T/F: Most immunodeficiencies are primary cause – congenital
False; most immunodeficiencies are acquired, congenital is less common
What kind of infections are you susceptible to when there is defect in the membrane attack complex (MAC) of complement system?
Increased cases of Neisseria bacteremia, meningitis
Notable Primary immune deficiencies of T cell is ______, combined B and T cell is _____, B cell alone is _____ , Immunoglobulin deficiency (technically still B cell)______, and phagocytes ____.
DiGeorge
SCID (specifically X-linked SCID)
Bruton agammaglobulinemia (XLA)
IgA deficiency
Leukocyte adhesion deficiency
T cell deficiencies are usually seen in which type of recurring infections?
Broad range: bacterial, fungal, viral, protozoal. Basically everything since you don’t have T cell to kill
T/F: T cell deficiencies of ten also lead to problems with B cell maturation
True. Since if there is no Helper T cell to present antigen to B cell, there won’t be activation of them
T-cell deficiency is usually seen in patients ______ of age, why?
6-12 months
That is when maternal antibodies are starting to go away
How can you treat T cell deficiency and what is the timing?
Treat with stem cell transplant but only before fulminant infections occur.
Cannot do transplant when fulminant infection has developed
T/F: without hematopoietic stem cell transplant, children with T cell deficiencies will require significant amount of live vaccinations to stay alive and help with immune response
False; without transplant, they rarely live past the age of 2. Vaccination is not a good idea
DiGeorge is failure to development which area?
Third and fourth pharyngeal pouches- significantly malforming the thymus
T/F: Antibody production in DiGeorge patients are unaffected because DiGeorge is a T cell deficiency disorder and antibodies are made by B cells
False; Antibody production in DiGeorge may be decreased because there is no mature T cell to signal B cell stimulation to produce antibodies when there is an infection
What type of infections are DiGeorge patients most susceptible to?
Severe pyogenic bacterial infections
Severe fungal, viral or protozoal infections occurring early in life
Namely: Pneumocystis jiroveci, Candida albican
T/F: DiGeorge is unusual in that this primary genetic immunodeficiency is not caused by defect in the bone marrow precursors
True; DiGeorge is a result of a defect in the third and fourth pharyngeal pouches during embryonic development
T/F: T-cell precursors are normal in DiGeorge’s, so thymus transplant can correct the defect and allow patient’s own T-cell precursors to mature
True; DiGeorge is a defect of the third and fourth pharyngeal pouches, bone marrow functions are intact so a transplant would help these patients’ immune function
_____ secretes IL-12 to activate ______ cell to secrete ______ cytokines. This cytokine then binds to ____ receptors on ______ (cell) to enhance intracellular killing.
Infected macrophage (mycobacteria or Salmonella)
CD4 T-cell/NK cell
INF-gamma
JAK1 and 2
The infected macrophage
Defects in IL-12, IFN-gamma or the receptors for these cytokine will lead to recurrent ______ and ______ intracellular infections
Mycobacteria and Salmonella
Mycobacteria and Salmonella intracellular infection can induce the macrophage to produce which cytokine?
IL-12
IFN-gamma is made by which cell? What is the function of this cytokine?
CD 4 Helper T cell
IFN-gamma will enhance macrophage killing of intracellular pathogen
Which primary immunodeficiency causes defects in all lymphocyte development?
SCID (defects in B, T and NK cells)
T/F: patients with T cell or B cell immunodeficiency presents with recurrent symptoms at a later age than patients with SCID
True; SCID usually affect early infancy (less than 3 months of age), which is much earlier than T or B cell deficiency since SCID is deficiency of all the lymphocytes
What is the immunoglobulin level of a SCID patient?
low (cuz they don’t have B cells, and tonsil and lymph nodes may also be absent)
T/F: SCID patient has absolutely no immune system activity, both innate and acquired immunity are abolished
False; their innate immunity is not directly affected, their neutrophils and macrophages are still present, they are just not able to clear infection due to a lack of acquired response
T/F: Children with SCID must be strictly isolated from potentially harmful microorganisms, so they should never be given live, attenuated vaccines
True!
