PHARM EXAM 2

What is the exaggerated or inappropriate immune response leading to pathology/extensive tissue damage?

Hypersensitivity

What is a pathological reaction against normal body component or the body’s immune system mounts an attack against its own cells?

Autoimmune disease

What is a failure of the immune system to protect body adequately from infection due to absence or insufficiency of some component process or substance?

Immunodeficiency

What is a toxin of other foreign substance which induces an immune response in the body, especially a production of antibodies?

Antigen

What are compounds of protein and sugars circulating in the blood stream which are created by the immune system to fight germs and foreign substances?

Antibodies

What are the antibody mediated hypersensitivity reactions?

• Type 1 → reaction mediated by IgE antibodies

• Type 2 → cytotoxic reaction mediated by IgG or IgM

• Type 3 → reaction mediated by immune complexes

What is the cell-mediated hypersensitivity reaction?

Type 4 → Delayed reaction mediated by cellular response

What is the sensitization phase of hypersensitivity reactions?

• Initial encounter with antigen

• Generates memory pool of allergen-specific b cells and helper T cells

What is the effector phase of the hypersensitivity reactions?

• Immunologic memory

• Results in tissue pathology with subsequent encounter with that antigen

What are the results of degranulation of mast cells and basophils?

• Histamine

• Leukotrienes

• Cytokines

What hypersensitivity reaction?:

• Happens quickly, sometimes within minutes

• Reaction mediated by IgE antibodies

• Re-expsure to antigen → IgE-mediated mast cell and basophil degranulation

• Result: anaphylaxis, hay fever, urticaria (hives), bronchoconstriction, hypotension, face/lip swelling

Type 1

What cells produce IgE?

B cells

What are common causes of type 1 hypersensitivity reactions?

• Food allergies

• Animal source

• Environmental factors

• Medications

What are examples of localized type 1 hypersensitivity reactions?

• Hay fever rhinitis

• Hives

• Asthma

What are examples of systemic type 1 hypersensitivity reactions?

• Severe bronchoconstriction

• Coronary artery contracts → chest pain

• Dilation of capillary beds → hypotension

• Edema

In the treatment of type 1 hypersensitivity anaphylaxis, what medication?:

• First line therapy

• Inc. vasoconstriction and peripheral vascular resistance → relieves hypotension

• Dec. airway or mucosal edema → relaxes bronchiolar smooth muscle → relieves bronchospasm

Epinephrine

In the treatment of type 1 hypersensitivity anaphylaxis, what medication?:

• Inhaled or nebulized beta-agonists (albuterol)

• Treats bronchospasm

Bronchodilators

In the treatment of type 1 hypersensitivity anaphylaxis, what medication?:

• Relieves hives, pruritis

• Adjunctive therapy

• Ex: (H₁ antagonist: Benadryl) or (H₂ antagonist: Pepcid)

Antihistamines

What medication would you not use for acute role in treatment of anaphylaxis due to its delay in onset of action?

Glucocorticoids

What hypersensitivity reaction?:

• “Cytotoxic hypersensitivity”

• Onset may be hours to days

• Involves IgG or IgM antibodies

• Cytotoxic antibodies against cell surface

• Results in tissue damage

Type 2

What hypersensitivity reaction involves IgE?

Type 1

What hypersensitivity reaction involved IgM and IgG?

Type 2 and 3

In type 2 hypersensitivity, what does the antigen appear on?

Healthy cells

What are the cytotoxic mechanisms of type 2 hypersensitivty reactions?

• Complement system

• Antibody-dependent cell-mediated cytotoxicity (ADCC)

• Opsonization and phagocytosis

What are the non-cytotoxic mechanisms of type 2 hypersensitivity reactions?

• Disruption of normal cellular function

• Antibodies bind to cell receptors to either block or mimic their function

• Ex: Myasthenia gravis, Graves disease

What disease is caused by type 2 hypersensitivity in which antibodies block ACh receptors?

Myasthenia gravis

What disease is caused by type 2 hypersensitivity in which antibodies stimulate TSH receptors?

Graves disease

Mechanism of complement system in type 2 hypersensitivity

Antibodies bind to cell surface antigens → activate complement → forms membrane attack complex (MAC) → MAC forms channels that interfere with phospholipid bilayer → cell lysis and death

What might the complement system reaction to penicillin result in?

