SFM Final Diseases (excluding Quiz 1 and 2)

Question 1

What microbe inhibits phagolysosome fusion?

Answer 1

Mycobacteria

Question 2

What microbe inhibits antigen presentation and interferes with the TAP transporter?

Answer 2

Herpes Simplex Virus (HSV)

Question 3

What microbe inhibits antigen presentation, proteasomal activity, and aids in the removal of MHC molecules from the ER?

Answer 3

Cytomegalovirus

Question 4

What microbe inhibits antigen presentation, proteasomal activity and produces IL-10, which leads to the inhibition of macrophage and dendritic cell activation?

Answer 4

Epstein-Barr Virus (EBV)

Question 5

What microbe inhibits effector cell activation by producing soluble cytokines receptors that bind to IL’s that would activate effector cells?

Answer 5

Pox Virus

Question 6

Give some examples of microbes that change their surface antigens to evade humoral immunity

Answer 6

HIV, influenza, neisseria gonorrhoeae, E. Coli

Question 7

Give some examples of microbes that have an outer capsule or coat that prevents complement activation

Answer 7

N. gonorrhoeae

Question 8

Give some examples of microbes that have a capsule that prevents the binding of antibodies and thus phagocytosis

Answer 8

Streptococcus

Question 9

Hyper IgM Syndromes

Answer 9

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

Question 10

Give examples of opportunistic pathogens (pathogens that don’t cause disease in immunocompetent individuals)

Answer 10

Candida, C diff, pneumocystis jiroveci, cryptosporidium, toxoplasma gondii, and cytomegalovirus

Question 11

Leprosy

Answer 11

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

Question 12

Toxic Shock Syndrome

Answer 12

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

Question 13

Superantigens

Answer 13

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

Question 14

Give examples of diseases that are the result of superantigens

Answer 14

Toxic shock syndrome, staphylococcal food poisoning, streptococcal toxic shock syndrome, scarlet fever, mycoplasma arthritidis (rodent), and clostridium perfringens

Question 15

What are some consequences of superantigen activation?

Answer 15

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

Question 16

Describe what an opportunistic organism is

Answer 16

They have low virulence and occur when the host defenses are immunocompromised by a PID, chronic disease, or treatment

Question 17

Describe why a PID is not typically detected in newborns

Answer 17

Because in the first 6 months, the baby is still receiving the mothers anti-bodies, but they have a half life of a month

Question 18

What are deficiencies that are seen in the innate immune system?

Answer 18

Deficiencies in phagocytosis and complement

Question 19

What are deficiencies that are seen in the adaptive immune system?

Answer 19

Antibody deficiencies
T cell deficiency
Combined deficiency

Question 20

How can you screen for a T cell, B cell, or combined cell defects?

Answer 20

Differential CBC of blood cells

Question 21

How can you screen for T cell defects?

Answer 21

DTH skin test; if it is negative, then there is an impaired T cell response

Question 22

What are the two ways that humoral immunodeficiencies can be diagnosed? (screened for)

Answer 22

1. Serum IgG, IgA, and IgM levels

2. Ab testing to specific Ag after immunization; looking for a decreased response

Question 23

How can you screen for a complement deficiencies?

Answer 23

Total hemolytic complement assay (CH50 and AH50)

Question 24

How can you screen for a phagocytic disorder?

Answer 24

nitro blue tetrazolium test

Question 25

SCID (general info)

Answer 25

``` 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) ```

Question 26

SCID (T-B-NK-)

Answer 26

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

Question 27

SCID (T-B-NK+)

Answer 27

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

Question 28

Purine Nucleotide Phosphorylase (PNP) deficiency

Answer 28

(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

Question 29

Describe an Artemis deficiency

Answer 29

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

Question 30

Omenn syndrome

Answer 30

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

Question 31

Jak 3 deficiency

Answer 31

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

Question 32

Agammaglobulinemia

Answer 32

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

Question 33

X-linked Btk Kinase Deficiency

Answer 33

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

Question 34

Isolated IgG subclass deficiencies

Answer 34

(B+T+NK+) Characterized by a decreased concentration of one or more IgG class sx: recurrent viral and bacterial infections in the respiratory tract

Question 35

What are low levels of IgG2 associated with in children?

Answer 35

poor responses to polysaccharide Age

Question 36

IgA deficicency

Answer 36

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

Question 37

How are patients that have an IgA deficiency able to overcome the deficiency itself and avoid the recurrent infections?

Answer 37

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

Question 38

Describe the anti-IgA antibodies and what can they lead to?

Answer 38

The anti IgA Abs are IgG family; can be linked with the non IgE mediated anaphylaxis which is problematic

Question 39

DiGeorge Syndrome

Answer 39

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

Question 40

Hyper IgM syndromes (HIGM)

Answer 40

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,

Question 41

Transient Hypogammaglobulinemia of Infancy

Answer 41

B+T+NK+ Low IgG/IgA; IgM is normal intrinsic IgG is delayed sx: increased susceptibility to sinopulmonary infections

Question 42

Common Variable Immune Deficiency (CVID)

Answer 42

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

Question 43

Common-gamma Chain Deficiency (IL-2R-gamma)

Answer 43

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***

Question 44

IL-7R Alpha Chain Deficiency

Answer 44

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***

Question 45

Bare Lymphocyte Syndrome Type II

Answer 45

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

Question 46

MHC Class I Deficiency

Answer 46

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)

Question 47

CD3 Complex Deficiencies

Answer 47

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

Question 48

Defects in IL-12/IFN-gamma Pathway

Answer 48

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

Question 49

Th17 Deficiency

Answer 49

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)

Question 50

IPEX (immunodysregulation, polyendocrinopathy and enteropathy, X-linked syndrome)

Answer 50

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

Question 51

ALPS (autoimmune lymphoproliferative syndrome)

Answer 51

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

Question 52

Wiskott-Aldrich Syndrome (WAS)

Answer 52

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

Question 53

NK Cell Deficiency

Answer 53

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

Question 54

Chronic Granulomatous Disease

Answer 54

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)

Question 55

G6PD Deficiency

Answer 55

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

Question 56

Leukocyte Adhesion Deficiency (LAD)

Answer 56

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

Question 57

Chediak-Higashi Syndrome

Answer 57

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

Question 58

C1, C2, and C4 Deficiencies

Answer 58

Manifest as SLE-like autoimmunity; associated with recurrent sinopulmonary infections, especially in C2 deficiency; increased susceptibility to neisseria species

Question 59

Properdin, Factor B, Factor H and Factor D Deficiencies

Answer 59

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

Question 60

What is the most common complement deficiency among caucasian populations?

Answer 60

C2 deficiency; found in young children who have recurrent infections with streptococcus pneumoniae

Question 61

C8 Complement Deficiency

Answer 61

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

Question 62

MyD88 Deficiency

Answer 62

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

Question 63

TLR3 Deficiency

Answer 63

Autosomal dominant disorder which results in increased susceptibility to HSV encephalitis