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What is the immune response?
A collective and coordinated response of cells of the immune system
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What are the 3 functions of immunity?
- Protect host from invasion of anything foreign
- Distinguish self from non-self
- Mediate healing
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Which cell of innate immunity Are phagocytic cells?
Monocytes, macrophages and dendritic cells
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Which cell of innate immunity Are antigen presenting cells (APC)?
Monocytes, macrophages and dendritic cells
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Are very important in Agn binding and non-specific phagocytosis?
Neutrophils
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Are also known as polymorphonuclear leukocytes?
Neutrophils
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Which cell of innate immunity Fight parasites?
Eosinophils
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Which cell of innate immunity Are very important in inflammatory response?
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Which cell of innate immunity release potent mediators during allergic responses?
Basophils
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Which cell of innate immunity have binding sites for IgE Abys?
Basophils
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Which cell of innate immunity releases histamine but is found in tissues?
Mast Cells
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Which cell of innate immunity can bind with Aby coated target cells?
Natural Killer Cells
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Which cell of innate immunity is involved in antibody dependent cell-mediated cytotoxicity?
Natural killer cells
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Which cell of innate immunity can attack virus-infected cells or cancer cells without help or activation first?
Natural killer cells
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Which cell of innate immunity can recognize Agn without MHC resitrictions?
Natural killer cells
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Which cell of innate immunity are regulated by cytokines, prostaglandins and thromboxane and release toxins?
Natural killer cells
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What happens when APCs are activated?
They secrete cytokines
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What are the two major components of adaptive immunity?
- Cell-mediated
- Aby-mediated
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Which type of immunity is specific and acquired?
Adaptive Immunity
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Which type of immunity is the first line of defense?
Innate Immunity
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What are cytokines made by?
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What is lymphokine?
Special cytokine released by lymphocyte
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What are released by immune cells and act on other immune cells?
Cytokines
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What part of the inflammatory response are cytokines important?
Early on
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What stimulates the acute phase protein production by the liver?
Cytokines
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What is the action of cytokines in adaptive immunity?
Activate immune cells to proliferate and differentiate into effector and memory cells.
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What is triggered when first line of defense’s integrity has been breached?
Inflammation
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What are the three steps of the vascular phase of acute inflammation?
- Rapid vasoconstriction of small vessels
- Rapid vasodilation of arterioles and venules
- Increased capillary permeability
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How long does an immediate sustained response last and what occurs as a result?
Several days and can cause vessel damage
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What is the delayed hemodynamic response?
Increased capillary response 4-24 hours after an injury
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What allows leukocytes to migrate to the local area during the cellular phase of inflammation?
- Release of cytokines by innate immunity cells
- Increased capillary permeability
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Which inflammatory mediater causes dilation and increased capillary permeability?
Histamine
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What is released from mast cells in response to binding of IgE Abys?
Histamine
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What are the two pathways that can metabolize arachidonic acid?
- Cyclooxygenase pathway
- Lipoxygenase pathway
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What does the cyclooxygenase pathway metabolism of arachidonic acid produce?
- Inflammation (prostoglandins)
- Platelet aggregation (TXA2)
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What inhibits the first enzyme in the cyclooxygenase pathway?
Non-steroidals (aspirin)
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What does the lipoxygenase pathway metabolism of arachidonic acid pathway produce?
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What do newer anti-asthma drugs (Singulair) target?
Lipoxygenase pathway of arachidonic acid metabolism
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What three actions does platelet activating factor produce?
- Platelet aggregation
- Neutrophil activation
- Eosinophil chemotaxis
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What is the primary mediator of the innate and adaptive humoral immune response?
Complement System
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What are the three pathways that activate the complement system?
- Classical Pathway
- Alternate Pathway
- Lectin Pathway
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What is the main activity of the Classical Pathway of complement activation?
- IgG or IgM binds to invading org.
- Bind complement to circulations Agn-Aby complex
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What is the main activity of the Alternate Pathway of complement activation?
Interactions between complement and polysaccharides on microbes
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What is the main activity of the Lectin Pathway of complement activation?
Binding proteins interacting with cell surface proteins in bacteria and yeast
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Where do the three pathways of activating the complement system converge?
