SFM Final Diseases (excluding Quiz 1 and 2) Flashcards
What microbe inhibits phagolysosome fusion?
Mycobacteria
What microbe inhibits antigen presentation and interferes with the TAP transporter?
Herpes Simplex Virus (HSV)
What microbe inhibits antigen presentation, proteasomal activity, and aids in the removal of MHC molecules from the ER?
Cytomegalovirus
What microbe inhibits antigen presentation, proteasomal activity and produces IL-10, which leads to the inhibition of macrophage and dendritic cell activation?
Epstein-Barr Virus (EBV)
What microbe inhibits effector cell activation by producing soluble cytokines receptors that bind to IL’s that would activate effector cells?
Pox Virus
Give some examples of microbes that change their surface antigens to evade humoral immunity
HIV, influenza, neisseria gonorrhoeae, E. Coli
Give some examples of microbes that have an outer capsule or coat that prevents complement activation
N. gonorrhoeae
Give some examples of microbes that have a capsule that prevents the binding of antibodies and thus phagocytosis
Streptococcus
Hyper IgM Syndromes
Cause: 5 types with 5 genetic defects that all lead to the inability to class switch; x-linked, defect in CD40L
Symptoms: prone to a variety of infections; neutropenia, FTT, thrombocytopenia and anemia are common
Give examples of opportunistic pathogens (pathogens that don’t cause disease in immunocompetent individuals)
Candida, C diff, pneumocystis jiroveci, cryptosporidium, toxoplasma gondii, and cytomegalovirus
Leprosy
Cause: M leprae colonizers macrophages and other host cells and multiplies within them; grows best at 86, hence predominant growth of lesions on extremities
Symptoms: cutaneous lesions, neuropathic changes and deformities; some symptoms vary depending on the type of immune response to the mycobacterium
Toxic Shock Syndrome
Cause: associated with localized S aureus infection, food poisoning, or local colonization
Symptoms: most cases occur in menstruating women, typically teens; tampons provide food source for bacteria to multiply if kept in the vagina longer than recommended
Superantigens
Bind to beta chain of the TCR, but not in the Ag binding groove; does not require Ag processing so very “fast” response; activates T cells in the absence of cytokines and co-stimulators ligand binding
Polyclonal activation - 10-20% of T cells systemically
Give examples of diseases that are the result of superantigens
Toxic shock syndrome, staphylococcal food poisoning, streptococcal toxic shock syndrome, scarlet fever, mycoplasma arthritidis (rodent), and clostridium perfringens
What are some consequences of superantigen activation?
Fever, rash, edema, hypotension, shock with multiple organ failure due to intravascular volume depletion
TNF-alpha and IL-1 contribute to increase in vascular permeability that leads to leakage of fluid from the intravascular space into the perivasculature
Describe what an opportunistic organism is
They have low virulence and occur when the host defenses are immunocompromised by a PID, chronic disease, or treatment
Describe why a PID is not typically detected in newborns
Because in the first 6 months, the baby is still receiving the mothers anti-bodies, but they have a half life of a month
What are deficiencies that are seen in the innate immune system?
Deficiencies in phagocytosis and complement
What are deficiencies that are seen in the adaptive immune system?
Antibody deficiencies
T cell deficiency
Combined deficiency
How can you screen for a T cell, B cell, or combined cell defects?
Differential CBC of blood cells
How can you screen for T cell defects?
DTH skin test; if it is negative, then there is an impaired T cell response
What are the two ways that humoral immunodeficiencies can be diagnosed? (screened for)
- Serum IgG, IgA, and IgM levels
2. Ab testing to specific Ag after immunization; looking for a decreased response
How can you screen for a complement deficiencies?
Total hemolytic complement assay (CH50 and AH50)
How can you screen for a phagocytic disorder?
