Immunopharmacology - Immune Diseases Flashcards
5 roles of the immune system? what are their implications?
- Defense against infections (vaccines)
- Defense against tumors (cancer)
- Clearance of dead cells and tissue repair (deficient:secondary infections, excessive:fibrosis/organ dysfunction)
- Injure cells and induce inflammation (allergic reactions/inflammatory diseases)
- Recognizes/responds to tissue grafts and new proteins (transplantations and gene therapy)
Two types of immunity? which one is always present? which one is more potent?
Innate : always present
Adaptive : more potent
Cells involved in innate immunity? (4)
Phagocytes
Dendritic cells
Complement
NK cells
Cells involved in adaptive immunity? (2)
B lymphocytes T lymphocytes (effector T cells)
3 types of cells of the immune system?
Lymphocytes
Antigen-presenting cells (APCs)
Effector cells
Role of lymphocytes?
Mediates adaptive immune response, only cells with specific receptors for antigens
Role of APCs? 4 cells?
capture, concentrate, display antigens for lymphocyte recognition
Dendritic cells, macrophages, B cells, follicular dendritic cells
Role of effector cells? 3 cells?
Eliminate microbes
Lymphocytes, Granulocytes, Macrophages
Which cells make antibodies?
B cells
How are B cells activated? (2)
Antigen must bind to sites
Stimulation by Helper T cells
3 types of T cells?
Helper T cells
Cytolytic T cells
T-regulatory cells (Tregs)
What do Helper T cells produce?
CD4, helps bind to class II MHC complexes on antigen presenting cells
What do Cytolytic T cells produce?
CD8 protein, binds transplanted tissue, infected cells, cancer cells
Role of Tregs?
Suppress activation of immune system to help maintain homeostasis
Development of B and T cells in Generative lymphoid organs (3) and Peripheral lymphoid organs?
Generative lymphoid organs : -B lymphocyte and T lymphocyte lineage produced by bone marrow stem cell -B transported to Bone marrow -T transported to thymus Peripheral: -Mature B circulates in blood -Mature T circulates in blood and lymph -Both transported to Lymph nodes, Spleen and Mucosal and cutaneous lymphoid tissues
Two types of adaptive immunity?
Humoral
Cell-mediated
Humoral immunity:
Which lymphocyte acts on microbe? Overall function?
B lymphocyte
Blocks infections and eliminates extracellular microbes
Cell-mediated immunity:
Two lymphocytes? Which type of microbes do they each respond to and what is their function?
Helper T lymphocyte:
Responds to phagocytosed microbes in macrophages, activates macrophages and kills microbes
Cytotoxic T lymphocyte:
Responds to Intracellular microbes, kills infected cells and eliminates reservoirs of infection
4 steps of the immune response?
- Antigen recognition and presentation
- IL-1 production
- IL-2 and other cytokine expression
- Lymphocyte proliferation and differentiation
What are immunomodulators: two types of immunomodulators?
Agents that will modulate the immune system
Immunosuppressants and immunostimulant
3 immunostimulatory cytokines?
Interleukins
Colony stimulating factors
Interferon
2 types of colony stimulating factors? what are their roles?
G-CSF
GM-CSF
Stimulates division and proliferation of various stem cell types
3 types of interferons? Which disease are they involved in? Are they all: viral or antiviral? proliferative or antiproliferative? Which one induces MHC II on top of MHC I?
alpha (anticancer) beta (relapsing MS) gamma (chronic granulomatous disease) -Antiviral -Antiproliferative -Gamma
2 other types of stimulants?
Thymic hormones
Adjuvants of bacterial origin
4 major classes of immunosuppressants?
Corticosteroids
Calcineurin inhibitors
Antiproliferative/Antimetabolic agents
Biologic (Ab)
3 examples of corticosteroids?
It decreases inflammation caused by what? (4)
Prednisone, Dexamethasone, Cortisol
Cytokines, NO, Prostaglandins, Leukotrienes
3 examples of NSAIDS?
Aspirin
Ibuprofen
Acetaminophen
3 drugs that reduce production of IL-2 from T cells
Cyclosporin A
Tacrolimus
Rapamycin
3 Anti-TNFa biologicals?
Infliximab
Etanercept
Adalimumab
4 treatments of auto-immune disease?
Corticosteroids
NSAIDS
Drugs that reduce IL-2 production
Anti-TNFa biologicals
Difference in potency between dexamethasone vs. prednisone and cortisol?
20-30x more potent that cortisol
4-5x more potent than prednisone
MOA of corticosteroids? (2)
Transactivation : activates expression of anti-inflammatory genes
Transrepression : decreases expression of pro-inflammatory genes
MOA of tacromilus?
binds to FK506-binding protein
forms FK506-FKBP complex
binds to and blocks CaN
FK506-FKBP-CaN complex inhibits activation of NF-ATc, preventing entrance into nucleus
MOA of cyclosporin?
CsA binds to immunophilin, cyclophylin (CpN
CsA-CpN binds to and blocks CaN function
Failure of CaN to dephosphorylate NF-ATc, inhibiting it’s transport into the nucleus
Anti-TNFa biologicals only bind human TNF-a with high…? (3)
Specificity
Affinity
Avidity
What is the main disease treated by immunosuppressants? What are two general mechanisms of this disease?
Autoimmune diseases
- Failure of auto-antibodies and T cells to recognize own cells
- Auto-antibodies and T cells launch attack against own cells
3 ways autoimmune diseases can develop?
