W3: clinical immunology Flashcards
How is the immune system generalised used in cancer therapy?
Antibodies against the regulators of the immune system are used to turn the immune system into over drive.
T cells with genetically engineered antigen receptors are used to target cancer cells.
How are immune checkpoint inhibitors used in cancer treatment?
T cell binds to antigen presented on cancer cell by MHC1
However, PD-1 on T cell is bound to by PD-L1 on the cancer cell, this stops the T cell from destroying the cancer cell.
Immune checkpoint inhibitors such as anti-PD-L1 can be used to stop this interaction allowing the T cell to kill the cancer cell
What are the two different extremes of an unbalanced immune system response?
Autoinflammatory or autoimmune disease - over reactive immune response kills self cells.
Immunodeficiency - underactive immune response, means more susceptible to cancer or disease.
What are the different types of immunodeficiency?
Primary immunodeficiency - from birth due to genetic mutation
Secondary immunodeficiency - due to environmental factors, develop later in life e.g HIV, severe malnutrition and chemotherapy.
How are primary immunodeficient patients useful on a research level?
Are gene knock-outs.
Removal of gene naturally, allow the absence of function to identify the function of that gene (whatever is not happening)
What is Severe Combined Immunodeficiency?
Causes by a loss of function in the RAG gene, unable to undergo somatic recombination so does not produce T or B cells. ( alongside many other potential causative mutations)
So no adaptive immune system.
How can SCID be treated?
Bone marrow transplant
Antibiotic Prophylaxis.
What is Mendelian Susceptibility to Mycobacterial disease?
A rare genetic disorder including may conditions, results in a loss of function of Th1 cells or Th1 cells are not produced, wont activate macrophages causing a loss in immune function. (Lack of communication between th1 and macrophage)
Type of primary autoimmune deficiency
What is IPEX?
Lack gene for T reg cells on X chromsome
Immune system attack all self endocrine organs.
What is neutropenia?
Low number of neutrophils in blood
Caused by diseases bone marrow, chemotherapy, infections and autoimmune disease.
Is associated with opportunistic infections particularly Pseudomonas aeruginosa.
Treated with G-CSF (granulocyte colony stimulating factor) therapy.
How does neutropenia often present?
Through an opportunistic pathogen
Rapid onset fever and sometimes sepsis
Abscesses
Dental infections
Peri-anal infections
Sunsitis
Tonsilitis
Pneumonia
Mild inflammation despite serious illness
What are some examples of secondary immunodeficiency?
Neutropenia
Acquired Immunodeficiency syndrome (AIDs)
What is AIDS?
HIV hijacks components of the immune system in initial infection, causing flu-like symptoms followed by a dormancy period.
Infects and destroys CD4 cells, this contributes to persistence of infections and reduces resistance to other infections
May spread by a dendritic cell taking up the virus and carrying it to the lymph node.
What happens in autoimmune disease when CD4 T cells are lost? (example in AIDs)
Loss of Th1 and Th17 limits effectiveness of inate immune response
Loss of B cell stimulation so no antibody production
Loss of antiviral and antitumour CD8 cells
Loss of T reg cell can result in autoimmunity.
How does AIDS often present itself?
Opportunistic infections
Loss of anti tumour function - Kaposi’s Sarcoma
Loss of t cell reg - autoimmune
Loss of B cell function - salmonella and pneumonia
Loss of T helper 1 - mycobacterium
Often causes rapid weightloss and extreme tiredness.
What can causes overactivation of the immune system?
Inappropriate activation - autoimmunity and allergy
Failure to switch off - chronic inflammatory disease
What are some examples of autoimmune diseases?
Multiple Sclerosis - targets myelin sheath around neurons
Type 1 diabetes - targets islets of langerhans so less/no insulin production
How can problems in the innate immune response lead to autoimmune disease?
Patern Recognition Receptor NOD2 receptors defects is associated with Crohns disease
Failure of early complement leads to systemic lupus and erthrematosus
What is Immue Mediated Inflammatory Disease?
Secondary immunodeficiency
Chronic inflammation damages cells and biological molecules
Rheumatoid Arthritis.
What happens in an allergy?
IgE antibodies are made against harmless antigens and can trigger an acute response on re-exposure.
What happens in an acute allergic reaction?
What happens in a chronic allergic reaction?
Acute - antibody against allergy is bound to receptors on mast cell, allergy binds to multiple antibodies of mast cell, cross linking receptors, causes a strong immune response and degranulation
Chronic - mast cell derives mediators leading to the recruitment of other specific T cells.
What are some general causes of systemic low grade inflammation?
Chronic infections
Physical inactivity/diet/obesity
Isolation and chronic stress
Disturbed sleep
Xenobiotics
Dysbiosis
What are some consequences of systemic low grade inflammation?
Metabolic syndrome such as type 2 diabetes
Cardiovascular disease
Cancer
Depression
Auto-immune disease
Neurodegenerative disease
Sarcopenia and osteoporosis
Immunosenescence
How can immunology be monitored in a clinical laboratory?
Using blood serum to measure the amount of antibodies.
Check for autoantibodies such as anti cyclic citrullinated peptide antibodies in R arthritis.
Looking for cells in the blood - AIDs diagnosis
What is flow cytometry?
Tags a specific cell with fluorescent labelled antibodies to measure the quantity of a specific cell and whether they are functionally based on their cytokine and surface marker profiles.
What does sotrovimab do?
Neutralising antibody against COVID-19,
Neutralises spike protein hence prevents the entry into body cells.
Used to prevent an infection and prevent the spread of an infection within the host.
How is interferon alpha used in hepatitis C treatment?
Stimulates immune cells and turns on anti-viral mechanisms in the infected cells.
Often given as a combined treatment with ribavirin (nucleoside analogue)
How is TNF-a used in rheumatoid arthritis treatment?
TNF-a is pro-inflammatory
Blocking signal can help stop inflammation in the joints.
How is tocilizumab used in COVID-19 patients?
Is an IL-6 inhibitor
Inhibitng IL 6 inhibts pro-inflammatory signals, inhibits the development of Th17 and Th FH cells from naive T cells.
How can antigen presentation be manipulated to treat autoimmunity?
Monocyte is isolated from a person
In a lab the monocyte is developed into a macrophage and given an antigen to present
Re-inserted into the person,
causes to turn on a tolerant response rather than an immune response.
