Term
What major processes occur in each of the following lymph node regions?
1) Follicle
2) Medulla
3) Paracortex |
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Definition
LN functions in non-specific filtration by macrophages, storage and activation of B and T cells, and antibody production
1) Follicle (outer cortex)
- Site of B cell localization and proliferation
- Either dense/dormant (primary) or active germinal centers (secondary)
2) Medulla
a) Chords (closely packed lymphocytes and Plasma cells)
b) Sinuses (Communicate with efferent lymphatics and contain reticular cells (fibroblasts with type III collagen) and Macrophages
3) Paracortex (between cortex and medulla)
- Houses T cells with high endothelial venules, through which T cells and B cells enter from the blood
- Enlarged in extreme cellular immunity (viral infection)
- Not well developed in DiGeorge q22 deletion |
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Term
Where are each of these cells predominantly found in the lymph nodes?
1) B cells
2) T cells
3) Macrophages
4) Plasma cells
5) Reticular cells |
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Definition
1) Cortex- active germinal centers and inactive dense follicles
2) Paracortex- post-capillary high endothelial venules
3) Medullary sinuses
4) Medullary chords
5) Medullary sinuses (produce type III collagen) |
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Term
What is the primary lymphatic drainage site for each of the following regions of the body?
1) Upper limb and lateral breast
2) Stomach
3) Duodenum and jejunum
4) SIgmoid colon
5) Rectum (lower portion above pectinate line)
6) Anal canal (below pectinate line)
7) Testes
8) Scrotum
9) Thigh (superficial)
10) Lateral dorsum of foot |
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Definition
Right lymphatic duct gets right arm and right half of head
Thoracic duct (T5) gets everything else.
1) Axillary LN
2) Celiac
3) Superior mesenteric
4) Colic to inferior mesenteric
5) Internal iliac
6) Superficial inguinal
7) Superficial and deep plexuses (para-aortic)
8) Superficial inguinal
9) Superficial inguinal
10) Popliteal |
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Term
What area of the body is drained by each of the following primary lymphatic drainage site?
1) Axillary LN
2) Celiac
3) Superior mesenteric
4) Colic to inferior mesenteric
5) Internal iliac
6) Superficial inguinal
7) Superficial and deep plexuses (para-aortic)
8) Popliteal |
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Definition
1) Upper limb and lateral breast
2) Stomach
3) Duodenum and jejunum
4) SIgmoid colon
5) Rectum (lower portion above pectinate line)
6) Anal canal (below pectinate line), scrotum, thigh (superficial)
7) Testes
8) Lateral dorsum of foot |
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Term
| Describe the functional anatomy of a basic lymph node |
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Definition
LN is surrounded by a fibrous capsule, and inside the capsule extends to form trabeculae.
1) Lymph flows into afferent vessels into the sub-capsular sinus, which drain into the trabecular sinuses and finally into medullary sinuses (macrophages and reticular cells)
2) Medullary sinuses converge at the hilum and lymph leaves via the efferent lymphatic vessel towards either a more central lymph node or ultimately for drainage into a central venous subclavian blood vessel via the postcapillary venules |
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Term
| What organisms are particularly worrisome in the case of splenic dysfunction and WHY? |
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Definition
1) Splenic dysfunction (SCD or hereditary spherocytosis, for example) leads to
- decreased IgM
- decreased complement activation
- decreased C3b opsonization
-increased succesbility to encapsulated organisms
2) S SHiN
- S. pneumoniae
- Salmonella
- H. influenzae
- N. meningitidis |
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Term
| What are the 3 major blood findings associated with status post-splenectomy? |
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Definition
1) Howell-Jolly Bodies
- Small nuclear fragments that could not be cleared by spleen
2) Target cells
- Also common in hemoglobinopathies
3) Thrombocytosis
- Hereditary condition |
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Term
Where are the following cells found in the spleen?
1) T cells
2) RBCs
3) B cells
4) Macrophages |
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Definition
1) PALS of white ulp
2) Red pulp
3) Follicles within white pulp (germinal centers when active)
4) Marginal zone and chords of billiroth (encapsulated bacteria removal) |
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Term
| What is the basic functional anatomy of the spleen? |
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Definition
Lies between the 9th and 11th ribs on the left hand side and recieves blood from short gastric arteries and splenic artery
**Like thymus, possesses only efferent lymphatic vessels (unlike LN)**
1) Red pulp
- Sinusoids are filled with blood
- Chords of reticular fibers (macrophages)
- Marginal zone (bordering on white pulp)
2) White pulp
- Follicles (B cells)
- PALS (T cells) |
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Term
| Where do T and B cells differentiate, respectively? |
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Definition
1) T cells differentiate and mature in Thymus
- forms from epithelium of 3rd branchial pouch
- positive (MHC restriction) occurs in cortex (dense with immature cells) and negative selective (nonreactive to self) occurs at cortico-medullary junction (pale with mature cells)
2) B cells arise and mature in bone marrow |
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Term
| What are the cells of the innate and adaptive immune systems, respectively? |
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Definition
1) Innate- fast, non-specific, no memory
- PMNs, macrophages, DCs, NK cells and complement
2) Adaptive- slow at first and then faster memory
- T cells, B cells and circulating antibody |
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Term
| What are the major types of MHCs and where are they expressed? |
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Definition
MHCs are encoded by HLA genes
1) MHC-1 (HLA-A, HLA-B and HLA-C)
- Found on all nucleated cells, with antigen-loading of intracellular peptides occurring in RER
- Binds CD8 and TCR- Viral immunity
2) MHC-2 (HLA-DR, HLA-DP and HLA-DQ)
- Expressed only on APCs with antigen loading following release of invariant chain in acidified endosome
- Binds CD4 and TCR |
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Term
| How are MHC-2 molecules synthesized? |
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Definition
Bind TCR and CD4 and involved in extracellular immnity
1) Alpha and Beta chains are made in RER and complexed with invariant chain polypeptide
2) Invariant chain complex moves MHC-II to Golgi, where it fuses with endocytosed lysosome and is degraded by Cathepsins.
