Immune deficiencies
21 important questions on Immune deficiencies
Why are immuno deficiencies more common in males?
When do we speak of a real indication of immunodeficiency in children?
Indication for ID when:
- >10 otitis media a year, >2 pneumonia a year.
- >2 severe (life threathening) infections per lifetime.
- Family history of ID
- Infections caused by unusual organisms (or when response to an organism is unusual).
What are the symptoms of phagocytic disorders en what kind of infections are most common?
Common infections are: mycobacteria, aspergilles, candida, catalase positive microorganisms.
- Higher grades + faster learning
- Never study anything twice
- 100% sure, 100% understanding
For my 1st exam I got a C. Then, I started looking for ways to learn better and I came across Study Smart. Since then I have scored a A+, A, A- and another A. I highly recommend it to everyone who wants to hear it. I am so happy with it!!
I was struggling to finish all my first-year subjects for 3 years. Then I discovered Study Smart, which helped me to finish all of them within 3 months.
Because of StudySmart, things are going well in many ways. Before, I always had study stress and no time for anything. Now I feel calm and confident (because of the program). I used to score a B, now I usually score an A or A+.
Hey Chris, I really want to thank you very much for developing the platform, I usually got around C for my exams, now I scored an A+, an A and a A- !!
Since using Study Smart, my average has increased significantly. I even completed a statistics course with a A+ while I'm bad at statistics. I took on extra courses this year, because of Study Smart. Thanks so much!
Ever since I started studying with StudySmart I passed all my exams !!! No more re-sits!! At first, I was happy with a pass and now I only get good grades. Many thanks!
I aced all the courses I studied with Study Smart. For law, I first scored a D, and now an A! I’m 100% sure that I’ll pass all the courses I study with Study Smart.
I always thought I studied well. My grades were fine. I could never have imagined that applying these study skills would have such a huge and direct impact on my grades, my speed and the pleasure I have in learning.
For the first time, I finally feel totally confident about the way I learn. I have the perfect overview and make great progress in terms of speed and the grades I get. Thanks, Chris!
I immediately started to enjoy learning again, and my grades soared. All of a sudden, everything went better. I highly recommend Study Smart to all students..
Being able to create my materials online made the process of studying so much smoother and quicker. I no longer have to spend a huge amount of my time on creating my summaries.
At first, my notes were a mess. Now I use Study Smart to take my notes in a perfectly structured way. It helps me to save a lot of time and do other things I enjoy.
Students that study with Study Smart get better grades. The system applies all the learning methods in such a way that both well-performing students and students who struggle perform much better.
Hi Chris, I would like to thank you very much. Last year I scored C on a course, and this year I got an A+ thanks to your method! Thank you very much!
The largest effect is that my child is more enthusiastic about school! Every parent wants their children to be happy at school, Study Smart made it happen.
In high school, I failed several exams, and that has really changed now. I actually needed this tool very much back then. Since I started studying with StudySmart, I haven't had any D's. My average score is now an A and those are results I would have never had in the past
With my old method, I passed only 3 out of 8 courses. Since I started taking my notes digitally in Study Smart, I have passed all my courses on the first try. For me, StudySmart takes away the stress of wondering if I will pass or not.
Thanks to StudySmart, I passed all my exams, and with better grades than before! On top of that, I have mastered a very good study method now, which I am confident will help me earn my degree.
Which phagocytic diseases do you know, what are the characteristics and how do they cause immunodeficiency?
- Chronic Granulomatous Disease: 70% xlinked, defect in NADPH oxidase, no ROS formation for microbe killing and protease activation, susceptible for catalasepositive bacteria.
- Leukocyte Adhesion Defect: leukocytes cant enter the tissue; recurrent skin infections, severe periodontal disease (tooth loss), delayed woond healing, leukocytosis (elevated leukocyte levels), leading to candidiasis (schimmelinfectie mond)
Which gene defects can cause Leukocyte Adhesion Deficiency?
- LADI: mutation in beta chain of integrin LFA1; reduced binding of mononuclear cells to the endothelial cells: no adhesion (and no extravasation).
- LADII: absence of sugar ligands for selectine beacause of defect in fucosetransporter gene: no roling.
- LADIII: activation of integrins is defective (activation and 3d transition does not occur): no adhesion.
Summary the development of a naive bcel to a IgM plasma cell
Affinity maturation by somatic hyper mutation in the lymph nodes (also tcell dependent_ "perfect" plasmacells migrate from the lymphnode and are able to produce specific antibodies.
