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ABAI 2020 REVIEW > Immunology > Flashcards

Immunology Flashcards

1
Q

Immune dysregulation, polyendocrinopathy, and enteropathy X-linked

(IPEX)

A

FoxP3 mutation (Treg express CD4, CD25, and FoxP3). A fatal autoimmune disorder characterized by a triad of watery diarrhea (~100%), eczema (~95%), and endocrinopathy (type I DM [~75%], cytopenias [~50%], thyroiditis [~40%]).

Diagnosis: Flow cytometry for intracellular FoxP3 expression in CD4+/CD25+ T cells (Tregs). The definitive diagnostic test is the mutation analysis FoxP3 gene.

Therapy: Immunosuppression (e.g. sirolimus) prior to definitive therapy. Definitive/curative therapy: HSCT.

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2
Q

Which TLRs are present in the intracellular compartment and implicated in HSV1 encephalitis?

A

TLR 3, 7, 8, and 9

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3
Q

Antigen processing and MHC Presentation (MHC I Pathway)

A

Key Factor: Viruses develop strategies to evade the MHC I presentation. HSV can block TAP transportation, CMV can remove MHC I form ER.

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4
Q

What enzyme is required for somatic hypermutation?

A

Key fact: CD40 ligand - CD40 interaction stimulates AID, which is crucial for SHM and isotype switching

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5
Q

What cytokines induce IgD class switching?

A

None

Do not require isotype switching, exact function unknown, B-cell maturation marker

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6
Q

Immune complexes tend to be the largest under which of the following conditions?

A

Extreme antibody excess

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7
Q

What is released by epithelial cells to maintain mucosal mast cells at the airway and skin surface?

A

Stem cell factor (SCF)

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8
Q

IgG and IgM activate which complement pathway?

A

Classical pathway

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9
Q

What is the target of RF, and what is the most common RF Ig isotype?

A

RF is an antibody against the Fc portion of IgG. RF is most commonly IgM.

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10
Q

Chemokines and Associated Conditions

A
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11
Q

Peripheral Tolerance and Maintenance

(T-lymphocytes)

A

Same outcomes as central tolerance: Anergy, deletion, or regulation. Lack of the second signal produces the anergy of the peripheral T lymphocytes (maintain by blockade of TRCsignaling, ubiquitin ligases, and inhibitor costimulatory molecules [e.g., CTLA-4 and PD-1]).

Maintenance of tolerance: Non-activated DC do not express receptors → Ag presented to T lymphocytes will not have a second signal ⇒ Tolerance

Key Fact: Treg (express CD4, CD25, FofP3) is critical in maintaining normal immune function.

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12
Q

Ig Structure

(heavy chains, light chains, Ig Fragments, hinge regions, variable regions, constant regions)

A

Heterodimer w/ 2 identical light chains and 2 identical heavy chains connected with disulfide bonds.

<span><b>Heavy chains</b></span> (γ, α, μ, ε, δ): IgG (IgG1, IgG2, IgG3, IgG4), IgA, and IgD have 3 CH domains. IgA and IgE have 4 CH domains.

<span>Light chains</span> (κ [chromosome 2] and λ [chromosome 22]): An IgG molecule has either κκ (60%) or λλ (40%) but never 1 of each.

Ig Fragments: Papain: cleaves Ig above the hinge ⇒ 2 Fab (can bind but not cross-link); Pepsin: cleaves Ig below the hinge ⇒ Fab’2 (binds and cross-link). Neither Fab nor Fab’2 will fix complement or bind to the Fc receptor on the cell surface.

Hinge regions: Proline-rich and provide Ig flexibility.

Variable regions (VL and VH): Ag-binding site (CDRs [there are 3 in each V region, CDR3 is the most variable])

Constant regions (CH and CL): C-terminal. Only CH mediates effector functions (binding to Fc receptors or binding complement).

Glycosylation: Critical to maintaining structure/stability/function (e.g., IgG has its glycosylation site at the Cγ domain, deglycosylated IgG cannot bind to FcγRs and C1q ⇒ ADCC and complement activation.

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13
Q

Classical Complement Pathway

A
  1. Activate by C1 binding to Ag-Ab complexes
  2. C1q binds to the Fc portion of an Ig cross-linked Ag
  3. Binding affinity of C1q: IgM > Ig3 > Ig1 > Ig2
  4. C1q - C1r → C1s → C4 / C2 ⇒ C4b2a (C3 convertase of the CP)
  5. C1 inhibitor → C1r - C1s (regulating the pathway)
  6. C4b → DAF (CR1 and C4BP) ⇒ Blocks further progression of the cascade
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14
Q

Which somatic recombination process introduces the greatest diversity in immune receptors and which enzyme is important in this process?

