Chapter 6
Pages 197-255
Immune System
1.
Hypersensitivity
2. What are the two phases of a type I hypersensitivity reaction and the effectors of each?
 Initial reaction: vasodilation, vascular leakage within 5-30 min., caused by mast cell
degranulation
 Late phase reaction: mucosal and epithelial tissue destruction 2-24 hours after exposure,
caused by eosinophils and mast cells
3.
What is inside those immediately released granules?
 Histamine (vasoactive amines)
 Proteases and hydrolases
 Proteoglycans (package and store amines)
 Leukotrienes B4, C4, and D4 (vasoactive and spasmogenic agents, chemotactics)
 Prostaglandin D2 (bronchospasm and mucus)
 Platelet aggregating factor
4.

5.


Why are eosinophils activated?
TH2 cells produce a number of cytokines upon subsequent encounter with an antigen; IL-4
stimulates class switching to IgE, and IL-5 activates eosinophils
i. Also mast cells to a lesser extent
What is type II hypersensitivity? What are 6+ situations in which this reaction occurs?
Antibody-mediated cell destruction or dysfunction
Tissue rejection (partly); erythrobalstosis fetalis; autoimmune hemolytic anemia,
thrombocytopenia, and agranulocytosis; certain drug reactions; Goodpasture disease;
myasthenia gravis, Graves disease
6.
What is type III hypersensitivity and its time frame? What are the three major targets? How
does affected tissue appear morphologically? What diseases involve type III?
 Deposition of immune complexes and C3 causing inflammation on site about a 10 days later
 Vessels (vasculitis), glomeruli (glomerulonephritis), and joints (arthritis)
 Fibrinoid necrosis
 SLE, post-strep glomerulonephritis, polyarteritis nodosa, reactive arthritis, serum sickness
7.
What kind of cells cause type IV hypersensitivity?
 Lymphocytes: CD4+ and CD8+
What kind of hypersensitivity would be a reaction to a nickel watch band? [test Q]
IV
8.
What do TH1 cells produce in type IV hypersensitivity? What cell type does this substance
activate, and how does it make these cells behave oddly? What kind of CD4+ cell is only
important in type IV reactions?
 IFN-γ
 Macrophages; display more class II MHC, secrete more IL-12 (amplifies TH1 cells)
 TH17
9.
How does a type IV reaction to nondegradable antigens look?
 Macrophages transform into epithelioid cells and are collared by lymphocytes
 This is a granuloma; precursor is perivascular cuffing
10. What is receptor editing?
 When a developing B cell recognizes self antigens in bone marrow, it either apoptoses or
reactivates its enzymes to rearrange the antigen receptor gene and begins to express new
antigen receptors
11. What are the three modes of peripheral tolerance?
 Anergy, suppression by regulatory T cells, and deletion by activation-induced cell death (Fas
mediated)
[important for antigens not present in thymus]
12. What are three immune-priveleged sites?
 Testis, eye, and brain do not ordinarily come in contact with blood or lymph
13. What gene is most frequently implicated in autoimmunity?
 PTPN-22
RA, type I diabetes, and others
14. What is epitope spreading?
 Tissue damage may cause release of new antigens and epitopes of the antigens that are
normally concealed from the immune system
15. How is a TH17 response different from a TH1 response?
 TH17 responses are neutrophil dominant
16. What is the major antibody produced in systemic lupus erythematosus ? What are the four
staining patterns, and what do they mean? Which specific antibody combination is diagnostic?
 Antinuclear antibodies (ANAs)
i. homogenous or diffuse nuclear staining: chromatin, histones, or DNA
ii. rim or peripheral staining: double stranded DNA
iii. speckled: nonspecific, non-DNA
iv. nucleolar: RNA
 diagonistic for SLE: Antibodies to double stranded DNA and the Smith antigen (Sm)
17. What are two other important kinds of antibody in SLE?
 Anti-blood component antibodies; cause hemolysis and cytopenias
 Antiphospholipid antibodies (40-50% of patients)
18. Because of antiphospholipid antibodies, what disease might show up as falsely positive and
why? How is coagulation influenced?
