Random Last Week Flashcards
What does the skin above the umbilicus drain to?
The axillary lymph nodes
What does the skin below the umbilicus drain to?
The superficial inguinal lymph nodes
X-linked Agammaglobulinemia (Brutons): What is the pathogenesis?
Defect in BTK (tyrosine kinase gene) so B cells can’t mature.
Number of B cells is low, but the ones that DO mature work just fine (unlike CVID)
X-linked Agammaglobulinemia (Brutons): What are the symptoms?
Usually a boy, after age 6 months, start getting:
- Bacterial infections
- Enterovirus infections (me: Includes Polio, Echo, Coxsackie, HAV)
- Giardia
- Issues with live vaccines (ex: Sabin Polio vaccine)
Also see small/no tonsils and lymph nodes
X-linked Agammaglobulinemia (Brutons): What are the labs?
- Low Ig (all kinds)
- No B cells in blood
- No germinal centers/follicles in lymph node
IgA deficiency: What is the pathogenesis?
Unknown. But its the most common immunodeficiency!
What is the most common immunodeficiency?
IgA deficiency
IgA deficiency: What are the symptoms?
most are ASYMPTOMATIC, but may get:
- Anaphylaxis to IgA products (ex: transfused blood products)
- GI infections (ex: Giardia… IgA is the main defense against that)
- Airway infections (ex: H. flu, S. pneumo)
- Autoimmune disease (ex: Celiacs often goes with this)
IgA deficiency: Labs?
Just low IgA levels, everything else normal levels
CVID: What is the pathogenesis?
There are many different causes, but basically B cells can’t differentiate well.
This is a QUALITY B cell problem (unlike x-linked brutons agammaglobulinemia), although numbers may be low in this too. However, x-linked agammaglobulinemia is more severe.
CVID: What are the symptoms?
Starting around age 20-30 yr old, get:
- Autoimmune disease
- Bronchiectasis
- Lymphoma
- Sinopulmonary infections
CVID: What are the labs?
- Low plasma cells
- Low Ig
What are the 3 B cell disorders, and what do they make people susceptible to in general?
- X-linked agammaglobulinemia (BTK mutation)
- IgA deficiency
- CVID
In general no B cells =
- Susceptibility to encapsulated bacteria
- Susceptibility to fecal-oral enteroviruses (No polio live vaccine)
- Susceptibility to Giardia
DiGeorge syndrome/Thymic aplasia: What is the pathogenesis?
Deletion at 22q11 causes failure to develop 3rd and 4th pharyngeal/brachial POUCHES, so the parathyroids and the thymus do not develop
- memory: Pharyngeal pouches = ear, tonsils, bottom-to, top
- memory: curious George was a monkey with a POUCH
DiGeorge syndrome/Thymic aplasia: What are the symptoms?
- Tetany (from hypocalcemia)
- Recurrent viral and fungal infections (candida, CMV, etc)
- Cardiac defects (truncus arteriosus, tetralogy of fallot)
DiGeorge syndrome/Thymic aplasia: What are the labs?
- Low T cells
- Low PTH (because parathyroids didnt develop)
- Hypocalcemia
- 22q11 defect detected on FISH
- No thymic shadow on X-ray
IL-12 receptor deficiency: What is the pathogenesis?
Autosomal recessive lack of IL-12 receptor means no Th1 response is formed (Normally, macrophages release IL-12 to stimulate Th1 cells, which then release IFNgamma to stimulate macrophages, etc)
IL-12 receptor deficiency: What are the symptoms?
- Mycobacterial infections (TB, leprosy?, etc)
- Fungal infections (candida, etc)
- May have problems after giving BCG vaccine (the TB vaccine)
IL-12 receptor deficiency: What are the labs?
Low IFN gamma
Job Syndrome (AD HyperIgE syndrome): What is the pathogenesis?
STAT3 mutation -> Deficient Th17 cells -> Imapired neutrophil recruitment
Job Syndrome (AD HyperIgE syndrome): What are teh symptoms?
“FATED” to get a Job
- Facies (coarse)
- Abscesses (cold, non-inflamed, staph)
- Teeth (retained baby teeth)
- E (increased IgE)
- Dermatologic (eczema)
- memory: A creepy face with eczema and pointy baby teeth says “JOB JOB JOB”
- memory: The JOB search is a COLD place.. cold abscesses
Job Syndrome (AD HyperIgE syndrome): What are the labs?
- High IgE
- Low IFN gamma (I guess because Th17 cells normally help secrete IFN gamma)
Chronic mucocutaneous candidiasis: What is the pathogenesis?
There are many causes, but basically they all lead in T cell dysfunction.
Chronic mucocutaneous candidiasis: What are the symptoms?
- Candida albicans infections of the skin and mucus membranes (non invasive because invasive is based on neutrophils!! and this is just T cell deficiency)
Chronic mucocutaneous candidiasis: What are the labs?
- In vitro, T cells do not proliferate in response to candida antigens
- Cutaneously, patient gets no response to candida antigen (I guess the subQ injection? idk)
What are the T cell deficiencies and what do they all generally predispose to?
Deficiencies:
- DiGeorge syndrome (no thymus)
- IL-12 receptor deficiency (no Th1)
- Job syndrome (no Th17)
- Candidiasis (many causes)
Predispose to:
- Candida (superficial infection)
- CMV
- EBV
- JCV
- VZV
- Chronic resp infection
- Chronic GI infection
- bacterial sepsis
SCID: What is the pathogenesis?
Many causes including:
- Defecting IL-2 receptor gamma chain
- > most common
- > x linked
- Adenosine deaminase deficiency
- > build up of adenosine/deoxyadenosine is toxic to lymphocytes
- > autosomal recessive
- Loss of IL-7 receptor
- MHC2 deficiency
- RAG deficiency
SCID: What are the symptoms?