A

Junctional diversity; TdT enzyme is important in this process.

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15
Q

What cytokines induce IgG (1, 2, 3, 4) class switching?

A
  • IgG1: INFγ and IL-4 (Th1 response, opsonization, best for ADCC)
  • IgG2: INFγ and TGFβ (antipolysaccharide-Ab, the latest to reach an adult level of all IgG subclasses)
  • IgG3: INFγ (shortest half-life in IgG-subclasses, opsonization)
  • IgG4: IL-4 and IL-13 (antipolysaccharide-Ab, elevated in immunotherapy)
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16
Q

IPEX-like Disorders

A

IPEX-like Disorder (CD25 deficiency): Chronic diarrhea and villous atrophy in infancy, type 1 DM, auto-antibodies, lymphadenopathy, hepatosplenomegaly. Early-onset CMV pneumonitis, candidal esophagitis, chronic GI infections.

IPEX-like Disorder (STAT5b Deficiency): Early-onset diarrhea, eczema, lymphocytic interstitial pneumonitis. Dwarfism, prominent forehead, saddle nose, and high pitched voice. Recurrent PCP, herpes, and varicella infections.

Decreased CD25 expression and Tregs, normal GH but depressed IGF-1 levels.

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17
Q

Anti-C1q Antibody

A

Autoantibody to the collagen-like region of C1q found in patients with hypocomplementemic urticarial vasculitis (HUVS → responsive to Plaquenil)

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18
Q

Structure of MHC Class I and Class II Molecules (Table)

A
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19
Q

AIRE

A

The autoimmune regulatory (AIRE) gene is expressed in the thymus. This gene promotes the expression of nonthymic tissue antigens in the thymus.

Key Fact: Mutation in the AIRE gene produces disorders such as autoimmune polyglandular syndrome (APS). Lymphocytes are not deleted or tolerized to endocrine-related self-antigens. The endocrine organs are attacked by autoreactive T lymphocytes and autoantibodies.

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20
Q

How long after drug initiation does serum sickness typically develop in a patient with no prior exposure to the medication in question?

A

1-3 weeks (other option 4 - 10 days)

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21
Q

What are the primary immunoglobulins involved with type II hypersensitivity?

A

IgM and IgG

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22
Q

What CD molecules are in the BCR coreceptor?

A

CD21, CD19, and CD81

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23
Q

What has been shown to be the earliest event in an active Arthus reaction?

A

Immune complex and complement deposition

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24
Q

Lectin Complement Pathway

A
  1. Activitated in the absence of Ab
  2. Mannose-binding lectin (MBL) binds to mannose residues on microbial polysaccharides, MBL-associated protease-1 and -2 → cleaves C4 and C2 ⇒ C3 convertase C4b2a
  3. C3 convertase cleaves C3 to C3b which binds to the convertase and forms C5 convertase (C3bBb3b in the AP and C4b2a3b in the CP and LP)
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25
Q

Where does omalizumab bind?

A

Omalizumab binds to the IgE Cɛ3 domains outside of the FcɛRI-binding site

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26
Q

Seven Ts of passive immunity

A
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27
Q

What is the only Ig to cross the placenta and to what receptor does it bind?

A

IgG

Binds to neonatal Fc receptor (FcRn)

Nadir around 4 - 6 months after birth

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28
Q

Central B-lymphocyte Tolerance

(Ig gene rearrangement and key B lymphocyte development checkpoints)

A

Precursor B lymphocyte is exposed to self-antigens in the BM. Three fates: apoptosis (negative selection), receptor editing (RAG1/RAG2), anergy.

Order Ig rearrangement: 1) D → JH (both chromosomes); 2) VH → DJH (one chromosome); 3) Vκ → Jκ (one chromosome); 3) Vλ → Jλ (one chromosome).

Key Fact: The κ light chains are rearranged first. If receptor editing is needed, a λ light chain will be used.

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29
Q

Which TLR does not signal through MyD88?