 Syphillis, because the cardiolipin antigen is used in syphilis serology, and the phospholipidB2-glycoprotein complex also binds to cardiolipin
i. Also interferes with PTT in vitro: “lupus anticoagulant”
 Patients are actually hypercoagulable: “secondary antiphospholipid antibody syndrome”
19. What immunological abberations may be present in patients with SLE (4)? What seems to be
the inciting event in pathogenesis? What environmental factors exacerbate SLE?
 Failure of self tolerance: B cells and CD4+ T cells, TLRs acting as second signal to activate B
cells, and production of type I interferons
 Defective clearance of apoptotic nuclei
 UV exposure, estrogen, hydralazine, procainamide, and D-penicillamine
20. What type of hypersensitivity causes the visceral lesions of SLE?
 Type III
21. Which type of lupus glomerulonephritis is included as a part of most other types? What is the
most common type? What type is similar but less severe? What is the most severe type? Lesion?
 Mesangial; granular mesangial deposits of immunoglobulin and complement; usually
w/increase in mesangial matrix and number of mesangial cells
 Diffuse proliferative: same as focal, but more than 50% of glomeruli are involved
 Focal proliferative glomerulonephritis: crescents, fibrinoid necrosis, infiltrating leukocytes,
and eosinophilic deposits / intracapillary thrombi; proteinuria and hematuria
 Mebranous glomerulonephritis: subendothelial deposits between GBM and visceral (internal)
epithelium—these create a “wire loop” lesion
22. Why do nervous system problems arise? What does the heart look like when affected?
 We don’t know, it’s not vasculitis, it’s probably an antibody
 Pericarditis; accelerated coronary artery disease; myocarditis; Libman-Sacks endocarditis—
verrucous deposits on any heart valve, most notably on both sides
23. What are the two most common causes of death from Lupus? What form of Lupus will give you
negative tests for dsDNA? What is an intermediate form that give you a widespread skin rash
and minor systemic manifestations? What antibodies is it associated with?
 Renal failure and intercurrent infection
 Discoid Lupus Erythematosus; usually only skin manifestations; ANA will remain positive
 Subacute cutaneous lupus erythematosus
i. Strong association with antibodies to SS-A antigen and HLA-DR3 genotype
24. What antibodies are common in drug induced lupus? What organ system is not affected?
 Histone antibodies
 No nervous system involvement
25. What antibodies are positive in Sjogren’s syndrome? Any genetic associations? What cancer are
patients at risk for? What are systemic manifestations?
 Ribonuclein protein (RNP) antigens SS-A and SS-B, RF, and ANA
[most to least common]



i. SS-A means more severe course and more systemic involvement
HLA-DQ associations (MHC II)
[Dairy Queen + saliva or something]
Marginal zone B-cell lymphoma; maybe related to the incredible lymphocytic infiltrate in
glands
Synovitis, pulmonary fibrosis, neuropathy, and renal tubular problems
26. What disease is characterized by chronic autoimmune inflammation, vascular damage, and
progresive interstial and perivascular fibrosis in the skin and organs? Why does it happen? Most
severe manifestation? What happens to some folk with the limited version of this disease?
 Systemic sclerosis (scleroderma)
 Caused by CD4+ reaction to an unknown antigen=> collagen deposition and vascular damage
i. GI, musculoskeletal, kidneys, lungs, and heart
 Malignant hypertension
i. although renal failure and pulmonary fibrosis are more likely to kill, they’re slow
 CREST syndrome: calcinosis, Raynaud’s phenomenon, esophageal dysmotility (also seen in
vanilla systemic sclerosis), sclerodactyly, and telangiectasia
27. What are two important antibodies that can (separately) show up in a minority of patients with
systemic sclerosis? What other antibody is ~always present?
 Topoisomerase I antibody (anti-Scl 70)=> diffuse systemic
 anticentromere antibody=> CREST
 ANAs
28. What is a common cause of death in systemic sclerosis? What other signs occur in this organ
system? What are the musculoskeletal problems reminiscent of?
 Renal failure
 Changes mimicking hypertension (concentric proliferation of intima, deposition of collagen),
but only occur in small vessels; actual malignant hypertension can develop suddenly
 Like RA
29. What does it mean if a patient has a high titer of antibodies to ribonucleoprotein particlecontaining U1 ribonucleoprotein? Clinical signs?
 Mixed connective tissue disease
 sort of a combination of SLE, systemic sclerosis, and polymyositis: renal disease and
pulmonary HTN
30. What is the most important part of the immune system for causing tissue rejection? What’s the
difference between the direct and indirect pathway? What else plays a role?
