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What is a vaccine?
Vaccine = fractions of organisms that are used to produce immunity
Herd immunity = most of the population is immune - no epidemics
Types of Vaccine
- 1. Attenulated whole agent - live but weakened - gain immunity quickly but can back mutate & cause disease in the immune compromised
- 2. Inactivated whole agent - dead - treated with phenol/ formalin
- 3. Toxoids - inactivated toxins - diptheria & tetanus
- 4. Subunits - fragments of organism - Hep B
- 5. Conjugated - toxoid + T independent Ag -for immature immune systems - childrens immune system s do not respond well to T ind Ag but itself until 15 month of age
- 6. nucleic acid - DNA vaccines
Current Vaccines Given
- I. Bacterial
- a. DPT -diptheria, pertussis, tetanus - toxoids, fragments
- b. meningicoccal
- c. H- flu
- d. Pneumococcal
- II. Viral
- a. smallpox - live attenuated
- b. polio - dead
- c. rabies - dead
- d. hep A - dead
- e. influenza - dead
- f. MMR - measels, mumps, rubella, -live attenuated
- g. chicken pox - live attenuated
- h. Hep B - fragments
Who get pneumococcal vaccine?
- Adults w/ chronic diseases
- people over 65
- children 2-23 months
Is polio virus used today dead or alive?
- Dead (Salk)
- used to use live attenuated (Sabin)
Name the 4 hypersensitivity reactions.
Do they require a sensitzing dose?
Hypersensitivity reactions - host responds to an allergen (Ag) - all 4 require sensitizing dose
- Type I - Anaphylaxis - systemic vs. localized
- Type II - Cytotoxic Rh ABO reactions
- Type IIII- Serum Sickness - immune complezes
- Type IV- Delayed hypersensitivity - T cell mediated
What does hypersensitivity mean?
What is an allergen?
hypersensitivity - an Ag response beyond what is considered normal - also called an allergy
Allergen - the Ag to which the body is responding
Person is sensitized by previous exposure to the Ag
Type I Hypersensitivity reaction- Anaphylaxis
Ag (allergen) + IgE (on mast cell) → degranulation=histamine (from mast cell) → edema, redness, bronchoconstriction
Ag must bind to & bridge
two IgE Abs to trigger degranulation
→ release of granules (histamine & other mediators)
- Systemic reaction - anaphlactic shock = vasodilation -low BP, bronchoconstriction →death
- Rx = EPI, steroids, antihistamine, IV fluid, O2
- Localized reaction - also called a anaphylactoid reaction - hives, hay fever, allergic asthma
- Rx = antihistamines (block histamine receptor sites)
Can skin test to see if allergic -" wheal" - rapid local inflammation
can desensitize person to allergen - give progressively larger doses of allergen - produced blocking Ags = IgG that binds to Ag before it binds to mast cell
What are mast cells and where are they found?
Mast cells are dereived from Basophils and are only found in CT - not in the blood
Type II hypersensitivity reaction - Cytotoxic reactions
Involves Ag on cell / Ab (Host cell) + complement
- I. Transfusion reaction (Does not require sensitization for ABO reaction):
- RBC Ag + Host Abs + complement = RBC hemolysis of donor blood (complment activation -MAC = RBC lysis)
- II. Erythroblastosis Fetalis (requires sensitization)
- 1. Rh (-) Mother + Rh (+) Baby
- 2. Maternal anti-Rh Abs bind to fetal RBCs → hemolysis
- 3. Rx = RhoGAM - passive immunity to mother - anti-Rh Abs bind to fetal Rh Ags - prevent mother from becoming sensitized
- (Rh named for Rhesus Monkey)
- Drug Induced thrombocytopenic purpura
- 1. drug (haptens)+ platelet → drug/platelet Ag → cytolysis of platelet
- 2. thrombocytopenia = low # of platelets
- - purpura = bruise
Type III hypersensitivity reaction - Serum sickness
reaction to drugs or allergens - floating Ags, not attached to cells
Ag (allergen) + serum IgG = Ag/ IgG complex → lodges in basement membrane (under endothelial cells) of blood vessels & causes inflammatory response (damages basement membrane)
immune complex glomeuronephritis - damage to kidney glomeruli = renal failure
- reaction to drugs or allergens - floating Ags, not attached to cellsAg
- (allergen) + serum IgG = Ag/ IgG complex → lodges in basement membrane (under endothelial cells) of blood vessels & causes inflammatory response (damages basement membrane)
immune complex glomeuronephritis - damage to kidney glomeruli = renal failure
Type IV hypersensitivity reactions- Delayed Cell Mediated (hypersensitivity reactions)
Cell Mediated - hypersensitivity caused by T cells
Delayed due to travel time of T cell to tissue (24-48 hours)
- Ag = hapten (allergen) + skin protein
- primary response = sensitization
- secondary response = memory T cells cytokins activate macrophages & initiate tissue damage
poison ivy, latex, metal, some drugs (PCN), transplant rejection
TB - tine test - reaction if memT cells exist
Four Types of Autoimmune Diseases and examples
Autoimmne Diseases are hypersensitivity reactions agaist self Ags - lack of self tolerance caused by a failure of clonal deletion mechanism
Self Ags - trigger immune response → disease
- Type II - Ab react with cell surface Ags
- Graves Disease - anti-thyroid Abs blocks TSH→hyperthyroid (goiter, bulging eyes)
- Myasthenia Gravis - anti ACH receptor Abs → receptors coated - muscle weakness
- Type III - immune complexes - deposit in tissue
- RA - rheumatiod arthritis - complex deposited in joints (synovum)
- Type IV - cell mediated - T cells -
- MS - multiple sclerosis - T cell attack myline sheaths of nerves
Rejections to Organ Transplant
- cell mediated immune response
- T cell reaction against non-self HLA Ags - by t cells, cytokins, complement, macrophages, complement fixing Abs
- Rx = cyclosporin -lowers cytokins (supresses secreation of IL-2) which disrupts cell-mediated immunity by cytotoxic T cells
- - steroids also decrease immune response
What is an immune privileged site?