A

TL3 and part of TLR4

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30
Q

B-1 B Cells

(characteristics)

A
  • Constitute 30-50% of the B cells in the pleural and peritoneal cavities
  • Different developmental lineage compared to B-2 and marginal zone B cells
  • Peripheral cells
  • Express very low levels of TdT (little N-nucleotide diversity)
  • Surface expression of CD20, CD27, and CD43, and are CD38low/intermediate
  • Secrete antibody without antigen stimulation (constitutively secrete antibody)
  • Limited antigen receptor repertoire that favors binding to microbial carbohydrate antigens
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31
Q

Superantigens

A

Antigens that activate a large number of polyclonal T lymphocyte by binding outside the MHC II antigen cleft (individual with Vβ). Cause massive cytokine release).

E.g., S aureus (SEB [food poisoning], SEC2 [food poisoning], TSST [Toxic shock syndrome]), S pyogenes (SPE-C [Streptococcal toxic shock syndrome]).

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32
Q

What immunoglobulin fixes complement most efficiently?

A

IgM

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33
Q

Autoimmune Polyendocrinopathy, Candidiasis, Ectodermal Dystrophy (APECED)/Autoimmune Polyendocrinopathy Syndrome Type 1 (APS1)

A

Genetics: Autosomal recessive defect in AIRE

APECED/APS1: Autoimmune polyendocrinopathy (e.g., hypothyroidism [85%], adrenal failure [72%], ovarian failure [60%], etc.), Candidiasis (mucocutaneous candidiasis [~100%]), Ectodermal Dystrophy (Nail dystrophy).

Diagnosis: AIRE mutation.

Evaluation: Monitoring endocrine function, evaluation for autoimmunity.

Autoantibodies to α-IFN are seen in the majority of patients, autoantibodies to IL-17/IL-22 found in some patients.

Therapy: Antifungals, replacement therapy for endocrine diseases, lung/liver/GI autoimmunity may require treatment with rituximab or azathioprine.

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34
Q

Abacavir

A

HLA-B*5701

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35
Q

Late Steps of Complement Activation

A
  1. C5 convertase cleaves C5 and initiates the formation of the MAC; C5a is released (most potent mediator of basophils and cutaneous mast cell degranulation [C5a > C3a > C4a])
  2. MAC is formed by (C5b - 8) polyC9; it creates pores in the membrane and induces cell lyses
  3. C9 is structurally homologous to perforin
  4. S Protein and CD59 inhibit the formation of the MAC
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36
Q

CD4 and CD8 cytoplasmatic signal

A

Src family tyrosine kinase (lck) → required for T-lymphocyte activation and maturation

Lck → phosphorylates ITAMs in CD3s and ζ proteins facilitating the recruitment and activation of ZAP70

Key fact: ZAP-70 deficiency ⇒ SCID (T-/B+/NK+)

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37
Q

Which integrin molecule is important for gut homing by binding to MAdCAM?

A

α4β7

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38
Q

Types of Antigens

A
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39
Q

EBV Induced Lymphoproliferative Syndromes

(XLP1 and XLP2)

A

XLP1: X-linked defect in SH2D1A/SAP gene encoding an adaptor protein that regulates intracellular signaling, iNKT cells virtually absent, NK cell activation via 2B4 is abnormal, lack of EBV specific cytotoxic T cells over time, switched memory (CD27+) B cells low.

XLP2: X-linked defect XIAP gene encoding X-linked inhibitor of apoptosis, iNKT cells low.

Clinical Manifestations

XLP -1

XLP-2

HLH with EBV

45%

~50%

Lymphoma (majority B cell)

~30%

0%

Hypo-/dysgammaglobulinemia (after EBV)

~40%

~30%

Splenomegaly without HLH

<10%

~90%

Hemorrhagic colitis

0%

~20%

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40
Q

What two molecules inhibit MAC (CD55) formation?

A

CD 59 (DAF) and S protein

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41
Q
A
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42
Q

Alternative Complement Pathway (figure)

A
  1. Activated by C3b binding to various activating surfaces (e.g., microbial surfaces).
  2. Factor D cleaves Factor B ⇒ C3bBb (C3 convertase of the AP)
  3. Properdin is the only known positive regulator of complement
  4. Regulation of this pathway occurs through Factor I-mediated cleavage of C3b
  5. Factor H, membrane cofactor protein (MCP/CD46), and decay-accelerating factor (DAF/CD55) serve as cofactors
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43
Q

B-cell coreceptor complex

A

CD21 - CD19 - CD81

when CD21 interacts with C3d, the complex is brought to the BCR

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44
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

A

CD59 (MAC) and CD55 (DAF)

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45
Q

Immunogen (lipids)

A

Activate NKT via CD1

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46
Q

Peripheral B-lymphocyte tolerance

A

Chronic antigen recognition downregulates CXCR5, inhibiting B-lymphocyte homing, and interaction with T lymphocytes ⇒ cell death.