 T cell response
 Direct = host dendritic cells present antigen to CD8+ T cells, which then become CTLs and kill
that graft up
 indirect = donor APCs present antigens, then the CD4+ T cells emit cytokines which cause a
delayed type hypersensitivity reaction
 Antibodies
31. If you failed to cross-match and so caused a hyperacute humoral reaction how would it look?
How does most antibody-dependent rejection manifest nowadays?


Immunoglobulin and complement would cause thrombi to form, and fibrinoid necrosis would
consume the organ
Rejection vasculitis
32. How does acute cellular rejection appear in the kidney? Acute humoral? Chronic rejection?
 Focal tubular necrosis, endothelitis (swelling of vascular endothelial cells)
 deposition of C4d, plus necrotizing vasculitis et al.
 Obliterative intimal fibrosis, loss of glomeruli, creatinine rises over ~5 months
33. What are three signs of acute graft-verus-host disease? Why is it dangerous to kill off the donor
T cells before transfusion (3)? What’s the most important infection of immunodeficiency?
 Skin rash=> desquamation; bile duct destruction=> jaundice; mucosal ulceration=> melena
 Thse cells are needed for successful engraftment and suppression of EBV infected B cells in
leukemic patients
 Cytomegalovirus infection
Immunodeficiencies
34. What happens in X-linked (Bruton’s) agammaglobulinemia? How does it present clinically?
Name specific microbes.
 A tyrosine kinase is mutated, causing a failure of light chain production during B cell
maturation
 Appears at 6 months of age as maternal antibodies run out, with respiratory infections by H.
influenzae, S. pneumoniae, or Staphylococcus aureus
 Also vulnerable to giardia and enteroviruses – NOTE: do not administer live polio vaccine!
 And higher incidence of autoimmune disease, oddly enough
35. What disease is similar, but presents later?
 Common variable immunodeficiency (CVID); presents in childhood or adolescence
 B cell levels are about normal, but nonfunctional
36. What is an odd way that people with isolated IgA deficiency can develop severe anaphylaxis?
 Blood transfusions containing normal IgA
37. What causes hyper-IgM syndrome? What branch of immunity is most damaged? What
infections are they prone to?
 Failure of class switching and affinity maturation, usually caused by an X linked mutation in
CD40L, in which case CD4+ T cells don’t work well either
 Pyogenic infections -- this one kind of takes characterisitics from both B and T cell defects
 Those with CD40L mutations also get Pneumocystis jirovecii
38. What disease causes loss of T cell mediated immunity, tetany, and congenital heart defects?
 DiGeorge; a deletion syndrome (tetany is from lack of parathyroid glands)
39. What is the most common mutation causing SCID (what is the most common mode of
inheritance)? Second most? What SCID mutation also gives you bare lymphocyte syndrome?
 γc cytokine receptor subunit (X-linked); thymus has lobules of undifferentiated epithelial cells
 Adenosine DeAminase (AR); thymus is small and devoid of lymphoid cells

Transcription factors required for MHC II expression
40. What is another name for Wiskott-Aldrich syndrome? What are the major defecits?
 Immunodeficiency with thrombocytopenia and eczema
[TIE the WhISK to ALDRICH]
 IgM low, poor protein antigen response
41. What is the result of a C1 inhibitor deficiency? What is the most common complement
deficiency? What is the result of late complement defciencies?
 Hereditary angiodema
 C2 – SLE-like symptoms
 Susceptibility to Neisseria infections (thin cell wall is normally vulnerable to complment)
42. What is the most common transmission route of HIV in the US?
 Heterosexual, male-to-female sex; same as in the rest of the world
 HIV-1 in the US and Europe, usually group M (Major), clade/subtype C
43. What three enzymes does HIV carry? What antibody is used for diagnosis? What are the three
principal genes? Which gene causes a 1000 fold increase in viral transcription?
