Immunopharmacology (Exam V) Flashcards
How many lines of defense does the body have?
Which of these are innate/nonspecific?
- 3
- First & second line of defense are innate/nonspecific.
What characterizes the body’s first line of defense?
- Physical barriers like skin.
What characterizes the body’s second line of defense?
- Phagocytosis
- Inflammation
- Fever
- Antimicrobial proteins
What characterizes the body’s third line of defense?
- B cells & T cells
What is acquired natural passive immunity?
How long does it last?
- IgE antibodies from maternity.
- 6-9 months
What is an example of acquired natural artificial immunity?
- Antivenom for snake bites
Where are B-cells developed?
Where are T-cells developed?
- Bone marrow
- Thymus
What do B cells do after interacting with an antigen?
- Turn into plasma cells (Ab producers)
- Turn into long-lived memory cells
What is opsonization?
- The coating of an antigen
MHC 1 is associated with what T-cell type?
MHC 2 is associated with what T-cell type?
- CD8 Killer cells
- CD4 helper cells
What cells are characterized by cell-mediated immunity?
What cells are characterized by humoral immunity?
- T-cells
- B-cells (Ab immunity)
What type of antibody is specific for a singular pathogen?
IgG
Is primary or secondary immunodeficiency genetic?
- Primary immunodeficiency
What characterizes Type I hypersensitivities?
- Mild or severe anaphylaxis (hay fever, food allergies, etc.)
What characterizes Type II hypersensitivities?
- Antibody-mediated hypersensitivities (Blood incompatibilities)
What characterizes Type III hypersensitivities?
- Immune Complex hypersensitivities (Rheumatoid arthritis)
What characterizes Type IV hypersensitivities?
What is unique about this class of hypersensitivities?
- Cell-mediated Delayed hypersensitivities (poison ivy example)
- No Ab involvement, just T-cells.
What are some examples of primary immunodeficiency?
- DiGeorge Syndrome (No thymus = no t-cells)
- Agammaglobinemia (no B-cells = no Ab’s)
What is an example of secondary (acquired) immunodeficiency?
- AIDS
What two scenarios for Type II Hypersensitivity reactions were discussed in lecture?
- Transfusion reaction
- Hemolytic disease of the newborn.
What is the pathophysiology of Newborn Hemolytic Disease?
What is the treatment?
- Rh⁺ fetus in an Rh⁻ mother (firstborn) → (secondborn) IgG from first pregnancy attacks newborns RBCs.
- RhoGAM
What is the hallmark sign of Type III Hypersensitivity reactions?
- Joint Pain
What does Rheumatic mean?
- Joint Cavity
What is the general pathophysiology of Type III Hypersensitivity reactions?
- Deposition of immune complexes in joints where WBCs migrate to and cause inflammation.
What is Rheumatic Disease?
- Rheumatoid Factor antibodies made against IgG causing progressive inflammation.
What is an Arthus reaction?
- Acute response to multiple vaccine injections at the same site causing immune complex formation in the subcutaneous tissue. Results in localized redness, hemorrhage, & eventual necrosis
What is the treatment for Type III Hypersensitivity reactions?
- NSAIDs
- Corticosteroids
What metal can actually cause Type 4 hypersensitivity reactions?
- Nickel
What characterizes a Host vs Graft infection?
- MHC-1 on the grafted organ attracts T-cells and macrophages. Host body attacks grafted organ/tissue.
What characterizes a Graft vs Host infection?
- MHC-1 on host cell is attacked by grafted tissue lymphocytes (usually bone marrow). Grafted tissue attacks all of host organs.
What is an example of a mild Type 4 reaction?
What about a severe type 4 reaction?
- Mild = poison ivy
- Severe = Graft vs Host
What are autoantigens?
What are autoantibodies?
- Self-antigens that induce an immune response
- Antibodies that attack autoantigens
What are the 4 theories of autoimmunity?
- Exposure to antigens previously sequestered from the immune system.
- Molecular mimicry - pathogen similar to host tissue (streptococcus pyogenes attacking heart valves causing rheumatic fever)
- Inappropriate expression of MHC II on cells that don’t normally express it (islet β cells = DM)
- Hygiene hypothesis
What is the most common symptom of rheumatic diseases caused by autoimmunity?
- Joint pain
What characterizes the pathophysiology of SLE?
- Autoantibodies attacking DNA structure.
- Affects sites of rapid cell turnover.
What symptom is present in 30-50% of SLE cases?
Why?
- Butterfly Rash
- Rapid cell turnover occuring on the face from sunshine exposure.
What is the first symptom noticed with multiple sclerosis?
- Muscular Weakness
What is the pathophysiology of multiple sclerosis?
- T-cell & autoantibody targeting of myelin sheath prevent normal neuron signaling.
What is the pathophysiology of myasthenia gravis?
- Autoantibodies attacking ACh receptors at the NMJ’s.
How do glucocorticoids work?
- Suppression of immune response by interfering with the cell cycle of B & T cells.
What are the side effects of glucocorticoid use?
- Immunodeficiency
- Exogenous Cushing’s Syndrome
What are glucocorticoids used for?
- Adrenal Insufficiency (Addison’s disease)
- Allergic & inflammatory reaction suppression
- Asthma
- Transplantation
What is Calcineurin?
- Protein necessary for T-cell signaling & activation.
What two Calcineurin Inhibitors were discussed in lecture?
What were these used for?
- Cyclosporine (peptide abx)- Transplants, GVHD, autoimmune disorders.
- Tacrolimus (macrolide abx) - topical dermatitis & psoriasis
At lower doses what is azathioprine used for?
What about at higher doses?
- Immunosuppressive
- Antineoplastic
How does Azathioprine treat autoimmune disorders?
What is the main side effect?
- Interference with purine metabolism blocks over-proliferation of cells.
- Leukocytopenia from bone marrow suppression
What is the metabolism pathway of Azathioprine?
Azathioprine → Xanthine Oxidase → 6-Mercaptopurine → 6-Thioguanine Nucleotides
What is the primary side effect of cyclophosphamide?
What type of agent is it?
- Severe Immunosuppression
- Alkylating Agent
What is the metabolism pathway of cyclophosphamide?
Cyclophosphamide → CYP450s → Acrolein & Phosphoramide Mustard (tissue toxicity & cell death)
What is a hybridoma?
- Petri dish plasma cells fused with an immortal cell line used to create monoclonal antibodies
Which monoclonal antibody suffix is indicative of mostly human origin antibodies?
-umab or -zumab
Which monoclonal antibody suffix is indicative of more chimera (human-mouse) antibodies?
-imab or -ximab
What is Omalizumab?
- Anti-IgE MAb used for severe asthma