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47
Q

Fc Receptors (Table)

A

Members of the Ig superfamily. Each FcR functions as a receptor specific for the CH region of the Ig molecule.

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48
Q

Autoimmune lymphoproliferative syndrome

(ALPS)

A

Mutation: Fas or caspase 10 → Autoimmune lymphoproliferative syndrome (ALPS). Lymphocytes do not know when to die. They accumulate in lymph organs. There is a lack of tolerance, producing autoimmune problems.

Diagnosis: Non-malignant lymphadenopathy, Increased (>1.5%) α/β DNT cells plus either, defective in vitro FAS induced lymphocyte apoptosis, genetic defect (the majority in FAS).

Clinical features: Autoimmune disease (cytopenias), typical histological findings, family history of similar clinical findings, lymphoma in the family (increased risk for lymphoma in ALPS).

Biomarkers​ (Fas mutation): Increase serum vitamin B12, IL-10, soluble FasL.

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49
Q

What is released by Th2 cells to stimulate mast cell proliferation?

A

IL-9

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50
Q

Affinity

A

Strenght of the binding between each molecule of Ig and antigen epitopes (Kd, lower Kd indicates higher affinity)

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51
Q

What is the most important cytokine for the T-lymphocyte survival signal, and receptor?

A

IL-2 and its receptor CD25

52
Q

TRC Complex

A

TRC complex consists of TCR, CD3, and two zeta (ζ) chains

Antigen-signaling: ITAMS

53
Q

Apoptosis

A
  1. Extrusion of vesicles containing cellular components
  2. Preservation of an intact cell membrane
  3. Fragmentation of DNA (karyorrhexis)

Key Fact: Extrusion of naked DNA into the extracellular environment is a feature of “ETosis”, a form of cell death distinct from apoptosis which leads to the generation of extracellular traps.

54
Q

NKT Cells

A

Express NK cell and T-lymphocyte markers

Key fact: NKT cells recognize lipids in the context of CD1

55
Q

Ig Forms

A

Two forms of IgG exist that differ in the aa sequence of the C-terminal end of the CH:

  • Membrane-bound Ig: Attached to B-lymphocytes (transmembrane region). Seve as B-lymphocyte Ag receptors ⇒ B-lymphocyte activation.
  • Secreted Ig: LAcks transmembrane region. Circulate in plasma, mucosal sites, and GI fluids. Monomers (IgG), dimers (IgA), pentamers (IgM).
56
Q

MHC

A

MHC molecules share certain features:

  1. Each MHC molecule has one binding site
  2. MHC molecules are bound to cell membranes
  3. Interaction with T lymphocyte requires direct contact
  4. Key fact: MCH molecules are co-dominant (MHC from both parents is expressed on cell surfaces)
57
Q

Facts about TSLP

A
  • Epithelial cells and mast cells release TSLP
  • TSLP acts on immature dendritic cells to mature.
  • TSLP stimulates the release of CCL17, which attracts Th2 cells via CCR4.

Key Fact: TSLP does not directly act on eosinophils and B lymphocytes. TSLP directly acts on Th2 cells which then release cytokines that act on eosinophils and B lymphocytes.

58
Q

Immunoglobulin Classes/Subclasses

(Table: functional activity and distribution)

A
59
Q

C3 Nephritic Factor

A

Autoantibody that binds and stabilizes C3bBb (results in unregulated consumption of C3)

SLE, associated with MPGN and partial lipodystrophy

60
Q

ALPS

A

Increased (>1.5%) alpha/beta DNT

61
Q

What is the MHC II binding site?

A

β2 region

62
Q

Selected SNPs Associated with Development of Atopic Disease

(Table)

A
63
Q

Costimulation between APC and T-lymphocytes (Table)

A

Key Fact: CD3 deficiency ⇒ SCID

64
Q

What is the MHC I binding site?

A

α3 region

65
Q

Which TLR binds lipopolysaccharide (LPS) on gram-negative bacteria?

A

TLR 4

66
Q

What is the Ig class with the highest total body concentration and daily production?

