Term
| Def'n of Hypersensitivity |
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Definition
| Undesirable (damaging, discomfort producing, sometimes fatal) reactions produced by normal immune response to harmless antigens |
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Term
| Types of Hypersensitivity? |
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Definition
Type 1: IgE-mediated (immediate, allergy atopy)
Type 2: antibody (IgG) mediated (cell or matrix-associated antigen)
Type 3: Immune Complex (IgG) mediated, soluble antigen
Type 4: T-Cell mediated (DTH, contact hypersensitivity) |
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Term
| Type 1 Hypersensitivity mediated by which antibody? |
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Definition
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Term
| Which immune cell is involved in early phase of immediate hypersensitivity? |
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Definition
| Mast cell activation (have Fc-epsilon recepetors, which cause release of granule contents) |
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Term
| Examples of IgE-mediated allergic reactions? |
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Definition
Systemic Anaphylaxis
Acute Urticaria
Seasonal Rhinoconjunctivitis
Asthma
Food Allergy |
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Term
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Definition
| Dust mites, mold spores, animal dander, pollen |
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Term
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Definition
| Der p 1 is a cysteine protease enzyme produced by the household dust mite; proteinase allergens are common and widespread (but, most allergens aren't proteases) |
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Term
| Mechanism for allergenicity of Der p 1? |
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Definition
Example of sensitization to an inhaled allergen:
Der p 1 able to penetrate the skin and gain access into tissues/cells.
APCs pick up antigens and present to T-cells, which activate B-cells
Degranulation causes allergic immune response |
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Term
| What is Netherton's syndrome? |
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Definition
| Characterized by high IgE and multiple allergies, associated with lack of serine protease inhibitor, SPINK5 |
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Term
| What is Spink5? Why does lack of SPINK5 in patients with Netherton's contribute to the development of allergic diseases? |
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Definition
| SPINK5 is serine protease inhibitor, mutations result in dysfunctional protein that has reduced capacity to inhibit serine proteases expressed in the skin. Ie Occupational allergy caused by allergens, meat processors are constantly exposed to Papain |
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Term
| Which subset of T helper cells makes Il-4? |
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Definition
| CD4 T Helper cells (Th2) produce IL-4, which is the main source of IL-4 required for IgE class switching |
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Term
| Isotype switching to IgE in B cells requires which cytokine? |
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Definition
| IL-4, secreted by Th2 cells as well as activated mast cells |
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Term
| What signal is most important in B cells for class switching? |
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Definition
| The contact signal interaction between CD40 on B-cells and CD40L on APCs |
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Term
| CD40 is expressed on which immune cells? |
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Definition
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Term
| CD40L is expressed on which immune cells? |
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Definition
| APCs (T cells, mast cells) |
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Term
| How can activated mast cells further drive IgE production by B cells? |
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Definition
| IgE secreted by plasma cells binds to a high-affinity Fc receptor Fc-epsilon on mast cells. Activated mast cells provide contact and secreted signals to B cells to stimulate IgE production. |
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Term
| Mast cells express what receptors for binding to IgE? |
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Definition
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Term
| Atopic individuals have higher levels of which antibody? |
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Definition
| Higher IgE, eosinophils, and are more susceptible to allergic diseases such as asthma. Atopic means IgE-related Th2 mediated immune response |
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Term
| What are the susceptibility genes for asthma? |
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Definition
They include genes regulating Th2 cell differentiation and an effector function such as GATA3 (a mast cell transcription factor for Th2) and IL-4.
Also includes genes expressed in epithelial cells such as chemokines and epithelial cell barrier (spink5, FLG) |
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Term
| What is hygiene hypothesis? |
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Definition
| Idea that less hygienic environments that predispose one to infections early in childhood help to protect against atopy and allergic diseases. Environmental factors (such as pollution, allergen levels, or dietary changes) & genetic factors play into determining if one will be atopic vs. non-atopic. Explains why allergy happens so frequently in "hyper-clean" industrialized society. |
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Term
| What immune cells express high affinity Fc receptor for IgE (Fc-epsilonRI)? |
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Definition
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Term
| What immune cells express high affinity Fc receptor for IgE (FC-episilonRI) upon activation? |
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Definition
| Mast cells, EOSINOPHILS, and basophils |
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Term
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Definition
CD23 is also known as FC-epsilonRII, a C-type lectin and low affinity receptor of IgE.
CD23 is present on the following cells: B-cells, activated T-cells, monocytes, eosinophils, platelets, follicular dendritic cells, some thymic epithelial cells; enhances IgE levels |
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Term
What are the effects of activated mast cells in airways?
What are the effects of activated mast cells in GI tract?
What are the effects of activated mast cells in blood vessels? |
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Definition
Activation and granule release.
GI tract: increased fluid secretion, increased peristalsis, expulsion of GI tract contents, diarrhea, vomiting
Eyes, nasal passages, and airways: decreased diameter, increased mucus secretion, congestion and blockage of airways (wheezing, coughing, phlegm. Swelling and mucus secretion in nasal passages.
Blood vessels: increased blood flow, increased permeability; increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and protein in tissues, increased effector response in tissues. Hypotension potentially leading to anaphylactic shock. |
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Term
| What are the products that are produced by activated mast cells? |
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Definition
Include:
Cytokines (such as IL-4 and IL-13) which stimulate and amplify the Th2-cell response (incite more switching to IgE and therefore stronger mast cell response)
Lipid mediators such as leukotrienes C4, D4, and E4, which aid in smooth muscle contractions- singulair blocks the biological effects of such leukotrienes |
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Term
| IgE-mediated responses can be divided into immediate and late-phase responses. What is the cell type that exerts the immediate response? What are the cell types that exert the late-phase responses? |
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Definition
Immediate: mast cells (caused by granules released by mast cell)
Late phase: eosinophils, basophils, and Th2 cells |
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Term
| What are the products produced by activated eosinophils? |
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Definition
Toxic proteins such as Major Basic Protein, which is toxic to parasite and mammalian cells, and triggers histamine release from mast cells.
Lipid mediators such as the leukotrienes C4, D4, and E4 which aid in smooth muscle contraction and lead to bronchoconstriction. |
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Term
| Which cytokine can increase the production of eosinophils? |
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Definition
| IL-5 can increase the production of Eosinophils |
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Term
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Definition
| Eosinophils' degranulation releases major basic protein, which in turn causes degranulation of mast cells and basophils |
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Term
| What is the function of eotaxins? |
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Definition
Eotaxins are involved in attracting and activating eosinophils. They include:
CCL11- eotaxin 1
CCL24- eotaxin 2
CCL26- eotaxin 3
Eotaxins are involved in the regulation of high-affinity IgE receptors (Fc-epsilon RI) as well as other receptors such as Fc-gamma and complement receptors. Upon activation, eosinophils, will upregulate their high-affinity IgE receptors (Fc-epsilon RI) |
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Term
| What is anaphylaxis? When the allergen is introduced into the bloodstream, activation of mast cells can cause a very dangerous reaction? |
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Definition
Anaphylaxis is the result of re-exposure to an antigen that elicits an IgE mediated response.
