MMSC415 Exam 2

sensitization

first exposure to an antigen; forms memory cells

Hypersensitivity

heightened or inappropriate immune response that can result in host tissue damage

Immediate, antibody mediated

Types I-III hypersensitivity reactions

delayed cell-mediated

Type IV hypersensitivity

allergens

noninfectious immunogens that induce a hypersensitivity reaction

chemotaxis

chemical signals attract phagocytes to microorganisms

histamine

A chemical released by the body during an inflammatory response that causes the blood vessels to dilate

Type I hypersensitivity reaction

anaphylactic (IgE), release of mediators from mast cells and basophils

IL-4 and IL-13

signals for class-switching to the IgE isotype

Type II hypersensitivity reaction

-Cytotoxic

-Antibody attacks the antigen leading to lysis (complement mediated)

-IgG & IgM are the principal antibodies involved

Type II

Blood transfusion reactions, hemolytic anemia, and rheumatic fever are all examples of what category of hypersensitivity reaction?

Type III hypersensitivity reaction

-Immune complex

-Occurs when an accumulation of antibody-antigen complexes have not been cleared

-This inflammatory state attracts neutrophils

-Lysosomal enzymes released by neutrophils leads to tissue destruction

-IgG & IgM are the principal antibodies involved

-Examples: Rheumatoid arthritis, systemic lupus erythematosus, serum sickness

Type IV hypersensitivity reaction

-Delayed hypersensitivity reactions; overreaction of CMI response

-Ex: tuberculin-type sensitivity and contact sensitivity

Tdth cells

delayed type hypersensitivity effector cells; CD4+ lymphocytes; MHC II class; similar to T helper cells

mast cells and basophils

nonphagocytic lymphocytes that degranulate and release heparin, histamine, proteases, etc.

Early phase of Type 1 hypersensitivity

mast cell degranulation occurs within seconds; activates platelets, increased capillary permeability, vasodilation

late phase of type 1 hypersensitivity

eosinophils, PMNs, and macrophages arrive and degranulate; 2nd release of mediators

anaphylactic shock

lightheadedness, fainting, low BP, difficulty/rapid breathing, wheezing, hives, rashes, nausea, vomiting

respiratory allergy

chest tightness, shallow breathing, coughing, wheezing

food allergy

tingling/itchy of mouth, hives, swelling of face/mouth/throat, wheezing, lightheadedness

asthma

environmental factors such as pollution, sulfur dioxide, nitrogen oxide, ozone, cold temps, and high humidity are known to trigger:

Radioallergosorbent test (RAST)

blood test that measures ANTIGEN-SPECIFIC IgE

Radioimmunosorbent test (RIST)

Measures total serum IgE

RIST

test that would used to determine if the patient is having an allergic reaction and severity of reaction; measures total serum IgE

RAST

test used to figure out exactly what patients are allergic to; measures Ag-specific IgE

immunotherapy (allergy shots)

desensitization; repeated injections of allergen that gradually increase and patient becomes tolerant of allergen; downregulation of TH2 cells and HMI response, upregulation of TH1 cells

incompatible

blood diffusions are _______ if RBCs are attacked by antibodies

incompatible blood transfusion

lower back pain, blood in urine, chills, fever, nausea, vomiting, shortness of breath, increased heart rate, pain at infusion sight, chest pain, bronchospasm, jaundice, acute kidney failure, low BP, and disseminated intravascular coagulation (DIC) are indicative of:

hemolytic disease of the newborn (HDN)

condition developing in fetus when mother's blood type is Rh-negative and baby's blood is Rh-positive; indicated by yellow amniotic fluid, hydrops fetalis

Drug-induced hemolytic anemia

symptoms include dark urine, fatigue, pale skin, rapid heart rate, shortness of breath, jaundice; drug acts as hapten; ex; Penicillin

rheumatic fever

Streptococcus pyogenes and Abs to M proteins; molecular mimicry

rheumatic fever

symptoms include fever, arthritis, congestive heart failure, fatigue, jerky/uncontrolled body movements, painless lumps, rash, heart murmur, enlarged heart, fluid around heart

Arthus reaction

localized areas of erythema and hard swelling (induration)

serum sickness

patients who receive heterologous serum; if antibodies in excess, small complexes are not cleared easily; symptoms include fever, hives, itching, rash, swollen lymph nodes

pneumonitis

characterized by chills, cough, dyspnea, fever; results from inhaled allergens

Farmer's lung

hypersensitivity pneumonitis caused by inhaling moldy hay

glomerulonephritis

inflammation of the glomeruli of the kidney; Streptococcus pyogenes can produce proteins with affinity for glomeruli; symptoms include pink/cola colored urine, foamy urine, hypertension, edema