3) CLIP fragment of invariant chain remains with alpha and beta chains, blocking their peptide-binding groove until the MHC molecule migrates to the cell membrane. |
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Term
| How are MHC-1 molecules synthesized? |
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Definition
Bind TCR/CD8 and involved in intracellular/viral immunity (also inhibits NK cell activity)
**Peptide-binding groove is in alpha chain!**
1) TAP1/2-mediated peptide transport to RER presents antigen to MHC molecule
2) MHC is stabalized (Calnexin) and chaperoned (TAP and Erp57 and Calreticulin) with peptide to the cell surfaee, where is associated with b2-microglobin. |
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Term
What disease is associated with each of the following HLA subtypes?
1) A3
2) B27
3) B8 |
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Definition
All HLA- meaning MHC-1/CD8 association.
1) A3- Hemachromatosis
2) B27- PAIR (Psoriasis, Ankylosing spondylitis, IBD, Reiter's syndrome)
3) Graves disease (autoimmune hyperthyroidism) |
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Term
What disease is associated with each of the following HLA subtypes?
1) DR2
2) DR3
3) DR4
4) DR5
5) DR7 |
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Definition
1) Multiple sclerosis, Hay fever, SLE, goodpastures.
2) DM type 1
3) RA and DM type 1
4) Pernicious anemia (B 12 deficiency), Hashimotos thyroiditis
5) Steroid-responisve nephrotic syndrome |
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Term
| How are NK cells activated and how do they destroy virally infected and tumor cells? |
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Definition
1) Stimulated by IL-12 (macrophages), IFN-b and IFN-a, or when MHC-1 is missing
2) Use perforin and granzyme to induce apoptosis |
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Term
Which of the following is not a major B cell function?
1) Opsonization
2) Complement activation
3) Type I hypersensitivity
4) Type IV hypersensitivity
5) Hyperacute organ rejection
6) Type II hypersensitivity |
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Definition
4) Type 4, delayed cell-mediated hypersensitivity reactions are carried out by T cells
- B cells carry out type I (IgE), type II (pre-formed antibody-IgG) and type III (IC: IgG)
- They opsonize bacteria with IgM/IgG, activate complement (IgM/IgG), sensitize mast cells (IgE) and neutralize viruses (IgG) |
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Term
Which of the following is not a major T cell function?
1) Type IV hypersensitivity reaction
2) Acute organ rejection
3) Chronic organ rejection
4) Macrophage activation
5) Hyper-acute organ rejection |
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Definition
5- Hyper-acute is B cell (antibody) mediated
Acute/chronic organ rejection is T-cell mediated, and CD4+ t cells help B cells make IF-y to stimulate macrophages.
CD8+ cells also kill viruses directly. |
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Term
| Describe the major steps of T cell differentiation. |
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Definition
1) Arise as precursor cell in Bone marrow
2) Migrate to thymus and express CD4, CD8 and TCR
- Undergo positive selection (TCR bind self MHC) in cortex
- Under negative selection (TCR with high affinity for self die) in medulla and the cortico-medullary junction.
3) Leave thymus expressing either CD4 or CD8 and migrate to LN
4a) CD4+ T cells become Th cells
- Th1 if stimulated by IL-12 (produce IL-2, IFN-y and activate macrophages and CD8+ T cells)
- Th2 if stimulated by IL-4 (produce IL4, IL5 and help B cells make IgE>IgG)
4b) CD8+ T cells become cytotoxic t cells
- Kill virus-infected cells
- Neoplastic cells
- Donor graft cells (acute and chronic, as well as Type IV hypersensitivity) |
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Term
| What are the major APCs and how do they activate T cells (e.g. signal 1 and 2). |
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Definition
1) APCs include macrophages, DCs and B cells
2a) Helper T cells
- Foreign body phagocytosis and antigen presentation on MHC II that is recognized by TCR on Th cell (signal 1)
- Co-stimulation from interaction of B7/B and CD28/T (signal 2)
- Th cells make cytokines
2b) Cytotoxic T cells
- Endogenously synthesized (viral and self) proteins presented on MHC-1 recognized by TCR on Tc (signal 1)
- IL-2 from Th1 cell activates Tc cell to kill virus-infected cell |
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Term
| How does T-cell dependent activation of B cells by APCs occur? |
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Definition
1) Th cell activation by signal 1 (MHC-II presentation and TCR recognition) and signal 2 (B7-CD28 co-stimulation)
2) CD40 receptor on B cell binds CD40L on Th cell (signal )3) Stimulated Th2 cell releases IL-4, -5, -6 and -10 and co-stimulation signal (B7-CD28) is given. |
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Term
Which of the following is NOT characteristic of a Th1 cell response?
1) Secretion of IL-2 and IFN-y
2) Inhibited by IL-10
3) Help B cells to make antibodies
4) Activates macrophage and CD8+ T cells
5) Involved primarily in cell-mediated immunity |
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Definition
3- This is a function of Th2 cells, which present antigens (MHC-II) to B cells and after receiving signal 1 with CD40-CD40L interaction, produce IL-4, IL-5, IL-6 and IL-10 to enable B cell class switching
Th1 cells release IL-2 and IFN-y, which activate CD8+ T cells and macrophages. They are inhibited by the Th2 response from IL-10 |
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Term
Which of the following is NOT characteristic of a Th2 cell response?
1) Humoral immunity
2) Secrete IL-4, -5, -6 and -10
3) Help B cells to make antibodies
4) Activates macrophage and CD8+ T cells
5) Inhibited by IFN-y |
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Definition
4- This is handled by Th1 cells in cell-mediated immunity.
Th-2 cytokines (IL-4,5,6 and 10) are important for B cell class-switching and they are inhibited by Th1 signals (IFN-y) |
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Term
| How do macrophages activate lymphocytes? |
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Definition
Produce IL-1 and TNF-a
They are activated by IFN-y |
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Term
What is the function of each of the following molecules in cell-mediated immunity?
1) Perforin
2) Granzyme
3) Granulysin |
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Definition
All released from cytotoxic granules in CD8+ T cells, in destruction of tumor cells, virally-infected cells and donor graft cells.
