Immunology III Flashcards
What is an Autoimmune disorder of Connective Tissue
caused by Activated Fibroblasts?
Scleroderma
*Fibroblasts > Collagen can’t stop won’t stop
What is an ANA?
Anti-nuclear Antibody
*diagnosis of autoimmune disorders
but “not diagnostic of any”
**higher titer, worse the disease
What 3 antibodies are specific to Scleroderma?
Name 1 factor commonly present in Scleroderma that is also seen in another disease.
Nucleolar
Anti-DNA topoisomerase Scl-70 (nonhistone, 70% of patients)
Anticentromere
Rheumatoid factor
What is Progressive System Sclerosis?
Scleroderma
What are the most common organs affected by Progressive System Sclerosis (Scleroderma)?
GI tract, heart, kidneys, muscles, lungs
T/F
Scleroderma limits itself to certain organs.
False.
Many organs involved
What autoimmune disorder begins with Raynaud phenomenon (distal ischemia)?
Scleroderma
*this can lead to auto-amputation
What often causes sudden death in Scleroderma?
Ventricular arrhythmias
What is the milder form of Scleroderma called?
CREST syndrome
What are the 5 features of CREST?
C Calcinosis R Raynaud Phenomenon E Esophageal dysfunction S Sclerodactyly T Telangiectasia (capillary dilation/purple clusters)
What are 2 Autoimmune diseases of the muscle?
note: they are chronic inflammatory myopathies
Polymyositis
Dermatomyositis
What virus has been implicated in Polymyositis/Dermatomyosits?
Picornaviruses
What are the most specific antibodies associated with Polymyositis/Dermatomyositis?
anti-Jo-1
*an MSA (myositis specific antibody)
What is Heliotropic Rash specific to?
note: this is humorally-mediated
Dermatomyositis eyelids
*no angiopathy in Polymyositis
What are Anti-centromeric antibodies associated with?
Both Scleroderma and CREST
Why are Polymyositis/Dermatomyositis considered to by paraneoplastic syndromes?
Esp. in men over 50, 3/4 with Polymyositis/Dermatomyositis already have cancer (or will within a year)
What cancers are most associated with Polymyositis and Dermatomyositis in men and women?
Men: Lung, colon, stomach
Women: Breast, ovaries, uterus
What 2 Autoantibodies are diagnostically definitive for Lupus?
Anti double stranded DNA (native DNA)
Anti Smith
*Rim and Speckled (diffuse also seen)
What does SLE stand for?
Systemic Lups Erythematosus
SLE affects all organs, but preferentially targets…
Kidneys
Serousal membranes
Joints
Skin
What are two risk factors involved in SLE?
Female sex hormones
Familial correlation
What is the staining pattern of a homogenous, non-specific ANA?
Diffuse
What is the staining pattern of Anti-double stranded DNA seen in SLE?
Rim
What is the staining pattern of the antibody to extractable nuclear antigens seen in Mixed Connective Tissue Disorder?
Speckled
What is the staining pattern seen in PSS (Progressive Systemic Sclerosis)?
Nucleolar
What staining pattern is seen for the antibody in CREST syndrome?
Centromeric
*Which of the following types of Lupus Glomerulonephritis is mildest with an excellent prognosis?
Mesangial Lupus
How does SLE manifest on the skin?
Butterfly on face
How does SLE affect serous membranes?
1/3 have pleuritis with pleural effusion
What causes changes in the brain in Lupus?
Interstitial fibrosis
Vasculitis leads to hemmorrhage and infarction
What type of carditis is involved in Lupus?
Pancarditis.
pericarditis - most common
endocarditis
myocarditis
(nonbacterial vegetations (Libman-Sacks Endo) in latter two)
What autoantibodies are prevalent in Drug-Induced Lupus?
Anti-Histone Antibodies
DS-DNA and SM antigen UNusual
What autoimmune Syndrome is characterized by dry eyes and dry mouth (keratoconjunctivitis and xerostomia), often secondary to SLE and RA?