If an allergen gets into the bloodstream, it can cause systemic anaphylaxis and anaphylactic shock, which has serious consequences such as:
Increased in vascular permeability
Loss of Blood pressure
Airway constriction (causing breathing difficulty)
Swelling of the epiglottis (can cause suffocation)
Symptoms include:
peripheral vasodilation (edema), bronchospasm (makes breathing hard/irregular), cardiac arrhythmias, smooth muscle contractions |
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Term
| This reaction can be rapidly controlled by the immediate injection of epinephrine (adrenaline) or EpiPen because it can relax the smooth msucle in airway |
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Definition
| EpiPen is the medicine of choice for treating an anaphylactic reaction, and is available by prescription as an auto-injector. It can relax the smooth muscle and inhibits the cardiovascular effects of anaphylaxis. |
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Term
| Allergen inhalation is associated with the development of rhinitis and asthma. Immune cells involved in acute asthmatic response? What are the immune cells involved in chronic asthmatic responses? |
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Definition
Immune cells involved in acute asthmatic response: first mast cells, later Th2, and eosinophils.
Chronic asthmatic responses are caused by cytokines from Th2 cells and granule proteins from eosinophils. |
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Term
| What is the feature of the airway walls from asthmatic patients? |
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Definition
| In asthmatic patients, there is often airway remodeling which involves a thickening of the airway walls due to hyperplasia and hypertrophy of the smooth muscle and mucous glands, and an eventual development of fibrosis. |
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Term
| In chronic asthmatics, a general hyperresponsiveness or hyperreactivity of the airways to non-immunological stimuli often develops... |
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Definition
| These non-immunological stimuli can include cigarette smoke, sulfur dioxide, viral, or bacterial respiratory tract infections, which exacerbate the disease. |
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Term
| Why mice lacking T-bet (a master TF for Th1 development) spontaneously develop asthma-like phenotype? |
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Definition
| This is because these T-bet-/- mice have a genetic imbalance toward Th2 response that can cause allergic disease such as the asthma-like phenotype (which results from airway remodeling) |
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Term
| What is IgE-mediated food allergy? |
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Definition
| IgE mediated food allergy results from defects in the IgE-mediated immune response which leads to one having an atopic allergic reaction to food antigens which should normally be seen as harmless by the immune system |
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Term
| Treatment for allergic disease? |
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Definition
Antihistamines/Beta-blocks such as albuterol: it is a beta-blocker that relaxes smooth muscle in the lungs to alleviate wheezing and immediately helps you breathe better.
Lipoxygenase inhibitors such as singulair: singulair inhibits the enzyme 5-lipooxygenase, which is required for the production of leukotrienes (LT), which normally cause bronchial smooth muscle contraction. By singulair's inhibition of 5-lipooxygenase, it decreases the production of leukotrienes and thereby relieves symptoms.
Corticosteroids (such as COX I or COX II) suppress the enzyme activity of cyclooxygenase, which plays an important intermediate role in the production of Prostaglandins and thromboxanes, which are commonly implicated in fever and pain. Cortical steroids thus suppress the expression of gene products related to allergic inflammation. |
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Term
| Type II or III hypersensitivity is mediated by which antibody? |
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Definition
Type II or III hypersensitivity is IgG-mediated
Type II is antibody IgG mediated (cell receptor-or matrix associated antigen)
Type III is immune complex (IgG) mediated (soluble antigen) |
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Term
| What is autoimmune hemolytic anemia? What type of hypersensitivity this disease belongs to? What are the two mechanisms that Ab-bound RBC can be destroyed? |
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Definition
Autoimmune hemolytic anemia is a type II hypersensitivity response where RBCs are damaged by anti-RBC IgM or IgG autoantibodies.
Ab-bound RBCs can be destroyed by FcR+ cells in a fixed mononuclear phagocytic system, leading ot phagocytosis and RBC destruction. Or Ab-bound RBCs can be destroyed by complement activation and intravascular hemolysis, leading to lysis and RBC destruction. |
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Term
| What are immune complexes? |
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Definition
(Type III hypersensitivity also caused by IgG)
Immune complexes are normally cleared efficiently by RBC bearing complement receptors or by phagocytes that have both complement and Fc receptors, and cause little tissue damage.
However, with the Type III hypersensitivity response there is a large amount of antigen, leading to the formation of large amounts of immune complex that overwhelm the normal clearance mechanisms. |
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Term
| Small immune complexes... |
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Definition
| Form when antigen is in excess tend to be deposited in blood vessel walls. These complexes can ligate Fc receptors on leukocytes, leading to leukocyte activation and tissue injury. |
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Term
| What is the arthus reaction? When antigen is injected locally into the skin, IgG forms immune complexes close to the site of injection. The immune complexes activate mast cells and other leukocytes containing FcgRIII, which results in a local inflammatory response and increase vascular permeability. The immune complex also activates complement, leading to the production of C5a. C5a interacts with C5a receptors on leukocytes to activate these cells including mast cells. What happens after mast cells being activated? |
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Definition
| Arthus reaction is classical example of local Type III hypersensitivity through the skin. Antigen injected in immune individual that already has an IgG Antibody, binds to Fc-gamma receptor. Immune complex formation activates the complement. Fc-gamma RIII activated on mast cells inducing granulation. Leads to local inflammation, fluid and protein release, phagocytosis, blood vessel occlusion. |
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Term
| What is serum sickness? Does it require large or small quantities of foreign antigens? The onset of this disease occurs 7-10 days after the injection of foreign antigens. Why does it require 7-10 days? |
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Definition
| Serum sickness is an example of Type III hypersensitivity that is more systemic. Serum sickness described the transient symptoms due to inflammation from antigen:Ab aggregates, which include fever, vasculitis, arthritis, and nephritis. |
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Term
| The immune complexes in serum sickness are deposited in small vessels and activate complement and phagocytes, which can cause widespread tissue damage and induce fever, vasculitis, arthritis, and nephritis. However, these effects are transient and why is that? |
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Definition
| Ag:Ab complex disappears b/c foreign antigen has certain half life, AB against foreign serum proteins forms and remains high for days. |
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Term
| Type IV hypersensitivity is mediated by which cells? |
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Definition
| Activated T-cells causing tissue damage. These T-cells in Type IV hypersensitivity include Th1 (CD4), Th2 cells (CD4), and CTL (CD8). |
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Term
| What is delayed type hypersensitivity? |
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Definition
| Antigens from proteins like insect venom or mycobacterial proteins can lead to skin swelling. |
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Term
| TB tests are used to determine whether an individual has been infected with M. tuberculosis. What type of hypersensitivity is TB test? |
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Definition
| The TB test is an example of Type IV hypersensitivity, specifically DTH. In the TB test, the TB antigen is delivered subcutaneously to test if you have sensitized T-cells. |
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Term
| Because the reaction for TB test evolves over 24-72 hours, this test is also called? What are the major cell types that involved in this reaction? |
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Definition
| Major cell types involved in this reaction are macrophages and Th1 effector cells. After the antigen is injected into subcutaneous tissue, it is processed by local APCs (macrophages). Subsequently, a Th1 effector cell recognizes the antigen, and releases cytokines (such as IFN-gamma), which act on the vascular endothelium. Finally, the recruitment of phagocytes and plasma to the site of antigen injection causes a visible lesion. |
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Term
| What is contact hypersensitivity (allergic contact dermatitis)? |
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Definition
This is the most frequently encountered DTH Type IV hypersensitivity. It's seen as the blistering skin lesions at the point of contact on patient with poison ivy contact dermatitis.
It involves the infiltration of large #s of blood cells combined with the localized death of tissue cells. Overall, this leads to the destruction of extracellular matrix that holds the layers of the skin.
