Term
hyperacute rejection (organ transplants) -how can these complement fixing Ab be generated? -why is it so fast?
-what type of hypersensitivity rxn is it? |
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Definition
| Type III fast, sometimes before operation is complete pre-formed, complement fixing Ab against blood group or HLA I -HLA-II can play a role b/c of upregulation of Class II Ag in the inflamed state of the donor graft and recipient Complement fixing Ab bind to vascular endothelium initiating complement & coagulation cascade Vasculature clots & leaks -initially pale then purple from hemorrhage, eventually ischemia Irreversible how generated? pregnancy, blood transfusion (HLA not assessed), previous transplants fast b/c it involves *complement* |
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Term
Understand the process of attenuation and the risks/benefits of attenuated vaccines
*which vaccines are LAV* |
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Definition
live organisms mutated to reduce pathogenicity; can be done by growing viruses on non-human cell lines/animals; can also be done by genetic engineering
benefits:
strong immune response, can mimic natural disease process,immunity is generated to target the infectious process - includes route of infxn
risks:
can cause problems in immunocompromised
pts, chance of reversion to pathogenic form
measles, mumps, polio (Sabin), yellow fever |
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Term
| What's a subunit vaccine? |
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Definition
use surface components of viruses or bacteria
-Hepatitis B virus is purified from blood from pts or recombinant pr
-Encapsulated bact - Ab responses against CAPSULAR POLYSACCHARIDES are protective - capsular polysaccharides can provoke T independent B cell responses, but not very immunogenic |
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Term
| Define conjugate vaccines and understand the mechanisms for generating protection against bacteria |
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Definition
| these vaccines conjugate toxoid to polysaccharide, converts to T dependent Ag |
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Term
Define an adjuvant and understand their uses
-Freund's complete adjuvant
-Aluminum hydroxide |
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Definition
Killed/non-viable vaccines aren't very immunogenic themselves, require adjuvant to enhance immunity
adjuvants are substances that induce inflammation by Ag-dependent mechanisms, enhance vaccinations
*a good adaptive immune response REQUIRES a state of inflammation* due to macrophage activation & recruitment of inflammatory cells
Freund's: emulsion of killed mycobacteria and mineral oil
Alum: only approved adjuvant in U.S., tends to promote *Th2-type* responses |
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Term
Know the challenges to vaccine design and improvement
-3 points
Challenges |
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Definition
Understand disease pathogenesis better to identify targets
-*recombinant DNA technology* - use to produce purified vaccine proteins (HBV-HBsAg) or reduce virulence (Salmonella)
understand *how the immune system best protects* from infections disease
-Th1 vs Th2: addition of IL-12 can promote Th1
-route of immunization-site of infection
*improve adjuvants*
-ISCOMS - immune stimulatory complexes
lipid molecules carrying class I restricted poly/peptides fuse with cell membrane, deliver them to cytoplasm
-cytokines as molecular adjuvants (GM-CSF, IL-2)
pathogens that provoke weak immune responses, that have large numbers of strains, that evade immune response and elicit chronic illness |
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Term
| Know the difference between autograft, xenograft, isograft and allograft |
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Definition
auto: graft from self
xeno: graft from different species
iso: from identical twin
allo: from someone else |
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Term
| Understand the importance of blood group matching for blood transfusion and organ transplant |
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Definition
A,B,O antigens expressed on endothelium of all BV
most solid organs must be matched for blood group to prevent hyperacute rejection
Anti-HLA Ab from previous sensitization (pregnancy, transfusion, transplant) can also cause rejection |
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Term
Understand the role of the bone marrow transplant and T cells during GVHD
-also GVL, GVT |
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Definition
In allogeneic transplants graft-vs-host disease (GVHD) occurs
-*mature T cells in transplanted BM* respond to recipient's HLA type
-10-28 days after transplant
-diarrhea, hyperbilirubinemia, erythematous rash
-severity correlates with degree of HLA mismatch
In allogeneic transplants reconstitution of the immune system by donor cells provides improved disease-free survival
-graft vs leukemia (GVL) or tumor (GVT) effect
-requires myeloablative therapy to prevent rejection of donor cells; this destroy's recipient's immune system
Pt is myeloablated, autologous or allogeneic cells are transplanted
-1.5 wks later engraftment begins
-neutrophils, then RBC's, then platelets
new immune system becomes tolerant of host |
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Term
Acute rejection (organ transplants)
-direct pathway of allorecognition
-indirect pathway of allorecognition |
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Definition
occurs in days to months; matching donor & recipient MHC improves outcome. Most tissues the major alloantigen will be MHC I
