11.10: Immunodeficiency Flashcards
What does ID refer to in this lecture?
Immunodeficiency
How to predict what type of ID is occurring?
- Specific defects lead to predictable disease
- Family history should be in HPI: very important
What should always be in your DD with dealing with and immunodeficient patient?
- Lymphoma
2. Autoimmune disease
What will you see in history of patient with a B cell defect?
- Recurrent sino pulmonary infections
- Septicemia from infection w/ bacteria w/ polysaccharide capsules
* **Cannot make antibody for polysaccharide - Staph, Strep, and Haem. predominate
- Susceptible to systemic and a typical CNS disease with enterovirus
- Manifests 3 - 6 months after birth
- Once maternal Ig no longer protects baby
Why does B cell defect lead to septicemia from infection w/ bacteria w/ polysaccharide capsules?
W/p B cells cannot make antibody for polysaccharide capsule
Why does B cell defect make you susceptible to systemic and a typical CNS disease with enterovirus?
- W/o B cell enteroviruses cannot be localized to the GI tract where they belong
- Disease will become systemic and move to CNS
What is recurrent sino pulmonary infections manifesting at 3 - 6 months indicative of?
- B cell defect
- Once maternal Ig is no longer around to protect baby it begins to get sick
What type of infections does T cell defect lead to?
Organisms requiring T cell / mac to control:
- Listeria
- Fungi
- Protozoa
- Most virus
What is necessary for CD8 control of infections?
- T cells
- If do not have this cannot control virus
When does T cell defect manifest?
Day 1 of life
What is sickness from day 1 of life indicative of?
T cell deficiency
What is SCID?
- Severe, Combined Immunodeficiency disease
- Sick from birth
- Defects in organ systems and white cell lines
What is sickness from birth with other generalized defects indicative of?
SCID
Question to ask to see if child truly does have recurrent infections?
Has child been hospitalized for infections
Are T or B cell disorders more susceptible to bacterial or viral infections?
T cell: Viral/fungal
B cell: bacterial
3 early branch points in DD for ID?
- Recurrent illness: hospitalization
- Viral or fungal infections
- CBC administration
- T cell defect: can ptn. mount response to skin testing?
- B cell defect: does kid have Ig?
What is ptn with no lymphocytes indicative of?
T cell defect
What is negative response to skin testing indicative of?
T cell defect
What is absence of Ig indicative of?
B cell defect
How to test for B cell function?
- Serum protein electrophoresis w/ Ig level quantification
- Perform titers if negative
- Flow cytometry to measure exact defect
How to test for T cell function?
- Lymphopenia on CBC: low T cells
- Flow cytometry to see what T cells they have
- Lymph node biopsy
Danger of lymph node biopsy?
- Can lead to infection that will kill ptn.
What is X linked Agammaglobulinemia?
- Mutation in tyrosine signalling necessary for B cell development
- Seen in males
- ZERO Ig cells in serum
- No B cells in marrow, blood, tissues
- Only “pure” B cell defect
What is no B cells in marrow, blood, tissues with zero Ig in serum indicative of?
Agammaglobulinemia
How do you treat Agammaglobulinemia?
IVIG monthly
Which disease can be treated with IVIG?
Agammaglobulinemia
What is X linked hyper IgM syndrome?
- Mutation in CD40L / CD 145 (receptor on T cells)
- High IgM with low IgA/G as B cells are not prompted to isotype switch
What is high IgM with low IgA/G indicative of?
X linked hyper IgM syndrome
How do you treat X linked hyper IgM syndrome?
Stem cell transplant
What is selective immunoglobulin “deficiency”?
- IgG /M normal with absent IgA: IgM/G takeover function of IgA: no real clinical problem
- Not associated with specific infections
- Problem is some ptns develop IgG ANTI IgA antibodies
- Can cause shock after RBC transfusions
What is IgG /M normal with absent IgA indicative of?
Selective immunoglobulin “deficiency”
What is danger in ptn. with selective immunoglobulin “deficiency”?
- They can develop anti IgA antibodies since have no IgA
- Giving transfusion can cause shock since IgA is likely in transfused blood
Signs associated with selective immunoglobulin “deficiency”?
- Increased risk of allergies
- Increased risk of autoimmune disease
What is EBV X Linked agammaglobulinemia indicative of?
- Mutation in signaling regulator of CD8s
- Mutation activated by EBV infection of B cells
- Once T cells kill infected B cells. cannot be turned off
- Can lead to death of ptn.
What is EBV?
- Mono virus
- Infects B cells causing to express EBV antigens signalling T cells to kill them
What is CVID?