(don’t want to give them autism too, so win-win….)
T/F: a 2 month-old septic looking girl brought in by parents presenting with fever and cough, you immediately conclude that it is X linked SCID.
False; while the age is appropriate for SCID, but most common SCID is X-linked, which would only affect Boys. There are other forms of SCID, so it is still possible its SCID when it’s a girl, but not X inked. Duh
X-linked SCID has defect in the _____ chain of ____ receptor. This protein chain is also found in multiple other receptors affecting other lymphocytes.
Gamma chain of IL-2 receptor
Other receptors with gamma chain: IL-4, 7, 9, 15, 21 (T and NK fail to develop, B is compromised)
T/F: telltale sign of X-linked SCID is young infant with candidiasis
True
T/F: Compared to normal 0-3 month olds, X-SCID total lymphocyte count is increased
False; total lymphocytes is low ( < 2000; normal is 3400-7300 in ages 0-3 months)
T cell primary deficiency is susceptible to opportunistic infections such as______ and ______. B cell primary deficiency is susceptible to recurrent ______ infections
Candida (T- deficient)
PCP (pneumocystis jiroveci) (T-Deficient)
Bacterial (B deficient)
____ cell primary deficient would have impaired responses to vaccines
B
What is the antibody level of B cell deficient patients?
Low or absent
1 year old boy presents with recurrent fevers, sinusitis and gastritis, in the context of immunodeficiency, what is the suspected organism causing this?
Encapsulated organisms
This is most likely a B cell deficiency given age, and the mucous membrane is often affected (lack IgA)
List the B-cell primary deficiencies:
X-linked
IgA deficiency
Hyper IgM
CVID- common variable immunodeficiency
Bone marrow of a 6+ month old boy: Pre-B cell are presents, but fail to differentiate into mature B cell, think:
XLA (Burton’s XLA)
Mutation of which gene results in XLA?
BTK (burton’s tyrosine kinase)
6 month old boy with XLA would likely present with recurrent ____ infections, often caused by these pathogens:
Giardia infection is seen often in infants with ______
XLA
Giardia is otherwise neutralized by IgA, but without IgA they cause infections
Most common antibody class deficiency:
IgA
Affecting the mucous membranes
IgA deficiency would result in recurrent ___ and __ infections
Lungs and sinus
IgA line the mucous membrane
T/F: IgA deficiency is a primary genetic immunodeficiency seen in young children
False; it is primary immunodeficiency but seen in older patients
What might be the cause of IgA deficiency?
Failure of heavy chain gene switching
Which antibodies compensates for the loss of IgA?
IgG and IgM
What is the name of the adhesin molecule that is mutated in Leukocyte Adhesion Deficiency Syndrome (LAD)?
Autosomal recessive mutation of Integrin, aka CD 18, aka adhesion (LFA-1) protein
In Leukocyte adhesion deficiency, what is the recurring infection?
Severe pyogenic infections early in life
T/F: in LAD (leukocyte adhesion deficiency), although they are immunosuppressed, they often have extremely high numbers of leukocytes in blood
True. These leukocytes remain in blood but they are unable to go into tissues to fight infections
T/F: Asplenia is a secondary acquired immunodeficiency, without spleen, antibody responses to new antigen are generally suppressed but previously encountered antigens are generally intact
True
Long-lived plasma cells responsible for circulating antibodies usually leave the _____ and reside in the ___
Spleen
Bone marrow
Post-splenectomy patients are at high risk for ____ infections
Encapsulated bacterial
Fungal
Which bacterial infection is seen in asplenic patients? (secondary/acquired immunodeficiency)
Nocardia
Nocardia is gram ____, ___ (shape) bacteria, that stains _____ and is an opportunistic infection often seen in ____ patients as a result of ____ immunodeficiency
