Intro to disorders of immunity Flashcards
Type I hypersensitivity is mediated by __, and starts within a half hour
Types __ and __ are antibody (or Ab-Antigen complex) mediated HSRs that take about __
Type __ is __ mediated and starts within 2-3 days
Type I hypersensitivity is mediated by IgE, and starts within a half hour
Types II and III are antibody (or Ab-Antigen complex) mediated HSRs that take about 8 or less hours
Type IV is cell mediated and starts within 2-3 days
Type I HSR is __ mediated and involves allergens. Describe the sequence of events involved in the Type I HSR.
IgE
(see image below)
Describe the initial phase of the Type I HSR and the late phase of the Type I HSR
Initial: starts w/in 30 mins post exposure (ends w/in 60 mins); IgE-Antigen binding >> Mast cell activation >> Histamine release
Late: w/in 24 hrs and may last days; other symptoms follow (chemokines, leukotrienes released >> inflammation + tissue damage)
The most severe Type I HSR is ___, which can be characterized by ___. Another reaction is __ (you have this)
Anaphylaxis
Laryngeal edema
Asthma
Examples of localized Type I HSRs include ___ (hay fever) and __, which arises from cross-linking of IgE on GI mast cells
Examples of localized Type I HSRs include allergic rhinitis (hay fever) and food allergies, which arise from cross-linking of IgE on GI mast cells
Describe the sequence of events resulting in asthma (Type I HSR)
(see image)
The Type II HSR involves which type of cells? Describe the sequence of events that occurs in Type II HSR.
Which 2 disease processes are examples of Type II HSR?
Circulating B cells
The B cells release Ig that activates that binds antigen and leads to cellular destruction (phagocytosis/complement activation/NK cells), inflammation and cellular dysfunction
Graves Disease ad Myesthenia Gravis
What events lead to autoimmune hemolytic anemia?
the Ig binds to a normal cell, which recruits neutrophils that end up destroying normal cells (result in autoimmune hemolytic anemia)
What events lead to Graves disease/hyperthyroidism?
Thyroid TSH receptor is bound by the Ab in Graves disease even in the absence of TSH, resulting in unregulated release of T3/T4
Describe the events that lead to Myesthenia Gravis
Ab binds and blocks Ach receptor, resulting in decreased ACh signaling >> neuromuscular problems
In the Type 3 HSr, the antibodies bind to antigen that is ___ and form __ that recruit immune cells. The downstream effect involves recuritment of which cell type and activation of which system?
In the Type 3 HSR, the antibodies bind to antigen that is free-floating and form Antigen-Ab complexes that recruit immune cells. The downstream effect involves recruitment of neutrophils and activation of complement
The downstream effects of Type III HSR include cytokine-mediated ___. Type III HSR is ass’d w/ ___ b/c these complexes like to form in blood vessels
The downstream effects of Type III HSR include cytokine mediated inflammation.
Type III HSR is ass’d w/ vasculitis b/c these complexes like to form in blood vessels
In type 3 HSR, antigens can either be __ or __, and the resulting disease processes can be generalized, e.g. in __, or localized, e.g. in ___
In type 3 HSR, antigens can either be exogenous or endogenous, and the resulting disease processes can be generalized, e.g. in Systemic Lupus Erythematosus, or localized, e.g. in autoimmune thyroiditis
The only HSR that doesn’t require antibody activity is Type ___. The type of immune cells involved here are __, __ and __.
The only HSR that doesn’t require antibody activity is Type IV. The type of immune cells involved here are CD4+ T cells, CD8+ T cells and macrophages.
What are the downstream effects of the Type IV HSR?
Inflammatory reaction: T cells secrete IL2, which is an inflammatory mediator
An example of a Type IV HSR is ___
Contact dermatitis
What are the cell types ass’d with each HSR?
Type I - Mast cells
Type II - plasma cells mainly
Type III - plasma cells + neutrophils
Type IV - T cells
Autoimmunity is defined a loss of __ and ___ tolerance
Where do either of these occur?
Central and/or peripheral tolerance
Central: Bone marrow + Thymus
Peripheral: in the periphery
Describe the difference between central and peripheral tolerance
Central tolerance: tolerance that occurs in the organs where the lymphocytes develop
T cells undergo positive (recognition of MHC) and negative selection (avid binding to MHC + binding of self antigen)
B cells undergo negative selection (avid binding to self antigen)
Peripheral tolerance: when cells are activated in the periphery (after the B and T cells have been released);
the point is to ensure that those self-reactive B and T cells that escaped selection don’t cause trouble either through anergy or apoptosis via the FAS death receptor pathway
Systemic Lupus Erythematosus is a Type ___ HSR
What are the events leading up to Lupus?