C3
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What does the membrane attack complex do?
Creates a hole in the target cell membrane causing lysis
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What four things result from the activation of C3?
- Inflammation
- Opsonization
- Chemotaxis
- Membrane attack complex
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What is opsonization?
Increased phagocytosis as a result of complement-binding
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What does anaphylatoxin induce?
Histamine release in mast cells and basophils
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What is the result of histamine release?
- Contraction of smooth muscle
- Increased muscle permeability
- Edema
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What causes chronic inflammation?
Moderate to low-grade persistent irritants
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What are two patterns of chronic inflammation?
- Non-specific diffuse accumulation of cells of the inflammatory response that leads to fibroblast proliferation and scar tissue
- Granulomatous lesion (local)
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What is exravascular influx of fluid with a high concentration of proteins, salts, cells and cell debris?
exudation
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What does exudation do?
- Dilutes injurous chemicals
- Brings complement, Abys and chemotaxic substances
- Pull water out of plasma and promotes containment of pathogens
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What is fibrinous exudate?
Contains large amounts of fibrinogen
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What type of exudate contains necrotic debris in fibrinous matrix on mucus membrane surface?
Membranous exudate
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Why does autocrine and paracrine signaling predominate in inflammation?
Inflammatory mediators have very short half lives
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When do systemic signs of inflammation appear?
When inflammation is large/robust enough
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What are signs of systemic inflammation?
- Increase in plasma proteins
- Increase erythrocyte sedimentation rate
- Fever
- Leukocytosis
- Muscle wasting (negative nitrogen balance)
- Lymphadenitis
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What is lymphadenitis?
Regional swelling of lymph nodes, painful upon palpation
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What is the focus of treatment for inflammation?
Prevent synthesis and release of pro-inflammatory mediators
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Which anti-inflammatory drugs inhibit cyclooxgenase?
NSAIDs
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What is cyclooxygenase?
An enzyme that converts arachidonic acid to prostaglandins and thromboxane
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Which anit-inflammatory drugs work in several ways, mostly to impair immune cell proliferation or cytokine release?
Steroids
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What is responsible for the adverse effects of NSAIDs?
Inhibition of COX-1
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Which COX inhibition impairs the GI mucosal barrier, impairs renal function and prevents platelet aggregation?
COX-1
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Which COX is predominantly in immune cells?
COX-2
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Which COX inhibition results in the therapeutically desireable effects of NSAIDs?
COX-2
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What is the result of inhibiting COX-2?
- Suppression of inflammation
- Alleviation of pain
- Reduction of fever
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Why should NSAIDs be avoided in mid- to late-pregnancy?
- May cause premature closure of ductus arteriosus
- Might cause prolonged bleeding following delivery because of their effect on platelets
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What is an irreversible inhibitor of both COX-1 and COX-2?
Aspirin
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What is aspirin metabolized into and how long does it take?
Salicylic acid, about 20 minutes
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What inhibits both COXs reversibly and has a longer half-life than aspirin?
Salicylic Acid
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What are the uses of Aspirin?
- Anti-inflammatory
- Anti-pyretic
- Analgesic
- Dysmenorrheal
- Suppression of platelet aggregation
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How is aspirin used to suppress platelet aggregation?
81-mg enteric coated tablet, 1/day
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What adverse effects are common to all aspirin formulations?
- Salicylism
- Reye’s syndrome
- Poisoning
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What are the symptoms of salicylism?
- Tinnitus
- Headache
- Dizziness
- Possibly rheumatoid arthritis and respiratory alkalosis
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What are five aspirin formulations?
- Plain aspirin tablet
- Buffered aspirin
- Enteric coated aspirin
- Time released
- Rectal suppositories
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What are adverse effects of nonspecific COX inhibitors?
Interaction with warfarin, increased bleeding
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What are adverse effects of specific COX-2 inhibitors?
Increased risk of heart attacks
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What are the major functional cells of the adaptive immune response?
- B-cell lymphocytes
- t-cell lymphocytes
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What are two types of t-cell lymphocytes?
- T-helper cells
- Cytotoxic T Cells
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Under what circumstances can a hapten become immunologically active?
When it is bound to a carrier protein
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What is the Major Histocompatibility Complex (MHC)?
