have receptors for, when they find the receptors they wreck havoc and treat the body as a pathogen and do everything in their power to destroy that piece of tissue
Three phases of progression of rheumatoid arthritis
1- initiation phase (due to non-specific inflammation), an amplification phase (due to T cell activation),
2- Chronic inflammatory phase
3- Tissue injury resulting from immune molecules
Cause of rheumatoid arthritis
T and B cells that should have been let out due to them being immune cells that attack self tissue
e.g. T cells start attacking tissue as they failed to be filtered at the thymus
Allergic reactions are …
Immune disorder because it is a result of the immune system going wrong
Allergy
Allergic diseases and symptoms occur because of an active immune system that reacts to things that are usually harmless, such as pollens, pet dander or foods.
Process of getting a peanut allergy
Originally not allergic and given a big dose of peanut butter on toast for example
Little proteins from the peanut get picked up by dendritic cells and they pick up peanut molecules thinking that they are a pathogen when they actually aren’t
Dendritic cell takes the molecule to one of the lymphoid tissues and searches around for T and B cells that have the same molecule recognition for the peanut molecule/allergen
B cells start pumping out IgE (a type of antibody). IgE tries to find a mast cells (WBC) (tail of IgE sticks to mast cells and the variable regions want the peanut allergens)
The next time you eat a peanut and the peanut allergen are released if any find their way to the mast cells (the IgE is all around) and the allergen foes into the IgE which stimulates the mast cells to explode
Releases immune chemicals and most importantly histamines which causes swelling (edema), heat and if this happens in your throat or mucosa of the throat and mouth then the individual can suffocate and then die
What does an epipen do?
Blocks all of the receptors that histamine act on
Type I hypersensitivity disease
IgE-mediated hypersensitivity (allergic reaction)
Type I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Exposure may be by ingestion, inhalation, injection, or direct contact.
Allergen induces cross linking of IgE bound to mast cells and basophils with the release of chemicals such as histamines.
Can present as allergies/anaphylaxis (fever, asthma, hives, food allergies and eczema)
Sequence of events in immediate (type I) hypersensitivity
First exposure to allergen
Antigen fires up T and B cells to form IgE
IgE find their way through the body and attach to mast cells
IgE are now attached and all that is need is for a second exposure to occur
This second exposure causes the immunological storm and the release of histamines (causes sneezing, brochoconstriction, itchiness, runny nose etc.)
Effector molecules and cells involved in the allergic reaction
Mast cells - make the type I hypersensitivity reaction so important
IgE - important antibody in type I hypersensitivity
Histamines - degranulation of mast cells releases histamines
Clonal selection
Clonal selection is a process proposed to explain how a single B or T cell that recognizes an antigen that enters the body is selected from the pre-existing cell pool of differing antigen specificities and then reproduced to generate a clonal cell population that eliminates the antigen.
