W3: clinical immunology Flashcards

1
Q

How is the immune system generalised used in cancer therapy?

A

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.

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2
Q

How are immune checkpoint inhibitors used in cancer treatment?

A

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

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3
Q

What are the two different extremes of an unbalanced immune system response?

A

Autoinflammatory or autoimmune disease - over reactive immune response kills self cells.
Immunodeficiency - underactive immune response, means more susceptible to cancer or disease.

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4
Q

What are the different types of immunodeficiency?

A

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.

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5
Q

How are primary immunodeficient patients useful on a research level?

A

Are gene knock-outs.
Removal of gene naturally, allow the absence of function to identify the function of that gene (whatever is not happening)

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6
Q

What is Severe Combined Immunodeficiency?

A

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.

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7
Q

How can SCID be treated?

A

Bone marrow transplant
Antibiotic Prophylaxis.

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8
Q

What is Mendelian Susceptibility to Mycobacterial disease?

A

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

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9
Q

What is IPEX?

A

Lack gene for T reg cells on X chromsome
Immune system attack all self endocrine organs.

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10
Q

What is neutropenia?

A

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.

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11
Q

How does neutropenia often present?

A

Through an opportunistic pathogen
Rapid onset fever and sometimes sepsis
Abscesses
Dental infections
Peri-anal infections
Sunsitis
Tonsilitis
Pneumonia
Mild inflammation despite serious illness

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12
Q

What are some examples of secondary immunodeficiency?

A

Neutropenia
Acquired Immunodeficiency syndrome (AIDs)

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13
Q

What is AIDS?

A

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.

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14
Q

What happens in autoimmune disease when CD4 T cells are lost? (example in AIDs)

A

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.

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15
Q

How does AIDS often present itself?

A

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.

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16
Q

What can causes overactivation of the immune system?

A

Inappropriate activation - autoimmunity and allergy
Failure to switch off - chronic inflammatory disease

17
Q

What are some examples of autoimmune diseases?

A

Multiple Sclerosis - targets myelin sheath around neurons
Type 1 diabetes - targets islets of langerhans so less/no insulin production

18
Q

How can problems in the innate immune response lead to autoimmune disease?

A

Patern Recognition Receptor NOD2 receptors defects is associated with Crohns disease
Failure of early complement leads to systemic lupus and erthrematosus

19
Q

What is Immue Mediated Inflammatory Disease?

A

Secondary immunodeficiency
Chronic inflammation damages cells and biological molecules
Rheumatoid Arthritis.

20
Q

What happens in an allergy?

A

IgE antibodies are made against harmless antigens and can trigger an acute response on re-exposure.

21
Q

What happens in an acute allergic reaction?
What happens in a chronic allergic reaction?

A

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.

22
Q

What are some general causes of systemic low grade inflammation?

A

Chronic infections
Physical inactivity/diet/obesity
Isolation and chronic stress
Disturbed sleep
Xenobiotics
Dysbiosis

23
Q

What are some consequences of systemic low grade inflammation?

A

Metabolic syndrome such as type 2 diabetes
Cardiovascular disease
Cancer
Depression
Auto-immune disease
Neurodegenerative disease
Sarcopenia and osteoporosis
Immunosenescence

24
Q

How can immunology be monitored in a clinical laboratory?

A

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

25
Q

What is flow cytometry?

A

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.

26
Q

What does sotrovimab do?

A

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.

27
Q

How is interferon alpha used in hepatitis C treatment?

A

Stimulates immune cells and turns on anti-viral mechanisms in the infected cells.
Often given as a combined treatment with ribavirin (nucleoside analogue)

28
Q

How is TNF-a used in rheumatoid arthritis treatment?

A

TNF-a is pro-inflammatory
Blocking signal can help stop inflammation in the joints.

29
Q

How is tocilizumab used in COVID-19 patients?

A

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.

30
Q

How can antigen presentation be manipulated to treat autoimmunity?

A

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.