clinical immunology Flashcards
Result of inappropriate activation of immune system?
Autoimmunity
Result of failure to switch off immune system?
Chronic inflammatory diseases
Result of failure of response of immune system?
Immunodeficiency
How else can the immune system be dysregulated?
Transplant rejection
Wrong kind of response is generated
What diseases and treatment can affect the immune system?
- immunosuppressant drugs (for organ transplantation)
- Chemotherapy for cancer (e.g neutropenia)
- Poor diet/stress
What can antibodies and other immune components be used for? (e.g in drugs)
To suppress/detect/eliminate things
What are monoclonal antibodies?
When antibodies are generated in the labs and used to treat disease (made by cloning a unique WBC)
Bind to antigen in body to try kill cancer cells for example
Used in drugs and clinical tests
What can immune cells do in drugs?
Kill cancers
Modulate inflammatory disease
Stages of allergic response
- Dendritic cells take up antigen= APC MHC II
- Dentritic APC activates naive T cell
- Naive T cell differentiates into Th2 cell (made when APC produces IL-4,IL-5,IL-13)
- Th2 cell activates B cell and releases more IL-4, IL-5 which induces class switching to IgE production of plasma cell
- Plasma cell releases IgE
- IgE binds to Fc receptor on mast cell
- When antigen(allergen) binds to IgE= cross links receptors
- This triggers mast cell degranulation= histamine is released
Which cytokines released from APC when in contact with naive T cell favour Th2 production?
IL-4,IL-5,IL-9,IL-13
Which cytokines released from APC when in contact with naive T cell favour Th1 production?
IL-12, IFN-Gamma, IL-23, IL-27
How are allergies diagnosed?
Antibodies (IgE) are looked for in serum of blood (liquid part of blood)
What happens in autoimmunity?
Tissues are chronically inflamed (can lead to systemic inflammation)
As a result immune system damages its cells and biomolecules
Examples of autoimmune diseases
Multiple sclerosis
Diabetes
Arthritis
How are autoimmune diseases diagnosed?
Look for antibodies in serum
The under microscope see if antibodies damage normal body tissue
3 types of immunodeficiency and what they mean
- Primary immunodeficiency (inherited from birth)
- Secondary immunodeficiency (induced by drugs e.g immunosuppressants)
- Acquired Immunodeficiency- AIDS - result of HIV A
How is immunodeficiency diagnosed?
- Under microscope look at number of cells- e,g count number of infected T cells= indicate how sick patient is
- Flow cytometer
What is flow cytometry
Cells are tagged with fluorescently labelled antibodies
These will bind to different CD markers on cell surfaces
Each cell has different CD marker
Shows deficiency of certain cells
e.g can show no. of neutrophils, macrophages, dendritic cells
What are ‘bubble babies’?
They have NO B/T cells= no specific adaptive immunity
As they lack a gene in BCR and TCR rearrangement
How can bubble babies be treated?
Bone marrow transplant
How can immunodeficient patients be used?
To discover how small components of immune system work
What are examples of innate immunity/inflammation in the clinic?
- Failure of PRR- NOD like receptors-defects- leads to susceptibility of Crohn’s disease
- Failure of early complement system- leads to systemic lupus, erythematosus, glomerulonephritis
Treatment involving innate immunity/inflammation in the clinic
Type 1 interferon- used to treat Hepatitis C infection
Treatment of blocking TNF-Alpha used to treat patients with rheumatoid arthritis and inflammatory bowel disease
What is neutropenia?
Abnormally low concentration of neutrophils - immunodeficiency
What causes neutropenia?
Bone marrow disease
Chemotherapy
Radiation
means more susceptible to infection due to low neutrophil numbers
What are neutrophils like?
Made in bone marrow
require high cell turnover- to maintain numbers
They are constantly replaced- as they are short lived
Clinical presentations of neutropenia
- Rapid onset of Fever and sepsis (medical emergency)
- Abscesses
- Dental and perianal infections
- Tonsillitis/pharyngitis
- Sinusitis
- Pneumonia
- Fewer signs of inflammation (milder fever)- as less neutrophils are recruited to site of infection
What organisms cause infection when a patient has neutropenia? (Immunodeficiency-weakened)
Opportunistic Commensal Organisms
Which opportunistic commensal organisms cause infections in patients with neutropenia
- Staphylococcus
- E.coli
- Pseudomonas
- Fungal disease e.g aspergillus
How is neutropenia managed?
- Good barrier care e.g dental hygiene and wound care
- Look for infection by culturing blood
- Antibiotics- e.g antifungals
- GCS-F- stimulate neutrophil production
Clinical scenarios linked to dendritic-T cell interaction
- HIV infection- failure of T helper cell
- Failure of Th1 response= susceptibility to mycobacterium
- Failure of self tolerance= thyroid autoimmunity (T cells attack own body)
How does HIV invade the body?
hijacks adaptive immune system
HIV infects host cell via CD4 and CCR5 (chemokine) in tissues
Infected tissue containing T helper and dendritic cells then migrate to lymph node = further viral replication occurs
What is the tropism for HIV? (Binds to)
CD4 receptor on T helper cell
CCR5 on dendritic cell
infects these cells
What organisms cause opportunistic infections?
Cryptococcus
Pneumocystis pneumoniae
toxoplasmosis
What infection occurs as a result of loss of B cell function?
Salmonella
Pneumoniae
What infections occurs as a result of Th1 loss of fucntion?
susceptible to mycobacterium
What does loss of Th1 mean?
Less activation of macrophages= less phagocytosis
What diseases occur as a result of loss of T cell antitumour function
Non-Hodgkin’s Lymphoma
Kaposi’s sarcoma
What diseases occur as a result of loss of T regulatory cell function
Autoimmune diseases
e.g ITP= blood doesn’t clot properly= excessive bleeding
High immunoglobulin levels
Examples of clinical scenarios linked to B cell
- Antibody fails to recognise new antigen(e.g influenza vaccine- diff strains)
- Failure of B cell antibody class switching (e.g IgE in allergy)
- T cell help for wrong B cells- molecular mimicry
