Ch 6 Slides Part 2 - Guerin Flashcards
1
Q
What is the mechanism of central tolerance for T cells?
A
Negative selection or deletion
2
Q
What are the immune-privileged sites?
A
Testis
Eye
Brain
3
Q
What HLA type is associated with Ankylosing spondylitis
A
B27
4
Q
What are 2 methods by which infections induce autoimmunity?
A
Costimulation on APSc
Molecular mimicry
5
Q
What is the classic example of molecular mimicry?
Causes what?
A
Rheumatic heart disease
Myocarditis
6
Q
Most autoimmune disease are caused by what?
A
Excessive Th1 and Th17 responses
7
Q
What group of people is most common to develop SLE?
A
Women
African American and Hispanic > White
8
Q
What ANAs are specific for SLE?
A
dsDNA
Sm antigen
9
Q
What antibodies are diagnostic for Sjogren syndrome?
A
Ro/SS-A
La/SS-B
10
Q
Antiphospholipid antibodies are found in what % of lupus patients?
Has what false positive?
Induces what state?
A
30-40%
Syphilis
Hypercoagulable state (INC PTT)
11
Q
What environmental factors induce SLE?
A
UV light
Sex chromosomes
Hydralazine, procainamide, D-penicillamine
12
Q
What are the blood vessels like in patients with SLE?
A
Acute necrotizing vasculitis involving capillaries, small arteries, and arterioles
13
Q
What are the joints like in patients with SLE?
Opposite of what?
A
Non-erosive synovitis with little deformity
RA
14
Q
Glomerular lesions are the result of what?
A
Immune complex deposition
15
Q
What is the most common and severe form of lupus nephritis?
A
Diffuse lupus nephritis (Class IV)
16
Q
What kind of effusions may be present with SLE?
A
Pleural and pericardial effusions
17
Q
What cardiovascular system effects are present with SLE?
A
Myocarditis
CAD
Valvular (Libman-Sacks) endocarditis
18
Q
What other organs are involved in SLE?
A
CNS
Spleen
Lungs (effusions), fibrosis secondary pulmonary HTN
19
Q
What are signs of renal involvement in SLE?
A
Hematuria, proteinuria, nephrotic syndrome
20
Q
What are the causes of death in SLE?
A
Renal failure
Infections
CAD
21
Q
How does chronic discoid lupus Erythematosus present?
A
Skin manifestations, rarely systemic
Skin plaques with erythema, scaliness, edema
Face and scalp usually
22
Q
How is subacute cutaneous Lupus distinguished from chronic discoid LE?
A
Skin rash is widespread, superficial, non-scarring
Mild symptoms
23
Q
What drugs induce lupus syndrome?
A
HIPD hydralazine Isoniazid Procainamide D-Penicillamine
24
Q
What organs are NOT affected in drug-induced LE?
A
Renal
CNS
25
What is Sjorgren characterized by?
Occurs bc of what?
```
Dry eyes
Dry mouth (xerostomia)
```
Immunologically mediated destruction of lacrimal and salivary glands
26
What are some clinical features of Sjogren?
Blurring of vision, burning, itching
Difficulty in swallowing solid foods, Dec ability in taste
Parotid gland enlargement
Epistaxis
27
What is the best way to diagnose Sjogren syndrome?
Biopsy of the lip to examine minor salivary glands
28
What kind of pathology may develop from Sjorgren syndrome?
Dominant B-cell clone and marginal zone lymphoma
29
What characterizes systemic sclerosis (Scleroderma)?
Chronic inflammation via autoimmunity
Widespread damage to blood vessels
Progressive interstitial and perivascular fibrosis in the skin
30
What are the Clinical features of scleroderma?
F to M ratio of 3:1
Peak incidence of 50-60 y/o
Cutaneous changes
Raynaud, dysphagia, respiratory difficulty, myocardial fibrosis, mild proteinuria
31
What are the symptoms of patients with limited scleroderma?