Sjogren Syndrome
What condition is marked by the lack of all immunoglubulin in the blood?
Agammaglobulinemia of Bruton
What type of disorder is Agammaglobulinemia of Bruton?
Congenital X-linked
What types of infections are handled well in pts with Agammaglobulinemia of Bruton?
Most viral/fungal
What gene and enzyme is broken in congenital x-linked Agammaglobulinemia of Bruton?
Xq21
B-cell Tyrosine Kinase
(ATK)
*critical for the maturation of B-cells
What types of infections are common in Agammaglobulinemia of Bruton?
What is the treatment for the disease?
Bacterial
Replacement of all immunoglobulins
When is Agammaglobulinemia of Bruton first observed?
5-8 months, when maternal antibodies wear out, usually with Pyogenic Infections
What causes RA-like conditions in x-linked agammaglobulinemia of Bruton pts?
Mycoplasma
What is another name for Swiss-type Agammaglobulinemia?
What does it affect?
Severe Combined Immunodeficiency
T and B cells
What are the two types of Severe Combined Immunodeficiency?
Treatment?
X-linked (more common)
Autosomal recessive
Bone marrow transplantation
(this is boy in the bubble)
What is embryologically defective in DiGeorge Syndrome?
3rd and 4th pharyngeal pouches
*Thymus and Parathyroids
hypocalcemia and tetany prevalent b/c no parathyroids
What cell is completely lacking in DiGeorge syndrome?
T-cells
no thymus
What are the internal and external manifestations of DiGeorge’s?
Internal: interrupted aortic arch, microencephaly
External: Low set ears, cleft lips
T/F
DiGeorge’s pts have a good response to Fungal and Viral infections.
False
complete lack of T-cells
What are the 4 main receptors on the HIV virus?
gp 120 (lollipop) gp 41 (lollipop stick)
p17 (outer)
p24 (inner)
What is the most common cause of meningitis in AIDS patients?
Cryptococcus
a fungus
What cells are affected in HIV?
these cells carry HIV
CD4 T-helper cells
What type of virus is HIV?
RNA retrovirus
What is the most common cause of death in AIDS patients?
Pneumocystis
What increases the transmission of HIV?
co-existing STI’s
male to female (not female to male)
anal sex
T/F
Breast milk cannot transmit HIV.
False
What are the 3 neoplasms of HIV?
Kaposi sarcoma
B-cell non-Hodgkin lymphoma (Primary lymphoma of brain)
Invasive caner of uterine cervix
What is the presumptive and definitive test for HIV?
ELISA - presumptive
Western Blot - definitive
What antibody is bound in Enzyme-Linked Immunosorbent Assay?
IgG
What test for HIV involves Acrylamide gel electrophoresis and measures HIV antibodies binding to separated viral proteins?
Western Blot
What CD-4 level do opportunistic infections usually begin to occur?
Below 200
What are some of the viruses that act synergistically with HIV?
How is this manifested?
HHV-8 (Kaposi’s Sarcoma)
HPV (Cervical cancer)
Microglial nodules with multinucleated giant cells in HIV are indicative of what?
AIDS Encephalopathy
What are some of the Parasites of concern with AIDS pts?
Pneumocystis carinii (protozoan causes pneumonia)
What are the most common viral infections of the brain in patients with HIV?
Herpesvirus
Cytomegalovirus
Name 4 parasites commonly found in AIDS patients.
Toxoplasmosis (brain)
Pneumocystis carinii (lungs)
Cryptosporidium (GI)
Isospora (GI)
Name 4 Fungi commonly affecting AIDS patients.
Cryptococcus
Histoplasma
Aspergillus
Candida
What makes up the Acute phase of AIDS?
What timeframe?
Initial spike of virus leveling at about 9 weeks
How long is the typical chronic phase of clinical latency?