Pentadecacatechol binds to proteins on surface of skin cells. Acts as hapten- small organic molecule that doesn't alone provoke an immune response. |
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Term
| What are the antigens that cause allergic contact dermatitis? |
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Definition
The antigens that cause allergic contact dermatitis include Haptens (small organic molecules of simple structure that don't provide immune reponses by themselves but bind to proteins on the surfaces of skin cells, in which they form their function as a Hapten and cause a reaction) such as pentadecacatechol (poison ivy) or DNFB.
Other antigens include small metal ions such as nickel or chromate. |
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Term
| What is pentadecacatechol? Where can we find this molecule? What disease does this molecule cause? |
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Definition
| Pentadecacatechol is the causative agent of contact sensitivity to poison ivy, found in the oils of the poison ivy shrub. If functions as a Hapten, meaning it's able to interact with host skin proteins and induce an immune response known as contact dermatitis type IV hypersensitivity. |
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Term
| Contact hypersensitivity is caused by small molecules that can easily penetrate intact skin. The chemical pentadecacatechol found in poison ivy contributes to what diseases? |
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Definition
Consequential local epidermal reactions seen in contact hypersensitivity or contact dermatitis include:
Erythema
Cellular infiltrate
Vesicles
Intraepidermal abscesses |
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Term
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Definition
| Celiac disease is an example of an autoimmune disease where chronic tissue damage in the gut is caused by hypersensitivity to a common food antigen (gluten, and specifically Gliadin which is a protein in grain flour in foods such as wheat, oats, and barley). It involves infiltration of plasma cells and lymphocytes into the lamina propria, an increase in the number of intra-epithelial lymphocytes and gamma/delta T cells, and leads to a loss of normal villous structure as they don't thrive as a consequence of not being able to absorb nutrients properly. The gut wall becomes chronically inflamed, the villi are destoryed, and the gut's ability to absorb nutrients is compromised. |
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Term
| Which food is responsible for Celiac disease? |
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Definition
Gluten, a protein component of grain flour found in foods such as wheat, oats, and barley.
Gliadin is actually the specific toxic peptide component of gluten that induces stress on cells for people with Celiac disease. |
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Term
| Induced T-regs are differentiated from CD4 or CD8 T cells? |
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Definition
| Induced Tregs are differentiated from CD4+ T cells in a certain cytokine environment. |
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Term
| What is the cytokine required for induced Treg differentiation? |
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Definition
| TGF-beta cytokine is required for iTreg differentiation. |
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Term
| What is the transcription factor that is required for Treg? |
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Definition
| FoxP3 TF, IL-2 signaling is essential for the maintenance of Treg cells. |
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Term
| What are the cell surface markers that are unique to Treg? |
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Definition
CD25
CTLA4
CD4 and FOXP3
CD25 is the IL-2 receptor alpha, a component of the high-affinity IL-2 receptor in activated T cells. CD25 is a marker for both activated T-cells and Treg, but you can distinguish by FoxP3, TF presence. |
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Term
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Definition
Scurfy mice are deficient in FoxP3 and Treg cells, giving them a lymphoproliferative disorder characterized by enlarged spleen and lymph nodes.
This phenotype can be corrected by transfer of Treg from WT mice. |
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Term
| What is the function of Treg? |
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Definition
| The function of CD4 Treg cells is to suppress the activation of conventional T cells and thereby suppress T cell responses in general. Too much Treg due to tumor growth or viral/bacterial infection, will suppress the immune response. Depletion of Tregs= autoimmune disease, reconstitution of Tregs inhibits autoimmunity. |
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Term
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Definition
Genetic defect in Treg
Responses to self antigens (autoantigens)
Leads to autoimmune disease and tissue damage |
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Term
| What are the types of tolerance for the immune system to discriminate self from non-self? |
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Definition
Central tolerance: deletion and editing, thymus & bone marrow
Antigen segregation: physical barrier to self-antigen access to lymphoid system, peripheral organs and thyroid, pancreas
Peripheral anergy: cellular inactivation by weak signaling without co-stimulus, secondary lymphoid tissue
Regulatory cells: suppression of cytokines, intercellular signals, secondary lymphoid tissue and sites of inflammation
Cytokine deviation: differentiation to Th2 cells, limiting inflammatory cytokine secretion, secondary lymphoid and ...
Clonal deletion: apoptosis post-activation, secondary lymphoid tissue and sites of inflammation |
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Term
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Definition
Autoimmune regulator
Controls expression of such proteins in thymic medulla
AIRE expression in the medulla induced by lymphotoxin (LT) signaling
Mature T cell repertoire recognizes self-peptide (self-MHC complex)
Problem: pancreatic insulin is not normally expressed in thymus
Individual organs in the body express tissue specific antigens: in the thymus, T cells apprise capable of recognizing tissue specific antigens. Under control of the AIRE protein- thymic medullary cells express tissue specific proteins- deleting tissue reactive T cells.
In the absence of AIRE- T cells reactive to tissue specific mature and leave the thymus |
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Term
| A mutation in AIRE gives rise to what problem? |
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Definition
autoimmune polyglandular syndrome type I- APS-1
Develop a wide range of autoantibodies against organ specific antigens in the endocrine glands, antigens in the liver and skin, against blood cells such as platelets. Also develop increased susceptibility to infection with yeast candida albicans.
Hashimotos thyroiditis: hypothyroidism
Graves disease: hyperthyroidism |
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Term
| What are examples of organ-specific versus system autoimmune disease? |
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Definition
Organ-specific: type 1 diabetes mellitus, good pastures syndrome, multiple sclerosis, graves disease, hashimotos, autoimmune hemolytic anemia, autoimmune addison's disease, vitiligo, myasthenia gravis
Systemic: rheumatoid arthritis, scleroderma, systemic lupus erythematous, primary sjorgen's syndrome, polymyositis |
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Term
| What is autoimmune hemolytic anemia? What type of hypersensitivity does this disease belong to? What are the two mechanisms by which Ab-bound RBC can be destroyed? |
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Definition
Autoimmune hemolytic anemia
Type II antibody against cell surface or matrix antigens
Antibodies specific for cell surface antigens can destroy cells
RBCs plus anti-RBC autoantibodies- FcR+ cells in fixed mononuclear phagocytic system - phagocytosis and RBC destruction.
Complement activation and intravascular hemolysis: lysis and RBC destruction |
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Term
| What is myasthenia gravis? |
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Definition
Organ specific autoimmune disease
Characterized by progressive weakness and lots of muscle control
Autoantibodies against nicotinic acetylcholine receptors
Muscle becomes less responsive to acetylcholine (reduced receptors for Ach) |
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Term
| What is Graves' disease? What type of hypersensitivity does this disease belong to? The autoantibody against what self-protein causes this disease? How can this autoantibody contribute to this disease? |
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Definition
ABs against the TSH receptor
Transferred across the placenta to the fetus and newborn infant.