1) Helps deliver contents of granules into target cell
2) Serine protease that activates apoptosis inside target cell
3) Antimicrobial, induces apoptosis |
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Term
| What is the function of CD3+, CD4+, CD25+ cells that produce IL-10 and TGF-b. |
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Definition
Tregs (Th phenotype) cells that suppres CD4+ and CD8+ T cell responses
IL-10 is Th2 cytokine that inhibits Th1
TGF-b inhibits CD8+ cells |
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Term
| Describe the basic structure of an antibody |
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Definition
Polypeptide with 2 identical heavy chains and 2 identical light chains connected by disulfide bonds.
1) Heavy chain determines class: IgA, IgD, IgE, IgG, IgM
- Each has constant region and the variable region
- Ch is the same for all antibodies from given B cell type
- Vh is the same for all antibodies produced by a single B cell or B cell clone
2) Light chain: lambda (λ) and kappa (κ)
- Always identical type |
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Term
| Describe the functions of the Fab and Fc portions of an antibody heavy chain. |
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Definition
Heavy chain determines antibody class (IgM, IgG ect) and has variable and constant regions.
1) Fab is antibody-binding fragment
- Determines idiotype: unique antigen binding pocket (1 type per B cell)
2) Fc- Constant, Carboxy terminal with Carbohydrate side Chains
- Determines Isotype (IgM vs. IgD, ect)
- Complement binding at CH2 (IgM + IgG only)
- Macrophage binding at CH2-CH3 junction |
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Term
| Describe the process by which antibody diversity is generated. |
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Definition
1) Random "recombination" of VJ (light-chain) or V(D)J (heavy-chain) genes
2) Random combination of heavy chains with light chains
3) Somatic hypermutation (following antigenic stimulation)
4) Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) |
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Term
Which of the following is NOT a mechanism by which antibody diversity is generate?
1) VJ (light-chain) or V(D)J (heavy-chain) genes
2) Random combination of heavy chains with light chains
3) Random combination of light chains on a given antibody
4) Somatic hypermutation
5) Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) |
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Definition
| 3- You can NEVER have 2 different light chains in a given antibody. You can have different light chains and different heavy chains and different combinations of the two, but you must ALWAYS have 2 kappa or 2 lambda in a given antibody. |
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Term
| What are the 3 major ways by which antibodies can dispose of bacterial particles? |
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Definition
1) Opsonization- promotes phagocytosis
2) Neutralization- preventing bacterial adherence to epithelium
3) Complement activation
- Antibody activates complement (Fc CH2 portion), enhancing opsonization (C3b) and lysis (MAC) |
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Term
Which IG isotype accomplishes each of the following?
1) Secondary, delayed antigen response, fixing complement, crossing the placenta, opsonizing bacteria and neutralizing bacterial toxins.
2) Prevent attachment of bacteria and viruses to mucus membranes. Fund in secretions (tears, mucus and saliva) and breast milk (colostrum). No complement fixation
3) Found on surface of many B cells and in serum, but unclear function
4) Binds mast cells and basophils; cross-linking in the presence of allergen. Also activates eosinophils in the presence of worms. Low levels in serum
5) Immediate response to antigen, fixing complement, but not crossing the placenta. |
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Definition
1) IgG- high in serum and handles delayed response
- Opsonization, neutralization, passive immunity, complement fixation.
2) IgA- Monomer (circulation) or Dimer (secreted). NO complement fixation
3) IgD
4) IgE- Helminthe (eosinophilic) and allergic (mast cell) immunity.
5) IgM- early complement fixation, but no crossing placenta (A and B antibodies except in type O individuals) |
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Term
| What is the difference between thymus-independent and thymus-dependent antigens? |
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Definition
1) Independent
- Lack a peptide component and cannot be presented by MHC to T cells (LPS and polysaccharide capsular antigen)
- Stimulate IgG antibodies only and do NOT cause memory
2) Dependent
- Contain protein component (e.g. conjugated H. influenzae vaccine). Class switching and immunological memory occur as result of direct contact of B cells with Th cells (CD40-CD40L) and release of IL-4, 5, 6 and 10. |
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Term
| True or False: the MAC of complement defends against gram-negative bacteria |
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Definition
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Term
What complement pathway is activated by each of the following and what are the basic steps?
1) Microbe surface molecules
2) IgG or IgM |
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Definition
1) Alternative
- Constant spontaneous C3 hydrolysis
- C3b binds B in presence of factor D (cleaves B to Ba and Bb), forming C3bBb, which acts as a C3 convertase
- C3b now binds C3bBb to form C5 convertase
2) Classic
- C1q2r2s complex binds Ab-Ag complex (q portion)
- C1 splits C4 (C4a and C4b) and then C2 (C2b and C2a)
- C4bC2a (C3 convertase) forms and splits C3
- C3b joins C4b2a to form C5 convertase
Both converge on final common pathway.
- C5a (anaphylaxis and neutrophil chemotaxis)
- C5b activates C6-C9, which activates the MAC, leading to lysis and cytotoxicity. |
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Term
| How is the lectin complement pathway activated and how does it proceed? |
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Definition
Opsonin, mannose-binding lectin (MBL) acts in place of C1q, binding mannose on microbial surfaces.
1) MBL activates the MBL-associated serine proteases, MASP-1, and MASP-2, which split C4 and C2 much like the common pathway.
2) C4b2a (C3 convertase) splits C3 and forms C3a (anaphylaxis) and C3b (opsonin).
3) C4b2a3b splits C5 to C5a (anaphylaxis and neutrophil chemotaxis) and C5b, which attracts C6-C9 to form MAC, which results in cellular lysis and toxicity |
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Term
| What are the roles of Factor H, I, P and D in complement activation? |
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Definition
Alternative pathway factors (Spontaneous and microbial surfaces).
1) Factor H rapidly inactivate C3 convertase (C3bBb) in fluid phase, as well as acting as cofactor for factor I in cleavage of C3b that is spontaneously generated by cleavage of internal thioester bond.
2) Factor I cleaves C3b and C4b
2) Factor P stabilizes C3bBb, amplifying alternative signal
3) Factor D Cleaves B to Bb and allows it to complex with C3b to form C3bBb (C3 convertase) |
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Term
What clinical symptoms arise from the following complement deficiencies?