A

IgA

It may take several years for IgA to reach adult levels.

In the GI tract, IgA is produced by plasma cells in the lamina propria and is transported across the mucosal epithelium by poly-Ig receptor (transcytosis).

67
Q

What immunoglobulin has the shortest half-life?

A

IgG3

68
Q

αβ TCRs

(characteristics)

A

Heterodimer of an α and β chain (each consist of a variable [V, determine CDR] domain, a constant [C] domain, and a transmembrane hydrophobic region).

Vβ → binding site for superantigens.

Key Fact: αβ TCRs recognize a single Ag only in the context of an HLA molecule. The receptor has no signaling ability and requires accessory molecules for signal transduction.

69
Q

What cytokines are released by Th2 cells?

A

IL-4, IL-5, IL-9, and IL-13

70
Q

What is the only X-linked complement component deficiency?

A

Properdin (only known positive regulator of complement)

Complement deficiencies are generally autosomal recessive

71
Q

Ig superfamily

A

TCR, MHC molecules, CD4, CD8, CD19, B7-1, B7-2, Fc receptors, KIR, and VCAM-1

72
Q

Why is measuring exhaled nitric oxide more useful as a marker of asthma than allergic rhinitis?

A

Nitric oxide is elevated in patients with allergic rhinitis. Nitric oxide is increased further during the late response to inhaled allergen. There is an increased expression of inducible nitric oxide synthase in airway epithelial cells.

73
Q

In resting Th2 cells, GATA3 is localized to the cytoplasm. What causes phosphorylation of GATA3 so that GATA3 is imported to the nucleus and binds to the promoter region of Th2 cytokine genes to activate gene expression and cause allergic inflammation?

A

Interaction with antigen-presenting dendritic cells activates the T cell receptor (CD3) and costimulatory molecule CD28 causing p38 mitogen-activated protein kinase (MAPK) signal transduction.

Key Fact: When IL-4 and IL-13 stimulate Jak1 and Jak3 to phosphorylate STAT6, GATA3 is activated (but not specifically moved from the cytoplasm to the nucleus)

74
Q

Which chemokine receptor is associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome?

A

CXCR4

75
Q

Factor H Deficiency

A

HUS, MPGN, and ARMD

76
Q

Fas ligand

(FasL/CD95L)

A

Cells presenting self-antigen w/o innate response or costimulation have other receptors on their surfaces, such as FasL/CD95L on T lymphocytes.

FasL: Upregulated on repeatedly activated T lymphocytes. Interacts w/ Fas/CD95 same cell or nearby cell) → deletion/death (Fas : FasL signals through the caspase system).

Mutation Fas or caspase 10 → Autoimmune lymphoproliferative syndrome (ALPS)

77
Q

Which component is shared by IL-4 and IL-13 receptors?

A

IL-4 Rα, which is targeted by dupilumab

78
Q

CHARGE syndrome

A

Infants with the CHARGE (CHD7 gene) association share phenotypic features with patients with 22qDS, including cardiac defects, cleft palate, and hearing loss.

CHARGE ≠ DGS: Coloboma, choanal atresia, genital anomalies, and lack of 22q11 deletion.

79
Q

Anaphylatoxins

A

C5a, C4a, and C3a

  • C5a is the most potent mediator of basophils and cutaneous mast cell degranulation (C5a > C3a (only chemotactic for eosinophils) > C4a)
80
Q

BCR Src Kinases

A

Lyn, Fyn, and BTK (unique to lymphocytes)

Like in the TCR, they phosphorylate the ITAMs, providing a docking site for Syk (ZAP-70 analog)

Key Factor: Mutation in BTK ⇒ Bruton’s agammaglobulinemia or XLA → Failure B-cell maturation

81
Q

Isotype Class Switching

A

Results in deletion of the constant region genes between Cμ and the new express heavy chain class/subclass

82
Q

What is the half-life of the Ig Isotypes (days)?

A
  • IgG1: 23 days
  • IgG2: 23 days
  • IgG3: 8 days
  • IgG4: 23 days
  • IgA (IgA1 and IgGA2): 6 days
  • IgM: 5 days
  • IgD: 3 days
  • IgE: 2 days
83
Q

What is the most variable part of the Ig molecule?

A

CDR3

84
Q

T cells inside the thymus (differentiation)

A
85
Q

What are the four families of chemokines?

