Term
| List the four types of hypersensitivity giving their effectors and mechanism of tissue damage? |
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Definition
Type I (Immediate);
-IgE mediates
-IgE attaches to mast cells (sensitizes them) and they degranulate upon contact with antigen
Type II (Antibody -mediated);
-Mediated by IgM & IgG
-Opsonization of CELL or TISSUE occurs, phagocytes and compliment are recruited, and localized damage occurs
Type III (Immune complex-mediated);
-Also mediated by IgG and IgM, but now they form FREE immune complexes
-The complexes lodge different places and cause systemic damage via the same methods as type II (compliment, phagocytosis, etc.)
-Note that II and III are the same except II is binding directly to cell (even when cell is circulating)
Type IV (Delayed-type)
-Mediated by TH1 cells (the cell mediator ones)
-They recruit/activate macrophages and CTLs to cause the tissue damage |
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Term
| Run through the process of developing a type I response? What is it naturally supposed to be for? |
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Definition
-First antigen exposure and antigen capture by B cells
-B cells present to T cells and they excrete IL-4 & IL-13 to stimulate Ig-E production
-Mast cells are loaded up with the Ig-E (via Fc receptors)
-After this, second exposure produces degranulation
-Normally for protection against helminths (fancy for parasitic worms)
-The secondary response happens within minutes |
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Term
| What are the three major cells of the immediate hypersensitivity response? |
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Definition
-Mast cells are the major ones
-Eosinophils are also attracted by eosinophil chemotactic factor from mast cells and are responsible for a lot of tissue damage
-Basophils also make it to the site (similar to mast cells except they are in circulation and not tissue) |
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Term
| What are the major stored mediators released by mast cells (3) and what do they do? |
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Definition
-Histamine; sm. muscle contraction, vasodilation, and increased vascular permeability
-Heparin; anticoagulant
-ecf-A (eosinophil chemotactic factor) |
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Term
| What is the late-phase reaction? What mediates it? |
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Definition
-It is a part of type I hypersensitivity that occurs 2-4 hours after the primary response
-Mediated by newly synthesized arachidonic acid cascade products;
-Prostaglandins & leukotrienes C4, D4, & E4; increased smooth muscle contraction and vascular permeability
-Leukotriene B4; chemotactic for neutrophils
-These hang around longer and can have more powerful effects (such as closing the trachea in allergic reaction) |
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Term
| Give type I hypersensitivity diseases (5)? |
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Definition
-Allergic rhinitis (allergies)
-Systemic anaphylaxis (insect bites, drug rxns)
-Food allergies
-Wheal and flare (local skin edema)
-Asthma |
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Term
| What are the three main effects of antibodies in type II? |
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Definition
-Opsonization of cells and compliment activation
-Recruitment of phagocytes
-Can also bind to receptors and interfere with their function (can block or overstimulate)
-The latter option represents the non-cytotoxic diseases |
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Term
| Give the cytotoxic examples of type II (5)? |
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Definition
**Autoimmune hemolytic anemia;
-Such as in hemolytic disease of newborn HDNB with Rh being targeted
-Compliment easily lyses RBCs
**Acute rheumatic fever;
-Antibodies produced against strep can sometimes cross react with heart cells causing myocarditis (sometimes arthritis as well)
**Goodpasture syndrome;
-Basement membrane collagen (type IV) is targeted in kidneys and lungs
-Results in nephritis and lung hemorrhage
-Causes smooth ribbon-like pattern on basement mem.
