-
disorder caused by the inability of the immune system to distinguish self antigens from foreign antigens.
- autoimmune disorders
- result in tissue damange
- may affect any cell in the body
-
common autoimmune disorders
- type I diabetes
- crohn's/ulcerative colitis
- myasthenia gravis
- multiple sclerosis
- Hashimoto thyroiditis/graves disease
- rheumatoid arthritis
- lupus
-
Etiology of autoimmune disorders
- unknown
- genetic suceptibility
- environmental factors
-
Most common autoimmune disorders
- rheumatoid arthritis
- thyroiditis
- more common in women (estrogen stiumlates immune fx)
- ~5% of the population of western coutnries
-
Immune tolerance
- ability of the immune system to distinguish self from non-self
- Human leukocyte antigens
- Accomplished by removing self reactive cells
-
Proposed mechanisms of loss of self tolerance
- loss of t cell anergy
- release of sequestered antigens and epitope reading
- molecular mimicry
- superantigens
- abnormal immunoregulatory mechanisms
-
Clinical presentation of autoimmune disorders
depends on the tissues damaged by immune response
-
Diagnosis of an autoimmune disorder
serological testing
-
non pharmacological treatment of autoimmune disorders
plasmaphoresis
-
pharmacologic treatment of autoimmune disorders
- immunosuppressive drugs
- cordicosteroids, monoclonal antibodies
- cyclophosphamide, azathioprine, tacrolimus
-
disorders in which there is an inappropriate or excessive immune system response
Hypersensitivity disorders
-
IgE mediated hypersensitivity
Type 1 hypersensitivity
-
Antibody mediated hypersensitivity
type II hypersensitivity
-
complement mdiated hypersensitivity
type III hypersensitivity
-
cell mediated hypersensitivity
type IV hypersensitivity
-
cause of Type I hypersensitivity
-
hypersensitivity reactions represent about _____ of all adverse drug reactions.
1/3
-
ADRs affect _____ of hospitalized patients and more than ____ of the population
-
Clinical presentation of systemic Type I hypersensitivity
anaphylaxis
-
clinical presentation of atopic type I reaction
- sneezing, itching
- watery nose/eyes
- malaise, fatigue
- headache
- dermatitis
-
non-pharmacologic treatment of Type I reactions
- avoidance of antigen
- airway maintenance
- education and medical alert bracelet
-
pharmacologic treatment for type I reactions
- epinephrine
- antihistamines/decongestants
- corticosteroids and cromolyn
- allergy shot desensitization
-
mechanism of cromolyn
stabilize mast cells
-
Abnormality of immune system that renders a person susceptible to diseases normally prevented by the immune system
immunodeficiency
-
primary immunodeficiency
congenital or inherited
-
secondary immunodeficiency
-
HIV infects
- CD4 T Lymphocytes
- Macrophages
- Dendritic Cells
-
AIDS is associated with
- sever immunosuppression
- opportunistic infections
- malignancies
- wasting
- CNS degeneration
-
Epidemiology of HIV/AIDS
- ~40 million people worldwide
- 2.9 million deaths in 2006
- 50% of new infections in women and young people
- Eastern europe and central asia
-
Horizontal transmission of HIV
fluid exchange
-
Verticle transmission
from mother to child
-
time before symptoms of HIV occur
1-3 months
-
Steps of HIV infection of cells
- 1. Binding to CD4 site
- 2. Entry of virus into cell
- 3. Reversetranscription of RNA from Virus
- 4. DNA incorporated into host DNA
- 5. DNA transcribed to mRNA
- 6. Protease cleaves DNA
- 7. New virus formed
- 8. Virus buds off of cell
-
The 4th stage where viral DNA is incorporated into the host DNA
Provirus Stage
-
Pathophysiology of HIV/AIDS
- HIV replication leads to death of CD4 cells
- CD4 count is depeleated
- Pt. loses the ability to initiate an immune response
- infection occurs in 3 stages over 8-12 years.
-
Primary HIV/AIDS stage
- occurs 1-4 weeks after exposure
- lasts for 7-10 days
- fever, fatigue, myalgias, sore throat, night sweats, GI issues, headache, rash, lymphadenopathy
-
secondary HIV/AIDS stage (latency)
- lasts around 10 years
- no signs or symptoms
-
tertiary stage of HIV/AIDS (overt)
- CD4 count <200 cells/microL
- opportunistic infections
- CNS disorders
- malignancies
- wasting/metabolic disorders
-
ELISA test
- enzyme linked immunosorbent assay
- detects HIV antibodies
- high false positive rates
-
Western blot assay
- more specific than ELISA
- used to confirm diagnosis
-
AIDS is diagnosed when
CD4 count is <200 and/or pt developes an AIDS defining illness
-
Non-pharmacologic treatment of AIDS/HIV
prevention
-
NRTI
Nucleoside/nucleotide reverse transcriptase inhibitors
-
NNRTI
non-nucleoside reverse transcriptase inhibitors
-
PI
- Protease Inhibitor
- inhibits cleaving replicated proteins into new viruses
-
FI
- Fusion Inhibitor
- prevents viral fusion with CD4 receptors
-
INSTI
- Integrase strand transfer inhibitor
- blocks integration of DNA into host DNA
-
Goal of HIV/AIDS therapy
- reduce amount of virus in the body
- inhibit or suppress viral replication
-
HAART
Highly active antiretroviral therapy
-
3 types of regimens for treatment of naive patients
- NNRTI + 2 NRTI
- PI + 2 NRTI
- INSTI + 2 NRT
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