Inborn Errors of Immunity

Question 1

What are the primary/central lymphoid organs?

Answer 1

Bone marrow —> B cells
Thymus —> T cells

Question 2

What are the 3 major secondary or peripheral lymphoid organs?

Answer 2

Spleen
Lymph nodes
Organ-associated lymphoid tissue (GALT, Peyer’s patches, MALT)

Question 3

Where is the MALT?

Answer 3

Mucosa-associated lymphoid tissue = type of organ-associated lymphoid tissue (pt of secondary/peripheral lymphoid organs)

in the bronchi

Question 4

What is the big differentiator between Innate v Adaptive?

Answer 4

Innate - present from birth and more pre-programmed

Adaptive - Memory + Specificity –> develops over one’s life as exposed to infection

Question 5

What are the 2 compartments of adaptive portion of immune system?

Answer 5

1. cellular-mediated by cells (T cells)
2. humoral-mediated by soluble factors (antibodies)

Question 6

What is a type of cell that arises from the Lymphoid progenitor cell but is NOT a part of the Adaptive system?

Answer 6

natural killer cell - bc they are programmed to kill cells that may be infected or have cancer, etc

Question 7

Myeloid progenitor cells give rise to what system?

Answer 7

Innate —> so inc Neutrophil, Eosinophil, Monocyte –> Macrophage, Dendritic cells

Question 8

Lymphoid progenitor cells give rise to what system?

Answer 8

Adaptive —> so mainly the T cells and B cells

EXCEPT Natural Killer cells also arise but are a part of the Innate Immune System

Question 9

Review timeline

Answer 9

okie dokie

Question 10

What are the 3 main categories of unwanted immune responses?

Answer 10

1. autoinflammation
2. autoimmunity
3. hypersensitivity = excessive adaptive immune response to benign antigen

Question 11

What is the main gist of autoinflammation?

Answer 11

overactivation of innate immune cells to an antigen

so Neutrophils + macrophages can overreact –> joint pain, rashes, ulcers

Question 12

What is the main gist of autoimmunity?

Answer 12

loss of tolerance to self mediated adaptive immunity

react against ourselves

Question 13

What is the main gist of hypersensitivity?

Answer 13

excessive adaptive immune response to benign antigen

overreact to foreign substances like peanuts or pollen

Question 14

We went from knowing 50 genetic causes of IE of Immunity to now what?

Answer 14

50 in 1983
416 in 2022

Question 15

How many categories have the International Union of Immunological Societies (IUIS) identified?

Answer 15

11
review these

Question 16

What makes up the majority of IEI subgroups?

Answer 16

antibody deficiencies - 65%

Question 17

What also makes up biggest subgroups of IEI aside from 65% attrib to antibody def?

Answer 17

15% = combined cellular + antibody def
10% = phagocytic def
5% = cellular def
5% = complement def

Question 18

What are the 3 main categories of symptoms of immunodef?

Answer 18

1. infections (mainly if freq, severe, hard to treat, unusual in childhood, FTT, etc)
2. Autoimmune disease
3. Immune dysregulation (like imp tumor surveillance, cancer, usu Adaptive problem)

Question 19

Review warning signs of immunodef

Answer 19

ok

Question 20

What do we mainly catch on NBS for IEI?

Answer 20

typically when looking at T cell receptor incision circles (?*) and a lower # is a red flag of IEI

Question 21

One great way to test if pt has functioning immune sys is ?

Answer 21

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

Question 22

What are the 2 classic treatments of IEI?

Answer 22

prophylactic antivirals, antibiotics, antifungals

intravenous immunoglobulins

Question 23

What are most recent and now can be classic treatments of IEI?

Answer 23

Immunomodulation - glucocorticoids and biologics (to tweak imm resp)

Bone marrow transplant

Screen for malignancy (esp Lymphomas)

Question 24

Ex: Patient with common variable immunodeficiency diagnosed with CTLA-4 haploinsufficiency —> what treatment can be indicated?

Answer 24

bone marrow transplant at an early age

Question 25

Severe Combined Immunodeficiencies (SCID) can lead to defect in ?

Answer 25

T cells and B cells

Question 26

What are those w SCID susceptible to?

Answer 26

Infections - all like even live vaccines and all infections

Question 27

What clinical features can we see w SCID?

Answer 27

FTT, chronic diarrhea, erythrodermia

gene defects have dif specifics

Question 28

Inheritance patterns for SCID?

Answer 28

mostly X-linked and sometimes AR

Question 29

How do we typically make the dx of SCID?

Answer 29

Lymphopenia, diminished/absent T cells, poor/absent in vitro mitogen-induced T cell proliferation in all

Question 30

What can be confusing about the maternal effects in SCID?

Answer 30

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

Question 31

What are those with Common Variable Immune Def (CVID) susceptible to?

Answer 31

Bacteria, common respiratory and enteroviruses (even vaccine strands), rotavirus, giardia, cryptosporidium

Question 32

What are some common clinical features of CVID?

Answer 32

recurrent sinopulmonary infections, bronchiectasis, diarrhea, arthritis, giardiasis, autoimmunity (20%), astham (10%), lymphoproliferative disease, gastric cancer, lymphoma

Question 33

What is the main inheritance for CVID?

Answer 33

de novo, some AR

Question 34

How do we usually diagnose CVID?

Answer 34

hypogammaglobulinemia (low IgG + low IgA or IgM), B cells present

low class switched memory B cells

impaired antibody response

Question 35

What is the clinical dx of CVID?

Answer 35

IgG <2SD + low IgA and/or low IgM

Question 36

Why might higher IgG trough levels be valuable with CVID?

Answer 36

might help preserve lung function even in absence of overt infections, esp in pts w chronic lung disease + detectable structural damage to the lung

Question 37

What genes account for the majority of CVID dx?

Answer 37

27% PIK3CD
27% LRBA
7% CTLA4

Question 38

What is the big takeaway with treatment?

Answer 38

we can tailor treatment to those w a genetic dx a lot of times, so dx early is great