Immunodeficiencies Flashcards
Lab tests for T-cell
Flow cytometry, functional assays (mitogen response, MLR, DTH skin test)
B-cell lab tests
circulating antibodies, flow cytometry
Macrophage lab test
Enumeration (=flow cytometry), nitroblue tetrazolium for function
Complement lab test
direct measurement of complement components, hemolysis assay
What does each system specialize in? What happens if it’s impaired?
- B-cells
- T-cells
- Phagocytes
- Complement
Which deficiecnies would cause cancer?
- B-cells (humoral, adaptive)= pyogenic bacteria= staph, strep, hemoph. Respiratory, GI, skin infections, sepsis, meningitis
- T-cells (cell mediated, adaptive)= Intracellular organisms= viruses and then bacteria. Viral infections. Increased risk of cancer when immunodeficient
- Phagocytes- catalase postive bacteria (Staph, kleb, e.coli); fungi lymphadenitis, skin liver, lung abcesses
- Complement- pyogenic bacteria, viruses systemic bacterial infections
X-linked agammaglobulinemia
- symptoms
- defect
- therapy
B-cell deficiency
- recurrent bacterial infections
- no BTK= b-cells arrested at pro-Bcell stage
3.
C3 Def
Recurrent infection with G- bacteria
Factor I def
low C3= susceptibility to encapsulated bacteria
C5-C9 def
No MAC complex, increased Neisseria infections
NEMO deficiency
No NFkB activation= no T-cell activation
Chronic bacterial and viral infections, developmental defectc
MBL def
No lectin pathway, less phagocytosis.
Infections from n. meningitidis
Chronic Granulomatous disease
NOX1 gene, no NADPH oxidase= impaired neutrophil function.
No respiratory burst= no phagycytes to kill bacteria.
Chronic bacterial and viral infections.
NK cell def
GATA2 gene, HSV infections
Hyper IgM
Defect in AICDA (activation induced cytosine deaminase), CD40, CD40L, IKBKG.
No isotype switching or somatic hypermutation
ECF bacterial and fungal infections
IgG2 def
encapsulated bacteria
SCID
No B-cell and T-cell function
Caused by: ADA, PNP def, thymic aplasia
All infections
**X-linked SCid gammac chain= T-cells only, bubble boy**
Omenn Syndrome
Rag1/Rag2 gene= impaired VDJ recombination.
All infections
MHC I def
TAP1/TAP2 = no MHC I receptors
Respiratory viral infections
Pre-B cell receptor def
No B-cells/antibodies
Persistnet bacterial infections
DiGeorge
no thymus and t-cells= all infections
APECED
AIRE defect, less T-cell tolerance for self-antigens
Autoimmune
IPEX
FoxP3 gene; lack of Treg cells and peripheral tolerance. Autoimmune
ZAP70 defect
T-cells cannot signoalr through antigen receptors
all infections
C4a, C4b
Reduced clearance of immune complexes
autoimmune disease and infections
Selective IgA def
MOST COMMON!!
No IgA= respiratory infections
Wiskott-Aldrich Syndrome
X-linked, defective WASP gene= Defective anti-polysaccharide Ab and impaired T-cell activation
Susceptible to encapsulated ECF bacteria
Leukocyte Adhesion deficiency
Phagocytic cell defect
CR3, CR4 and LFA-1 adhesion defects= defective migration of monocytes and neutrophils==>widespread infection from encapsulated bacteria.
Chedlak-Higashl SYndrome
Phagocyte problem
- Lysosomal traffiking regulator protein defect
- Defective fusion of endosome and lysosome, defective phagocytosis
- Recurrent/persistent bacterial infections, granuloma formation
Causes of secondary immunodeficiencyes
- Steroids, cytotoxic drugs, chemotherapy, irradiation
- AIDs (no CD4 cells)
- Nutritionals (protein, calorie, biotin, B12, iron)
- Post infections
- Cancer metastases to bone marrow
- Asplenia
HIV–> AIDs
- when is it AIDs
- How does the HIV infection happen (receptors?)
- What does HIV NEED for replication?
<500CD4 cells
HIV gp120 binds CCR5 or CXCR4= endocytosis
- CCR5=M-tropic-Virus infects macrophages, CD and some t-cells= spread of virus to others
- CXCR4=t-tropic- virus infects T-cells= disease
HIV replication requires T-cell activations= NFKB
How is HIV so effective?
- changes viral antigens and enzumes
- targes CD4 TTcells
- HIV evades host immune systm (via error prone reverse transcriptase)
Antigenic drift
Mutation of serotypes/antigens on outside= epidemic
Pandemic=
HSV strategies (x2, CMV does one of them too)
- reduce IFN-g effect on MHC I= no recognition of APC by CD4 **CMV does this too
- Inhibition of TAP= no peptide presentation via MHC I
How do viruses evade humoral immunity?
Virally encoded complement control prtoein= less complement activation. ==Vaccinia does this.
How do viruses inhibit inflammatory response?
- Produce soluble cytokine receptors–cytokines bind viral receptors instead of host= no inflammation (wastes cytokines)= vaccinia
- Encoding IL-10 (EBV)
How doe these pathogens subvert the immune system?
- M. Tb
- Listeria
- terponema pallidum
- Staph
- Mycobacteria
- M. Tb= prevent phago=lysosome fusion
- Listeria= escapes phagosome
- terponema pallidum= coats itself with human protiens
- Staph= makes super antigen- polyclonal t-cell activation (no specificity)- binds CD28 and TCR of t-cell, and MHCII of APC
- Mycobacteria= induces Th2 response
During pregnancy, immune response is?
Autoimmune diseases improve/worsen?
Reduced- don’t want to reject fetus
- FActors: a-fetoprotein, IL10, TGF-beta
- improved autoimmune disease states until birht, then rebounds
- Lupus gets worse.