9 weeks to 9 or 10 years
At what T-cell level does a patient go from HIV to AIDS?
What does the CDC call this?
200 CD4 T-cells/mm3
CDC group 4
Aseptic meningitis occurs on what percentage of cases?
When does this occur?
10%
within 1-2 weeks of seroconversion (contracting virus)
When do the lymph nodes become infected with the HIV virus?
When do they involute?
Initial seeding comes from acute spike
(HIV replication continues in nodes throughout chronic phase)
Involution in Crisis phase
What invasive fibrillar condition causes atrophy through pressure to adjacent tissue?
Amyloidosis
What is the makeup of Amyloid tissue?
95% Fibrillar
5% Glycoproteins
arranged into beta-pleated sheets
What is the cause of Amyloidosis?
Immune system pathology/abnormality -or-
Abnormal response to Chronic Infection
What are the 2 types of Amyloid and their derivations?
AL Amyloid: antibody light chains from neoplastic B-cells
(cancers like lymphoma/multiple myeloma)
AA Amyloid: Liver
AA Amyloid (from the liver) is produced in response to what 4 things?
Infections - TB
Inflammations - Alzheimers, RA, Inflammatory Bowel
Neoplasms - Renal cell carcinomas
I.V. drug use
T/F
Amyloid is a type of cancer.
False
This tissue doesn’t invade so much as compress.
Amyloid biopsies are analyzed using what stain?
What does this look like under light microscopy?
Polarized light?
Congo Red
Red
Apple-green birefringence
Name 3 Granulomatous causes of fever.
Sarcoidosis Crohn's Disease Giant Cell (temporal) Arteritis
What class of drugs is associated with Neuroleptic Malignant Syndrome? examples?
Anti-psychotics and neuroleptics
Thorazine, Haloperidol, Metoclopramide
If a FUO (fever of unknown origin) is present, what organ systems are most likely?
Respiratory
Urinary
Skin
Soft Tissue
(these make up 80% of infections)
Any substance causing a fever is called?
a Pyrogen
In what 2 ways do bacteria cause fever?
Directly - bacterial pyrogens
Indirectly - Cytokines
What are the dominant cytokines that cause fever?
IL-1, 2, and 6
TNF
What mediates Cytokine action in the Hypothalamus?
the hypothalamus synthesizes this in response to cytokines
Prostaglandins (PGE-2)
What directly affects the hypothalamic thermoregulatory center?
PGE-2
prostaglandin
How does aspirin block fever?
Inhibits IL-1 from making PGE-2 in hypothalamus
What type of bacteria release endotoxins?
Gram negative
What substance in gram negative bacteria make up endotoxin?
LPS - lipopolysaccharide
What does the complex of LPS/LPS binding protein in serum bind to?
Toll-like receptors
*on WBC’s/tissues. This releases inflammatory mediators
What do Toll-Like receptors do?
Release Inflammatory Cytokines
What is another name for fever?
Pyrexia
Neoplasms in what areas most often cause fever?
Blood, Lymph, Kidney, Liver, Brain
Systemic Inflammatory diseases are either _____ or ______.
Autoimmune
Granulomatous
T/F
Sickle cell, seizure, dehydration, and gout can all cause fever.
True
Name on enterotoxin that cause fever.
St aureus
What 3 cytokines stimulate the production of PGE-2?
IL-1, IL-2, and TNF
What causes Septic shock?
LPS from Gram Negative bacteria
Gram Positive Fungi
*over 100k deaths/yr in ICU’s
What are the most common Gram negative bacteria causing Septic shock?
(probably not on test)
E.coli Proteus Serratia Pseudomonas K. pneumoniae Bacteroides
T/F
Abnormal hypothalamic function is a common cause of fever.
False
very rare
What is an autosomal dominant skeletal muscle condition involving hypothalamic dopamine inhibition that causes increased temperature in response to Halothane or Succinylcholine?
This presents with muscle breakdown (rhabdomyoloysis) and rigidity.
