Dysregulation & Deficiency Flashcards
About how much of the world’s population is infected with TB?
1/3
Where in the normal immune response does TB go wrong?
TB organism modifies on surface of phagosome instead of fusing with lysosome and being destroyed
When the TB organism kills the macrophage during its escape, how does it harm the host?
Necrotic debris from killed macrophage are released into lung tissue (inflammatory response) leading to tissue damage
What are cathelicidins?
Antimicrobial enzymes whose release is stimulated by vitamin D
How does one recover from TB and then live with the chronic infection?
1 INF-gamma hyperactivates macrophages which are able to deal with TB organism
2 Macrophages and other cells (neutrophils) eliminate invader
3 T cells come into play
4 Vitamin D stimulates release of antimicrobials (cathelicidins)
When does sepsis occur?
When chemicals released into bloodstream to fight infection trigger inflammation throughout body
How can sepsis lead to death?
Multiple organ failure, septic shock leading to dropped BP then death
Sepsis is most serious in what group of people?
Elderly or immunocompromised
Is sepsis not an issue in the U.S.?
Still is: 250,000 die per year
What major cytokine is involved in sepsis, and what is its effect?
TNF; increased vascular permeability, fluid loss, decreased blood volume and BP, septic shock and heart failure
How does vagal stimulation affect macrophage release of TNF?
Inhibitition
Allergies are typically associated with which helper T cell bias?
2
Non-allergic people produce more of which antibody?
IgG
What helper T cell bias is associated with non-allergic people?
Th1
What causes allergies?
Overproduction of IgE antibodies
Th2 cells involved in an allergic response secrete which cytokine to recruit many eosinophils from the bone marrow?
IL-5
Which cells play a prominent role in the delayed allergic phase?
Eosinophils
What is the normal function of mast cells, basophils, and eosinophils?
Provide defense against parasitic infection that are too large to be phagocytized by macrophages and neutrophils
When is the only time that mast cells, basophils, and eosinophils SHOULD degranulate?
In response to IgE binding to parasite, limiting collateral damage in tissues
Why is the fetus representative of a Th2 bias?
Half the fetus is paternal and could be seen as foreign by the mother so this provides protection
What makes up the Th1 subset of cytokines?
TNF, IL-2
What is the function of TNF?
Activate NK cells
What is the function of IL-2?
Proliferation of NK cells and CTLs
What is the role of the placenta when it comes to helper T cell bias?
Produces large quantities of IL-4 which causes both maternal and fetal helper T cells to become Th2
It is advantageous to bias the fetus AWAY from which helpter T cell bias?
Th1
What is thought to shift the newborn back to a Th1 bias after birth?
Contact with soil microbes and early childhood infections (possible allergy prevention)
What is the relationship because location of upbringing as a child and incidence of allergies/asthma?
Farm life - lower incidence
City life - higher incidence
(also lower incidence when growing up with dogs)
If one identical twin has allergies, what is the likelihood for the other to develop the same ones?
50%
What kind of people are more likely to have inherited particular class II MHC genes?
Atopic (allergic) people
What cytokine is responsible for class switching to IgE thus having an impact on over-abundance of allergic reactions?
IL-4
How do glucocorticoids (cortisol) work to treat allergies?
Block cytokine production by Th cells activating fewer B cells
What is the downside to using glucocorticoids as treatment for allergies?
Increased susceptibility to infectious disease and immunosuppression
What treatment for allergies functions to block the binding of IgE to mast cells?
Xolair (Omalizumab)
What is the downside to Xolair for treating allergies?
Crazy expensive ($1000 per month)
How do Claritin and allegra work to treat allergies?
Block histamine (H1)
How do infections of gradually increasing doses of crude extracts of allergens work to treat allergies?
Patient become tolerant because B cells class switch from IgE to another like IgG (iTregs are generated to produce cytokines like IL-10 that suppress IgE production)
What cytokines are associated with a Th2 bias?
IL-4, IL-5, and IL-13
Autoimmune disease affected what percentage of the U.S. population?
5-7.5% (15-23 million Americans)
Autoimmune disease is more common among which gender?
Women
About how many known autoimmune disease are there?
100
How much more common are autoimmune diseases now than just several decades ago?
3X
Molecular mimicry can lead to what serious immune system issue?
Autoimmune disease (if natural guards are broken)
There may be a link between Myasthenia gravis and what virus?
Polio virus
Which type of antibody complexes can activate macrophages leading to chronic inflammation in Rheumatoid arthritis?
IgM-IgG
What condition is a result of the immune system attacking the myelin of the PNS?
Guillain-Barre
What is transverse myelitis?
Inflammatory process of the spinal cord that can cause axon demyelination
What is autoimmune lymphoproliferative syndrome?
Genetic defect where T cells refuse to die when chronically stimulated by self antigens (defect in apoptosis due to defect in Fas or Fas ligand proteins)
What 3 things must be necessary to develop an autoimmune disease?
1 must have MHC molecules that can present self-antigen
2 must have T lymphocytes and some B lymphocytes with receptors to recognize self antigens
3 environmental factors leading to breakdown of tolerance mechanisms for self-reactive lymphocytes
Autoimmune diseases frequently follow what conditions?
Bacterial or viral infections
What is probably one of the key environmental factors that triggers autoimmune disease (along with environmental pollutants and possibly chronic inflammation)?
Bacterial or viral infections
Can molecular mimicry alone cause an autoimmune disease?
No; must also be an inflammatory reaction going on in the same tissues that express self antigen
What is the result of a mutation leading to a nonfunctional CD40 (B cell) or CD40L (Th cell)?
B cells unable to class switch and secrete mainly IgM
What condition is the result of a malformation and dysfunction of the thymus, and what is the problem with it?
DiGeorge Syndrome (thymic tissue missing –> no T cell function)
What is the problem with severe immunodeficiency syndrome (SCIDS)?
Neither B cells nor T cells function due to defected protein that is required to produce BCR and TCR
What cells are primarily targeted by AIDS?
Helper T cells (but also macrophages, dendritic cells, CD4 protein)
What is usually the cause of death in those with AIDS?
Opportunistic infections that the body can’t fight off (examples = Kaposi sarcoma, pneumocytis carinii)
Why is HIV-1 able to defeat the immune system in many cases?
It is a slowly replicating lentivirus (retro RNA virus) that sits in a latent state and is undetected by CTLs
Also, high mutation rate
What is the drug treatment for AIDS?
Highly Active Anti-Retroviral Treatment (HAART) of nucleoside/tide reverse transcriptase inhibitors to inhibit high mutation rate
The innate immune cells in the less than 1% of those able to control their HIV infection secretion more of which substances?
IFN-alpha and IFN-beta
What else is different in the small percentage of those who can control their HIV infection?
More efficient MHC molecules to present HIV-1 peptides and activate CTLs earlier, more vicious CTLs, quicker responses overall