Type III
Antigen-antibody complexes deposit in multiple tissues, resulting in activation of complement
Decreased Ch50 (suggests complement components being used)
Antibodies are directed against host nuclear material
Early complement deficiency (deficit in C1q, C4 and C2**)
What are the clinical features of SLE? (hint: DOPAMIN RASH)
What are the specifc features that’ll allow you to know that this is SLE and not something else?
D - Discoid Rash
O - Oral ulcers
P - Photosensitivity
A - Arthritis
M - Malar rash
I - Immune markers – anti-dsDNA or anti-smith or anti phospholipid antibodies
N - Neuro findings – psychosis, seizures
R - Renal involvement
A - Anti nuclear Abs (abs that attack something within a nucleus); not so specific for lupus
S – Serositis, Pleuritis, Pericarditis
H - Hematological – anemia, thrombocytopenia, leukopenia
What are the types of antinuclear Abs that are seen in the following conditions?
SLE
Drug induced lupus (which drugs? HIP)
Sjogren syndrome
Systemic sclerosis
SLE - anti dsDNA and Smith (rhymes with dsd for ds-dna+ s is for smith)
Drug induced ( Hydralazine, Isoniazid, Procainamide) - anti histone (anti-HIPtone >> HIP drugs + histone)
Sjogren Syndrome: (SS = SS) anti-SS A and B (aas’d w/ neonatal lupus)
SysTemIc SCLerosis: anti Scl70 (anti-topoisomerase) or anti-centromere
Define CREST syndrome. What disease is this ass’d with?
Calcinosis
Raynaud
Esophageal
Sclerodactyly
Telangectasia
Ass’d w/ limited type Systemic sclerosis
Amyloidosis is a disorder in which ___ deposits accumulate in organs
You can tell amyloidosis on congo red staining and flourescence. What are the features that tell you you’re dealing with amyloidosis?
Proteins
Congo red - it’ll stain pinkish
Flourescence: apple-green brifringence
Primary amyloidosis is ass’d w/ what type of malignancy?
Multiple myeloma
Primary immunodeficiencies are ___ whereas secondary immunodeficiencies can arise from ___
Genetic
Infections e.g. HIV infection/ Immunosuppression/ Malnutrition (or pregnancy)
Why do B cell deficiencies manifest at about 6 months? What’s one way to recognize that a pt has a B cell immunodeficiency?
4 examples of B cell immunodeficiencies are X-linked agammaglobulinemia, ___, X linked hyper IgM syndrome, and ___ (which is the most common)
Probably related to maternal antibodies going away and kid builds up her own system
Recurrent infections (esp w/Giardia and bacterial infections)
Congenital (Bruton) X-linked agammaglobulinemia
Common variable immunodeficiency
X linked hyper IgM syndrome
Selective IgA deficiency
If you have a T cell deficiency, you’ll be more susceptible to infections with which 3 organisms?
Viruses, parasites and fungi
___ syndrome is T cell deficiency resulting from a mutation in 22q11.
This diease results in t cell deficiency because there’s lack of ___ development, thus the pt has no thymus
The patient also has hypocalcemia because there are no __ due to developmental failure of the ___ pouch
DiGeorge syndrome is T cell deficiency resulting from a mutation in 22q11.
This disease results in T cell deficiency because there’s lack of 3rd pharyngeal pouch development, thus the pt has no thymus
The patient also has hypocalcemia because there are no parathyroids due to developmental failure of the 4th pharyngeal pouch
What are the features of Di George syndrome?
CATCH 22
Cardiac defects
Abnormal faces
Thymic hypoplasia
Cleft palate
Hypocalcemia
22q11 deletion
Severe Combined Immunodeficiency is called this because ___. SCID can arise because of __, ___
Combined B and T cell deficiency
Cytokine mutations or MHC II mutations
___ ___ Syndrome is an X-linked combined B and T cell deficiency characterized by thrombocytopenia, eczema and recurrent infections. This disorder results from a defect in the ___ gene
Wiscott Aldrich Syndrome is an X-linked T cell deficiency characterized by thrombocytopenia, eczema and recurrent infections. This disorder results from a defect in the WASP gene
**remember WATER** (+ hypothyroidism)
Complement deficiencies (esp in C5-C9) result in recurrent infections with which microbe?
Complement deficiencies (esp in C5-C9) result in recurrent infections with Neisseria
