Immune Flashcards
REQUIREMENTS OF AUTOIMMUNITY
● The presence of an immune reaction specific for some self antigen or self tissue
● Not secondary to tissue damage but is of primary pathogenic significance
● Absence of another well-defined cause of the disease
Diseases mediated by antibodies
Hemolytic anemia Thrombocytopenia atrophic gastritis of pernicious anemia Myasthenia gravis Graves disease goodpasture syndrome SLE
Diseases mediated by T cells
T1 DM Multiple sclerosis Rheumatoid arthritis Systemic sclerosis Sjogen sydndrome
Diseases postulated to be autoimmune
IBD Primary biliary cirrhosis Autoimmune hepatits Polyarteritis nodosa Inflammatory myopathies
Phenomenon of unresponsiveness to an antigen
induced by exposure of lymphocytes to that
antigen
IMMUNOLOGIC TOLERANCE
CENTRAL TOLERANCE:
Originates in the_______
primary lymphoid organs
Process where your immature T cells
express receptors specific to self
antigen. When these proliferate, they are
self reactive. The body kills these cells
through apoptosis
Negative Selection or clonal deletion
T cells (thymus)
stimulates expression of
some peripheral tissue restricted self
antigens in the thymus and is thus critical
for deletion of immature T cells specific
for these antigens
AIRE (autoimmune
regulator)
Cells are still intact but the receptor is
changed into another type so that the
potentially reactive lymphocyte will no
longer react to its own tissue.
● Receptor Editing
This occurs when self-reactive cells escape the
central lymphoid organs reaching the periphery
and so the mechanisms are also different.
PERIPHERAL TOLERANCE
The best-defined regulatory T
cells are___ cells that express high
levels of CD25, the α chain of the IL-2
receptor, and FOXP3,
CD4
Activation of antigen-specific T cells
requires two signals:
recognition of peptide antigen in association with self MHC molecules on the surface of APCs and a set of costimulatory signals (“second signals”) from APCs
binds ligand of T cell from your APC.
If this signal is absent or is unresponsive
there is no binding. This is failure to
respond
co-stimulatory signal (such as CD28),
HLA associated diseases
RA T1 DM Multiple sclerosis SLE Ankylosing spondylitis (100-200) Celiac disease
which
encode your tyrosine phosphatase and involved
in Rheumatoid Arthritis and Type 1 DM and
Inflammatory bowel disease
genes associated with your PTPN22
Best known for inflammatory bowel
disease.
- associated with crohn’s disease
NOD2
Polymorphisms in the gene encoding
the IL-2 receptor (CD25) are associated
with
Multiple sclerosis
antibodies against strep proteins
cross react with myocardial proteins and cause
myocarditis. The immune responses initially
directed against microbial antigens, also result in
activation of self-reactive lymphocytes. Aside
from attacking just the strep protein, it also
attacks own tissue
Rheumatic Heart Disease
Some viruses, such as EBV and HIV, cause _______, which may result
in production of autoantibodies.
polyclonal B-cell activation
T or F
infections promote low-level
IL-2 production, and this is essential for
maintaining regulatory T cells
T
In addition to infections, _____causes cell death and may lead to the
exposure of nuclear antigens, which elicit
pathologic immune responses in lupus; this
mechanism is the proposed explanation for the
association of lupus flares with exposure to
sunlight.
ultraviolet (UV)
radiation
T or F
Smoking is a risk factor for rheumatoid arthritis,
perhaps because it leads to chemical
modification of self antigens.
T
Autoimmune disease involving multiple organs,
characterized by a vast array of autoantibodies,
particularly antinuclear antibodies (ANAs), in
which injury is caused mainly by deposition of
immune complexes and binding of antibodies to
various cells and tissues
SYSTEMIC LUPUS ERYTHEMATOSUS
In SLE, injury to the _____________ is prominent.
The disease is very heterogeneous, and any
patient may present with any number of these
clinical features
skin, joints, kidney, and serosal
membranes
SLE is a Type___Hypersensitivity Reaction
III
Clinical/immunologic criteria: (this is important to
the diagnosis of SLE) cutaneous lupus ____(acute) & ____ (chronic).
malar rash; discoid rash
A RASH POINT MD
Mnemonic: A RASH POINT MD
● Arthritis
● Renal disease, ANAs, Serositis, Hematological
disorders
● Photosensitivity, Oral Ulcers, Immunological
Disorders, Neurological Disorders
● Malar Rash, Discoid ulcers
For a patient to be classified having SLE you need to have ______ both have clinical and
immunological.