1) C1 esterase inhibitor deficiency
2) C3 deficiency
3) C5-C9 deficiencies
4) DAF (GPI anchored enzyme) deficiency |
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Definition
1) Aberrant complement activation
- Hereditary angioedema (autoimmune). Avoid ACE-inhibitors
2) Severe, recurrent pyogenic sinus and respiratory tract infections
- increased susceptibility to type III hypersensitivity
3) recurrent Neisseria bacteremia
4) Complement-mediated lysis of RBCs and PNH |
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Term
What is the function of each of the following complement components?
1) C1, C2, C3, C4
2) C3b
3) C3a
4) C5a
5) C5b |
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Definition
1) Viral neutralization
2) Opsonization (bind bacteria
3) Anaphylaxis
4) Anaphylaxis and neutrophil chmeotaxis
5) Cytolysis by MAC (recruits C6-C9) |
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Term
| What are the functions of IL-1 through IL-5? |
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Definition
Hot T-Bone stEAK
IL-1 (fever)
IL-2 (T cells)
IL-3 (Bone marrow)
IL-4 (IgE production)
IL-5 (IgA production) |
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Term
| Which cytokines are secreted by macrophages and what are their primary functions? |
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Definition
1, 6, 8, 12, TNF-a
1) IL-1- fever and acute inflammation
- activates endothelium to express adhesion molecules
- induces chemokine secretion to recruit leukocytes
2) IL-6- endogenous pyrogen and stimulates acute phase reactant production (also Th2 cytokine)
3) IL-8- major neutrophil recruitment
4) IL-12- Th1-cell stimulation and NK cell activation (also secreted from B cells)
5) TNF-a- Acute phase reactant in septic shock that activates endothelium and causes leukocyte recruitment/vascular leakage |
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Term
Which cell type secretes each of the following and what is its function?
1) IL-2
2) IL-3
3) IL-8
4) IL-12
5) IL-10
6) IL-4
7) IL-5 |
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Definition
1) Secreted by Th1 cells to stimulate growth of Th and Tc cells
2) Secreted by all T cells to stimulate growth and differentiation of bone marrow stem cells (like GM-CSF)
3) Secreted by macrophages to recruit neurophils
4) Secreted by macrophages and B-cells to stimulate Th1 phenotype and NK cell activation
5) Secreted by Th2 cells and Tregs to inhibit activates T cells and Th1 cells, while activating Th2 cells
6) Secreted by Th2 cells and induces differentiation of Th2 cells and promotes growth of B cells (enhancing class switching to IgE and IgG)
7) Secreted by Th-2 cells, promoting differentiation of B cells (IgA class switching) and stimulates growth and differentiation of eosinophils |
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Term
| What are the primary Th2 cytokines and what are their functions? |
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Definition
IL-4, IL-5, IL-6, IL-10
1) IL-4 promotes B cell development (class switching to IgG and IgE)
2) IL-5 promotes B cell development (class switching to IgA) and stimulates growth and differentiation of eosinophils
3) IL-6 is endogenous pyrogen (also secreted by macrophages) that cause fever and stimulates acute phase reactant production
4) IL-10 (also secreted by Tregs) suppresses activated T cells and Th1 cells, while activating Th2 |
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Term
| What are the primary Th1 cytokines and what are their functions? |
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Definition
1) IFN-y: Activates macrophages and Th1 cells, while suppressing Th2 cells
- antiviral and tumor-supressing properties
2) IL-2
- Stimulates helper and cytotoxic T cell growth
All T cells secrete IL-3 as well, to stimulate bone marrow growth (similar to GM-CSF) |
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Term
| How do Interferon proteins interfere with viruses? |
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Definition
alpha, beta and gamma forms place un-infected cells in anti-viral state
Induce production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but NOT host)
1) alpha and beta inhibit viral protein synthesis
2) gamma increases MHC I and II expression and and antigen presentation in all cells
3) All 3 activate NK cells |
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Term
What are the important cell surface proteins that are characteristic of the following cell types.
1) T cells
2) B cells
3) Macrophages
4) NK cells |
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Definition
All except RBCs have MHC-1
1) T cells
- TCR (binds antigen-MHC complex)
- CD3 (TCR signal transduction)
- CD28 (co-stimulation binding B7 on APC)
2) B cells
- CD19, CD20, CD21 (EBV receptor), CD40 (T-cell activation), MHC II, B7
3) Macrophages
- CD14, CD40, MHC II, B7
- Fc and C3b (enhanced phagocytosis)
4) NK cells
- CD16 (binds Fc on IgG)
- CD56 (unique marker) |
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Term
| What is meant by cellular "anergy"? |
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Definition
| Most common in T cells when self-reactive T cells become nonreactive without co-stimulatory molecule |
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Term
| Why do so-called "superantigens" from S. aureus and S. pyogenes cause toxic shock syndrome? |
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Definition
| Cross-link the beta region of TCR to the MHC-II molecule on APCs, resulting in uncoordinated release of IFN-y from Th1 cells and subsequent release of IL-1, IL-6 and TNF-a from macrophages. |
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Term
| How do gram-negative bacteria activate an inflammatory response? |
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Definition
| Endotoxins/LPS direct stimulates macrophages by binding to endotoxin receptor (CD14); Th cells no involved. |
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Term
| What forms of major and minor antigenic variation occur in influenza virus? |
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Definition
Hemaglutinnin allow viral binding to sialic acid residues on host cell and NA cleaves sialic acid to allow budding forms to be released from cells.
1) Major- Antigenic shift (only in Influenza A)
- Exchange of DNA/RNA segments between viruses
- Example would be H1N2 and H2N1 forming H1N1
2) Minor- Antigenic drift
- Natural mutation over time of known strains of influenza , which may lead to a loss of immunity, or in vaccine mismatch. |
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Term
| What characteristic bacterial and parasitic species exhibit antigenic variation? |
|
Definition
1) Bacteria
- Salmonella (2 flagellar variants)
- Borrelia (relapsing fever)
- N. gonorrhoeae (pilus protein)
2) Parasites
- Trypanosomes (programmed rearrangements in VSG) |
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Term
| What are the major differences between the types of immune processes that are occurring during vaccination vs. delivery of a humanized monoclonal antibody? |
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Definition
1) Vaccination (like toxoid and natural infection) is Active
- Slow-forming antibodies in response to exposure to foreign antigens leading to formation of long-lasting (memory) antibodies.