A
  • C
  • CC → Eosinophils, Basophils, and Monocytes ⇒ ALLERGY
  • CXC →PMNs ⇒ INFLAMATTION
    • ELR - angiogenic, act through CXCR2
    • Non-ELR - angiostatic, acts via CXCR3B, induced interferons__​
  • CX3

Key Fact:

  • Homeostatic: CCL19/CCL21 → CCR7 → Lymphocyte homing
  • Inflammatory: CCL17/CCL22 → CCR4 → pro Th2 response
86
Q

What is released by epithelial cells to act on CCR4 to attract Th2 cells?

A

CCL17 and CCL22

87
Q

What disease presents with early-onset hypogammaglobulinemia with autoimmunity and immune dysregulation?

A

Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency. LRBA maintains intracellular stores of CTLA4, which can stop T-cell activation.

LRBA deficiency causes an AR combined immunodeficiency with severe autoimmune and inflammatory manifestations, including IBD and autoimmune cytopenias. Chronic diarrhea is a frequent and often severe symptom.

Kef Fact: CTLA4 deficiency is similar to LRBA-deficient patients

88
Q

What interleukin is excessively produced in cryopyrinopathies?

A

IL-1β

89
Q

Contact activation pathway is initiated by which factor?

A

Factor XII

90
Q

Avidity

A

The net effect of affinity and valance (overall strength of the binding between Ig and antigen).

A low-affinity IgM can produce a high-avidity interaction by simultaneous binding to multiple antigen epitopes through 10 contact sites on each IgM molecule.

91
Q

Important Chemokine Ligands and Receptors (table)

A
92
Q

Which cytokines are important for Tregs?

A

IL-10 and TGFβ

93
Q

BCR signaling (Figure)

A
94
Q

MHC I Deficiency

A
  • Mutation: TAP
  • AR
  • Clinical features: Sinopulmonary infections, granulomatous skin lesions, and necrobiosis lipoidica
  • Laboratory: CD8 lymphopenia, PBMC on flow cytometry lack MHC I
  • Treatment: Treat pulmonary infections
95
Q

What cytokines induce IgA class switching?

A

TGFβ and IL-5

Mucosal immunity, IgA1 in serum and respiratory tract, IgA2 in the lower GI tract.

96
Q

What receptor is involved with the inflammasome?

A

NODs

97
Q

T regulatory

(Treg)

A

Suppression immune response of other cells. Thymic emigrants that respond to self-Ag. Development → binding affinity between the cells and self-peptide MHC II (T cell with intermediate binding).

Treg:

  • Express CD4, CD25 (IL-2Rα chain), and FoxP3 (master transcription factor).
  • Survival: IL-2 and TGFβ
  • Tolerance/regulation: IL-10 (targets MΦ and DC), TGFβ (inhibits lymphocytes and MΦ).
98
Q

IVIG causes a downregulation through __________ receptors.

A

FcγRIIB

99
Q

MHC II Deficiency

A
  • Mutation: Several transcription factors required for MHC I expression (MHC2TA, RFX5, FRXAP, and FRXANK)
  • AR
  • Clinical features: Diarrhea, hepatosplenomegaly, transaminitis, sclerosing cholangitis (C parvum), pulmonary infections (PCP, encapsulated bacteria, Herpesviridae, and RSV), and meningitis
  • Laboratory: CD4 lymphopenia (reversed CD4: CD8), lack of HLA-DP, -DQ, -DR on lymphocytes, delayed hypersensitivity test, hypogammaglobulinemia, absent germinal centers from LN
  • Treatment: HSCT
100
Q

TCR signaling (Figure)

A
101
Q

RAS Associated Leukoproliferative Disorder

(RALD)

A

Somatic mutation in NRAS or KRAS, primary features include monocytosis, splenomegaly, normal DNTs. There is some overlap with ALPS (however, remember that in ALPS, there is an increase [>1.5%] α/β DNT cells)

102
Q

What is the main source of Factor D?

A

Adipose tissue

103
Q

Bare Lymphocyte Syndromes (Table)

A
104
Q

T-lymphocytes costimulation

A

Interaction between CD28 (T-cell) and both CB80/86, CD2, and CD58 → SLAM (signaling lymphocyte activation molecule) → activation/survival/stability/immune synapse

SLAM has an ITSM that binds to SAP → links SLAM and Fyn (linked to CD3).