Transfusion reaction;
-RBCs targeted b/c of ABO glycoproteins
Autoimmune thrombocytopenic purpura;
-Platelets are targeted resulting in bleeding problems (purpura) |
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Term
| Give the non-cytotoxic examples of type II (4)? |
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Definition
**Myasthenia gravis;
-Acetylcholine receptors are BLOCKED off
-Results in progressive muscle weakness
**Graves disease;
-Ab binds to thyroid stimulating hormone (TSH) receptors causing their OVERSTIMULATION
-Causes hyperthyroidism, and later hypothyroidism
Type II diabetes mellitus;
-Insulin receptors are blocked (insulin insensitivity)
Pernicious anemia
-Intrinsic factor (B12 absorption) is blocked off
-Causes anemia |
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Term
| What is HDNB? What is targeted and by what? When is it a problem? How do we treat it? What test do we use to detect it? |
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Definition
-Hemolytic disease of the newborn
-The RhD RBC proteins of the fetus in an Rh- mother are targeted by anti RhD IgG which can cross the placenta
-This is not a problem in the *first pregnancy because the mother is not exposed to the antigen until birth (remember miscarriages/abortions count)
-We treat it with RhoGAM at 28 weeks gestation and also right after birth to prevent memory generation
-RhoGAM is a preparation of human anti-RhD IgG that will give a high enough amount to take care of fetal cells in the mother (doesn't allow generation of memory cells), but not enough to harm the fetus (only gives about 1:4 titer)
-Essentially it mimics the normal memory response (passive immunization)
-After alloimmunization (from previous pregnancy) we have to use intrauterine transfusion into umbilical vein
-We use Combs test to detect (indirect typically, with a titer of 1:32 being the danger zone) |
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Term
| What is the major difference in mechanism between myasthenia gravis and graves? |
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Definition
| -In graves we get stimulation, in MG we get blockage |
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Term
| Give examples (5) of type III hypersensitivity diseases? What is targeted and how does it present? |
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Definition
**Systemic lupus erythematosus (SLE);
-dsDNA and nucleoproteins are targeted
-Nephritis, arthritis, vasculitis, *butterfly facial rash
**Rheumatoid arthritis;
-IgM targets IgG's Fc region (forms RHEUMATOID FACTOR)
-Joint pain and erosion
-This one is properly classified as type III, but it usually progresses to type IV (so may see as either and Lima classifies as type 4)
**Poststreptococcal glomerulonephritis;
-Strep Ag gets stuck in basement membrane of glomerular cells
-This time we get "lumpy-bumpy" appearance of basement membrane (compare to goodpasture syndrome)
Serum sickness;
-From non-human injected antibodies (antivenom etc.)
-Systemic effects (arthritis, nephritis, vasculitis, etc.)
Arthus reaction;
-From any injected protein
-Effects are localized in this case |
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Term
| What is a histological difference between goodpasture and poststreptococcal glomerulonephritis or lupus? What is the basis? |
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Definition
-Goodpasture shows "ribbon-like" whereas the other two show a "lumpy-bumpy" damage to the glomerular basement membrane
-The difference is that in the type II example (GP), the cells are targeted directly, whereas in the nephritis caused by type III hypersensitivities, the immune complexes are getting randomly sucked down onto the cells |
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Term
| What is rheumatoid factor? |
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Definition
-IgM that has latched onto the Fc region of IgG
-It is an immune complex that settles out of solution and into the joints |
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Term
| What is type IV hypersensitivity? What's the time frame? What types of antigen are targeted? With what type of infections do we see this most? |
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Definition
-It is the delayed-type where TH1 cells activate macrophages (with IFN-γ) and CTL, which then destroy the tissue
-Does not involve antibody!
-It's about 2 to 3 days after exposure
-It can be autoimmune or specific against foreign Ag
-Often seen in chronic intracellular infections |
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Term
| Give some examples of type IV (8)? |
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Definition
**Tuberculin test;
-PPD (purified protein derivative) test reaction
**Contact dermatitis;
-Poison ivy/oak, nickle (cheap jewelry) etc.