Malignant Hyperthermia
Band neutrophils at 12-15k WBC/mm3 suggest what?
Leukocytosis/Acute inflammation
An amorphous eosinophilic hyaline-appearing extracellular substance:
Amyloidosis
What type of deposit is typical in Alzheimer’s Disease?
Amyloid
What is the most common organ affected by amyloidosis (causes most deaths)?
What is the general features of gross examination on all organs?
Kidneys (all nephrons affected)
Waxy, pale
What is often the 1st symptom in Amyloidosis?
Proteinuria
Nephrotic Syndrome 70% pts
Why don’t AIDS pts die of bacterial infections?
B-cell humoral immunity remains intact.
What are the two HIV types?
What is most common in the US?
HIV-1 and HIV-2
HIV-1 in US
HIV-2 in Africa
Pneumocystis in AIDS patients is caused by what?
a fungus
What blood product used by hemophiliacs transmitted HIV?
Factor 8
What is the risk of accidental seroconversion with HIV?
Hep B?
0.3%
30%
HIV preferentially infects T-helper lymphocytes, but also infects what other cells?
Monocytes (macrophage) Dendritic cells (fixed macrophage) Microglial cells (brain macrophage)
What is a common fatal tumor in AIDS patients?
B-cell Non-Hodgkin’s Lymphoma
from brain
Kaposi Sarcoma is caused by an ______ that is activated in endothelial cells in the small bv’s.
Oncogene
HIV and EBV may also act as oncogenes
A disease affecting the lymph nodes is…
Lymphadenopathy
Why does the last stages of AIDS almost never contain granulomas?
No immune cells
What is the only organ that shows HIV-specific changes?
Brain
AIDS Encephalopathy - microglial response
What presents as dementia in AIDS patients?
HIV Subacute Encephalitis
What is the disease of the spinal cord found in 20-30% of AIDS pts resembling B12 deficiency?
Vacuolar Myelopathy
What are the 2 neurologic manifestations of AIDS in children?
Microencephaly
Spasticity
DiGeorge Syndrome, aka…
Thymic Hypoplasia
What is the chromosome and gene affected in DiGeorge?
22
TBX1
note: this is 90% cases, other 10% autosomal dominant
What is a treatment for DiGeorge’s?
Thymic or Marrow transplant
What causes Chronic Mucocutaneous Candidiasis?
Congenital lack of T-cell function
T/F
Only males have Agammaglobulinemia of Bruton
True
*Remember, this is a B-cell disorder
What is the gene and chromosome defect in Agammaglobulinemia of Bruton?
Xq21 (Tyrosine Kinase ATK)
X chromo
What is the most common primary immunodeficiency?
Selective IgA
What disease results in hypogammaglobulinemia from failure of B-cells to mature (by defect or improper T-cell signaling)?
Common Variable Immunodeficiency (CVID)
What is the classic triad of Wiskott-Aldrich Syndrome?
Thrombocytopenia
Infections
Eczema
Describe platelets in Wiskott-Aldrich Syndrome
Small in number
Small in morphology
What antibody is absent or low in WAS?
What cures WAS in 90% cases?
IgM
Marrow transplant
What is the Boy in the Bubble disease?
What enzyme is lacking?
Treatment?
Severe Combined Immunodeficiency
ADA - adenosine deaminase
Bone marrow transplantation
What does a titer measure?
The dilution at which detectable
What is the second most common autoimmune disorder that destroys the lacrimal and salivary glands?
Sjogren Syndrome
What antibodies are present in Sjogren’s?
SS-A
SS-B
also Rheumatoid factor
If diagnosed with Sjogren’s Syndrome, the risk of _____ increases 40x.
Lymphoma
What combines some features from SLE, Scleroderma, and RA?
Mixed Connective Tissue Disease
MCTD
What ANA’s are present in Mixed Connective Tissue Disease?
UI-RPN
Uridine-rich ribonucleoprotein