- Differentiates between self and non-self
- Differentiates individuals within same species
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Which cells recognize MHC complexed with antigen?
- Cytotoxic T Cells
- T Helper Cells
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Which MHC are found primarily on Agn presenting cells?
MHC II
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Which MHC are found on most all nucleated cells of the body?
MHC-I
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Where do lymphocytes stem cells reside?
Bone marrow
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Which lymphocytes migrate through lymphoid tissue?
B cells
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Which lymphocytes undergo a genetic rearrangement that results in a unique receptor and type of effector Aby?
B lymphocytes
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What do B lymphocytes differentiate into with the help of T helper cells?
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What occurs during the primary immune response?
- Agn is introduced into body
- Agn is processed
- MHC-Agn complex is ID by T helper cell
- Activated T helper cells release cytokines
- Cytokines trigger B cells to make plasma and memory cells
- Plasma cells release Aby
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What occurs during secondary immune response?
Memory cells ID Agn and respond quickly
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Which Aby is found primarily on a cell membrane of B lymphocytes and acts an antigen receptor?
IgD
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Which Aby is involved in inflammation, allergic responses and combating parasitic infections?
IgE
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Where do T-cells undergo genetic modification to form a unique T-cell Agn receptor?
Peripheral lymphoid organs
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What is a T-cell receptor with a CD4+ protein called?
T-helper cell
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What is a T-cell receptor with a CD8+ protein called?
Cytotoxic T-cell
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Which T cell is the regulatory master switch of the immune system?
Helper T cell
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Which T-cell is an effector cell?
Cytotoxic T-cell
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What activates T-helper cells?
Agn recognition and cytokines
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Why are secondary lympoid organs important?
Support lymphocytes
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What are three secondary lymphoid organs?
- Lymph nodes
- Spleen
- MALT (Mucosa-Associated Lymphoid Tissue)
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When are adult levels of Igs reached?
Between 1-2 years
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Which Ig can transform into other Igs after Agn stimulus?
IgM
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What kind of immunodeficiency is a primary disorder and causes a delay in the maturation of B cells in children?
Transient Hypogammaglobulinemia of Infancy
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What are children who have Transient Hypogammaglobulinemia more prone to?
Upper respiratory and middle ear infections
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What is the source of primary immunodeficiency?
Defective congenital or inherited genes
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What are three rare primary immunodeficiencies?
- X linked agammaglobulinemia-Bruton’s (no Abys)
- DiGeorge Syndrom (lack of thymus)
- Severe combined immunodeficiency syndrome (no T/B cells)
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What is the source of secondary immunodeficiency and when do they occur?
- Later in life…
- Selective loss of Igs through GI or GU tract
- Chronic/recurrent infections
- Neoplasia
- Iatrogenic causes
- Stress/aging
- Drug abuse, maternal alcoholism
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What are the four types of hypersensitivity disorders?
- Type I: IgE mediated
- Type II: Aby-mediated
- Type III: Immune Complex Allergic Disease
- Type IV: T-cell mediated
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Which hypersensitivity disorder is short-term, causes itchy skin and can cause anaphylaxis and is triggered by binding of Agn to mast cell or basophil with attached IgE?
Type I: IgE-mediate
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What is released during the primary phase of Type I: IgE-mediated hypersensitivity?
- Histamine
- Compliment is activated
- Ach causes bronchoconstriction and vasodilaion of small vessels
- Chemotaxis
- Kinis are activated
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What is released during secondary phase of Type 1: IgE mediated hypersensitivity?
- Leukotrienes
- Cytokines
- Platelet activating factor
- prostaglandins
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What are two types of IgE-mediated disorders?
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Which IgE-mediated disorder is local-anaphylaxis?
Atopic
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What are common allergens for non-atopic IgE mediated disorders?
Nuts, shellfish, penicillin, insect stings
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What kind of receptor does an antihistamine block?
H1
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What else do most first generation H1 blockers also block that have sedating effects?
Muscarinic receptors
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What are some examples of Type II-Aby mediated disorders?
- ABO antigens in blood transfusion reactions
- Rh Antigens of fetus
- Drug Reactions
- Autoimmune hemolytic anemia
- Graft rejections, parasites
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Which hypersensitiviy involves antibody cytotoxicity?