Explain the difference between the primary and secundary (bcell) respons
Secondary respons: memory IgG cells can directly be activated by antigen; + SHM due to tcell interaction = a lot of IgG with high affinity.
Explain what primary B cell deficiencies are and appoint the clinical signs
- Disorders characterized by reduction and/or change in composition or absence of serum Ig (antibodies).
- Clinical signs are; recurrent sepsis and bacterial infections with encapsulated (kapsel) bacteria (opsonisation is defect!), bronchiectasia (widening of breathing tubes due to damage caused by inections) leading to cough, chronic gastroenteritis (darm en maagontstekingen), failure to thrive (groei/ontwikkeling verstoring).
What categories of primary bcell deficiencies do you know?
- Defect in early bcell development
- Class switch recombination defects
- Common variable immunodeficiencies
What is the underlying mechanism of early b cell development defects? What is an example of a early bcel development disease?
X linked agammaglubulinaemia: mutation in Btk results in a pre-BCR signalling defect, leading to failure to produce mature b lymphocytes and Ig.
What is the underlying mechanism of class switch and somatic hypermutation? What is an example of a disease?
X-linked hyper IgM syndrome (HIGM1): mutation in CDL40 ligand on tcells, leading to 1) only IgM, 2) no class switch 3) no somatic hypermutations.
What is the mechanism of cell mediated defects?
X-linked SCID: deficiency in common gammachain.; present in IL receptors; defective cytokine signaling (tcells, bcells and nk cells).
Treatment of bcell, tcell and phagocytic defects:
What is the definition of secondary immunodeficiencies and what kind of infections are caused by secondarty immunodeficiencies?
- Defects in Ig/complement/phagocytic cells leads to pyogenic bacterial infections.
- Defects in cell mediated immunity leads to viral, fungi and intracellular microorganism infections. (tcells viral/fungi, bcells bacterial)
What are causes of secundary immunodeficiency?
The immune system is supressed due to...
- Infection (HIV, measles)
- Iatrogenic (immune blockers and stem cell transplantation)
- Malignancy (cancer)
- Biochemical/nutritional disorders (diabetic, renal insufficiency)
- Other conditions (trauma, stress)
What is the difference between immune deficiency and auto immune disease?
Immune def: system works too little
What are the three mechanisms immune deficiency?
- Killing of cells (low numbers)
- Disrupted function (recognition)
- Disrupted localization of cells
Explain how aging influences immune deficiencies
Children: developing memory
Eldery: frail immunosenecense; sensitivity for disease increase and vaccination loses effect.
The neonatal immune system is in a continues state of tolerance (less cytokines, only maternal Ig, less tcell activity, less complement).
- Probably due to a combination of immaturity and active suppression.
- This tolerance is there to prevent immunopathology upon contact with new pathogens.
- Nucleated erythrocytes are only demonstrated in neonates and actively suppres the immune system
Explain how immunosupressive drugs can cause immune deficiencies. When are those drugs used?
- Glycocorticoids: Inhibit inflammation.
- Calcineurine (small molecule): Hinders tcel activation
- Inhibitors of nucleotide syntheses: no proliferation (like chemo).
- Antimetabolites: these are analogs for nucleotides; also no proliferation
- Fingolimod: hinders localization of immune cells
- Protein drugs: depleting antibodies, nondepleting antibodies, intravenous Ig
Explain the mechanism of multiple sclerosis. What is possible as treatment?
What is a risk of this treatment?
Fingolimod: Tcell does not express S1P1receptor anymor; this treatment ensures that this receptor cant be recycled but is downregulated in proteasomes --> Tcell cant leave the lymph nodes.
Other option: Alemtuzumab; inhibits active tcells.
Risk of fingolimod: immunodeficieny!: reactivation of the normally latent virus "JC" in the brain, because Tcells cant reach the brain anymore.
Explain how bone marrow supression (secondary to chemo, due toradiotherapy or due to infiltration of malignant cells into the bone marrow) leads to immune deficiency. Which deficiency?
Dus beenmerg remmen kan door chemo of door de kankercellen zelf...
Stopping chemo if infection is severe; quick reconstiitution of neutrophils.
Reconstitution of tcells is slower; so log after cancer treatment higher risk on viral and fungi infections.
The question on the page originate from the summary of the following study material:
- A unique study and practice tool
- Never study anything twice again
- Get the grades you hope for
- 100% sure, 100% understanding