Type II hypersensitivity
TSHR- leads to hyperthyroidism
Autoantibodies are agonists for the TSH receptor, stimulative excessive production of thyroid hormone, inhibit TSH
Autoimmune B cell makes antibodies against TSH receptor that also stimulate thyroid hormone production
Thyroid hormones shut down TSH production but have no effect on autoantibody production- which continues to cause excessive thyroid production |
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Term
| Describe the feedback regulation of thyroid hormone production |
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Definition
Pituitary gland secretes TSH, which acts on the thyroid to induce the release of thyroid hormones
Thyroid hormones act on the pituitary to shut down production of TSH- suppressing further TSH production |
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Term
| What autoimmune diseases can be transferred across the placenta to the fetus and newborn infants? |
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Definition
Myasthenia gravis
Graves' disease
Thrombocytopenic purpura
Neonatal lupus rash and/or congenital heart block
Pemphigus vulgaris |
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Term
| What is Goodpasture's syndrome? What is the autoantigen involved in this disease? What type of hypersensitivity does this disease belong to? Why does this binding of this autoantibody cause tissue damage in this disease? |
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Definition
Autoantigen- noncollagenous domain of BM collagen type IV
Type II autoimmune disease
Consequence is glomerulonephritis, pulmonary hemorrhage
Autoantibodies against BM- collagen IV
Bind Fc receptors- activation of monocytes, neutrophils, and tissues basophils and mast cells.
Release cytokines that attract influx of neutrophils
Complement activation via binding to Fc receptors
IgG deposition in renal glomerulus, glomerulonephritis and tissue injury. |
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Term
| How to clear immune complexes? |
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Definition
Normally cleared efficiently by RBC bearing complement receptors. By phagocytes that are both complement and Fc receptors- cause little tissue damage
Large amount of antigen- leading to the formation of large amounts of immune complex that overwhelm the normal clearance mechanisms |
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Term
| Examples of immune complex diseases? |
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Definition
Rheumatoid arthritis
Anti-IgG auto AB = rheumatoid factor
Infiltration of joints by leukocytes |
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Term
| What is the disease characterized by inflammation of the synovium (the thin lining of a joint)? What is the rheumatoid factor? |
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Definition
Immune complex disease
Anti-IgG autoantibody- rheumatoid factor
Infiltration of joints by leukocytes
Inflammatory response in joint
Treated with anti-inflammatory and immunosuppressive drugs
Anti-TNF-alpha antibody therapy
Chronic disease characterized by inflammation of synovium
Inflamed synovium invades and damages cartilage- followed by erosion of the bone |
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Term
| What is the cell in the synovium that destroys the bone? What is the cytokine expressed in the inflammed joint that can activate this bone-destroying cell? |
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Definition
Osteoclasts destroy the bone
TNF-alpha and IL-6 expressed, induces production of MMP and RANK by the fibroblasts
MMPs attack tissues- activation of the bone destroying osteoclasts- resulting in the joint destruction |
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Term
| What is experimental autoimmune encephalomyelitis (EAE)? EAE is mediated by what type of Th cells? |
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Definition
T cell specific for myelin basic protein mediate inflammation of the brain in EAE- experimental autoimmune encephalomyelitis- mouse model for MS.
Injecting mice to isolate spinal cord homogenized in complete Freunds adjuvant
Autoantigen myelin basic protein- MBP
Inflammation of the brain and paralysis is mediated by Th1 and Th17 cells specific for MBP
BMP specific Th1 cells can transfer symptoms to EAE to naive recipients |
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Term
| EAE is a mouse model for which human disease? |
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Definition
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Term
| What is pathogenesis of MS? What are the autoantigens found in the brain that contribute to MS? |
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Definition
Autoimmune disease evolve into a chronic state
The constant presence of autoantigen leads to chronic inflammation- tissue damage- release more autoantigens.
Positive feedback loop established from inflammation- start the cycle over again.
MBP- proteolipid protein- myelin oligodendrocyte glycoprotein.
T cell mediated chronic neurological disease- caused by the destructive immune response against brain antigen |
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Term
| What is a microglial cell? Where can we find this cell? |
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Definition
Phagocytic macrophage, likes cells as APC
Found in brain |
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Term
| What is sysmetic lupus erythematous (SLE)? |
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Definition
Systemic disease, circulating autoantibodies initially against cell surface, anti-DNA/RNA antibodies, anti-nucleoprotein antibodies, deposition of complexes in tissues results in more inflammation.
Butterfly rash due to complexes in skin
Example of epitope spreading
Deposition of immune complex leads to activation of phagocytic cells through their Fc receptors- tissues damage- release more nucleoprotein- dna components- form more immune complexes. In SLE- autoantibodies cause damage by both Type II and Type III mechanism, requires the help from T cells. |
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Term
| What are the autoantigens involved in SLE? |
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Definition
Anti-DNA/RNA antibodies
Anti-nucleoprotein antibodies
Autoantigens are from dead and dying cells and are released from injured tissues
Available extracellular and participate in immune-complex formation |
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Term
| What is the special feature in the face of SLE patients? |
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Definition
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Term
| What causes renal failure in SLE patients? |
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Definition
| Large amounts of small immune complexes are produced continouously, deposited in walls of small blood vessels in renal glomerulus- renal failure |
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Term
| What is epitope spreading? |
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Definition
Responses to autoantigens tend to become more diverse as the response persists, due to the autoimmune response to new epitopes.
A B cell presents the H1:MHCII- activates H1-specific Th and B cells
H1-specific Th cell activates DNA-specific B cell
In SLE patients, autoantibodies against both the protein and DNA components of chromatin are found |
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Term
| What is type 1 diabetes? Which cell in pancreas makes insulin? What immune effector cell is responsible for the tissue destruction in this disease? Can patient with type 1 diabetes make insulin? |
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Definition
Type 1 diabetes: lack of insulin
A protein unique to beta cells is the source of autoantigens recognized by the pathogenic CD8 T cells, possibly the peptides from insulin.
Insulin- Beta cells
Glucagon- alpha cells
Effector T cells responsible for the tissue destruction in this disease
No insulin can be made |
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Term
| Mutation of FOXP3 leads to which disease? |
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Definition
Mutation in FOXP3 - IPEX
Immunodysregulation polyendocrinopathy, enteropathy, X-linked
Decreased generation of Tregs |
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Term
| Mutation of AIRE leads to which disease? |
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Definition
| autoimmune polyglandular syndrome type 1 APS1 |
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Term
| Mutation of FAS or FASL leads to which disease? |
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Definition
| Autoimmune lymphoproliferative syndrome (ALPS) |
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Term
|
Definition
Nonfunctional Fas gene, uncontrolled lymphoproliferation
Failure to apoptotic death of self reactive T or B cells, mutation in FAS or FASL |
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Term
| Population studies show association of susceptibility to autoimmune diseases with HLA (MHC Class II) genes- not a question |
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Definition
Susceptibility to type 1 diabetes
Mutation in MHCII binds poorly so negative selection in T cells is less effective |
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Term
| What is molecular mimicry? How can molecular mimicry contribute to autoimmune disease? |
|
Definition
Cross-reactivity
Foreign materials mimic self-antigens leading to T cells attacking viral proteins, side effects is attacking your own tissues with similar antigens. |
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Term
| Name types of transplantation: |
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Definition
Transfusion: blood and blood-derived products
Organ/tissue: solid organs and tissues
Bone marrow: hematopoietic stem cells
*T cell responses to the highly polymorphic MHC molecules trigger a response against the grafted organ* |
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Term
| What is allogeneic draft? What is xenograft? |
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Definition
Allogeneic graft: from another person
Xenograft: from a different species
Syngeneic: from genetically identical person
Autograft: tissue from yourself |
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Term
| In organ transplantation, what is acute rejection? What is accelerated rejection? Why it takes shorter time for the occurrence of the accelerated rejection? |
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Definition
Graft rejection is the result of a T-cell mediated anti-graft response (CD8, CD4)
Graft rejected rapidly- first set rejection
Antibody can also contribute to second-set rejection of tissue grafts (since autobodies are already produced, the graft rejection will occur faster)
Acute rejection: 10-13 days, first set rejection
Accelerated rejection: 6-8 days, second set rejection |
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Term
| What is the most potent antigen that triggers the rejection of initial grafts? |
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Definition
| MHC (major histocompatibility complex), minor histocompatibility antigens can also cause slow graft rejection |
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Term
| What cells express MHC Class II antigen? What cells express MHC Class I antigen? |
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Definition
MHC Class I- predominantly in most tissues
MHC Class II- predominantly in APC |
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Term
| Which T cell recognizes antigens presented by MHC Class I? MHC Class II? |
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Definition
Class I- CD8
Class II- CD4 |
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Term
| When donor and recipient differ at the MHC, an alloreactive immune response is directed at the allogeneic MHC on the graft. Therefore, matching donor and recipient at the MHC can improve the outcome of transplantation. Even with matched MHC, rejection still occurs. Why doesn't this occur and what is the antigen responsible for this type of rejection? |
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Definition
| Even complete matching at the MHC doesn't ensure graft survival due to minor H antigens |
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Term
| What is minor histocompatibility antigen? (Minor H antigen) |
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Definition
Peptides derived from polymorphic cellular proteins bound to MHC Class I
Polymorphic self proteins that differ in amino acid sequence between individuals give rise to minor H antigen differences between donor and recipient |
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Term
| How does hyperacute graft rejection occur? What are the immune responses that are involved in this type of rejection? |
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Definition
Caused by preexisting host antibodies that bind to antigens present in the graft endothelium- antigen recognition activates the complement system and clotting, induces an influx of neutrophils.
