Hypersensitivity Flashcards
Type I hypersensitivity is ____-mediated. What is the time frame?
IgE mediated; usually arises within minutes.
What are the mediators of Type I hypersensitivity?
Vasoactive mediators, lipid mediators, cytokines
Examples of Type I hypersensitivities?
Allergic diseases (e.g. anaphylaxis)
Which hypersensitivity reactions are mediated by antibodies?
I, II, and III
Type II hypersensitivity is ___-mediated
IgG and IgM
Goodpasture Syndrome:
An example of Type II hypersensitivity; Abs against basement membrane in kidney and lung activate Fc receptors, fix complement, resulting in inflammation.
Idiopathic thrombocytopenic purpura
Autoantibodies against platelets (–> opsonization). Type II.
Autoimmune hemolytic anemia:
Autoantibodies against RBC membrane proteins - type II hypersensitivity.
Myasthenia Gravis is an example of what type of hypersensitivity?
Type II
Graves disease is an example of what type of hypersensitivity?
Type II
Acute rheumatic fever is an example of what type of hypersensitivity?
Type II (against myocardial Ags)
Pemphigus vulgaris is an example of what type of hypersensitivity?
Type II (against desmosomes)
Pernicious anemia is an example of what type of hypersensitivity?
Type II (against intrinsic factor)
What is the classic example of Type III hypersensitivity?
Serum sickness
What is the time frame of Type III hypersensitivity?
Generally the first encounter will take 1-2 weeks (antibodies need to develop), followed by rapid (3-10 hours) with subsequent exposures
What type of hypersensitivity is Lupus?
Type III
Poststreptococcal glomerulonephritis is an example of ?
Type III hypersensitivity
Polyarteritis nodosa is an example of what?
Type III hypersensitivity
Type IV hypersensitivity reactions are ___-mediated
T-cell
Poison ivy is an example of ?
Type IV hypersensitivity reaction
A food allergy is an adverse health effect arising from a specific _______ that occurs ______ on exposure to a given food
immune response; reproducibly
What mediates the immediate Type I hypersensitivity reaction vs. the late-phase reaction?
Immediate is mediated by vasoactive amines and lipid mediators. Delayed is mediated by cytokines
What cytokine is important for IgE class switching?
IL-4
_____ is the receptor that IgE binds to on mast cells and basophils
High affinity Fc epsilon receptor
Describe the structure of Fc epsilon receptors:
Composed of 1 alpha chain (IgE binding) and 1 beta and 2 gamma chains (signal transduction)
What cytokine stimulates mast cell development/growth?
IL-3
What cytokine stimulates basophil development/growth?
IL-3
Mature mast cells are found in _____. Mature basophils are found ____.
Mast cells - Mucosa (and connective tissues). Basophils - Blood.
What is the cytokine that promotes eosinophil growth?
IL-5
Allergen-triggered cross-linking of __-____ complexes results in mast cell ____ and _____
IgE-FceRI; mast cell activation and degranulation
Immunologic tolerance:
unresponsiveness to self-antigens
Tolerogens:
Antigens that induce tolerance
Immunogens:
antigens that induce an immune response
Autoimmunity:
Failure of self-tolerance and resulting immune reaction to self-antigens
Central tolerance occurs in the:
thymus and bone marrow
Peripheral tolerance occurs in the:
peripheral tissues
Explain central tolerance:
In primary lymphoid organs, if a B or T cells is found to recognize a self-antigen strongly, it can either undergo apoptosis, undergo receptor editing (B cells only), or develop into regulatory T lymphocytes (CD4+ T cells only).
Explain peripheral tolerance:
Mature B or T cells that encounter and bind a self-antigen in the periphery can be controlled via anergy, apoptosis, or suppression via regulatory T cells.
B cells can be controlled in central tolerance via:
Receptor editing, deletion, or anergy
T cells can be controlled in central tolerance via:
Deletion, regulatory T lymphocytes
T cells can be controlled in peripheral tolerance via:
anergy, suppression, or deletion (apoptosis)
B cells can be controlled in peripheral tolerance via:
anergy, suppression, deletion
During development in the thymus, positive selection occurs in the ____ and negative selection occurs in the _____
Positive selection - cortex. Negative selection - medulla.
Positive T cell selection occurs in the ____ with the help of _____
Occurs in the cortex, with the help of cortical epithelium (cTEC)
Negative T cell selection occurs in the ____ with the help of ____
Occurs in the medulla, with the help of medullary epithelium (mTEC)
AIRE is a ____ that resides in _____ and controls expression of ____, playing a critical role in ______
AIRE is a TRANSCRIPTION FACTOR that resides in mTECs and controls expression of PERIPHERAL TISSUE SELF-ANTIGENS, playing a critical role in NEGATIVE SELECTION AND SELF TOLERANCE
APECED stands for:
Autoimmune PolyEndocrinopathy Candidiasis Ectodermal Dystrophy
What is the classic triad of APECED?