Key fact: Mutation in SAP ⇒ X-linked lymphoproliferative syndrome (XLPS)

105
Q

What has been associated with decreased galactosylation?

A

Inflammatory and infectious diseases (remember glycosylation of IgG is critical to maintaining structure/stability/function). Diseases associated with decreased galactosylation include RA, SLE, Chron’sdiseas, TB.

106
Q

What lipid mediators are considered to be anti-inflammatory and play a role in the resolution of allergic inflammation?

A

Lipoxin A4

Resolvin E1

Protectin D1

107
Q

What is the result of IFNγ receptor deficiency?

A

IFNγ receptor deficiency results in susceptibility to Mycobacterium tuberculosis and other intracellular bacteria.

108
Q

Bim

A

Self-Ag repeatedly recognized by a T lymphocyte without costimulation activate Bim, which is a proapoptotic member of the Bcl-2 protein family. Bim leads to cell apoptosis through the mitochondrial pathway.

109
Q

What is the first Ig produced after birth, the first to reach an adult level, and the first to be synthesized following antigenic stimulation?

A

IgM

110
Q

Immunoglobulin Isotypes

(Table)

A
111
Q

Antigen processing and MHC Presentation (MHC II Pathway)

A

Key Fact: HLA-DM is an intracellular protein involved in MHC IIantigen processing and does not present antigenic peptides nor is it a component of MHC II.

Remember CLIP

112
Q

What cytokines are released by Th17 cells?

A

IL-17 and IL-22

113
Q

LAD type 1

A

CR3 or CR4 deficiency and is due to a rare mutation in the beta-chain (CD18) common to the CD11 or CD18 family of integrin molecules.

114
Q

Hapten

A

Small-molecule antigen, bound to a carrier protein, elicit the production of antibodies

115
Q

MHC (Constitutive and Cytokine)

A

MHC I: Most nucleated cells. Cytokines: INFα, INFβ, and INFγ.

MHC II: APC (dendritic cells, MΦ, and B cells). APC can express both MHC I and II. Cytokines: INFγ.

Key Fact: T cells only recognize antigens that are presented as part of the MHC complex (“MHC restriction”), which is restricted to peptides. Lipids, nucleic acids, and polysaccharides are not presented by MHC molecules.

116
Q

Conjugated vaccines

A

Key Fact: T-independent antigens linked to a carrier protein that triggers T-dependent response and memory. E.g., Prevnar-13, Hib, MCV4-Menactra, and Menveo.

117
Q

Epitope (Antigenic Determinant)

A

Recognized by B lymphocytes:

  • Linear determinants or tertiary structure in “native” conformation
  • Carbohydrates, amino acids (4 to 8 residues), nucleic acids, and phospholipids

Recognized by T lymphocytes:

  • Linear determinants of amino acids only
  • Length limited by MHC binding cleft (MHC I [8 - 11 aa], MHC II 10-30 aa)
118
Q

What cytokines induce IgE class switching?

A

IL-4 and IL-13

Allergic reaction, the only Ig to bind to mast cells

119
Q

MHC Genes

A

MHC I: HLA-A, -B, and -C

MHC II: HLA-DP, -DQ, -DR

120
Q

Adjuvants

A

Molecules that are given in vaccines to enhance immune response (involves activation of the innate system leading to costimulatory expression and cytokine production). E.g., Alum, Freund’s (BCG), Titermax (POP, POE).

Key Fact: Adjuvants are necessary to achieve maximal adaptive immune response to a vaccine.

121
Q

MCH (structure)

A

MHC I:

  • α chain: α1 & α<em>2</em> (binding site for peptide [8 - 11 aa, intracellular]), α<em>3</em> (binds CD8)
  • β2-microgobulin

MHC II:

  • α and β​ chains: α1 & β1 (binding site for peptide [10 - 30 aa, extracellular]), β2 (binds CD4), α<em>2</em>
122
Q

What cytokines induce IgM class switching?

A

None

Primary response (e.g., isohemagglutinin and RF)

123
Q

Complement Deficiencies (figure)

A
124
Q

Which cytokines increase eosinophil apoptosis?

A

IL-4

125
Q

Immunosuppressant cyclosporine binds to which molecule in the T-cell signaling pathway?

A

Cyclosporine binds to cyclophilin (also called immunophilins). The drug-protein complex inhibits calcineurin and therefore NFAT translocation to the nucleus.

ABAI 2020 REVIEW (10 decks)

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