4/11 of criterion
The hallmark of SLE is the production of
autoantibodies, several of which (_________) are virtually diagnostic
antibodies to
double-stranded DNA and the so called Smith
[Sm] antigen
ANA’s. These are directed against nuclear Ag
and can be grouped into four categories based
on their specificity for:
○ DNA
○ Histones
○ Non histone proteins bound to RNA
○ Nucleolar Ag
is the most
widely used method for detecting ANA, which can
identify Ab that binds to a variety of nuclear Ag.
The pattern of nuclear fluorescence suggests the
type of Ab present in a patient’s serum
Indirect Immunofluorescence
● Antibodies to chromatin, histones and
occasionally, double stranded DNA
● Most specific
Homogenous or diffuse nuclear staining
Most often indicative antibodies to double
stranded DNA and nuclear envelope proteins
Rim or peripheral staining
● Presence of uniform or variable-sized speckles
● Most commonly observed patterns of
fluorescence and therefore the least specific
● Antibodies to non-DNA nuclear constituent such
as Sm antigen(SLE), ribonucleoprotein (SLE and
others) and SS-A and SS-B (Sjogren)
Speckled pattern (
● Antibodies specific for centromeres (Systemic
sclerosis, Sjogren)
● Stain Ab to centromere
Centromeric pattern
● Ab to RNA
● Presence of few discrete spots of fluorescence
within the nucleus.
● Most often in patients with systemic sclerosis
Nucleolar pattern
SLE- most specific is _______ and also
associated with _____.
Generic ANA involved there are 95 to 100
percent positive for SLE, but the problem for this
is not specific. Sm antigen there is 20-30 percent
positive
Sm antigen; Antiphospholipid syndrome
is specific for CCP (cyclic
citrullinated peptides)
Rheumatoid arthritis
The fundamental defect in SLE is a failure of the
mechanism that maintains___________
self-tolerance
T OR F
Lack of your complement may impair removal
of circulating immune complexes by
mononuclear phagocyte system and since they
are not removed, favoring deposition in the
tissues, leading to tissue anergy
T
T or F
There is a higher rate of concordance (>20%) in
monozygotic twins when compared with
dizygotic twins (1% to 3%).
T
Specific alleles of the _______ locus have been
linked to the production of anti–double-stranded
DNA, anti-Sm, and antiphospholipid antibodies,
although the relative risk is small
HLA-DQ
play a role in lymphocyte
activation in SLE.
Type I interferons
-are antiviral
cytokines that are normally produced during
innate immune responses to viruses.
T or F
The autoantibodies in
SLE show characteristics of T cell-dependent
antibodies produced in germinal centers, and increased numbers of follicular helper T cells
have been detected in the blood of SLE patients.
T
TLR engagement by nuclear DNA and RNA
contained in immune complexes may activate______
B lymphocytes
Drugs such as ___________can induce an SLE- like
response in humans
hydralazine, procainamide, and
D-penicillamine
● Most common mechanism of tissue injury
● DNA and anti-DNA complexes deposit in the glomeruli and small blood vessels, and they go into tissues resulting in a low level of serum
complement. Because they are deposited in
glomeruli and other tissues
Deposition of Immune complexes (Type 3
Hypersensitivity
Most common disorder caused is Immune Thrombocytopenic Purpura (ITP)
Autoantibodies specific for RBCs, WBCs and
platelets (Ab-mediated type 2 hypersensitivity)
● Secondary APS
● Venous and arterial thrombosis associated with
recurrent spontaneous miscarraige and focal
cerebral or ocular ischemia
Antiphospholipid antibody Syndrome (APS)
Antibodies cross the BBB and react with
receptor or neuron for various neurotransmitter
● Cytokine may involved in cognitive dysfunction
Neuropsychiatric manifestations
Nuclei of damaged cells
react with your ANAs, they lose their chromatin
and become a homogenous material to produce_______
LE body
Usually seen in blood vessels and usually
manifested as thrombosis (venous or arterial) or
vasculitis. Mechanism for patients with recurrent
miscarriages because of antiphospholipid
antibodies.