“Common variable Immunodeficiency”
- Normal up to 2 - 4 yo
- Slowly declining Ig levels eventually leading to B cell type infections
- Progress to T cell type infections, then autoimmune diseases ending in lymphoma
- *Caused by B cells not being able to become plasma cells
How do diagnose CVID?
- B cell infections followed by T cells
- Normal / plentifull B cells in periphery
- Lymph nodes with no Germinal centers
How to treat CVID?
- IVIg works until enter T cell stage
- Stem cell transplant
- Surveillance for lymphomas
What is thymic aplasia?
“22q11.2 deletion syndrome”
- Patient lacks thymus
- Sick from birth with fungal infection
- Arises from structural mutation in 3rd/4th branchial pouches
- **Always CV abnormalities: tetralogy of fallot or pulmonary stenosis
- Absent parathyroid glands with symptomatic hypocalcemia
What is tetralogy of Fallot?
- Pulmonary stenosis
- Overriding Aorta
- Ventricular septal defect
- RVH
What is CV abnormalities with hypocalcemia and facial dysmorphism characteristic of?
Thymic aplasia
How do diagnose thymic aplasia?
- No thymic shadow on chest film at birth
- Severe lymphopenia
- Normal Ig at birth
- 22Q11 Deletion
What is ADA?
“Adenosine deaminase”
- Defect can cause SCID
Signs of SCID?
- Infections from birth
- Decrease TRECs
How to treat SCID stemming from ADA deficiency?
- If stem cell replacement is not viable, enzyme replacement therapy can work
What is a TREC?
- T cell Receptor Excision Circle
- Formed during rearrangement of T cell receptor
- Moves into cytoplasm to be detected by PCR
What does it mean if TRECs are present?
- Ptn. has thymus that is generating T cells
- Used in newborns to screen for SCID
What is used in newborns to screen for SCID?
TREC analysis
What is Wiskott Aldrich Syndrome?
Will be on test
- Eczema
- Thrombocytopenia
- Moderate T cell deficiency
- Decreased IgM with not polysaccharide Ig
- High incidence of autoimmune disease
- Females carr, males present
What are the following indicative of?
- Eczema
- Thrombocytopenia:; BLEEDING
- Moderate T cell deficiency
- Decreased IgM with not polysaccharide Ig
- High incidence of autoimmune disease
- Females carr, BOYS present
Wiskott Aldrich Syndrome
What is eczema and bleeding in a boy indicative of?
Wiskott Aldrich Syndrome
What is Ataxia telangiectasia?
- Early cerebellar dysfunction
- Telangiectasia of eyes
- Loss of DNA repair gene: EXTREMELY SENSITIVE TO RADIATION
- Almost all develop leukemia or lymphoma
What is telangiectasia?
Dilation of capillaries, causing to appear as small red or purple clusters, often spidery in appearance, on skin / surface of organ
What is disease in which ptn. is extremely sensitive to radiation?
Ataxia telangiectasia
What is Bare lymphocyte syndrome?
- Defects in MHC I / II on cell membrane
- I: can’t deal with virus
- II: Can’t deal with TB
Defects in MHC I / II on cell membrane?
Bare lymphocyte syndrome
What is Job syndrome?
“Hyper IgE syndrome”
- Eczema w/ recurrent T and B cell infection
- High IgE with low Th17 function
- High IL 4 and 13 levels
What is the following indicative of?
- Eczema w/ recurrent T and B cell infection
- High IgE with low Th17 function
- High IL 4 and 13 levels
Job syndrome, aka: “Hyper IgE syndrome”
What does normal Ig, Neutrophil count and function hint at?
Defect in complement system
What is Chediak Higashi syndrome?
PROBLEM WITH NEUTROPHILS
- Albinism
- Easy bleeding
- Lymphomas
- Normal T and B cells
- Huge neutrophils with blue granules
What is normal T/B cells, recurrent infection and huge neuts w/ blue granules often found in albinos indicative of?
Chediak Higashi
What is Chronic granulomatous disease?
- Mutation in NADPH respiratory burst system
- Neuts can phagocytose by cant kill because of low H2O2
- Frequent infections with Catalase plus orgs: staff and fungi
- Neisserial infections seen
What types of infections are seen in Chronic granulomatous disease?
- Catalase positive organisms usually staff and fungi
- Catalase destroys basal level of H202 in neuts so they cannot kill bugs
- Basal level is sufficient for neuts to kill cat negative orgs
What types of vaccines should not be used in ID ptn.?
Live
How to treat B cell deficiency?
IVIg