Privlidged donor sites?
transplats to immune privleged sites do not cause immune response - no host Abs (no blood flow to area)- corneal transplants
Privleged donor tissue - no Ags for host to react to - pig heart valves
- Autograft - from self (skin graft)
- Isograft - same genetically (twin)
- Allograft- another person
- Xenograft - another species (pig heart valve)
- Graft-vs-host-reaction - graft rejects host (bone marrow transplant to an immune compromised host)
What type of virus is HIV?
What is AIDS?
- HIV = Human Immunodeficiency Virus (RNA retrovirus)
- AIDS = Acquired Immuno Deficiency Syndrome (disease)
What is the structure of HIV?
- 1. 2 identical strands of RNA
- 2. capsid
- 3. reverse transcriptase attached to RNA
- 4. envelope - with spikes
How does HIV replicate in host cell?
1. Spikes on envelope bind to CD4 on host T cell + co-receptor MUST bind also- CCR5 or CXCR4
- 2. Viral RNA + reverse transcriptase = double stranded DNA → provirus (inserts in host DNA)
- -replicates when T cell replicates
- - can be transcribed into RNA =HIV viron
3. HIV can infect a macrophage after it is eaten
3 stages of HIV infection
How long does progression take?
Category A: lymphadenopathy - assympathetic - swollen lymph notes
Cat B: persistent Candida albicans infection (thrush) -fungal infection
- Cat C: Clinical AIDS - opportunistic infections called AIDS defining infections
- Clinical AIDS defined at CD4 T cell population < 200/mm3
Median time of HIV infection to AIDS onset =9-10 years
Why do you die from AIDS?
Opportunistic infections -healthy people dont get these diseases
- Kaposi's sarcoma - skin & mouth cancer - ADI
- neumocystis carinii - ADI
Exposed but not infected
Exopsed by not infected - 1% of population have no CCR5 co-receptors on thier T cells - cant become infected with HIV
Long-Term nonprogressors - HIV infected but does not progress from latent stage - no known reason
What does Seroconversion mean?
Can take up to 3 month before HIV Ab can be detected in patients serum - Red Cross has it down to two weeks (for testing blood donors)
How is HIV detected in an infected person?
ELISA test - detects patients Abs to HIV-quick
Western Blot test - detects HIV Ags- used to confirm ELISA
Plasma viral load - tells amount of virus in blood
How is HIV spread?
- spread in body fluids - but NOT SALIVA
- -breast milk
What is the probability of a healtcare worker getting HIV from a needlestick?
.3% 1 in 333
What are universal precautions?
- Treat every patient as if they have HIV
- a. gloves, gowns, masks, goggles
- b. do not recap needles - into sharps box
What group of people carry HIV the most?
- male-to-male sexual contact
- then heterosexual
- then drug users
How many cases of HIV/AIDS are there now in the US?
What is a clade?
Why is it hard to make an HIV vaccine?
- 1. mutations - rapid
- 2. Clades - many subtypes
Drug Therapy for HIV/ AIDS
4 classes of drugs
What is AZT? What class of drug is it?
What is HAART?
1. Reverse transcriptase inhibitors (nucleoside analogues)
2. Protease inhibitors - block viral assembly
3, Fusion inhibitors - block viral attachment
4. Integrase inhibitors - block provirus formation
- AZT = Zidovuedine - reverse transcriptase inhibitor
- HAART = highly active anti-retroviral therapy - combination of the above drugs used simulaneously
turmor specific Ags
some cancer cells present specific Ags
immune surveillance - T cells recognize and destroy some cancer cells - this funciton deteriorates with age