Inborn Errors of Immunity Flashcards
What are the primary/central lymphoid organs?
Bone marrow —> B cells
Thymus —> T cells
What are the 3 major secondary or peripheral lymphoid organs?
Spleen
Lymph nodes
Organ-associated lymphoid tissue (GALT, Peyer’s patches, MALT)
Where is the MALT?
Mucosa-associated lymphoid tissue = type of organ-associated lymphoid tissue (pt of secondary/peripheral lymphoid organs)
in the bronchi
What is the big differentiator between Innate v Adaptive?
Innate - present from birth and more pre-programmed
Adaptive - Memory + Specificity –> develops over one’s life as exposed to infection
What are the 2 compartments of adaptive portion of immune system?
- cellular-mediated by cells (T cells)
- humoral-mediated by soluble factors (antibodies)
What is a type of cell that arises from the Lymphoid progenitor cell but is NOT a part of the Adaptive system?
natural killer cell - bc they are programmed to kill cells that may be infected or have cancer, etc
Myeloid progenitor cells give rise to what system?
Innate —> so inc Neutrophil, Eosinophil, Monocyte –> Macrophage, Dendritic cells
Lymphoid progenitor cells give rise to what system?
Adaptive —> so mainly the T cells and B cells
EXCEPT Natural Killer cells also arise but are a part of the Innate Immune System
Review timeline
okie dokie
What are the 3 main categories of unwanted immune responses?
- autoinflammation
- autoimmunity
- hypersensitivity = excessive adaptive immune response to benign antigen
What is the main gist of autoinflammation?
overactivation of innate immune cells to an antigen
so Neutrophils + macrophages can overreact –> joint pain, rashes, ulcers
What is the main gist of autoimmunity?
loss of tolerance to self mediated adaptive immunity
react against ourselves
What is the main gist of hypersensitivity?
excessive adaptive immune response to benign antigen
overreact to foreign substances like peanuts or pollen
We went from knowing 50 genetic causes of IE of Immunity to now what?
50 in 1983
416 in 2022
How many categories have the International Union of Immunological Societies (IUIS) identified?
11
review these
What makes up the majority of IEI subgroups?
antibody deficiencies - 65%
What also makes up biggest subgroups of IEI aside from 65% attrib to antibody def?
15% = combined cellular + antibody def
10% = phagocytic def
5% = cellular def
5% = complement def
What are the 3 main categories of symptoms of immunodef?
- infections (mainly if freq, severe, hard to treat, unusual in childhood, FTT, etc)
- Autoimmune disease
- Immune dysregulation (like imp tumor surveillance, cancer, usu Adaptive problem)
Review warning signs of immunodef
ok
What do we mainly catch on NBS for IEI?
typically when looking at T cell receptor incision circles (?*) and a lower # is a red flag of IEI
One great way to test if pt has functioning immune sys is ?
seeing if pt has vaccine titers to tetanus and pneumonia vaccine
so like give baseline titer, give ammonia shot, then see them back to examine the titers
What are the 2 classic treatments of IEI?
prophylactic antivirals, antibiotics, antifungals
intravenous immunoglobulins
What are most recent and now can be classic treatments of IEI?
Immunomodulation - glucocorticoids and biologics (to tweak imm resp)
Bone marrow transplant
Screen for malignancy (esp Lymphomas)
Ex: Patient with common variable immunodeficiency diagnosed with CTLA-4 haploinsufficiency —> what treatment can be indicated?
bone marrow transplant at an early age
Severe Combined Immunodeficiencies (SCID) can lead to defect in ?
T cells and B cells
What are those w SCID susceptible to?
Infections - all like even live vaccines and all infections
What clinical features can we see w SCID?
FTT, chronic diarrhea, erythrodermia
gene defects have dif specifics
Inheritance patterns for SCID?
mostly X-linked and sometimes AR
How do we typically make the dx of SCID?
Lymphopenia, diminished/absent T cells, poor/absent in vitro mitogen-induced T cell proliferation in all
What can be confusing about the maternal effects in SCID?
maternal T cell engraftment can confuse things
so even like kids can have normal T cells, but mom’s are better, so you want the child to have their own T cells that are ready to function
What are those with Common Variable Immune Def (CVID) susceptible to?
Bacteria, common respiratory and enteroviruses (even vaccine strands), rotavirus, giardia, cryptosporidium
What are some common clinical features of CVID?
recurrent sinopulmonary infections, bronchiectasis, diarrhea, arthritis, giardiasis, autoimmunity (20%), astham (10%), lymphoproliferative disease, gastric cancer, lymphoma
What is the main inheritance for CVID?
de novo, some AR
How do we usually diagnose CVID?
hypogammaglobulinemia (low IgG + low IgA or IgM), B cells present
low class switched memory B cells
impaired antibody response
What is the clinical dx of CVID?
IgG <2SD + low IgA and/or low IgM
Why might higher IgG trough levels be valuable with CVID?
might help preserve lung function even in absence of overt infections, esp in pts w chronic lung disease + detectable structural damage to the lung
What genes account for the majority of CVID dx?
27% PIK3CD
27% LRBA
7% CTLA4
What is the big takeaway with treatment?
we can tailor treatment to those w a genetic dx a lot of times, so dx early is great