Alloantibodies- antibodies produced to non self antigens from another member of the same species. Alloantibodies are developed against blood group antigens.
Explanations for preexisting antibodies that initiate hyperacute rejection:
Recipients of blood transfusions sometimes develop antibodies to MHC antigens from the transfused blood- if some of these antigens match from those in a graft, then hyperacute rejection may result.
Multiple pregnancies may also expose the woman to the paternal antigens of the fetus- resulting in creation of antibodies.
Prior recipients of transplants may have already formed antibodies to other MHC antigens, so they may be present at the time of a second transplant- can avoid by screening for anti-graft antibodies.
In kidney transplants (into a recipient with preexisting antibodies against donor antigens) antibodies against donor antigens bind the vascular endothelium of graft, and initiate an inflammatory response which occludes blood vessels.
The graft becomes engorged and purple in color because of the hemorrhage.
Rejection usually occurs within the first 24 hours after transplantation and occurs so quickly that the tissue never becomes vascularized. |
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Term
| Why do patients need bone marrow transplantation? What is the purpose of bone marrow transplantation? |
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Definition
Replaces the entire hematopoietic system
Use in patients with genetic disease to try and correct the defect- SCID, Fanconi Anemia, Sickle Cell Anemia, severe forms of thalassemia
Use in patients receiving high dose/chemo radiation therapy for cancer: destroys the blood system, leukemia and breast cancer |
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Term
| What is hematopoeisis? Where can we obtain the hematopoietic stem cells? |
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Definition
Hematopoiesis: formation and development of the cells of the blood
Hematopoietic stem cells reside in the bone marrow, able to give rise to all the different types of mature blood cell types |
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Term
| Where do B cells complete most of their development? |
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Definition
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Term
| Where do most of the immune cells including APCs complete their development? |
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Definition
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Term
| The progenitor T cells will migrate to where to complete their development? |
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Definition
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Term
| What is function of the positive selection and MHC restriction during T cell development in the thymus? |
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Definition
| Positive selection is used to generate T cells that can recognize foreign or non self antigens in the context of self MHC |
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Term
| Positive and negative selection: |
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Definition
| Bone marrow transfer from a donor that has both MHC A and MHC B, recipient A responds better to MHC A when immunized. Showing positive selection of T cells is taking place in the recipients. |
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Term
| Why do the bone marrow donor and recipient not need a complete match, but only need to share at least some MHC molecules to restore immune function? |
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Definition
| Bone marrow transplanted- one MHC allele shared- donor cells undergo selection on MHC B in the recipient thymus- MHC B restricted T cells can be activated by MHC AxB APC and recognize infected MHC B cells |
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Term
| When donor marrow (MHC axb) was transplanted to recipient (MHC-b), the APC developed in the recipient will be which MHC type? |
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Definition
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Term
| The thymus environment in the recipient shown in the figure at right is which MHC type? Therefore, based on the MHC restriction, T cell developed in the recipient will be restricted to which MHC type? This type of T cells in the recipient will recognize antigen presented by APC containing which MHC type? |
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Definition
Thymus environment of recipient= MHC-b
T cells developed will be restircted to MHC-b
Will recognize antigen presented on APC containing MHC-b |
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Term
| If the MHCa bone marrow is transplanted into recipient (MHC-b), can the recipient produce mature T cells? What type of MHC that the T cells in the recipient will have? APCs produced in the recipient will have which MHC type? Can the mature T cells in the recipient recognize the antigen presented by APC? |
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Definition
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Term
| What is graft versus host disease (GHVD)? When does this disease occur? |
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Definition
Mature donor T cells that contaminate the allogeneic bone marrow attack the tissues of the recipient
Complement T cells from the recipient attack the bone marrow of the donor, leading to transplant rejection
Can be seen acute (within 100 days) or chronic (after 100 days post transplant)
Symptoms: rash (often starts on the face), diarrhea, pneumonitis, and liver damage |
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Term
| What is the cell type responsible for the tissue attack in GVHD? Does this immune cell come from the donor or recipient? |
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Definition
T cells are responsible for the tissue attack in GVHD
Immune cells come from the donor |
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Term
| What host versus graft disease? |
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Definition
Mature T cells in the HOST recognize GRAFT cells as foreign, resulting in graft failure.
Minimize the threat of HVGD: treat bone marrow recipients with irradiation that kills their own lymphocytes |
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Term
| We can avoid GVHD by extensive depletion of T cells from the donor bone marrow. However, patients have high risk of recurrent leukemia due to loss of T-cell-mediated what effect? What lymphocyte can be replaced to overcome this issue for providing graft-versus tumor (leukemia) effect? |
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Definition
HIgh risk of recurrent leukemia is due to graft versus leukemia effect. Allogeneic bone marrow recognizes tumor antigen expressed by the leukemic cells, leading donor cells to kill the leukemic cells.
"Megadoses" of CD34+
Hematopoietic progenitor cells leads to extensive T cell depletion- elimination of mature T cells from the donor blood marrow. T cell depletion is associated with the high risk recurrent leukemia due to loss of T-cell mediated graft-versus-tumor effect.