2) Human monoclonal antibody (like IgA in breast milk and antitoxin) is passive
- Fast acting, pre-formed antibodies with short life-span (3 weeks).
- Pre-formed antibodies are given for Tetanus toxin, Botulinum toxin, HBV, or Rabies (To Be Healed Rapidly) |
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Term
| Under what conditions might you want to give pre-formed antibodies to a patient rather than a toxoid or vaccination? |
|
Definition
When you need To Be Healed Rapidly
Give pre-formed antibodies for
1) Tetanus toxin
2) Botulinum toxin
3) HBV
4) Rabies virus |
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Term
| What are the pros and cons of using a live, attenuated vaccine vs. an inactivated/killed vaccine? |
|
Definition
1) Live Vaccine (Lost pathogenetic but can still grow transiently- Cellular immunity)
- Pro (induces strong, often life-long immunity
- Con (may revert to virulent form)
**Used for Measles, Mumps, Polio (sabin), Varicella and Yellow Fever**
2) Inactive- Heat-innactivated maintaining epitope structure (Humoral immunity)
- Pro (stable and safer)
- Con (weaker immune response; booster shots usually required)
**Used for Cholera, Influenza, Hepatitis A, Polio (Salk) and Rabies** |
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Term
What kind of vaccine is used for each of the following?
1) Influenza
2) Rabies
3) Measles
4) Polio
5) Mumps
6) Cholera
7) Mumps
8) Rubella
9) Varicella
10) Yellow Fever |
|
Definition
Inactive- Rabies, Cholera, Salk Polio, Hepatitis A, Influenza
Active- Varicella, MMR, Sabin polio, Yellow fever |
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Term
True or False:
Live attenuated vaccines induce a primarily "cell-mediated" immune response |
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Definition
True!
These vaccines have lost pathogenicity, but maintain transient growth in host leading to cell-mediated immune response that is more long-lasting than the humoral response from killed vaccines |
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Term
Describe the basic mechanism underlying a skin rash following PCN administration.
How would you test for this type of reaction? |
|
Definition
Type 1 hypersensitivity- Fast and Fast (anaphylaxis) with pre-formed antibody
1) Free antigen cross links IgE on "pre-sensitized" mast cells and basophils, causing release of vasoactive amines that act on post-capillary venules (histamine)
2) Scratch test and Radioimmunosorbent assay |
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Term
Describe the basic mechanism underlying a hemolytic anemia following PCN administration.
How would you test for this type of reaction? |
|
Definition
Type-2 hypersensitivity: drug-induced
1) Antibody mediated (IgM, IgG) fixation of aintigen on "enemy" cell, leading to complement mediated lysis (classical) or phagocytosis
- PCN attaches to RBCs and acts as hapten to produce antibodies that activate complement.
2) Direct and Indirect Coombs |
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Term
| What are the 3 possible mechanisms of a type 2 hypersensitivity reaction? |
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Definition
IgG, IgM mediated MAC lysis: tested for with Coomb's
Examples include Autoimmune hemolytic anemia · ITP · Bullous pemphigoid · Pemphigus vulgaris · Rheumatic fever · Goodpasture's syndrome
1) Antibodies opsonize cells or activate complement
2) Antibodies recruit PMNs and phages that incite tissue damage.
3) Antibodies bind normal cellular receptors and interfere with functioning |
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Term
What type of hypersensitivity reaction underlies each of the following.
1: Fever, urticaria, arthralgia, proteinuria and lymphadenopathy 5-10 days after taking a drug.
2) Edema and necrosis of skin following intradermal injection of antigen |
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Definition
Both are type III- IgG immune complex (antibody, antigen and complement)
1) Serum sickness (more common)
- Antibodies to foreign proteins are produced (5 days), forming ICs that are deposited in membranes, where they fix complement
- mostly caused by drugs (not serum).
2) Arthus reaction (less common)
- Local subacute antibody-mediated type III reaction when intradermal injection of antigen induces antibodies to form ICs in skin. |
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Term
| How do you test for type III hypersensitivity? What about type II? Type IV? |
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Definition
ACID:
Anaphylactic and Atopic= I
Cytotoxic (antibody mediated)= II
Immune complex= III
Delayed (cell mediated)= IV
Type 3= Immunoflourescent staining
Type 2= Direct and indirect coomb'
Type 4= Patch test (PPD)
Type 1= Scratch test or radioimmunosorbent |
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Term
| What type of immune reaction is exhibited by a positive PPD test? |
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Definition
Type IV- delayed (cell-mediated hypersensitivity)
- Sensitized T lymphocytes encounter antigen and then release lymphokines, leading to macrophage recruitment (no antibody)
Not transferable by serum (cell mediated!)
4 T's= T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermatitis) |
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Term
What type of hypersensivity reaction is described by each of the following?
1) Transplant rejection
2) Serum rejection
3) Rash
4) Contact dermatitis
5) PCN hemolytic anemia
6) Arthus reaction |
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Definition
1) 4- delayed/cell-mediated
2) Serum sickness is type III, ABO rejection is type II
3) 1- Atopic
4) 4
5) 2- antibody-mediated
6) 3- immune complex |
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Term
What diseases are associated with each hypersensitive described below?
1) Immediate, anaphylactic reaction
2) Disease specific to tissue or site where antigen is found
3) Response does NOT involve antibodies
4) Associated with vasculitis and systemic manifestations |
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Definition
1) Type 1
- Anaphylaxis (bee sting, food/drug)
- Allergic and Atopic (rhinitis, hay fever, eczema, hives, asthma)
2) Type II
- Hemolytic anemia
- Pernicious anemia
- ITP
- Erythroblastosis fetalis (Rh-D)
- Acute hemolytic transfusion reactions
- Rhematic fever
- Goodpastures
- Bullous pemphigoid
- Pemphigus vulgaris
- Grave's disease
- Myasthenia gravis
3) Type IV
- MS
- Guillain-Barre syndrome
- Hashimoto's
- GVHD
- PPD
- Contact dermatitis (poison ivy, nickel allergy)
4) Type III
- SLE
- RA
- Polyarteritis nodosum
- Post-strep GMN
- Serum sickness
- Arthus reactions (swelling and inflammation following tetanus vaccine)
- Hypersensitivity pneumonitis (farmer's lung) |
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Term
Name the type of hypersensitivity reaction associated with each of the following diseases.
