Immune Deficiencies (compare and Contrast) Flashcards
(25 cards)
What immune Deficiencies result in a complete lack of CD4+ and CD8+ cells?
- Common Features?
- How do these diseases Differ, where does the problem arise?
Common Feature:
- No CTLs or Helper T cells would result in no B cell activation and no killing of Virally/intracellularly infected cells.
Diseases:
- ADA / PNP defect - toxic nucleotides build up killing all T cells and B cells
- CD3 deficiency - without CD3 no positive selection can take place for CD8 or CD4 cells
- DiGeorge Syndrome - No Thymus = No T cells
What immune deficiencies lead to differential numbers of CD8 and CD4 T cells?
- How do these diseases differ?
- Which cell type is depressed?
- Is the remaining Cell type still effective?
Diseases:
- ZAP-70 - this is needed for ITAM signaling => CD8 cells DIE, CD4 cells survive but are INeffective
- MHC II Bald Lymph. Syndrome - CD4 cells DIE b/c they cannot be Positively selected; CD8 cells are ALIVE and EFFECTIVE
- MHC I Bald Lymph. Syndrome - CD8 cells DIE b/c they cannot be Positively Selected; CD4 cells are ALIVE and EFFECTIVE
- CD8 protein mutation - see MHC-I BLS ^
What are they only SCID disease in which CD4 and CD8 cells are present in normal numbers?
- What renders these cells ineffectual?
- Distinguishing Clinical Features?
- Distinguishing immunological Features?
Wiskott-Aldrich
- Cytoskeletal Issues Prevent Cross-Talk
- THROMBOCYTOPENIA
- B cells = normal STRUCTURE and Numbers
Common Gamma Chain Defects:
- No Interleukin Signaling (from: IL-2, IL-4, IL-7, IL-9, or IL-15)
- B cells = BALD B CELLS, normal B cell numbers
JAK-3 deficiency:
- Same effect as common gamma chain defect
What patients with SCID could also mount a T-INdependent response to an encapsulated bacteria?
*In order to generate T-independent response, B cells should be present in normal Numbers and have a normal Structure
- MHC II Bald Lymphocyte Syndrome
- CD3 Defects
- DiGeorge Syndrome
Why does Omenn Sydrome suck so bad?
- A few Oligoclonal T-cells are left in the repertoire and these are self reactive so you end up with an Autoimmune Defect in addition to SCID
In which SCID diseases would you expect Development Defects independent of the immune deficiency?
- ADA and PNP deficiency
- DiGeorge Syndrome
What Immune Deficiencies are specific to CD8 T cells?
- Do these cause SCID?
- Explalin.
CD8 specific Diseases:
- CD8 protein Defects - Prevents Positive Selection
- TAP transporter Defects - No TAP = Degraded MHC-I => Prevents Positive Selection
- Perforin Deficiency- No Killing Function of CD8 cells OR of NK cells
SCID?:
- These diseases do NOT cause SCID because both CD4 T cells and B cells are still functional
*Perforin Defect would be the most devastating
Of the CD8 T cell specific Diseases, which will result in Reduced CD8 cell count?
Both CD8 mutations and TAP transporter mutations would result in Low CD8 cell count
- Perforin Deficiency would NOT change the number of CD8 T cells
What Immune Deficiencies Result in complete lack of CD4 T-cells?
- what is the result of no CD4 T-cells?
- How do these diseases differ, where does the problem arise?
Overall Result:
- NO CD4 -> NO B CELLS produces SCID because there is no APC or B cell activation
Diseases:
- Bare Lymphocyte Syndrome - no MHC II will be on APCs - Problem arises in Positive Selection
- ADA / PNP deficiency - Toxic Nucleotide Catabolites Kills almost all Lymphocytes (T and B cells) in development
- COMPLETE DiGeorge Syndrome - Individuals are Athymic (No CD8 or CD4)
- CD3 Deficiency - No CD4 or CD8 cells b/c of Absence of Thymic Selection
What deficiency should be suspected of a patient who suffers from disseminated Listeria or Mycobacterium Avium infections but appears to respond adequately to most other types of infection?
- is this an issue with the Cell mediated or Humoral Response?
IL-12 or IL-12 Receptor Deficiency should be suspected
- with intracellular bacteria being the only susceptibility you can assume this is an issue of TH1 macrophage activation via IFN-gamma
1
**No other Deficiency would target just these cells (besides IFN-gamma)
Besides IL-12/IL-12 receptor Deficiency, what other disease polarizes patients away from TH1 cell activation?
- Why does this polarization happen?
- how is this different from IL-12 deficiencies?
Hyper IgE syndrome / Job Syndrome:
- Results from Ineffective STAT3 receptors that are needed for signal transduction in NEUTROPHILS and in IFN-gamma signal transduction
- Without IFN-gamma stimulation TH0 cells are much more likely to take on the TH2 phenotype - IL-4 production by TH2 promotes IgE production
- STAT3 deficiencies differ in that Neutrophils cannot respond to signals (was not mentioned by Dr. M, but it seems like disseminated intracellular bacterial infections would be an issue for these people too)
What immunodeficiency results in low B and T cell numbers in addition to elevate Alpha Fetal Protein (AFP)?
- what causes this disorder?
- other clinical features?