Tuberculin reaction

Acute skin inflammation at the injection site following an extract of Mycobacterium tuberculosis; PPD; occurs in individuals infected with or vaccinated against TB

contact dermatitis

An inflammation of the skin caused by having contact with certain chemicals or substances (usually haptens); symptoms include skin pain, rashes, redness, blisters, hives, peeling, ulcers

Granulomatous inflammation

allergen persists; chronic exposure to antigens; granulomas form to try to contain Ag; symptoms = fever, chest pain, swollen/sore glands, persistent runny nose, skin irritation, mouth swelling/redness, GI problems

primary immunodeficiency

congenital; immunodeficiency results genetically

acquired immunodeficiency

loss of function after exposure to some agent; can be transient

tumor surveillance hypothesis

Paul Ehrlich; immune cells recognize other cells so they could potentially destroy tumor cells (not true); major cancers do not occur at a higher rate

Severe Combined Immunodeficiency (SCID)

family of disorders that results from a defect in lymph development that affects either T or B cells; failure to perform HMI or CMI response

Th cells (low in SCID)

a defect in these cells can lead to SCID because they affect the HMI and CMI response

Chronic Granulomatous Disease (CGD)

- Lack of NADPH oxidase activity --> impotent phagocytes

-Phagocytosis can't happen due to lack of ROI's

indicators of immunodeficiencies

chronic and recurrent infections, increased incidence of tumors

X-linked agammaglobulinemia (XLA)

defect in protein kinase (Bruton tyrosine kinase, BTK), intracellular signaling in B cells; B cells do not mature; B cells are in bone marrow but no where else; characterized by low level/absent Abs

Selective IgA deficiency

Most common primary immunodeficiency; increased upper respiratory tract infections; inability to detect IgA

DiGeorge Anomaly

thymus fails to develop; affects T cells; immature T cells are produced but have no thymus to mature in; hypoparathyroidism -> hypocalcemia

- developmental delays and cleft palate

X-linked hyper IgM syndrome

defect in CD40L on activated T cells; results in decreased T-cell dependent responses; cannot undergo class-switching (IgM only)

Adenosine deaminase (ADA) deficiency

approx. 20% of patients w/ SCID; leads to accumulation of toxic metabolic by-products; similar to Purine Nucleotide Phosphorylase (PNP)

Wiskott-Aldrich Syndrome (WAS)

- x-linked

- WAS protein (WASp) defective

- affects interactions between T and B cells and other cells

- severity increases with age

- small & abnormal platelets (decreased clotting)

- thrombocytopenia (decreased platelets)

- impares cell signaling and actin cytoskeleton function

Ataxia telangiectasia (Louis-Bar Syndrome)

mutated AT involved in DNA repair; decreased IgA; increased a-fetal protein & carcinoembryonic Ag (often used to screen for cancer)

- Poor Coordination and small dilated blood vessels

- Mutation to ATM gene and inhibits DNA repair

classical pathway

decrease in C1qrs, C2, C3, C4 leads to an increase in infections and decrease in what complement pathway?

Complement Pathway Deficiency

-C1, C4, and C2

- Decrease in immune complex clearance

-C3

-Decrease to opsonization

-Increased susceptibility to encapsulated bacteria

evaluation of B cells

- Tests for IgG, IgA, and IgM

- HMI response

Evaluation of T Cells

- CMI Response

- Initial screen for HIV

- Check T cells with CD3, CD4, and CD8

- Skin testing

Autoimmunity

attacking one's immune system attacking its own healthy tissues or cells, affects 5-10% of the population

loss of tolerance

when own immune system cannot distinguish self vs. non-self

- Negative selection of B and T cells

- Lymphatic exclusion of brain, eyes, and testes

- Treg cell suppression (inability to shut down T cells)

molecular mimicry

Structural similarities between microbial and self antigens

possible mechanisms causing autoimmune disease

- loss of self-tolerance

- impaired Treg cells

- enhanced Th cells

- viral infection

- heredity

- sex hormones

- mimicry/cell damage

multifactor

meaning influenced by polygenic and environmental factors (could be genetic, but triggered by an environmental stimuli)

systemic lupus erythematosus (SLE)

highly variable chronic inflammatory disease alternating flares and remissions; fever, fatigue, butterfly rash, arthritis, hepatic inflammation, glomerulonephritis, hemolytic anemia, lymphadenopathy

antinuclear antibody (ANA)