1) Bee sting
2) Goodpasture's
3) SLE
4) Type 1 DM
5) Serum sickness
6) PPD
7) GVHD
8) Hashimoto's thyroiditis
9) Erythroblastosis fetalis
10) Pemphigus vulgaris |
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Definition
1) I
2) II (anti-BM)
3) III (anti-dsDNA and ANA)
4) IV (anti-glutamate decarboxylase)
5) III
6) IV
7) IV
8) IV (Anti-thryoglobulin, anti-microsomal)
9) II
10) II (Anti-desmoglein) |
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Term
Name the type of hypersensitivity reaction associated with each of the following diseases.
1) Rhinitis
2) Rheumatic fever
3) Post-strep GMN
4) Bullous pemphigoid
5) Reaction to tetanus vaccine
6) Poison ivy allergy
7) Guillain-Barre
8) Pernicious anemia
9) Grave's disease
10) Myasthenia gravis
11) Hypersensitivity pneumonitis |
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Definition
1) I
2) II (anti-IgG RF)
3) III
4) II
5) Arthus-III
6) IV
7) IV
8) II
9) II
10) II
11) III |
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Term
What type of blood transfusion reaction is described in each of the following clinical presentations? In each case, give an example etiology.
1) Dyspnea, bronchospasm, hypotension, respiratory arrest and shock
2) Fever, headaches, chills and flushing
3) Urticaria, pruritis, wheezing, fever
4) Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular) |
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Definition
1) Type 1- Anaphylaxis
- Severe reaction- Watch out for IgA in IgA-deficient folks
2) Febrile non-hemolytic transfusion reaction
- Type II hypersensivity (host antibody against donor HLA and leukocytes)
3) Type 1- allergy
- reaction against donor plasma proteins
4) Acute hemolytic transfusion reaction (HTR)
- Intravascular hemolysis (ABO)
- Extravascular hemolysis (host antibody against foreign antigen on donor RBC) |
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Term
What disorders are associated with the following autoantibodies?
1) ANA
2) Anti-dsDNA, anti-Smith
3) Anti-histone
4) Anti-IG (RF)
5) Anticentromere |
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Definition
1) SLE, nonspecific
2) SLE
3) Drug-induced lupus
4) RA
5) Scleroderma (CREST) |
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Term
What disorders are associated with the following autoantibodies?
1) Anti-Scl-70 (anti-DNA topoisomerase I)
2) Anti-mitochondrial
3) Anti-gliadin, antidenomysial
4) Anti-BM
5) Anti-desmoglein |
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Definition
1) Scleroderma (diffuse) vs. Anti-centromere in CREST
2) Primary biliary cirrhosis
3) Celiac disease
4) Goodpasture's
5) Pemphigus vulgaris |
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Term
What disorders are associated with the following autoantibodies?
1) Anti-microsomal, antithyroglobulin
2) Anti-Jo-1
3) Anti-SS-A (Anti-Ro)
4) Anti SS-B (Anti-La)
5) Anti-U1 RNP (ribonucleoprotein) |
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Definition
1) Hashimoto's thyroiditis
2) Polymyositis, Dermatomyositis
3) Sjogrens
4) Sjogrens
5) Mixed connective tissue disease |
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Term
What disorders are associated with the following autoantibodies?
1) Anti-smooth muscle
2) Anti-glutamate decarboxylase
3) c-ANCA
4) p-ANCA |
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Definition
1) Autoimmune hepatitis
2) Type 1 DM
3) Wegener's
4) Polyangiitis and other vasculitides |
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Term
What types of bacterial infections is a patient with each of the following deficiencies particularly vulnerable to?
1) No complement
2) No T cells
3) No B cells
4) No granulocytes |
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Definition
B cell deficiencies tend to cause recurrent bacterial infections while T cell deficiencies produce more viral and fungal infections
1) Neisseria (no MAC)
2) Sepsis
3) Encapsulated (no antibody opsonization)
- Strep, Staph, Haemophilus, Moraxella
4) Staph and Peudomonas |
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Term
What kinds of viral and fungal infections are likely to occur in patients without T cells and B cells, respectively.
What about no granulocytes? |
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Definition
B cell deficiencies tend to cause recurrent bacterial infections while T cell deficiencies produce more viral and fungal infections.
1) Viral
- No T cells: CMV, EBV, VZV, chronic infection with resp/GI viruses
- No B cells: Enteroviral encephalitis, poliovirus (live vaccine contraindicated)
2) Fungal
- No T cells: Candida, PCP
- No B cells: GI giardiasis (no IgA)
- No granulocytes: Candida and Aspergillus |
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Term
8 month old presents with recurrent streptococcus infections.
You run some labs and determine normal pro-B cell levels, but decreased numbers of mature B cells and IG of all classes.
What is the pathogenesis of this condition? |
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Definition
X-linked recessive: Bruton's aggamglobulinemia
- Defect in BTK, a tyrosine kinase gene, blocks pre B cells from becoming mature B cells.
Recurrent bacterial infections, lack of mature B cells and pan-lack of IG suggests B-cell disorder.
These are classic Bruton's agammaglobilunemia, since all IG is decreased. |
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Term
11 month old presents with recurrent episodes of very high fever.
You run some labs and discover high IgM levels, but low IgA/IgG/IgE levels.
What is the pathogenesis of this condition? |
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Definition
Severe pyogenic infections early in life with selective increase in IgM fits Hyper-IgM syndrome
- Defective CD40L on Th cells (important for co-stimulation with B cells in T-dependent class-switching) |
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Term
8 month old presents with a URI. They have a h/x of sinus infections and have allergies to milk with diarrhea.
As a newborn, they once had an anaphylactic reaction while breast feeding, at which time he was switched to formula.