nitro blue tetrazolium test
SCID (general info)
Severe combined Immunodeficiency Two phenotypes (T-B-NK- and T-B-NK+) Typically diagnosed in infancy secondary to chronic diarrhea, failure to thrive, and frequent infections (more detail in cards to come)
SCID (T-B-NK-)
Deficiency in the ADA which is involved in the breakdown of adenosine; without it, there is a toxic buildup of purine metabolites. B and T cells are at risk here as they are HIGHLY proliferative cells, so they are undergoing DNA replication and formation a LOT, so these toxins build up quickly; T cells are MORE susceptible
Low IgG, IgA, and IgM
sx: severe lymphopenia, opportunistic infections, diarrhea, failure to thrive
AVOID ALL LIVE VIRAL VACCINES
SCID (T-B-NK+)
Deficiency in Artemis, which is an enzyme in the VDJ recombination, repairing double stranded breaks; this effects both T and B cells, making them
OR
RAG1 and RAG2 deficiencies; these are involved in VDJ recombination, TCR maturation, which directly effects T cells
sx: severe lymphopenia, opportunistic infections, diarrhea, failure to thrive
AVOID ALL LIVE VIRAL VACCINES
Purine Nucleotide Phosphorylase (PNP) deficiency
(T-B+NK+)
Normal IgM, IgG, and IgA
Autosomal recessive
leads to an accumulation of intracellular dGTP which is toxic to lymphocytes, leading to a decreased peripheral T cell number
sx: neurological abnormalities; can be associated with autoimmune disorders; hemolytic anemia, thyroid disease, arthritis, lupus
Tx: HSCT
AVOID ALL LIVE VIRAL VACCINES
Describe an Artemis deficiency
T-B-NK+
Low IgG, IgA, and IgM
autosomal recessive
Radiosensitivity
Sx: diarrhea, candidiasis, and fungal infections. Patients are also more prone to develop lymphomas
AVOID ALL LIVE VIRAL VACCINES
Omenn syndrome
Deficiency in the RAG1/RAG2 proteins that cause an impaired VDJ recombination which leads to defective BCR and TCR
sx: severe erythroderma, splenomegaly, eosinophilia, high IgE levels
AVOID ALL LIVE VIRAL VACCINES
Jak 3 deficiency
T-B+NK+
VERY low IgG, IgA, and IgM
autosomal recessive
Mutation in the JAK3 which causes a defect in the IL-2 receptor signaling
AVOID ALL LIVE VIRAL VACCINES
Agammaglobulinemia
X linked OR autosomal dominant
Early B cell development is arrested at the pre-B cell stage, which means that there are no functional BCRs and B cells are absent or low in number
X-linked Btk Kinase Deficiency
B-T+NK+
No IgG, IgM, IgA
X-linked; only in males
defect in the rearrangement of the Ig heavy chains; diagnosed in infancy due to the maternal Ig half lives
Isolated IgG subclass deficiencies
(B+T+NK+)
Characterized by a decreased concentration of one or more IgG class
sx: recurrent viral and bacterial infections in the respiratory tract
What are low levels of IgG2 associated with in children?
poor responses to polysaccharide Age
IgA deficicency
high incidence; effects the peripheral B cells in that they are not able to mature and terminally differentiate including the formation of plasma cells
males>females
sx: recurrent infections with encapsulated bacteria; autoimmune diseases and allergies
How are patients that have an IgA deficiency able to overcome the deficiency itself and avoid the recurrent infections?
because of the translocation of IgM across the mucosal epithelium; it acts as the IgA and is able to activate complement and the innate immune system
Describe the anti-IgA antibodies and what can they lead to?
The anti IgA Abs are IgG family; can be linked with the non IgE mediated anaphylaxis which is problematic
DiGeorge Syndrome
T-B+NK+
Normal IgG, IgA, IgM
caused by a microdeletion of 22q11.2 region
sx: cardiac abnormalities, hypocalcemia, and hypo plastic thalamus which leads to T cell dysfunction, humoral immunity is intact, frequent upper respiratory infections
LIVE viral vaccines can be given to patients who have a CD8 T cell count above 300 cells/mm3
Hyper IgM syndromes (HIGM)
B+T+NK+
High IgM, low IgG, IgA
characterized by impaired class switching and somatic hypermutation; normal peripheral B cells but LOW CD27+ B memory cells; typically due to a mutation in the CD40L gene of the T cell which is not able to bind to the B cell’s CD40, causing decreased class switching and somatic hypermutation
sx: increased susceptibility to bacterial infections,
Transient Hypogammaglobulinemia of Infancy
B+T+NK+
Low IgG/IgA; IgM is normal
intrinsic IgG is delayed
sx: increased susceptibility to sinopulmonary infections
Common Variable Immune Deficiency (CVID)
B-/+T+NK+
reduced number of B cells that fail to differentiate into plasma cells
Defect in Ab production associated with hypogammaglobulinemia
-mutations in the B cell growth factors and costimulators
sx: recurrent sinopulmonary infections; increased risk of infection, autoimmune disease, and malignancies
Onset at 4-5 but diagnosed in the 20s or 30s
Common-gamma Chain Deficiency (IL-2R-gamma)
Cause: gene encodes gamma-chain shared by IL-2R-gamma receptor and other growth factor receptors; most common (45%) form of SCID; inherited x-linked recessive
Symptoms: very low IgG, IgA, and IgM; T-/B+/NK- phenotype; FTT, severe thrush, opportunistic infections, chronic diarrhea
AVOID ALL LIVE VIRAL VACCINES
IL-7R Alpha Chain Deficiency
Cause: IL-7R alpha chain deficiency; autosomal recessive form of SCID
Symptoms: very low to absent IgG, IgA, and IgM; T-/B+/NK+ phenotype; classic SCID symptoms (candidiasis, chronic diarrhea, pneumonia, severe viral infections)