Can be overcome by NK-cell mediated graft versus tumor effect in setting of KIR ligand mismatching |
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Term
| What is mixed lymphocyte reaction (MLR)? |
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Definition
Detection of the presence of alloreactive donor T cells
Assays (as shown above) do not accurately quantify alloreactive T cells |
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Term
| What is missing self hypothesis? |
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Definition
Capacity to attack self cells that extinguish expression of MHC Class I molecules
One function of NK cells is to recognize and eliminate cells that fail to express self MHC Class I molecules
Postulates that NK cells are activated to kill target cells, including tumor and virus infected cells, when the NK cell encounters a host cell that lacks self class I MHC
Integration of inhibitory and activating NK cell receptor signals regulates NK decision to kill |
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Term
| What is the function of inhibitor receptors on NK cells? |
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Definition
Key inhibitory KIR recognize MHC Class I alleles providing potential for KIR ligand mismatch- remove the off switch
Most KIR are inhibitory and dominant- regular cells express MHC class I and are therefore recognized by KIR receptors and NK cell killing is inhibited
Inhibitory ligand binding to ITM inhibits dephosphorylation
Receptors are ITIMs: KIR-2DL, KIR-3DL, CD94, NKG2A, B
Key inhibitory receptor in humans= KIR1/2 ligand |
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Term
| What is the function of activating receptor on NK cells? |
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Definition
Bind the activating ligand on the cell and activate the NK cell to trigger death of certain types of target cells, especially those host cells infected with virus or those host cells that have become cancerous
Receptors are ITAMs: KIR-2Ds, KIR-3DS, CD94, NKG2C,E
Stimulatory ligand binding to ITAM leads to cytokine production and cytolytic granule formation |
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Term
| Why is the fetus that is considered as an allograft not rejected by the mother? |
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Definition
Allograft is from genetically dissimilar person, hypotheses for tolerance to the allograft fetus:
Trophoblast (interface between fetal and maternal tissues) doesn't express MHC
Expression of nonclassical HLA Class I (HLA-G) binds inhibitory receptors (KIR1 and KIR2) and inhibits NK killing
The fetus occupies a site protected by an immunological privileged site (tissue barrier is nonimmunogenic)
Uterine epithelium and trophoblast secrete cytokines IL-10 and TNF-alpha that promote an immunosuppressive response in the monitor |
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Term
| What types of cells are directly involved in adaptive immunity? |
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Definition
Cell mediated immunity: CD8 T - cytotoxic T lymphocyte (CTL), Th cells
Humoral immune response- antibodies by B cells |
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Term
| Memory Immune responses are usually developed from which arm of immunity? |
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Definition
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Term
| Before the development of adaptive immune responses, the innate immunity of the host can mediate the initial defense mechnisms. |
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Definition
Pathogens must overcome innate host defenses to establish a focus of infection
The non-specific innate immunity is necessary for an adaptive immunity to be initiated |
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Term
| How are innate immune cells (ie macrophages) activated? |
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Definition
Bindinf of PPR such as TLR will induce the production of what agents, which contributes to local inflammatory responses:
Activation of macrophages: signaling through some receptors- such as TLRs- causes secretion of pro-inflammatory cytokines (IL-1Beta, IL-6, TNF-alpha), chemokines, other chemical mediators, and co-stimulatory molecules
Activation contributes to local inflammatory response
Macrophages express receptors for other bacterial constituents (in add'n to TLRs) including mannose-binding lectin, NOD-like recetors, and NOD |
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Term
| Interferon is important to innate host defense against virus infection, which interferons can interfere with viral replication in host cells? |
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Definition
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Term
| Which innate lymphocytes are critical in early host responses against virus infection? |
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Definition
| NK cells- mediate killing of infected cells ~1-6 days after viral infection |
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Term
| Name examples of effector T cells |
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Definition
CD8 cytotoxic T cells
CD4 Th 1 cells
CD4 Th 2 cells
CD4 Th 17 cells
CD4 regulatory T cells (Tregs) |
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Term
| What is the hallmark of cytokine that is produced by Th1 cells? |
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Definition
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Term
| What are the cytokines that are produced by Th2 cells? |
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Definition
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Term
| What is the hallmark of cytokine that is produced by Th17 cells? |
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Definition
IL-17 (involved in recruitment, activation, and migration of neutrophils)
Il-6
IL-21
IL-22 |
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Term
| What is vaccination? Purpose of vaccination is to generate what? |
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Definition
Administration of antigenic material (the vaccine) to induce protective immunity to a disease
Generates:
Neutralizing antibodies
Effector T cells
Long-lived immunological memory |
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Term
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Definition
Attentuated whole live organisms: viruses (measles, mumps, rubella, varicella/zoster, yellow fever, rotavirus, intranasal, influenza, vaccinia) bacteria (BCG, oral typhoid)
Killed organisms: viruses (polio, hepatitis A, rabies, influenza), bacteria (pertussis, typhoid, cholera, plague)
Fractional vaccines: toxoids (diphtheria, tetanus), protein subunits (HBV, influenza, acellular pertussis, anthrax, papillomavirus) polysaccharides (pure, and conjugate- pneumococcal, meningococcal)
DNA Vaccine |
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Term
| What are the features of effective vaccines? |
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Definition
Safe: vaccine must not itself cause illness/death
Protective: vaccine must protect against illness resulting from exposure to live pathogen
Give sustained protection: protection against illness must last for several years
Induce neutralizing antibody: Some pathogens such as polio virus, infect cells that can't be replaced, neutralizing antibody is essential to prevent infection of such cells
Induces protective T cells: some pathogens, particularly intracellular, are more effectively dealt with by cell mediated responses
Practical considerations: low cost per dose biological stability, ease of administration, few side effects |
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Term
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Definition
Injection of DNA into muscle
Novel means of raising an adaptive immune response (unknown reasons). Upon injection, DNA is expressed and elicits antibody and T cell response to the protein encoded by the DNA
Use of DNA vaccines raises both humoral and cellular immunity |
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Term
| What is adjuvant? What is the function of adjuvant? |
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Definition
Adjuvant is any substance that enhances the immune response to an antigen with which it is mixed
Function: induce the production of pro-inflammatory cytokines, chemokines, and the expression and activity of co-stimulatory molecules
3 types:
Freund's adjuvant: vaccine is suspended in oil droplets and when injected into body, vaccine slowly diffuses out of the oil drop
Alum: when alum/vaccine is injected into body, slowly dissolves
MPL: activates TLR-4 and down-regulates Th2 responses
Mode of action: antigen persistence prolonged, co-stimulatory signals enhanced, local inflammation increased, non-specific stimulation of lymphocytes via induced cytokines.
Adjuvants such as LPS that induce co-stimulatory activity can be co-injected with protein antigens to enhance the immunogenicity |
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Term
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Definition
Incomplete freunds adjuvant: oil in water emulsion
Complete freunds adjuvant: oil in water emulsion with dead mycobacteria
Freunds adjuvant with MDP: oil in water emulsion with muramyldipeptide MDP- constituent of mycobacteria
Alum- aluminum hydroxide gel, good to induce Th2 responses
Alum plus bordatella pertussis- aluminum hydroxide gel with killed B. pertussis
Immune stimulatory complexes- ISCOMs- matrix of Quil A containing viral proteins |
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Term
| Aluminum hydroxide gel is able to induce Nalp3 inflammasome complex that result in the production of which cytokines? |
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Definition
| In vitro, alum/antigen complex increases antigen uptake by APC and induces direct activation of Nlrp3 (Nalp3) inflammasome complex and synergizes with LPS stimulation of TLR4 for the secretion of pro-inflammatory cytokines such as IL-1Beta, IL-18, and IL-33 |
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Term
| Immune stimulatory complexes (ISCOMs) are able to deliver antigens to cytosol for antigen presentation via which pathway (MHC 1 or 2). Therefore, it is potent adjuvant for induction of CD4 or CD8 T cell responses? |
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Definition
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Term
| Examples of immunosuppressive drugs: |
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Definition
Anti-inflammatories: corticosteroid family drugs such as prednisone.