Type II-Aby-mediated
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What is Type III-Immune Complex allergic disease triggered by?
Formulation of insoluble Agn-Aby complexes in blood circulation or extravascular sites that lead to precipitate formation and complement activation
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What type of injuries are caused by Type III-Immune Complex Allergic Disease?
- Change in blood flow
- Vacular permeability
- Inflammatory response
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What can localized reactions of Immune Complex disorders lead to?
- Vasculitis
- Immune Complex Pneumonitis
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Which hypersensitivity has a delayed response, is triggerd by specifically sensitized T-lymphocytes and not antibodies and are not tissue specific?
Type IV T-Cell mediated
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What are three types of Type IV T-cell mediated hypersensitivity?
- Contact dermatitis
- Response to the Tuberculin test
- Granulomatous inflammation with large, insoluble Agns
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What is Host Versus Graft Disease?
A cell-mediated response where recipient attacks donor cells
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What three responses occur when T-helper cells activate the production of antibodies and targe graft vasculature?
- Complement-mediated toxicity (Type II)
- Agn-Aby complexes (Type III)
- Antibody-mediated cytolysis (Type II)
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What immune disease may be T cell-mediated or Agn-Aby complexes, more common in females and elderly, tissue or system specific.
Autoimmunity
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What is Rheumatoid Factor an antibody against?
IgG
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What are rheumatoid nodules?
bumps that form under the skin close to the joints
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What are three major systemic manifestations of RA?
- Vasculaitis
- Pleuritis
- Pericarditis
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What signs are used to diagnose RA?
- Morning stiffness for > 1 horu
- Swelling of >3 joints for >6 weeks
- Symmetric joint swelling
- Rheumatoid nodules
- Presence of serum RF Aby
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What medications are used to treat RA?
- NSAIDs
- Disease Modifying Anti-Rheumatic Drugs
- Immunosuppressants
- Corticosteroids
- Combo therapy
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What are two actions of disease modifying anti-rheumatic drugs?
- Reduced number of immune cells
- Block cytokines
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What are primary causes of OA?
Idiopathic, no identified risk factors
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What are secondary causes of OA?
- Joint stress
- Congenital abnormalities
- Joint instability
- Trauma
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What are some signs and symptoms of OA?
- Sudden/insidious
- Mild synovitis
- Hip, knee, lumbar an cervical region
- Joint enlargment
- Hard joint
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What are the main differences between RA and OA?
- No or very little synovitis
- No systemic signs and symptoms
- Normal synovial fluid (no pannus)
- Affects cartilage and subchondral bone only
- Not always symmetric
- Not always polyarticular
- Hardness around joint
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What are some causes of secondary immunodeficiency?
- Nutrition
- Chemotherapy
- Burns
- Stress
- AIDS
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Two big risk factors for patients infected with HIV?
- Opportunistic infections
- Neoplastic complications
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What are the components of the HIV viral genome?
- Two short strands of RNA
- Three major genes that encode reverse transcriptase, protease and integrase
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What are the components of the outer lipid envelop of the HIV viron?
GP 120 Antigen, which binds to CD4 of T-helper cell
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What is used to classify HIV infection?
CD4 cell count
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Which classification of HIV infection is characterized by a positive test for HIV Aby’s but only produces mild disease or is asymptomatic?
Primary Infection
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Which classification of HIV infection may last 10 years and is concentrated in the lymph nodes, is asymptomatic and not very well detected in blood?
Latent Period
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What happens to CD4 cell count during latent period HIV infection?
Falls gradually
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What is clinically apparent HIV disease characterized by?
- Persistent generalized lymphadenopathy
- Fatigue, weight loss, night sweats
- Diarrhea
- Fungal infections
- CD4 count < 500 cells
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What is full blown AIDS characterized by?
- CD4 count < 200 cells
- Opportunistic infections
- Neoplastic malignancies
- Wasting Syndrome
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What are patients with HIV disases most likely to die from?
Neoplastic complications and opportunistic infections
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How is HIV diagnosed?
- HIV aby test
- Western Blot
- CD4 count
- Symptoms
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