- Failure to thrive
- Chronic diarrhea (B cells in guit)
- Thrush (T cells do candida of skin)
- Recurrent infections of all kinds (bacterial, fungal, viral, protozoal)
- Susceptible to live vaccines
SCID: What is is the treatment?
Bone marrow transplant
- NO concern for rejection!! Because body has nothing to figh tit with
SCID: What are the labs?
- Absent TRECs (how you diagnose)
- No thymic shadow on X-ray (like DiGeorge)
- No germinal centers in lymph nodes (like Agammaglobu)
- No T cells on flow cytometry
Ataxia Telangiectasia: What is the pathogenesis?
Mutation in ATM gene -> Can’t repair ds DNA breaks -> cell cycle arrest
Ataxia Telangiectasia: What are the symptoms?
- Ataxia/ “drunk toddler” from cerebellar defects
- Angiomas (telangiectasia)
- igA deficiency
Ataxia Telangiectasia: What are the labs?
- High AFP
- Low IgA, IgG, IgE
- Lymphopenia
- Cerebellar atrophy
Hyper IgM syndrome: What is the pathogenesis?
X-linked mutaiton in CD40L on Th cells -> no B cell class switching
Note tha tB cells can still be activated by an antigen binding their IgM, but cannot be activated by MHC2 presentation to T cells. No memory B cells form.
Hyper IgM syndrome: What are the symptoms?
- Pneumocystic infection
- Cryptosporidium infection
- CMV infection
- Pyogenic infections early in life, very severe
Hyper IgM syndrome: What are the labs?
High IgM, very low IgG, IgA, IgE
Wiskott-Aldrich Syndrome: What is the pathogenesis?
X-linked mutation in WAS gene -> T cells can’t reorganize their actin cytoskeleton -> T cells die, so B cells have issues too because depend on T cells
*memory: WASP automotive works on cars, which are basically one piece of metal cytoskeleton
Wiskott-Aldrich Syndrome: What are the symptoms?
“WASps MATER too”
- Malignancy associated with it
- Autoimmune associated with it
- Thrombocytopenia
- Eczema
- Recurrent infections
Wiskott-Aldrich Syndrome: What are the labs?
Lowish IgG, IgM
Highish IgE, IgA
Platelets are few and small
What are the combined B/T dysfunctions?
- SCID (ADA deficiency, IL-2R deficiency)
- Ataxia Telangiectasia (ATM gene, nonhomolog end joining)
- Hyper IgM (CD40L defect)
- WAS (T cell cytoskeleton defect)
Leukocyte Adhesion Deficinecy Type 1: What is the pathogenesis?
AR defect of CD18 integrin in LFA-1 protein on phagocytes -> can’t leave blood to get to tissues
Leukocyte Adhesion Deficinecy Type 1: What are the symptoms?
- Delayed separation of umbilical cord (>30 days)
- Impaired wound healing (no phagocytes to take away debris)
- Recurrent skin + mucosal infections from bacteria, but NO PUS!
Leukocyte Adhesion Deficinecy Type 1: What are the labs?
- Neutrophilia (no LFA-1 to bind ICAM-1 to leave blood)
- No neutrophils at infection sites
Chediak-Higashi Syndrome: What is the pathogenesis?
autosomal recessive LYST gene mutaiton -> microtubule dysfunction -> bad lysosomal trafficking -> no phagosome-lysosome fusion
*memory: chediak and higashi are 2 fat guys that cant eat because one has the food and the other the utensils
Chediak-Higashi Syndrome: What are the symptoms?
“SPAN” of symptoms
- Staph/strep pyogenic infections
- Pancytopenia
- Albinism (mealnocytes cant pass melanin)
- Neuropathy (peripheral AND neurodegeneration) (neurons cant traffic proteins down their axons)
also
- infiltrative lymphohistocytosis
- horizontal nystagmus?
Chediak-Higashi Syndrome: What are the labs?
- Giant granules in granulocytes (no microtubules to spread them out)
- Giant granules in platelets
- Pancytopenia (cells cant divide well with no microtubules)
- Mild coagulation defects (because platelet microtubules are slightly affected)
Chronic granulomatous disease: What is the pathogenesis?
- Defect in NADPH oxidase -> Cant convert O2 to O2- -> no respiratory burst
- Usually x linked recessive
Chronic granulomatous disease: What are the symptoms?
Susceptibility to catalse + organisms (Nocardia, Pseudomonas, Listeria, Aspergillis, Candida, E Coli, Staph, Serratia) – pathoma says kelbsialla too
Chronic granulomatous disease: What are the labs?
- Abnormal di-hydro-rhodamine test on flow cytometry
- Negative NBTZ (nitro blue tetrazolium) test, because the test measures O2 -> O2- and turns blue if you make it
What are the 3 phagocyte dysfunction immunodeficinecies?
- LAD1
- Chediak-Higashi
- CGD
Someone has adrenal failure, chronic candida infections, and hypoparathyroidism– what do they have?
APES (autoimmune polyendocrine syndrome) due to AIRE mutation, so self reactive T cells dont die
Someone has recurrent infections, thyroiditis, type 1 diabetes, diarrhea, and they are a boy with an uncle affected– what do they have?
IPEX syndrome (immune def, polyendocrinopathy, enteropathy, x-linked) due to fox p3 mutation
What do low granulocytes/neutrophils predispose you to?
- systemic candida
- aspergillus *naSSSty aSSSpergillus
- staph (me: cat+)
- pseudomonas (me: obligate aerobe)
- nocardia (me: obligate aerobe)
- serratia
- burkholderia cepacia