Cytotoxic drugs: inhibit proliferation of lymphocytes by interfering with DNA synthesis
Fungal and bacterial derivatives (aka non-cytotoxic drugs): cyclosporin A- inhibits T cell proliferation
Rapamycin inhibits effector T cell proliferation
Fingolimod: blocks lymphocyte trafficking out of lymphoid tissues |
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Term
| Corticosteroid drug such as prednisone is an anti-inflammatory, what is the mechanism of this drug to suppress inflammation? |
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Definition
Steroid receptors are found in the cytoplasm complexed with heat shock protein, Hsp90
Since the corticosteroid is lipid-soluble, it is able to enter the cell by diffusing across the plasma membrane. Once inside, it binds to the steroid receptor complex, releasing Hsp90. Corticosteroid replaces Hsp90, binds to steroid receptor.
Corticosteroid: steroid receptor complex can now cross the nuclear membrane, steroid receptor interacts with NFkB and thereby inhibits transcription of NFkB target genes. |
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Term
| The effects on gene regulation by corticosteroid therapy |
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Definition
Corticosteroids regulate the expression of many genes, with a net anti-inflammatory effect:
Reduce the production of inflammatory mediators, usually turned on by NFkB, but corticosteroid suppresses. Inhibit migration of inflammatory cells.
Promote cell death |
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Term
| What is the function of NFAT during T cell activation? |
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Definition
NFAT, once dephosphorylated, is able to enter the nucleus and activate IL-2 gene transcription. IL-2 functions in: promoting T cell proliferation, survival, activation, and differentiation into effector T cells.
NFAT phosphorylated by serine/threonine kinase and remains inactive in the cytosol. When Ca binds to calmodulin, causes a conformational change which allows calmodulin to complex with Calcineurin. Calcineurin, serine phosphatase, dephosphorylates NFAT in cytosol, nuclear import, activates IL-2 gene transcription. |
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Term
| What are the drugs that can interfere with T cell signaling, and therefore are used as immunosuppressive agents? |
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Definition
Cyclosporin A
FK506 (Tacrolimus)
Rapamycin (sirolimus)
Fingolimod (FTY720) |
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Term
| Mechanism of cyclosporin A for suppressing immune response |
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Definition
| CsA and FK506 are selective inhibitors of calcineurin. Binding of CsA to intracellular protein immunophilin creates a complex that inhibits calcineurin activation by calmodulin, leading to a downstream effect of interfering with the clonal expansion of lymphocytes. This prevents calcineurin from carrying out its normal function of dephos NFAT, and in doing so prevents IL-2 gene txn and the T-cell responses that come with it. |
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Term
| What is immunosuppressive drug FTY720? What is the mechanism for this drug? |
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Definition
FTY720 is an immunosuppressive drug belonging to the fungal/bacterial family of drugs
The exit of T cells from the lymph node involves the lipid sphingosine 1-phosphate; it allows naive cells that dont' get activated to exit the 2ndary lymphoid organs.
Naive T cells have higher levels of S1P1, and exit the lymph node.
Activated T cells downregulate S1P1, and don't exit for a few days.
FTY720 mimics Sp1 as an agonist, and blocks lymphocyte trafficking out of 2ndary lymphoid tissues (T cells from returning to circulation), by interfering with signaling by the sphingosine-1 phosphate receptor. It causes rapid lymphopenia (T cells all stay in the secondary lymphoid organ), and is used to inhibit the immune responses of transplantation and autoimmunity. |
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Term
| What is S1P1? What type of T cells express higher levels of Sip1? |
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Definition
S1p1 is a lipid with chemotactic activity that controls the exit of T cells from lymph nodes
Naive T cells express higher levels of S1P1 |
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Term
| Why can cytotoxic drugs such as cycylophosphamide be used to suppress immune responses? |
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Definition
Cytotoxic drugs can be used to suppress immune responses because they all block DNA replication and cell division
They are also cytotoxic to dividing T cell lymphocytes and are now used to decrease immune function by reducing immune cell numbers. Side note: originally used in chemo to kill hyperproliferating cancer cells. |
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Term
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Definition
Inhibits cell growth and proliferation by selectively blocking the Ras/MAPK pathway activation of the mTOR kinase mediated by RAPTOR
Rapamycin binds FKBP and this acts to inhibit only the RAPTOR-mediated activation of mTOR (no effect on RICTOR, other PI3-kinase pathway activation)
Thereby selectively reducing T cell growth and proliferation, protein translation, and autophagy by blocking the kinase activity of mTOR |
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Term
| Antibodies can be used to eliminate lymphocytes subsets (B or T) or to reduce lymphocyte function. Name few examples: |
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Definition
O= mouse/murine, all mouse aa's, Muromonab
Xi= chimeric- human constant C and mouse variable V, ex Rituximab
Zu= humanized, mouse complementarity determining regions (CDRs) ie Alemtuzumab
U= human, all human aa, Adalimumab |
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Term
| Antibodies that can be used to reduce lymphocyte functions by binding to cytokine receptors. Name a few examples. |
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Definition
Daclizumab and/or Basiliximab are Anti-IL2R Abs that reduce T-cell activation, and are indicated in kidney transplantation.
Infliximab, Certolizumab, Adalimuab, and/or Golimumab Anti-TNF alpha Abs inhibit inflammation induced by TNF-alpha, and are indicated in Crohn's disease (Infliximab) and RA |
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Term
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Definition
CTLA-4 (cytotoxic lymphocyte antigen-4): a CD28 homologue that binds to B7 with higher affinity than CD28
CTLA-4 is a high-affinity receptor for B7 molecules on T-cells; it is inhibitory in that its binding blocks CD28 co-stimulatory binding (and CTLA-4 has a higher affinity than CD28 for B7), thereby suppressing T-cell activation
Activated T cells express CTLA-4; CTLA-4 transduces a negative signal to T cells and functios to attenuate the immune response, so this is the theoretical "brake" to the CD28 "gas" and is how T-cells regulate their activation |
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Term
| What is CTLA-4 Ig? Why can CTLA-4 Ig suppress T cell response? |
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Definition
| It's a soluble recombinant protein made up of CTLA-4 fused to the Fc portion of human Ig, it binds to B7 molecules on APCs and inhibits CD28- B7 co-stimulatory interactions, and thereby suppresses the T cell response |
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Term
| Antibody can be used to suppress the immune responses that are involved in the pathogenesis of a number of autoimmune diseases, name examples of antibody used for rheumatoid arthritis (RA): |
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Definition
Certolizumab, adalimuab, and/or golimumab are anti-TNF alpha Abs inhibit inflammation induced by TNF-alpha, and are indicated in RA.
Tocilizumab is an anti-IL6R Ab that blocks inflammation induced by IL-6 signaling, and is indicated in RA. |
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Term
| Method (or drugs developed) to block inflammation caused by IL-IBeta? |
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Definition
Anakinra is an IL-1 receptor agonist that leads to blockage of the IL-1Beta receptor
Canakinumab is a Anti-IL-1Beta Ab that blocks inflammation caused by IL-1 and is indicated in muckle-wells syndrome |
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Term
| Antibody that is used to block lymphocyte trafficking as a treatment for MS? |
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Definition
| Natalizumab is an Anti-alpha 4 integrin that blocks lymphocyte trafficking (prevents homing of immune cells to CNS, and is used to treat MS |
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Term
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Definition
Indoleamine 2,3, dioxygenase
Subsequent to CTLA-4 binding to B7 on APC, IDO activity decreased the amount of free tryptophan in the tissue microenvironment, an essential AA for Teff proliferation |
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Term
| Colitis is an inflammatory bowel disease, and can be treated by transfer of what type of T cells? |
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Definition
Colitis can be treated by transfer of CD4/CD25 Treg cells
CD4 CD25 Treg cells proliferate and inhibit the pathogenic effector T cells
CD4 CD25 Treg cells suppress the autoreactive T cells in the inflamed GI tract so they cannot proliferate |
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Term
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Definition
Carcinomas are based on the cells derived from the inner cell layer, endoderm during development. This includes the epithelia of the lungs, liver, gallbladder, pancreas, esophagus, stomach, and intestines.