-Causes rash
**Hashimoto's thyroiditis;
-Unknown Ag in thyroid is targeted causing destruction
-Get lumpy goiter
**Multiple sclerosis;
-Myelin basic protein is targeted
-Causes spastic paralysis
Diabetes mellitus type I (insulin dependent);
-Islet cells are targeted and destroyed
**Guillain-Barre syndrome;
-Myelin gangliosides (glycolipids) of peripheral nerves are targeted
Celiac disease;
-Gluten intolerance (to gliadin specifically)
Rheumatoid arthritis
-The actual pathology of RA is cell mediated |
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Term
| What are the three ways infections may trigger autoimmunity? |
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Definition
-Bystander activation; T cells that are not specific to the infection are often activated
-Molecular mimicry; Antigens sometimes cross-react or mimic self antigens
-Inflammation; Can damage cells and expose intracellular self antigens which are normally concealed |
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Term
| How do we tell the difference between MS, myasthenia gravis, and guillain-Barre syndrome? |
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Definition
-The MS will give spastic paralysis, whereas myasthenia gravis will present with weakness paralysis
-Both start with blurred vision and paralysis
-MS is type IV and MG is type II (non-cytotoxic)
-Guillain-Barre syndrome on the other hand will give ascending peripheral paralysis |
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Term
| What genetic determinant is the most commonly associated with autoimmunity? |
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Definition
-MHC class II genes
-Remember, it is a polymorphic protein |
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Term
| In general, how do we treat autoimmune diseases? |
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Definition
-Mostly we target T cells (with steroids and other compounds)
-We also can use monoclonal antibodies against cell markers (drugs always end in -mab and are wicked stupid expensive... like 10k a dose) |
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Term
| Following are Lima's from autoimmunity; |
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Definition
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Term
| What HLA type is frequently associated with autoimmune diseases? What is an HLA-disease combo that has an almost 100% association? |
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Definition
-HLA-DR
-Ankylosing spondylitis and HLA-B27 |
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Term
| Who gets autoimmune diseases more, women or men? |
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Definition
| -Women because estrogen increases antibody response |
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Term
| What is the gene stipulating antigen presentation in the thymus by epithelial cells for negative selection? What diseases/conditions does this cause (3)? Who is more at risk? |
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Definition
-AIRE gene (AutoImmune REgulator)
-APD (AI polyglandular disease) or APECED (AI polyendocrinophathy) results
-Finns, Sardinians , and Iranian Jews are most at risk
-These are both just combination autoimmune diseases where glands and other tissues are targeted
-Patients also present with candidiasis (nail infections) |
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Term
| What is the important downregulator, that if absent can cause autoimmunity? What diseases is this linked to? |
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Definition
-CTLA-4 binds to B7 to downregulate the interaction of B7 with CD28 (which acts to activate)
-Without it, we have overactive T cells
-Graves'(2), Hashimoto's(4), and IDDM(4) have all been linked |
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Term
| What cells are most responsible in preventing autoimmunity? What is the mechanism? What marks this cell? What is it's master regulator gene associated with this cell type? |
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Definition
-Treg cells
-Treg cells have to be bound at the same time as a Th cell to the self cell, they then secrete cytokines to inhibit the Th cell (IL-4,10, & TGF-β)
-CD25 and CD4 mark the Treg
-FoxP3 is the regulatory gene on the X-chrom; it's absence is incompatible with life |
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Term
| What are a few examples of autoimmune diseases caused by cross-reacting or mimicry antigens? What are the infections? |
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Definition
-Rheumatic fever; strep
-Reiter's disease & reactive arthritis (both arthritis); associated with food poisoning and GI infections |
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Term
| What can result from an early compliment deficiency? What is the receptor for compliment? |
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Definition
-Lupus, from complexes not being cleared
-Also called systemic lupus erythematosus
-Usually C3b binds to antigen and erythrocyte at CR1** and is cleared by the spleen
-Remember C1,2,&4 are all involved in C3 production (esp. in response to humoral rxn) |
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Term
| What is pemphigus vulgaris? |
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Definition
-Autoimmune disease of the skin where IgG is directed against desmogleins*; part of desmosomes that bind keratinocytes* together
-Get lots of blistering |
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Term
| What is the specific mech. for generation of lupus? What is diagnostic of lupus? |
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Definition
-Free DNA is internalized to B cells and bound by TLR-9** in an endosomal compartment, which sends a stimulatory signal (activating a silent-auto reactive cell)
-Butterfly rash on face |
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Term
| What actually does the destruction in IDDM? |
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Definition
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Term
| What is Lima saying RA is? |
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Definition
| -She is going with type IV |
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Term
| What is Sjogren's syndrome** and how do we classify it? |
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Definition
-Chronic inflammatory disorder of exocrine glands (esp. salivary and lacrimal)
-Get dry mouth, swollen parotid, dry eyes
-Usually in post-menopausal women
-More or less a mix of RA and lupus (both rheumatoid factor and antinuclear antibodies are present) so it is a type III hypersensitivity (more or less)
-[Lima has family history] |
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