• Hemolytic anemia

• Thrombocytopenia

• Neutropenia

Mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) in type 2 hypersensitivity

Natural killer cells recognize antibody-coated cells via Fc receptors → release cytotoxic granules → cell death

What is the process of coating pathogens or particle with opsonins (antibodies or complement proteins) to enhance phagocytosis?

Opsonization

Mechanism of opsonization and phagocytosis in type 2 hypersensitivity?

IgG or complement coat target cell → recognized by macrophages or neutrophils → phagocytosis and destruction

What hypersensitivity reaction?:

• Immune complex-mediated reactions

  • Antibodies bind free-floating (soluble) antigens

• Can develop over hours, days, weeks

• May be drug-induced

• Ex: vasculitis, serum-sickness, post-streptococcal glomerulonephritis

Type 3

Mechanism of type 3 hypersensitivity

Immune complexes deposit on vessel wall → activates complement and neutrophils → release of pro-inflammatory cytokines, enzymes, ROS → tissue damage

Examples of type 3 hypersensitivity

• Vasculitis

• Serum sickness

• Systemic lupus erythematosus

• Post-streptococcal glomerulonephritis

• Rheumatoid arthritis

What type of hypersensitivity?:

• “Cell-mediated” or “Delayed type”

• T-lymphocyte mediated

• CD4/Helper T-cells induce reactions through cytokine recruitment of inflammatory cells

• Typically starts 2-3 days after exposure and lasts for many days

Type 4

Examples of type 4 hypersensitivity

• Purified protein derivatives (PPD) → TB reaction test

• Medications (allopurinol)

• Poison ivy

• Contact dermatitis

• Graft versus host disease (GVHD)

What refers to medications that suppress, modulate, or stimulate immune functions?

Immunopharmacology

What are mechanisms of pharmacologic immune suppression?

• Suppression of gene expression

• Attack on clonally expanding lymphocyte lines

• Inhibition of intracellular signalsl

• Neutralization/disruption of cytokine signals

• Depletion B/T cells

• Inhibition of APC co-stimulation

• Inhibition of lymphocyte/target cell interaction

What are the risks of immunosuppression medications?

• Malignancy: lymphoma, skin cancer, leukemias

• Infection w/ fever

• Activation of TB

• Potentiation of hepatitis

What should you do prior to initiation of immunosuppressants?

• PPD test to screen for TB

• Hepatitis serology

• Vaccinations if needed

  • Avoid live vax on immunosuppressants

What medications have the greatest effect on rapidly dividing cells?

Cytotoxic

What medications suppress cells involved in hyperactive immune response and have anti-inflammatory effects?

Cytotoxic

Cytotoxic medication side effects in bone marrow suppression

• Neutropenia

• Anemia

• Thrombocytopenia

Cytotoxic medication side effects on GI

• Diarrhea

• Stomatitis

Cytotoxic medication side effects

• Alopecia

• Hyperuricemia → cell death, purines from DNA metabolized to uric acid

• Hyperkalemia

• Hyperphosphatemia

• Azotemia

• Hypocalcemia

What medications decrease inflammation and immune response?

Glucocorticoids

In glucocorticosteroids, how are the immunosuppressive and anti-inflammatory effects mainly mediated?

Through induction or repression of gene transcription

What happens when glucocorticoids inhibit phospholipase A₂?

Blocks release of arachidonic acid from membrane phospholipid and blocks inflammatory response

What are examples of glucocorticoid medications?

• Dexamethasone

• Hydrocortisone

• Prednisone, prodrug of prednisolone

• Prednisolone

• Methylprednisolone

What are the adverse effects of glucocorticoids?

• Decreased growth in children

• Osteoporosis

• Increased appetite → weight gain

• Glaucoma

• Inc. risk of infeciton

• Emotional disturbances

• Hypertension

• Centripetal distribution of body fat (moon face)

• Inc. risk of diabetes (inc. glucose levels)

• Hypokalemia

• Peripheral edema

What nomeclature refers to the fusion of a receptor to the Fc part of human immunoglobulin G1 (IgG1)?

-cept

What nomenclature indicates a monoclonal antibody?

-mab

What nomenclature indicates a chimeric mAb?

-ximab

What nomeclature indicates a humanized mAb?

-zumab

What nomeclature indicates a fully human mAb?

-umab