2 major categories of carcinomas:
Squamouse cell carcinomas: form protective cell layers
Adenocarcinomas: secrete substances |
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Term
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Definition
Sarcomas are from non-epithelial tissues derived from mesoderm.
Ie fibroblasts, adipocytes, osteoblasts, myocytes |
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Term
| What is leukemia? What is lymphoma? |
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Definition
Both leukemia and lymphoma are non-epithelial cancers in the hematopoietic system derived from hematopoietic immune cels.
Leukemia is defined by malignant derivatives of several of the hematopoietic cell lineages that move freely through the circulation.
Lymphoma is defined by tumors of lymphoid lineages (B and T) that aggregate to form solid tumor masses, most frequently found in lymph nodes, rather than dispersed, single-cell populations of tumor cells seen in leukemia |
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Term
| B cell development takes place in where? |
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Definition
| In bone marrow where B-cell precursor rearranges its Ig genes and negative selection takes place. After this, there is migration of B cells to secondary lymphoid tissues and activation by binding to foreign antigens. Activated B cells give rise to plasma cells and memory cells in bone marrow and lymphoid tissue. |
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Term
| What is plasma cell? What is multiple myeloma? |
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Definition
Plasma cells are activated B- cells that secrete antibodies. From the germinal center (site of rapid B-cell proliferation and differentiation), plasma cells migrate to the medullary cords or leave via the efferent lymphatics and migrate to the bone marrow.
Multiple myeloma is a tumor of plasma cells in the bone marrow; it is marked by the accumulation of malignant plasma cells in bone, which has eroded the normal calcification in the bone and left an empty looking spot as seen via x-ray. |
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Term
| Where is the primary organ that plasma cell migrate to? |
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Definition
| The majority of plasma cells migrate to the bone marrow |
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Term
| Where does T cell development take place? |
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Definition
| T-cell precursors migrate to the thymus, where T-cell development takes place |
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Term
| In healthy individuals, immature thymocytes should stay in where? Mature T cells "single positive" thymocytes will be found in the periphery... |
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Definition
| In healthy individuals, immature "double positive" or DN thymocytes should stay in the thymus |
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Term
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Definition
A type of cutaneous T-cell lymphoma that clinically presents as mushroom-like tumors, 3 phases of progression:
1. macular erythematous eruption
2. plaque/patch phase, resembles eczema/psoriasis
3. tumor nodules/erythroderma and associated adenopathy or visceral involvement
In sezary syndrome, a transformed mature T-cell type of tumor, one witnesses generalized erythroderma and puritis as well as circulating malignant Sezary T cells |
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Term
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Definition
YES, they're immunogenic since tumors expressing specific antigens; they can be considered as seen by the body as host or foreign.
This was shown via mouse experiment; tumor rejection antigens are specific to individual tumors. |
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Term
| Examples of tumor antigens? |
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Definition
MAGE-1, MAGE-3, NY-ESO1 for Melanoma and breast
Her-2/neu for breast
Wilm's tumor for leukemia
GP100 and TRP2 for melanoma |
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Term
| What is cancer immunosurveillance? Three E phases? |
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Definition
Cancer immunosurveillance is the ability of the immune system to detect tumor cells and destroy them, controlling malignant cells; lymphocytes act as sentinels in recognizing and eliminating continuously arising, nascent transformed mutant cells.
Elimination
Equilibrium
Escape |
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Term
| Propose mice study to prove concept of cancer immunosurveillance? |
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Definition
Do transgenic mice knockouts:
RAG2 ko
IFN-gammaR ko
STAT1 ko
When immune system compromised, tumor incidence is dramatically increased. |
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Term
| Variant tumor cells lacking MHC Class I will be the target for which innate immune cells? |
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Definition
Variant tumor cells lacking MHC Class I will be the target for NK cells. NK cells mediate cytotoxicity of cells which have down-regulated their MHC Class I via ADCC (antibody dependent cell mediated cytotoxicity) using perforin, granzymes, and Fas L
NK activity is spontaneous and occurs immediately in the absence of deliberate prior sensitization. It isn't MHC restricted and doesn't require target cell expression of self-MHC Class 1 or class 2 antigens. It uses multiple cell surface receptors, activating receptors ITAM and inhibitory receptors ITIM |
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Term
| Name mechanisms by which tumors avoid immune recognition |
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Definition
Low immunogenicity- down-regulation of MHC expression
Tumor treated as self-antigen
Antigenic modulation
Tumor-induced immune suppression- IDO depletes tryptophan, TGF-beta can cause Treg proliferation
Tumor-induced privileged site |
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Term
| Can chronic inflammation promote cancer development? |
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Definition
Yes, if tumors cause bad or chronic inflammation they suppress good inflammatory T cell responses. In this cause, instead chronic inflammation results in failure to eradicate tumor cells, and switches on angiogenesis favoring tumor growth.
Increased infiltration and activation of immune cells- perpetuation of inflammation- activated phagocytic cells at site of inflammation- ROS- oxidative stress can cause oxidative deamination, a DNA damaging mutagenic event that downstream may lead to cancer development |
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Term
| What is cancer immunotherapy? |
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Definition
| Cancer immunotherapy is harnessing our immune systems to enhance anti-tumor immunity and eliminate malignant tumor cells. Methods include cellular therapy, cancer vaccines, cytokine immunotherapy, monoclonal antibody immunotherapy. |
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Term
| Types of antibody-mediated cytotoxicity? |
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Definition
Tumor-specific antibody, anitbodies bind to the tumor cell, NK cells with Fc receptors (CD16) are activated to kill the tumor cells
Tumor-specific antibody conjugated to toxin: antibody toxin conjugates bind to the tumor cell, conjugates are internalized killing the cell
Tumor-specific antibody conjugated to radionuclide: radioactive antibody binds to the tumor cell, radiation kills the tumor cell and neighboring tumor cells |
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Term
| How can NK cells kill tumors if anti-tumor antibody binds to the tumor cells? |
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Definition
| NK cells with Fc gamma receptors (CD16) are activated to kill tumor cells via ADCC (antibody dependent cell mediated cytotoxicity) |
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Term
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Definition
Anti-CD11a AB blocks interaction between LFA-1 on T cells and adhesion molecules ICAM-1 on APCs
Integrin LFA-1 inhibits migration of DCs and T cells into psoriatic skin lesions and reduces inflammation |
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Term
| Immunomodulatory effects of VItamin D3? |
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Definition
Essential hormone for bone and mineral homeostasis. Vitamin D3 inhibits expression of costimulatory molecules and peptide: MHC complexes in DCs, resulting in reduced efficiency of antigen presentation to T cells
Inhibits IL-12 production and results in shift from Th1 to Th2/Treg production |
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