-differences in other antigens (minor histocompatibility Ag), can lead to rejection; rejection not as rapid
Recipient T-cells reactive against non-self HLA I (CD8)/II (CD4) Ag on donor tissue (graft)
-produce effector CD4 & CD8 cells that attack graft
Direct pathway:
-donor dendritic cells are carried to secondary lymphoid tissue, depletion of dendritic cells
-activated recipient T cells recognize allogenic Class I or II molecules with donor peptides
-Th1 cells activate macrophages, CD8 kill
Indirect:
-recognize processed donor material presented by recipient cells
-donor dendritic cells migrate to LT, die
-usually chronic
-the graft cells as they’re replenishing within graft shed Ag that are from donor tissue
-Usually endocytic pathway, macrophage mediated
-membrane fragments of dead dendritic cells are processed, presented by recipient dendritic cells
-stimulate a *CD4* response specific for donor HLA peptides & recipient HLA II
-inflammation, damage to endothelium, thickening of BV walls, damage to vascular supply |
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Term
chronic rejection
-Ag of which HLA class type incite inflammation? why? |
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Definition
| months-yrs; alloreactive T-cells stimulated by indirect pathway drive Ab response Ab specific for graft *class I Ag* incites inflammation -HLAI Ag is highly expressed on vascular tissue damage to vessel walls --> thickening --> ischemic damage to graft |
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Term
What are pts who have had a splenectomy susceptible to?
vaccine? |
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Definition
Blood borne infxn, encapsulated bact, gram neg rod, others
Pneumovax (prophylactic abx therapy), due to reduced levels of opsonins and IgG; otherwise pt only has innate immunity |
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Term
| What must the DPT vaccine undergo (specifically, the pertussis portion) in order to make it effective? |
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Definition
conjugation to a toxoid - elicits T cell response, opsonization
Ab-FcR --> phagocytic cell engulfs |
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Term
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Definition
prevents genital warts, cervical cancer
Subunit Vaccine (virus coat proteins) |
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Term
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Definition
use antigenic viral components to direct protective neutralizing Ab
HBV |
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Term
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Definition
attenuated strain of bovine TB
PPD skin test: patients may test POSITIVE |
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Term
what happens during a blood transfusion rxn?
2 reasons that could have caused it?
what is a more serious complication that can arise? |
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Definition
naturally occurring IgM Ab react to transfused RBC (type II). Doesn't require sensitization
IgE-mast cells -> histamine release (type I)
Ab:Ag:complement causing Ab-mediated inflammation (type II) - recipient responds to allergens in the blood by attacking donor Ag
acute hemolytic rxn -> widespread hemolysis within vasculature from IgM binding to RBC, complement activation -> chills, SOB, urticaria, DIC |
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Term
| In BM transplantation, why must patient and donor have HLA allotypes in common? |
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Definition
the more they share, the better it works
T cells in the pt's new immune system must be positively selected by thymic epithelial cells expressing the recipient's HLA allotypes, AND
to be activated by infxns, those T cells also need to interact with donor-derived dendritic cells that present pathogen-derived Ag on donor HLA allotypes |
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Term
| Minor histocompatibility antigens |
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Definition
alloantigens, such as H-Y antigens, in which the allogeneic difference is due to the bound peptide and not to the MHC molecule
e.g. brother receiving a BM transplant from an HLA-identical sister
this is why immunosuppressive drugs are still required, even when MHC is matched |
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Term
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Definition
inactivated toxin
stimulate the generation of toxin-specific neutralizing Ab
purified, treated with formalin
e.g. diptheria or tetanus toxin |
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Term
| ex of a combination vaccine? |
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Definition
DPT
the immune response to the diphtheria and tetatus toxoids is enhanced by the adjuvant effect of the whole pertussis bacteria, produces a strong inflammatory rxn at the site of infxn |
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Term
| Killed vaccines, whole organisms |
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Definition
viruses: (Salk polio, influenza, rabies), chemically treated with formalin/heated irradiated
-only viruses whose nucleic acid can be reliably inactivated will work
bacteria: pertussis or cholera - killed organism or extract |
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Term
| what type of vaccine should not be given to an immunocompromised patient? |
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Definition
| live-attenuated virus vaccines |
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