```
CREST
Calcinosis
Raynaud
Esophageal dysmotility
Sclerodactyly
Telangiectasia
```
32
What disease often affects middle-aged and older men and is 1st characterized in autoimmune pancreatitis?
IgG4 Related Disease
33
What is Mikulicz syndrome?
Associated with what?
Enlargement and fibrosis of salivary and lacrimal glands
IgG4
34
What characterizes IgG4 disease?
Storiform fibrosis
Obliterative phlebitis
INC serum IgG4
35
The Direct pathway uses what molecules?
Class I MHC
| Class II MHC
36
The indirect pathway of recognition of alloantigens involves what cells?
B cells -> Abs -> endothelial injury
37
What characterizes acute cellular rejection?
Commonly seen when?
Increased vascular permeability, local accumulation of mononuclear cells
With initial months after transplantation
38
What characterizes chronic rejection?
Lymphocytes react against alloantigens in the vessel wall
Secrete cytokines that induce local inflammation
39
What mediates acute cellular and chronic rejection?
T-cells
40
Hyperacute rejection occurs when?
Develops in who?
Preformed antidonor antibodies are present
Previous transplant, prior blood transfusions, multiparous women
41
Acute antibody-mediated rejection occurs when?
What is the initial targets of these antibodies?
Antidonor antibodies produced after transplantation
Graft vasculature
42
Chronic antibody-mediated rejection develops how?
Affects what?
Insidiously
Vascular components
43
What alleles are matched for kidney transplants?
HLA-A, HLA-B, HLA-DR
44
What is allele matching not done for?
Liver, heart, lungs
45
What drugs are given for immunosuppressive therapy?
Steroids
Mycophenoalte mofetil
Tacrolimus (FK506) - inhibits T cell functions
46
In kidney transplant recipients what virus can reactivate and infect renal tubules, may even cause graft failure?
How to stop?
Polyoma virus
Reduce immunosuppresion
47
Immunosuppressed individuals are susceptible to what latent viruses?
EBV-induced lymphomas
HPV-induced squamous cell carcinomas
Kaposi sarcoma (HHV8)
48
What organs can be transplanted?
Kidney is the most
Also liver, heart, lungs, pancreas
49
When is GVHD most commonly seen?
HSC transplantation
50
Patient presents with a rash and diarrhea after weeks of allogenic bone marrow transplantation, what is going on?
Acute GVHD
51
What are the major organs affected from acute GVHD?
Immune system, skin, liver, and intestines
52
What characterizes chronic GVHD?
Extensive cutaneous injury
| Chronic liver disease
53
What mediates GVHD?
T lymphocytes from the donor
54
Depletion of donor T cells before transfusion eliminates GVHD but leads to what?
Recurrence of tumor in leukemia patients
Increased incidence of graft failure
Increased rates of EBV-related B-cell lymphoma
55
SCID affects what immune responses?
Presents in who with what?
Humoral and cell-mediated
Infants present with thrush, extensive diaper rash, failure to thrive, rash (GVHD)
56
What severe infections are SCID patients susceptible to?
PPV w/your CC
Pneumocystis jiroveci
Pseudomonas
Varicella
Candida albicans
CMV
57
What inheritance is most common in SCID?
X-linked
58
What is the major defect in X-linked Agammaglobulinemia?
Aka what?
Failure of B-cell precursors (pro and pre) to develop into mature B cells
Bruton
59
What are the characteristics of X-linked Agammaglobulinemia?
B cells absent or very low in circulation
Serum levels of all Igs low
NO plasma cells
Apparent after 6 months
60
What bacterial infections are common in X-linked Agammaglobulinemia?
HSS
Haemophilus influenzae Streptococcus pneumoniae
Staphylococcus aureus
61
What viruses are common in X-linked Agammaglobulinemia?
```
PECG
Poliovirus
Enterovirus (echovirus)
Coxsackievirus
Giardia lamblia
```
62
35% people with X-linked Agammaglobulinemia develop what?
Arthritis and dermatomyositis
63
DiGeorge Syndrome is due to what?