 Protease, reverse transcriptase, and integrase
 p24, the major capsid protein
 gag, pol, and env
 tat
44. How does HIV infect cells (2 stages)? When does it lyse the cell?
 Uses CD4 as a receptor (thus targets mostly CD4+ T cells, as well as monocytes and dendritic
cells)
 Its gp120 must also bind to chemokine receptors like CCR5 to gain viral entry
i. “elite controllers” have chemokine receptor mutations
 replication and lysis occur when the cell is activated by NF-KB; integrated DNA is activated
too
45. How do noninfected cells die? What are two resevoirs of HIV, especially once most CD4+ cells
have died? What cells take an active role in spreading HIV from mucosal cells to lymph nodes?
 Lymphoid architecture gets wrecked, activation induced death, loss of immature precursors,
fusion of infected cells to unifected cells by gp120, CD8+ killing of CD4+ cells coated in gp120
 Macrophages are hardy and survive while allowing viral replication
 Dendrocytes
46. What happens to B cells in an HIV infection?
 They undergo profound activation, but still fail at immunity, because of some unknown
intrinsic deficiency coupled with lack of T cell assistance
47. What cells contain the infection in the acute phase? What is the best blood marker for the
extent of HIV progression? What marker tells you when to start antiretroviral therapy?
 HIV-specific CD8+ T cells, viral titer drops by about 12 weeks
 HIV-1 RNA levels
 CD4+ count is the best short-term indicator
48. What microbe causes pneumonia in the HIV+? When does chorioretinitis occur and what causes
it? What does HIV diarrhea look like and what microbes cause it?
 The fungus Pneumocystis jirovecii
 CD4+ counts below 50; caused by CMV; also causes esophagitis and colitis
 Chronic, profuse, watery diarrhea; protozoans like Cryptosporidium, Isopora belli, or
microsporidia; less commonly enteric bacteria Salmonella, Shigella, MAC
49. What vascular tumor occurs in AIDS patients? Give a couple of characteristics? How is it
different from the sporadic form clinically? What can it lead to?
 Kaposi sarcoma; spindle cells, slitlike vascular spaces; HHV8/KSHV
 More widespread—infects GI tract, lungs, lymph nodes, mucus membranes, and skin
 Body cavity based primary effusion lymphoma (B cell lymphoma) and multicentric Castleman
disease
50. Where are AIDS-related lymphomas most likely to strike? What factors encourage lymphomas
to occur? What other cancers are more likely to occur b/c of AIDS?
 Central nervous system (“primary CNS lymphoma” in chapter 28)
 EBV and IL-6
 Cervical and anal
CNS issues are described in chapter 28
51. What is it called when a person undergoes clinical deterioration while on HAART with increasing
CD4+ levels? Other general AIDS issues?
 Immune reconstitution inflammatory syndrome
 Lipoatrophy in the face, lipoacculmulation centrally, elevated lipids, insulin resistance,
peripheral neuropathy, and cardiovascular, kidney, & hepatic disease
52. Which kind of amyloid can be produced in the liver from serum amyloid associated protein
(SAA) during chronic inflammation? What kinds of amyloidosis is it associated with (2)?
 The amyloid fibril protein AA (amyloidosis associated)
 reactive systemic amyloidosis (Secondary amyloidosis), familial Mediterranean fever
53. What molecule in amyloid deposits complicates things for patients on hemodialysis? How does
it present? What amyloid form is deposited in familial amyloid[otic] [poly]neuropathies? What
else is amyloid made up of this molecule?
 Amyloid β2-microglobulin (Aβ2m)
i. present with carpal tunnel because of deposition on tendon sheaths
 transthyretin
 amyloid of aging
54. What is the most common kind of amyloidosis? When does it often occur?—be specific!
 Primary amyloidosis of immunocyte dyscrasias with amyloidosis
i. AL (amyloid light chain) form deposited
 Multiple myeloma, when Bence-Jones proteins with high “amyloidogenic potential” are
produced
55. When does reactive systemic amyloidosis occur?
 RA, IV drug abusers, or other connective tissue disorders like ankylosing spondylitis or IBS,
Hodgkin lymphoma, and renal cell carcinoma
i. AA form deposited
56. How do amyloid deposits appear when stained with Congo red and placed under polarized
light? What organ is most commonly affected in amyloidosis? What are the two patterns of
splenic amyloidosis?
 Green and birefrigent
i. [Immuno]Electrophoresis is more sensitive
 Kidney; subtle thickening of mesangium which progresses to narrowing of capillaries and
obliteration of the glomerulus
 Sago (tapioca granules) and lardaceous (maplike deposition)