Nonspecific screening antibody, often associated with SLE

- ~95% of Lupus patients will have positive ANA antibodies

ELISA

semi-automated ANA method; determines titer quickly

- Used as an assay, labeled antibody will change color

Immunofluorescence

ANA method where cells are affixed to slides and serum; if Ab is present, it will bind to Ag and glow; advantage = different staining patterns for different autoimmune diseases

anti-dsDNA

SLE specific test that has a higher positive predictive value (PPV) than ANA

Anti-phospholipid (aPL) antibody

less sensitive SLE diagnostic test with higher PPV than ANA; anti-cardiolipin

Anti-Sm (Smith)

most specific test for SLE

rheumatoid arthritis

conditions with symptoms of joint pain, swelling, and progressive destruction of cartilage

homogeneous

even, smooth stain of nuclei (most common in SLE) in ANA testing

speckled

small signals within nuclei of ANA testing method

nucleolar

darker staining of nucleus in ANA method

nuclear membrane

darker staining of membrane in ANA method

rheumatoid factor

IgM against Fc portion of self IgG

RA diagnosis

1. Erythrocyte sedimentation rate (ESR) or CRP to confirm inflammation

2. ANA to test for auto-antibodies

3. RF test to test for Rheumatoid Factor

Multiple Sclerosis (MS)

genetic disorder in which molecular mimicry of myelin basic protein (MBP); results in inflammation surrounding the venules of the CNS and extends into myelin sheath

Multiple Sclerosis (MS)

symptoms of the condition include: disturbance in visual acuity, motor disturbances; cognitive function is unaffected

Multiple sclerosis diagnosis

-clinical signs and symptoms

-CNS MRI

-increased oligoclonal IgG in cerebral spinal fluid (CSF)

-Anti-MBP Ab, serum and CSF

myasthenia gravis

neuromuscular junction release acetylcholine (ACh), which binds to acetylcholine receptor (AChR); auto-antibodies to AChR; prevents muscle contraction

myasthenia gravis

symptoms include specific muscle weakness, ocular disturbances, oropharyngeal muscle weakness

blepharoptosis

drooping eyelids

diplopia

double vision

diagnosis of myasthenia gravis

Anti-AChR Abs; Anti-muscle specific tyrosine kinase (muSK)

diabetes mellitus

genetic form; polygenic genotype of MHC II genes (DR3&4) are strongest determinants, selective destruction if the insulin-producing beta cells in pancreas; 50% concordance rate in monozygotic twins suggests non-genetic factors involved

north-south gradient

as you get closer to the equator, the prevalence of disease decreases

diabetes mellitus

symptoms include fatigue, joint aches, poor-circulation, kidney disease, impaired visual activity, peripheral neuropathy

Hashimoto thyroiditis

autoantibodies destroy thyroid cells, resulting in hypothyroidism

Graves disease

Autoantibodies bind to the thyroid-stimulating hormone receptor causing hyperthyroidism

Hashimoto thyroiditis diagnosis

Antibodies to thyroperoxidase and thyroglobulin; increased thyroid stimulating hormone; thyroid biopsy

graves disease diagnosis

increased T3 & T4; decreased thyroid stimulating hormone (TSH) levels

goiter

swelling of the thyroid gland

Autoimmune hemolytic anemia

cold agglutinating syndrome (CAS), paroxysmal cold hemoglobinuria (PCH), and warm autoimmune hemolytic anemia

cold agglutinating syndrome (CAS)

cold agglutinins; Mycoplasma pneumoniae; IgM to human blood group I Ag

Paroxysmal Cold Hemoglobinuria (PCH)

IgG coats RBCs at cold temperatures but lyses RBCs at body temperature (biphasic hemolysin); more common in children

Warm autoimmune hemolytic anemia

IgG coats RBCs at body temperature; most common autoimmune hemolytic disease

Cold agglutinins

autoantibodies produced by persons infected with certain diseases that target RBCs; cause RBCs to clump together at cold temps and increase the destruction of RBCs in cold

scleroderma (CREST syndrome)

vascular damage; activation of immune response

Cryoglobulins

Antibodies that precipitate at temperatures below body temperature; seen in certain infectious diseases (i.e. HCV)