AVOID ALL LIVE VIRAL VACCINES
Bare Lymphocyte Syndrome Type II
Cause: mutations in genes encoding transcription factors that regulate expression of MHC II; autosomal recessive inheritance form of SCID
Symptoms: deficiency of CD4+ T cells; variable hypogammaglobulinaemia (mainly IgA and IgG2); leads to recurrent respiratory, gastrointestinal, and urinary tract infections and frequently death in early childhood
MHC Class I Deficiency
Cause: mutation in TAP1 molecules to transfer peptides to ER
Symptoms: CD8+ T cells deficient, but CD4+ normal; normal Ab production; normal DTH (delayed-type hypersensitivity)
CD3 Complex Deficiencies
Cause: deficiency of CD3 subunits (delta, gamma, epsilon, or zeta); autosomal recessive SCID
Symptoms: lymphopenia, decreased T cell numbers; decreased Ab responses; FTT, opportunistic infections, chronic diarrhea
Defects in IL-12/IFN-gamma Pathway
Cause: mutations in IL-12 or IL-12R genes that results in primary immunodeficiencies
Symptoms: no Th1 cytokine IFN-gamma production, which controls intracellular bacterial infections; susceptible to atypical mycobacteria, candida, and salmonella; also have defects in IL-17 producing Th17 cells which leads to recurrent fungal infections
Th17 Deficiency
Cause: mutations in genes encoding for either IL-17, IL-17R, or transcription factors STAT1, STAT3, or AIRE
Symptoms: susceptible to chronic mucocutaneous candidiasis; prior to Th17 diagnosis, patients were categorized as having hyper IgE syndrome (severe atopic diseases and recurrent staph aureus skin abscesses)
IPEX (immunodysregulation, polyendocrinopathy and enteropathy, X-linked syndrome)
Self-reactive T effector cells are not inhibited because of a mutation in FOXP3, which results in loss of inhibition by CD4+CD25+ Treg cell
ALPS (autoimmune lymphoproliferative syndrome)
Defects in either Fas, FasL, caspase-8, or caspase-10 genes that results in abrogated formation of the death-inducing signaling complex (DISC) and resistance of effector T cells to apoptosis
Wiskott-Aldrich Syndrome (WAS)
Cause: mutations in the Wiskott-Aldrich Syndrome Protein (WASP); x-linked disorder
Symptoms: thrombocytopenia, eczema, cellular and humoral immunodeficiency, autoimmune disease, and malignancy; low IgM, normal IgG, elevated IgA and IgE; T-/B+/NK- phenotype; decreased NK function
NK Cell Deficiency
Cause: mutations in multiple genes; can be classical (absence of NK) or functional (defective NK activity) without NK cell lymphopenia
Symptoms: multiple severe/disseminated viral infections including herpesvirus, varicella pneumonia, disseminated cytomegalovirus, and herpes simplex virus
Chronic Granulomatous Disease
Cause: enzymatic deficiency of NADPH oxidase in phagocytes, so they fail to generate superoxide anion and other O2 radicals; form granulomas
Symptoms: defective elimination of extracellular pathogens such as bacteria, fungi; susceptible to recurrent infection with catalase-positive organisms (staphylococci)
G6PD Deficiency
Cause: G6PD deficiency; x-linked recessive; causes lack of substrate for NADPH
Symptoms: most are asymptomatic; manifests same as CGD and characterized by the tendency to form granulomas
Leukocyte Adhesion Deficiency (LAD)
Cause: type-I is mutation in beta-2 integrins (CD11/CD18) and type-II is impaired function of PSGL-1 caused by mutations in a fucosetransporter
Symptoms: neutrophil levels 2x normal even without an infection; recurrent infections with bacteria and fungi and inability to form pus at extravascular sites; delayed attachment of umbilical cord, slow wound healing; usually leads to early death
Chediak-Higashi Syndrome
Cause: molecular defect in structure of neutrophil granule appearing as abnormal giant granules; autosomal recessive
Symptoms: recurrent Phoenix granulomas caused by bacterial infections; second phase of disease is accelerated lymphoproliferative syndrome; no NK activity; giant cytoplasmic inclusions
C1, C2, and C4 Deficiencies
Manifest as SLE-like autoimmunity; associated with recurrent sinopulmonary infections, especially in C2 deficiency; increased susceptibility to neisseria species
Properdin, Factor B, Factor H and Factor D Deficiencies
Properdin, Factor B, and Factor D: present with severe infections caused by neisseria meningitis and other extracellular bacteria
Factor H: associated with atypical hemolytic uremic syndrome or glomerulonephritis
What is the most common complement deficiency among caucasian populations?
C2 deficiency; found in young children who have recurrent infections with streptococcus pneumoniae
C8 Complement Deficiency
Cause: inherited deficiencies, acquired deficiencies, or complement consumption; autosomal recessive
Symptoms: absent C8 levels in the presence of normal or low C3 and C4 values; increased susceptibility to invasive neisserial infections
MyD88 Deficiency
Cause: MyD88 deficiency of innate immune system that results in impaired signaling for all TLR’s except TLR3 (it is MyD88-independent)
Symptoms: abnormally frequent and severe infections caused by pyogenic bacteria; normal resistance to bacteria, viruses, fungi, and parasites; characteristic lack of fevers; during infection, TNF-alpha, IL-1, and IL-6 are low
TLR3 Deficiency
Autosomal dominant disorder which results in increased susceptibility to HSV encephalitis