Deficiency in what?
What chromosome abnormality?
Failure of 3rd and 4th pouches
T-cells
22q11 deletion
64
Sx of DiGeorge Syndrome?
Poor defense against fungal and viral infections
Hypocalcemia -> tetany
Congenital defects of heart and great vessels
Abnormal facial and ear appearance
65
What characterizes Hyper-IgM syndrome?
Defect in what?
Make IgM, cannot make any others
T helper cells cannot deliver activating signals to B cells and macrophages
66
What kind of inheritance with Hyper-IgM syndrome?
Patients present with what type of infections?
X-linked (70%) or autosomal recessive
Pyogenic infections or Pneumocystis jiroveci pneumonia (CD40L mutation)
67
CVID is characterized by what?
Normal B cells that are unable to differentiate into plasma cells
68
Isolated IgA deficiency is common in whom?
Susceptible to what problems?
European descent (1 in 600)
Sinopulmonary infections and diarrhea
69
Patients transfused with IgA-containing blood can develop what?
Anaphylactic reactions because the IgA behaves like foreign
70
What disease is associated with thrombocytopenia, eczema, and recurrent infection?
Is also X-linked
Wiskott-Aldrich syndrome
71
What autosomal-recessive disease is associated with Telangiectasia, neurologic deficits and increased incidence of tumors?
Ataxia Telangiectasia
72
What can cause secondary immunodeficiency?
```
Malnutrition
Chemotherapy
Irradiation
Infections
Cancers
```
73
Globally what is the most common mode of transmission of HIV?
Heterosexual contacts
74
What major capsid protein is the most abundant viral protein and what test is used to diagnose HIV infection?
P24
ELIZA
75
What is contained in the virus core?
P24
2 copies viral RNA
Protease, reverse transcriptase, integrase
76
What is the virus core of HIV surrounded by?
Matrix protein p17
77
What studs the viral envelope?
gp120 and gp41
78
What does HIV first infect?
What do they all have?
T cells
DCs
Marcophages
CD4
79
The M-tropic strain preferentially infects what?
What strain and chemokine receptor?
Monocyte/macrophage
R5 strain
CCR5
80
The T-tropic strain uses what strain and chemokine receptor?
X4
| CXCR4
81
HIV infects what?
Memory and activated T cells
82
What is the active form of enzyme in the HIV genome?
What viral protein binds this?
APOBEC3G
Vif
83
What viral gene in HIV-1 infects macrophages?
Vpr
84
HIV infects what in the brain?
Macrophages and microglial cells
85
Acute retroviral syndrome occurs when?
What are the symptoms?
3-6 weeks after infection
Sore throat, myalgias, fever, weight loss, fatigue
Rash, cervical adenopathy, diarrhea, vomiting
86
Where are the sites of continuous HIV replication and cell destruction?
LNs
| Spleen
87
How does HIV evade immune detection?
Destroys CD4+ T Cells
Antigenic variation
Down-modulates class I MHC
Can use CXCR4 or CCR5 to enter cells
88
Immune reconstitution inflammatory syndrome may occur with what?
HAART treatment
89
What are the adverse side effects of HAART?
```
Lipoatrophy
Lipoaccumulation
Elevated lipids
Insulin resistance
Peripheral neuropathy
Premature cardiovascular, kidney, liver disease
```
90
Hemodialysis associated Amyloidosis as what major fibril protein?
What precursor protein?
What disease?
Abeta2m
Beta2-microglobulin (Class I MHC)
Chronic renal failure
91
Reactive systemic Amyloidosis has what major fibril protein associated with it?
What precursor protein?
What associated disease?
AA
SAA
Chronic inflammatory condition
92
Primary Amyloidosis has what major fibril protein?
What precursor protein?
What associated diseases?
AL
Ig light chains (lambda)
Multiple myeloma
Monoclonal plasma cell proliferates
93
Type 1 Diabetes and M.S. Are what kind of diseases?
Organ-specific