- Is this an acquired or Innate Immune Disorder
Ataxia Telangiectasia
- lack of ATM (a DNA repair enzyme) results in this phenotype
Other Clinical Features:
- Ataxia
- Spider Angiomas
- IgA or IgE deficiency
*Acquire Immunodeficiency
What two diseases resemble mutliple myeloma?
- what are some defining characteristics of these diseases?
*Both usually occur in people 50 and up
Waldenstrom Macroglobulinemia
- Abnormal B cell proliferation (Cancer) causing too much IgM to form
- More common in men
- NO BONE LESIONS like their are in Multiple Myeloma
- CAUSES ANEMIA
Benign Monoclonal Hypergamma (Monoclonal gammapathy)
- Asymptomatic
- NO BENCE JONES PROTEINURIA
What non-SCID diseases result in lowered or absent numbers of B cells?
- Common Features of these diseases?
- How does the pathogenesis of these diseases differ?
CVID
- Not typically diagnosed until 20 or 30 y/o
- Patients will have Hypogammaglobulinemia but NOT Agammaglobulinemia
XLA (X-linked Agammaglobulinemia)
- Bruton Tyrosine Kinase Issue = NO B CELLS
- UNDERDEVELOPED TONSILS
Ataxia Telangiectasia
- ATM defect (ATM needed for DNA repair)
- ELEVATED ALPHA FETAL PROTEIN
Pre-B cell Receptor (lambda 5)
- Mutation of Lamba 5 Surrogate Light Chain
- B cells undergo APOPTOTIC death
A white female with a known acquired immunodeficiency is given a blood transfusion after a car accident. She immediately becomes hypovolemic and experiences tachycardia.
- What immune deficiency did she likely have?
- What diseases is she predisposed to?
IgA deficiency
- Patients with IgA suffer from Anaphylactic Shock if they are given a blood transfusion with IgA in the transfused blood
Other Disease:
- Autoimmune Diseases such as SLE, Rheumatoid Arthritis, and Immediate type Hypersensitivities are more common in these patients
A patient has high levels of IgM in the blood and very little of any other Isotype. A lymph node biopsy is taken.
- How will looking at the lymph node biopsy aid in identifying the cause of the disorder?
Hyper IgM has two main causes:
1. No CD40 (receptor or ligand) this is MOST common - patients with this disease will show no germinal center formation in their biopsy
- No AID is just needed for class switching so these patients WILL still get germinal center formation
A child shows low levels of IgG in the blood, which isotype of IgG is most likely lacking?
- what if it were an adult in this scenario?
Selective IgG deficiencies:
Child - IgG2 = more clinically significant because IgG2 is the 2nd most common isotype of IgG
Adult - IgG3 = more likely in an adult
Someone comes in with cheesy looking fingernails and they suffer from an immune deficiency in the acquired immune system.
- What is the disease?
- What cells are involved?
- Disease = Chronic Mucocutaneous Candidiasis
- Cells = T CELLS
Using flow cytometry for CD4 and CD8 cells as well as clinical features of each disease, how would you distinguish between ALPS, APECED, and IPEX?
ALPS
- ENLARGED spleen and Lymphnodes
- DOUBLE NEGATIVE CD4-/CD8- cells
APECED
- TOTAL baldness and Chronic Candidiasis infections are common in these people
IPEX
- Early Onset
- Coombs Positive Anemia
What are 2 diseases of the acquired immune system that result in neutropenia?
-why does this cause neutropenia?
X-linked Hyper IgM Syndrome
- CD40/CD40 L deficiency
- AID deficiency
X-linked Agammaglbulinemia
- BTK deficiency
**Some patients with these diseases produce neutrophil specific Abs
What phagocyte deficiencies result in neutropenia?
- what genes/gene products are responsible for this deficiency?
- What kind of pathogens are these patients particularly Susceptible to?
Kostmann Syndrome (Severe congenital neutropenia) - Defective G-CSF/G-CSF Receptor
Cyclic Neutropenia
- ELA-2 defect (codes for elastase)
**Extracellular Pathogens are Bad for these people
What two deficiencies will show negative results for a Nitro Blue test?
- what does a negative result indicate?
- What is the underlying Process?
- How can you differentiate these two diseases?
- How are these diseases inherited?
Negative Nitro Blue Test:
Chronic Granulomatous Disease
Glucose 6-Phosphate Dehydrogenase Deficiency
CGD:
- p91-PHOX gene defect
- Lack of NADPH oxidase = Very Little ROS generation
- X-linked
G6P def:
- Lack of G6P-dehydrogenase = no NADPH => Very Little ROS
- Intrinsic lack of NADPH = Inability to use Glutathione Reductase => ANEMIA
- X-linked
How would you treat a patient with a p91-PHOX deficiency?
- what organism and and infection define this disease?
- Other common organisms?
Prophylactic TMP-SMX (cotrimoxazole)
Itraconazole
IFN-gamma
Organism/Inf.
- Bone or Skin infection with Serratia Marcescens
Others: E. Coli Serratia Marcescens Norcardia Aspergillus Candida Klebsiella Staph Aureus
You have an Albino patient that has a long history or pyogenic staph and strep infections.
- What disease does this person have?
- Affected Gene?
- Pathohistology?
- How should this patient be treated?
Disease:
Chidiak-Higashi
Gene:
LYST gene
Pathohistology:
- Giant Granules in Neutrophils
Treatment:
BONE MARROW transplant; if not done patient will die of a lymphoproliferative disorder