Antinuclear Antibodies
In SLE, the most clinical involvement is the ____
Kidney (50% of SLE patients)
Class 1 glomerular patterns
-is very uncommon and is characterized by immune complex deposition in the mesangium
Minimal mesangial lupus nephritis
-No infiltrates yet but Mesangial deposits are present by IgG (granular type)
Class 2 glomerular patterns
MESANGIAL PROLIFERATIVE LUPUS
NEPHRITIS
Class 1 are identified by ______
IF and EM
● Mesangial proliferation often with accumulation
of mesangial matrix and granular mesangial
deposits of immunoglobulins and complement
● No involvement of capillaries
Class 2 Mesangial proliferative lupus nephritis
Class 3 glomerular patterns
Focal lupus nephritis
● <50% glomeruli involved (segmental-portion or
global-affects whole)
● Endothelial and mesangial cell proliferation
● Leukocyte accumulation
● Capillary necrosis and hyaline thrombi
● Extracapillary proliferation
● Crescent formation
● With hyaline thrombi (pink material) meaning
there is involvement of capillaries
Class 3: Focal lupus nephritis
The clinical presentation ranges from mild hematuria and proteinuria to acute renal insufficiency.
Class 3: Focal lupus nephritis
Class 4 glomerular patterns
Diffuse lupus nephritis
● Most common type
● Severe form
● >50% glomerular involvement
CLASS 4 : DIFFUSE LUPUS NEPHRITIS
● Endothelial, mesangial and epithelial cell
proliferation
● Crescent formation
● “Wire loop” lesion - subendothelial deposits
CLASS 4 : DIFFUSE LUPUS NEPHRITIS
Class 5 glomerular patterns
MEMBRANOUS LUPUS NEPHRITIS
● Same with class 4
● PAS stain, capillaries are well distinct because of
thickening
● This patient has severe proteinuria
● Diffuse thickening of capillary walls due to
subepithelial deposits
CLASS 5: MEMBRANOUS LUPUS NEPHRITIS
The immune complexes are usually accompanied by increased production of basement membrane-like material.
Class 5: membranous lupus nephritis
Class 6 glomerular patterns
ADVANCED SCLEROSING NEPHRITIS
● >90% glomerular involvement ● End-stage renal disease ● With lots of fibrosis and fibrinoid necrosis of tubules and arterioles, ● Kidneys are not functional anymore
CLASS 6: ADVANCED SCLEROSING NEPHRITIS
TUBULOINTERSTITIAL LESION
● Immune complexes in tubular or peritubular
capillaries
● Well-organized B cell follicles in the interstitium
Thick capillary loop no longer delicate so this
produces characteristic wire loop lesions so as
you can see here is quietly thick already
SLE
In SLE, there is vacuolar degeneration of basal layer in this area
Epidermis
In SLE, variable edema and perivascular
inflammation occur in this area
Dermis
endocarditis associated with the
use of steroids
Libman sacks endocarditis
T or F
Vegetation in infective endocarditis are
smaller and confined to the lines of closure of the
valve leaflets
False
Vegetation in Rheumatic heart disease are
smaller and confined to the lines of closure of the
valve leaflets
In SLE, Central penicilliary arteries show concentric
intimal and smooth muscle cell hyperplasia
producing _________
Onion-skin lesions
● Skin manifestations of SLE but rare systemic
manifestations
● Skin plaques with varying degrees of edema,
erythema, scaliness, follicular plugging and skin
atrophy surrounded by an erythematous border
● (+) generic ANAs, (-) anti-dsDNA
CHRONIC DISCOID LUPUS ERYTHEMATOSUS
CHRONIC DISCOID LUPUS ERYTHEMATOSUS:
IF: _____ deposition at dermoepidermal
junction
Ig and C3
● Intermediate between SLE and chronic discoid
lupus
● Predominant skin involvement
● Skin rash is widespread, superficial and nonscarring
● Mild systemic symptoms consistent with SLE
● (+) anti-SSA and HLA-DR3 phenotype
SUBACUTE CUTANEOUS LUPUS
ERYTHEMATOSUS
● Induced by: Hydralazine, procainamide, isoniazid
and D-penicillamine
● Anti-TNF therapy
+ anti-histone antibodies
DRUG-INDUCED LUPUS ERYTHEMATOSUS
● chronic inflammatory disease that involves the
joints with subsequent involvement of the extra
articular tissues such as the skin, blood vessels,
lungs, and heart
RHEUMATOID ARTHRITIS
● Chronic disease characterized by:
1) dry eyes (keratoconjunctivitis sicca
(2) dry mouth (xerostomia)
SJOGREN SYNDROME
aka Sicca syndrome
Primary sjogen syndrome