Mucocutaneous candidiasis, adrenal insufficiency, and hypothyroidism
Regulatory T cells can be identified by what cell surface markers?
CD3+CD4+CD25high and FoxP3+
What cytokines are produced by regulatory T cells?
TGF-B and IL-10
CTLA-4:
a co-receptor that exists on regulatory T cells
What processes result in anergy?
If a signaling block occurs during APC/T cell binding or there is an engagement of APC receptors with CTLA-4
Ipilimumab:
Blocks CTLA-4, resulting in T cell activation. This is used to boost immune response to certain cancers, but can cause autoimmune disease
Abatacept:
A recombinant CTLA-4 fused to an Fc portion of an IgG molecule. Given to people with arthritis, because the CTLA-4 mimickers engage the CD80/86, which prevents engagement of CD28 (and thus prevents activation)
Name 3 ways that regulatory T cells suppress the immune response:
Produce inhibitory cytokines, express CTLA-4, and expression IL-32 receptors, capturing IL-2.
IPEX stands for:
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome
IPEX is caused by what mutation?
Mutation in Fox-P3 gene (X-linked recessive)
How is apoptosis initiated in Peripheral T lymphocyte deletion?
- If antigen is presented with out co-signal, inducers of apoptosis are released from mitochondria. 2. Fas and FasL act as co-stimulators and induce death.
ALPS stands for:
Autoimmune Lympho-Proliferation Syndrome
ALPS is a disorder of ___
apoptosis
ALPS can arise due to a mutation in what?
Fas, FasL, caspase 8, or caspase 10
Describe the clinical presentation of a patient with ALPS
Lymphoproliferation, exhibited by splenomegaly, lymphadenopathy, and/or hepatomegaly
AIRE gene defects are associated with:
Autoimmune polyendocrine syndrome (APS-1)
FOXP3 gene defects are associated with:
X-linked polyendocrinopathy and enteropathy (IPEX)
FAS gene defects are associated with:
Autoimmune lymphoprolierative syndrome (ALPS)
SLE is associated with defective ___ lymphocyte tolerance
B and T
Direct Coomb’s autoimmune hemolytic anemia is an example of what type of hypersensitivity?
Type II
Immunological self tolerance is unresponsiveness to specific antigens ____ by exposure of lymphocytes to that antigen
induced
What environmental factors can make a person more susceptible to autoimmunity?
Infection, UV radiation, Drugs and chemicals
Autograft:
A graft between different sites on the same individual. “autologous transplantation”
Isograft:
Between the same inbred strain of animals or between monozygotic twins
Allograft:
One between non-identical animals/humans of the same species
Xenograft:
between different species
Allogenic hematopoietic stem cell grafts contain ______ that can target cancer
donor-derived immune cells
_____ is not the goal of SCT
Complete donor/recipient tolerance
T cell depletion of donor stem cell graft increases _____
relapse
If a cancer patient treated with stem cells relapses, what is the best way to treat them?
These patients can be successfully treated with more T cells from the donor.
Syngenic transplants are associated with a higher rate of ______
relapse
Removing T cells from a stem cell graft ______ change of relapse by 3x (increases or decreases)
INCREASES
Using a genetically identical (syngenic) donor _____ relapse risk by 3x (increases or decreases)
INCREASES
The odds of any sibling being an HLA match is:
1/4
Haplo-identical:
Half HLA matches (parents and children of patient - usually these need to be T cell depleted and risk of relapse is high)
SCT can/can’t be performed across ABO incompatibilities (explain)
CAN be performed, because hematopoiesis will be provided by the donor’s stem cells.
GFVD:
Graft Vs. Host Disease; where donor-derived, T cell mediated reactivity occurs against recipient tissues.
How is GVDH treated?
immunosuppressive drugs
acute GCHD attacks what tissues?
skin, colon, liver
chronic GVHD affects:
skin, eyes, GI tract, liver, lung
miHA:
minor histocompatibility antigens
miHA are ____-specific
tissue
Hyperacute graft rejection:
Occurs within hours (antibodies must be preformed), such as anti-A or anti-B blood group antibodies or anti-HLA antibodies. Results in complement fixation, vascular damage, and thrombosis
Direct allorecognition:
Recipient T cells recognise peptide/HLA complexes presented by donor (graft) APC. T cell reactivity depends on donor APCs, which decrease over time.
Indirect allorecognition:
Recipient APC processes donor proteins and present on recipient HLA.
Acute Rejection:
7-21 days after transplant. Recipient derived cell-mediated cytotoxicity. Humoral graft rejection (antibodies are not preformed)
Chronic Rejection:
> 21 days after transplant. Interstitial fibrosis. Mononuclear cell infiltration. Leads to organ ischemia.