- Spontaneous
- MHC associated genetic predispositions
- Infectious agents
MOA of autoimmune disease induction? (6)
- Infectious agent causes disease
- Recovery from disease (T cell and Ab response)
- A portion of a protein from infectious agents mimics a self protein
- Due to MHC composition, some T cells specific for infectious agent protein also cross-react with self protein
- T cell becomes pathogenic, responds to self antigen, recruits other immune cells
- Tissue destruction
How is the classification of autoimmune diseases separated? Three classes?
Effector mechanism
Type II, Type III, Type IV
Type II autoimmune disease is a _______ mediated disease
antibody
Example of a type II autoimmune disease?
Graves disease
Graves disease happens in the ______ and it makes antibodies for which receptor? This leads to what disorder?
These antibodies act as _____
Thyroid
Thyroid-stimulating hormone receptor (TSHR)
Hyperthyroidism
Agonists
Is it possible to transmit Graves Disease to fetus?
How can this be cured
Yes, antibodies can cross the placenta
Plasmapheresis removes maternal anti-TSHR Abs and cures the disease
Type III autoimmune diseases are ______-_____ diseases
Immune-complex
4 processes that immune complexes can be subject to?
Complement deposition
Opsonization
Phagocytosis
Processing by proteases
Immune complexes in which autoimmune diseases? (5)
Lupus erythematosus Cryoglobulinemia Rheumatoid Arthritis Scleroderma Sjogren's syndrome
Type IV autoimmune diseases are mediated by which cells?
T cells
4 examples of Type IV autoimmune diseases?
Diabetes mellitus
Rheumatoid arthritis
MS
Celiac disease
Antigen and consequence of Insulin-dependent diabetes mellitus?
Pancreatic Beta-cell antigen
Beta-cell destruction
Antigen and consequence of Rheumatoid Arthritis?
Unknown synovial joint antigen
Joint inflammation and destruction
Antigens (2) and consequences (2) of MS?
Myelin basic protein, proteolipid protein
Brain degeneration, paralysis
Antigen and consequences (2) of Celiac disease?
Gluten modified by tissue transglutaminase
Malabsorption of nutrients
Atrophy of intestinal villi
4 T-cell mediated effects in type IV autoimmune diseases?
- T cell cytotoxicity via CD8+ cytotoxic T lymphocytes
- Self-destruction of tissue cells induced cytokines
- Recruitment and activation of macrophages leading to bystander tissue destruction
- Induction of target tissue apoptosis by the T cell membrane protein FasL
In rheumatoid arthritis, _____antigens cause non-specific activation of T-cells resulting in what? (2)
Superantigens
Polyclonal T cell activation
Massive cytokine release
In rheumatoid arthritis, the immune complex precipitates on synovial lining, what is the MOA? (6)
- Complement deposits
- Macrophages infiltrate synovium and become activated
- CD4 and CD8 lymphocytes infiltrate synovium
- Th1 cytokine secretion predominates
- Infiltration of B cells
- Acute inflammation occurs with destruction of cartilage and bone
Psoriasis is a Type IV autoimmune disease that causes activation of T cells where?
in skin cells
Topical medications of psoriasis? (7)
Corticosteroids Vitamin D analogue creams Topical retinoids Moisturizers Topical immunosuppressants Coal tar Anthralin
Example of a vitamin D analogue to treat psoriasis?
It acts mainly on which receptor?
Vitamin D3 inhibits production of ___ and ____
Blocks transcription of ______ and _______
Inhibits activity of which cells? (2)
Calcipotriene (Dovonex) Vitamin D receptor (VDR) IL-2 and IL-6 IFN-gamma and GM-CSF Cytotoxic T cells and natural killer cells
Vitamin D3 inhibits proliferation of which cells?
Keratinocytes
Which biological agent interferes with lymphocyte activation?
Alefacept
Which biological agent blocks TNFa and TNFB binding to receptor?
Etanercept
Which two biological agents and monoclonal antibodies that block TNFa binding to receptor?
Infliximab
Adalimumab
Three types of organ donors? Explain
Syngeneic : between genetically identical individuals
Allogeneic : from one individual to another of the same species
Xenogeneic : between individuals of different species
3 Types of Host vs. Graft organ rejection?
Hyperacute
Acute
Chronic
Onset of hyperacute organ rejection?
Mechanism?
Immediate
Abs against donor tissue, caused by accidental ABO blood type incompatibility.
Presents while still in surgery with thrombosis and occlusion of graft vessels
Onset of acute organ rejection? Mechanism?
Weeks to months
T-Cell mediated response against foreign MHC.
Inflammation and Leukocyte infiltration of graft vessels
Onset of chronic organ rejection? Mechanism?
Months to years
T-cell mediated process from foreign MHC looking like self-MHC carrying an antigen.
Results in intimal thickening and fibrosis of graft vessels
Mechanism of “Graft vs. Host” organ rejection?
Donor T-cells in graft proliferate and attack recipient’s tissue.
Commonly in bone marrow transplants. Presents with diarrhea, rash and jaundice
Prior to transplants, patients receive which immunosuppressive regimen? (4)
Antithymocyte Globulin, Muromonab-CD3, Daclizumab or Basiliximab
Muromonab-CD3 blocks what?
blocks killing by cytotoxic human T cells
Basiliximab is what type of immunoglobulin? Role?
Similar drug? Where does this one bind?
IgG1
Binds to CD25, the IL-2 receptor alpha chain on lymphocytes
-IL-2 antagonist, blocks IL-2 from binding to lymphocytes
Daclizumab : binds to alpha subunit of IL-2
