Lec 13- Immunotherapy I Flashcards
Breast feeding
-This is the preferred way of doing things because the baby will get passive immunity from the milk (Abs)
Immuno-modulatory therapy
-Administration of immune system factors for protection and therapy
Immunity
-The ability to resist infection with a particular pathogens (different ones)
-Infection may lead to disease, can lead to death
-Immunity may protect against disease
Active (make yourself)
-Adaptive immunity that results from natural exposure to a pathogen or vaccine
Passive (get from somwhere else)
-The acquisition of immunity by receipt of pre-formed Abs
Immuno-modulatory therapy
Immune based -Abs: Herceptin (breast cancer); infliximab (RA); Tetanus immunoglobulins (TIG); IVIG -Cytokines: IFN-a (anti-viral) -Vaccines NON immune based -Anti-inflammatory agents -Corticosteroids -NSAIDs (COX inhibitors) -Others: methotrexate; anti-histamines
How does the immune system protect- innate
Innate immune system
-Barriers (mechanical, chemical and microbiological)
-Phagocytes with ROI (Reactive O2 intermediates), RNI (Reactive N2 Intermediates), anti-microbial peptides
-Complement
-Inflammation
Features
-Rapid
-Limited and fixed specificity
-No memory cells (each response identical)
How does the immune system protect- Adaptive immunity
Ab- dependant -Ig A, E, G, M (No IgD but we don't no what it does) Cell mediated -Lymphocytes -B cells -T cells: Helper, Cytotoxic Features -Slower response time -Highly specific -Repeat exposure in more rapid and specific (Memory cells)
Humoral immunity
- B cells make Ab with help of Th cells
- Ab promotes a range of effects
- B cell activation by Ag and helper T cell
- Ab secretion causes
1) Neutralisation: Ab prevents bacterial and toxin adherence
2) Opsonisation: Ab promotes phagocytosis
3) Complement activation: Ab activates complement, which enhances opsonisation and lyse some bacteria
ADCC
-NK cells
+Natural killer cells (non-B and T- Lymphoid cells
+Have FcR on their surface
-Ab binds Ag on the surface on target cell
-FcR on NK cells recognise bound Abs
-Cross linking of Fc receptors signals the NK cell to kill the targets
-Target cell apoptosis
Different Abs do different things in different places- What are the best Abs for certain jobs- Functional activity
Neutralisation, opsonisation, sensitisation for killing by NK. cells; Sensitisation of mast cells; activates complement system
1) Neutralisation
- IgG1-4 and IgA ++
- IgM +
2) Opsonisation
- IgG1 +++
- IGg3 ++
- IgG4, IgA, IgM +
3) sensitisation for killing by NK cells
- IgG1, IgG3 ++
4) Sensitisation of mast cells
- IgE +++
5) Activates complement
- IgM, IgG3 +++
- IgG1 ++
Different Abs do different things in different places- What are the best Abs for certain jobs- Distribution:
Transport across epithelium, transport across placenta; diffusion into extravascular sites; mean serum levels
1) Transport across epithelium
-IgA +++ (dimer)
2)Transport across placenta
-IgG1 +++
-IgG3 ++
3) Diffusion into extravascular sites
-IgG1-4 +++
-IgA ++ (monomer)
4)Mean serum level (mg ml-1)
IgM= 1.5; IgD= 0.04; IgG1= 9; IgG2= 3; IgG3= 1; IgG4= 0.5; IgA=2.1; IgE= 3x10-5
Diseases caused by exotoxins
-IgG and IgA can neutralise and protect from disease
Abs neutralise toxins
- Toxins binds to cellular receptors
- Endocytosis of toxins; receptor complex
- Dissociation to release active chain which poisons cells
- Abs protect cell by blocking binding of toxins (they must have higher affinity than receptors)
Ab can block bacterial infection: Haemagglutinin and influenza
- Virus binds to receptors on cell surface
- Receptor-mediated endocytosis of virus
- Acidification of endoscope after endocytosis triggers fusion of virus with cell and entry of viral DNA
- Ab blocks binding to virus receptor and can also block fusion event
Ab can block bacterial infection
-Some bacteria need to adhere to cause infection
+Salmonella
+Neisseria
-IgA at mucosal surfaces can prevent this
-IgG in tissues
-Colonisation of cell surface by bacteria which bind to surface via bacterial adhesion
-Some bacteria become internalised and propagate in internal vesicles
-Abs against adhesions block colonisation and uptake
Neonatal immunity
-Neonates
+Vulnerable
+No previous exposure to microbes of their new environment
Protection
-Passive (no memory cells)
-Stop-gap until they generate their own immunity