What is the pathogenesis of this condition? |
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Definition
Sinus and Lung infections in patient with milk and diarrhea allergies suggests selective IgA deficiency, a defect in isotype switching of IG.
- Failure of plasma cell maturation leeds to decreased IgA secretion.
Mother's milk likely had IgA, which was the cause of his past anaphylaxis. |
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Term
23 year old male presents with a sinopulmonary infection.
You run some labs and discover a normal level of CD19+ CD20+ cells but very few CD79+ cells and Immunoglobulin.
What is the pathogenesis of this condition? |
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Definition
Sinopulmonary infection with low plasma cell and IG levels in patient 20-30 suggests CVID.
- Acquired defect in B cell maturation that increase risk for autoimmune disease, sinopulmonary disease and lymphoma. |
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Term
| What are the major immune deficiencies related to B-cells? |
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Definition
B cell deficiency tends to produce recurrent bacterial infections (Haemophilus, Step, Staph, Moraxella)
1) Bruton's agammaglobulinemia- X-linked recessive defect in BTK prevents maturation of pre-B cells to mature cells (recurrent bacterial infections after 6 months due to lack of own IG)
2) Hyper-IgM Syndrome- Defective CD40L on Th cells prevents class-switching and causes severe pyogenic infections early in life
3) Selective Ig deficiency- most commonly IgA
- Anaphylaxis with exposure to blood products (milk) with IgA
4) CVID- acquired defect in B cell maturation causes sinopulmonary infection, autoimmune disease and lymphoma in individuals 20-30
- Normal B cell levels with decreased plasma cells and IG |
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Term
| Why might you see an absent thymic shadow on CXR in an individual with tetany, VSD and recurrent viral/fungal infections? |
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Definition
DiGeorge syndrome- Thymic aplasia
- 22q11 deletion (failure of 3rd and 4th pharyngeal pouches)
- Thymus (T cells) and Parathyroid (PTH and Ca2+) fail to form, leading to T cell deficiency, hypocalcemia and congenital heart/great vessel defects. |
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Term
| What immune deficiency in particular predisposes individuals to disseminated mycobacterial infections? |
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Definition
| IL-12 receptor deficiency: decreased Th1 response and low IFN-y, so inadequate activation of MHC-1 and MHC-2 presentation and defective neutrophil chemotaxis |
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Term
| What condition is associated with coarse Facies, cold (non-inflamed) staph abscesses, retained primary teeth, increased IgE and eczema? |
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Definition
Hyper-IgE syndrome (Job's), where Th cells fail to produce IFN-y, causing an inability of neutrophils to respond to chemotactic signals.
FATED- coarse Facies, cold Abscesses, retained primary Teeth, high igE and Dermatologic issues. |
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Term
| What are the 4 primary immunodeficient conditions related specifically to T-cell disorders? |
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Definition
1) DiGeorge- Thymic aplasia (22q11 deletion with absent thymus, parathyroid and congenital heart defects)
2) IL-12 receptor deficiency: lack of Th1 response with disseminated mycobacterial infection and decreased IFN-y
3) Hyper-IgE-Job's (Facies, cold Abscess, primary Teeth, high igE and Derm issues- FATED) due to low IFN-y.
4) Chronic mucocutaneous candidiasis: T cell dysfuncion with C. albicans infections of skin and mucous membranes. |
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Term
| What are the primary forms of SCID and how might they present? |
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Definition
Recurrent bacterial, viral, fungal and protozoal infections from B and T cell deficiency requiring a BMT.
Look for absent thymic shadow, germinal centers on biopsy and B cells in peripheral blood
1) Defective IL-2 receptor: X-linked (most common)
- Low IL-2R= low Th1 cell activation
2) Adenosine deaminase deficiency
- Increased adenosine is toxic to T and B cells
- Decreased dNTPs and decreased DNA synthesis)
3) Failure to synthesize MHC-II antigens |
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Term
| Why might a child have ataxia, spider angiomas and a selective IgA deficiency? |
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Definition
Combined B and T cell issue
Triad of Ataxia Telangiectasia: Defects in ATm gene, which codes for DNA repair enzymes |
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Term
Why might a child present with TTP, recurrent infections and Eczema?
Labs show decreased IgM with increased IgE and IgA |
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Definition
Triad (TIE) of Wiskott-Aldrich syndrome
- X-linked recessive defect with progressive deletion of B and T cells |
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Term
Which immunodeficiency is described by each of the following?
1) X-linked recessive defect resulting in progressive T/B cell deletion and presenting with TTP, recurrent infections and eczema
2) Defects in ATM gene leading to defective DNA repair
3) Defect in LFA-1 integrin (CD18) on phagocytes in a patient with delayed separation of the umbilical chord
4) Lack of NADPH oxidase causing increased susceptibility to catalase-positive organisms.
5) AR defect in LYST in a patient with partial albinism and peripheral neuropathy |
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Definition
1) TIE triad of Wiskott Aldrich syndrome- look for LOW IgM and high IgA/IgE
2) Ataxia telangiectasia with cerebellar ataxia, telangiectasias and IgA deficiency
3) Leukocyte adhesion deficiency (type 1) with Neutrophilia, causing recurrent bacterial infecionts with absent pus formation
4) CGD causes decreased ROS and absent respiratory burst in PMNs, which makes catalase-positive organisms like S. aureus, E. coli and Aspergillus (can break down ROS) particularly suited for infection.
5) Chediak-Higashi (phagocyte dysfunction)
- Dysfunctional microtubules in phagosome/lysosome fusion
- Recurrent pyogen infections by stpah and strep |
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Term
| Why might you see recurrent bacterial infections in a patient with Neutrophilia and absent pus formation? |
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Definition
Phagocyte dysfunction in Leukocyte adhesion deficiency (type 1).
Defect in LFA-1 integrin (CD18) protein on phagocytes
- also associated with delayed separation of umbilical chord |
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Term
| What patients suffer from partial albinism and peripheral neuropathy with recurrent pyogenic staph and strep infections? |
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Definition
Chediak-Higashi (phagocyte dysfunction)
AR mutation in LYST causing microtuble dysfunction in phagosome-lysosome fusion. |
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Term
| How do you diagnose a patient who seems to have increased susceptibility to catalase-positive organisms like Staph, E. coli and Aspergillus? |
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Definition
Sounds like CGD, a defect in NADPH oxidase that leads to decreased production of ROS and defective oxidative burst from PMNs.
Diagnose with negative Nitroblue tetrazolium dye reduction test. |
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Term
What is the appropriate time period and pathogenesis of each of the following types of transplant rejection?
1) Hyper-acute
2) Acute
3) Chronic
4) GVHD |
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Definition
1) Minutes- Antibody-mediated (type II) ue to presence of pre-formed anti-door antibodies
- occludes graft vessels causing ischemia and necrosis
2) Weeks later
- Cell-mediated due to CTLs reacting against foreign MHCs (can reverse with immunosuppressents like cyclosporine, OKT3)
- Causes vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
3) Months to years
- Class 1-MHC (non-self) is perceived by CTLs as class 1-MHC (self) presenting a non-self antigen
- Irreversible CTL and antibody-mediated vascular/tissue damage (obliterative fibrosis)
4) Variable
- Graft immunocompetent T cells proliferate in irradiated immunocompromised disease host and reject cells with "foreign" proteins, resulting in organ dysfunction.
- Maculopapular rash, jaundice, hepatosplenomegaly and diarrhea (see in BMT and liver transplant and can be beneficial in BMT) |
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Term
What type of transplant rejection is described by each of the following?
1) Maculopapular rash, hepatosplenomegaly, jaundice and diarrhea following BMT
2) Ischemia and necrosis of graft vessels within minutes of transplant
3) Irreversible vascular and tissue fibrosis with CTl and antibody-mediated damage
4) Graft vessel vasculitis with dense interstial lymphocytic infiltrate: reversed by cyclosporine |
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Definition
1) GVHD- donor T cells proliferate in irradiated host.
- can actually be a good sign in BMT, if organ damage is not significant.
2) Hyperacute type II rejection.
3) Chronic reject- years later
- MHC-1 (non-self) is perceived as MHC-1 (self) presenting a foreign antigen.
4) Sub-acute rejection (within weeks) with CTL-mediated reaction against foreign MHCs |
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Term
How do each of the following immunosuppressants work?
1) Cyclosporine
2) Tacrolimus (FK506)
3) Sirolimus (rapamycin)
4) Daclizumab
5) Azathioprine
6) Muromonab-CD3 (OKT3) |
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Definition
1) Calcineurin inhibitor prevents IL-2 production and inhibition of its receptor- blocks differentiation/activation of T cells
2) Binds FK-bining protein, inhibiting IL-2 and other cytokines.
3) Inhibits mTOR: Inhibits T cell proliferation in response to IL-2
4) Monoclonal antibody against IL-2 receptor on activated T cell
5) Anti-metabolite precursor to 6-MP, a purine analog that interferes with synthesis of nucleic acids: toxic to proliferating lymphocytes
6) Monoclonal antibody against CD3 (epsilon chain) on surface of T cells. Blocks interaction with CD3 protein responsible for T cell signal transduction. |
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Term
What is the target of each of the following antibodies and how are they used therapeutically?
1) Muromonab-CD3 (OKT3)
2) Daclizumab
3) Digoxin Immune Fab
4) Infliximab
5) Adalimumab
6) Abciximab
7) Trastuzumab (Herceptin)
8) Rituximab
9) Omalizumab |
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Definition
1) CD3- prevent acute transplant rejection
2) IL-2R- prevent acute rejection of kidney
3) Antidote for digoxin intoxication
4) TNF-a in CD, RA, ankylosing spondylitis and psoriatic arthritis
5) TNF-a in CD, RA and psoriatic arthritis
6) GPIIb/IIIa used to prevent cardiac ischemia in unstable angina and patients treated with PCI
7) erb-B2 used in HER-2-over-expressing breast cancer
8) CD20- B cell NHL
9) IgE- Severe asthma (additional line) |
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Term
Under what conditions is each of the following recombinant cytokines used?
1) Aldesleukin (IL-2)
2) EPO (epoetin)
3) Filgrastim (GCSF)
4) Sargramostim (GM-CSF) |
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Definition
1) Renal cell carcinoma, metastatic melanoma
2) Anemia (especially in renal failure)
3) Recovery of bone marrow
4) Recovery of bone marrow |
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Term
Under what conditions is each of the following recombinant cytokines used?
1) INF-a
2) IFN-b
3) IFN-y
4) Oprelvekin (IL-II)
5) Thrombopoiten |
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Definition
1) Hep B and C, Kaposis sarcoma, leukemias, malignant melanoma
2) MS
3) CGD
4) Thrombocytopenia
5) Thrombocytopenia |
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Term
| What monoclonal antibodies are available to prevent acute organ transplant rejection? |
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Definition
Cell-mediated rejection in weeks.
1) Muromonab-CD3 (OKT3) : anti-CD3
2) Daclizumab: IL-2 (renal only) |
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Term
| What anti-TNF-a antibodies are available to treat RA? |
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Definition
Inflixumab and Adalimumab
Inflixumab is good for CD, RA, psoriatic arthtis and ankylosing spondylitits
Adalimumab is good for CD, RA and psoriatic arthritis |
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Term
What are the important toxicities are associated with each of the following immunosuppressants.
1) Cyclosporine
2) Tacrolimus (FK506)
3) Sirolimus (rapamycin)
4) Daclizimab
5) Azathioprine
6) Muromonab-CD3 (OKT3) |
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Definition
1) Inhibits calcineurin (prevents IL-2 mediated T cell activation)
- Viral infections and lymphoma; nephrotoxicity (prevent with mannitol); gout
2) Binds FK-binding protein, inhibiting IL-2 secretion
- Nehrotoxicity, peripheral neuropathy, HTN, pleural effusion, hyperglycemia
3) Inhibits mTOR. T-cell proliferation in response to IL-2
- Hyperlipidemia, TP, leukopenia
4) Monoclonal antibody against IL-2- no toxicity known
5) Azathioprine: anti-metabolite precursor to 6-MP interferes with nucleic acid synthesis (toxic to proliferating lymphocytes)
6) Monoclonal antibody against CD-3
- Cytokine syndrome, hypersensitivity |
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