Immunotherapeutic agents

Question 1

Immune system: three lines of defence

Answer 1

(Non-specific and fast)

Barriers (innate external)
• Skin & Mucosal membranes
Prevent pathogens from getting into the body.

Innate
• Born with intact system, fast response (sec – hrs)
- Cells: Phagocytes (Macs & neutrophils), natural killer cells, basophils, eosinophils, mast cells
- Chemicals - interferons and complement

(Specific and slow)

Adaptive (acquired)
• Develops and is educated as we grow, slow response
(days)
- Cellular Imm. T cells (T-lymphocytes)
- Humoral Imm. B-cells / plasma cells & antibodies

Question 2

Adaptive immune response: Revision

Answer 2

1: Antigen presenting cells
• Macrophages
• Dendritic cells (pros)
Monitor the body for invaders, eat them & present antigen to T-cells in lymph nodes via MHC-II

Lymphocytes

2: B cells
• Originate AND mature in bone marrow
• Produce antibodies

3: T cells
• Mature in the Thymus
• Direct the adaptive response (CD4 helpers)
• Directly kill infected cells

Question 3

Immunostimulants

Answer 3

Activation
o Vaccines (stimulate a specific immune response => antibody production)

o Antisera (e.g. antivenoms: ready made neutralising antibodies)

Enhancement - Cytokines
o Colony stimulating factors (details shortly)

o Interferons
- stimulate antiviral response,
- stimulate macrophage & CTL function
Use: some cancers, viral infections, multiple sclerosis

o Interleukins
- B and T cell proliferation & activation

Question 4

Immunological memory - memory cells

Answer 4

• Memory cells are long lived and primed to the original antigen
=> response to second exposure is faster, more effective, more prolonged.

The generation of Abs and memory B and T cells to a specific pathogen is the basis of vaccinations

Question 5

Vaccines

Answer 5

Vaccination vs Immunisation ?
vaccination = administration of a vaccine
immunisation = immune response to a vaccine has been achieved

Antigen(s*) in the vaccine induce protective immunity (Abs) against a particular pathogen and the disease it causes.

Antigens may be:
o live attenuated viruses, (mumps and rubella)

o live attenuated bacteria, (bacille Calmette–Guérin in tuberculosis vaccine) o killed or inactivated viruses, (hepatitis A)

o killed or inactivated bacteria, (Q fever vaccine)

o pathogen specific protein/component = antigen(s) of interest, (hepatitis B)

o toxoids (bacterial toxins that have been made non-toxigenic), (tetanus & diphtheria)

Question 6

Active and Passive immunisation

Answer 6

Active immunisation induces an immune response in the person receiving the vaccine.

Passive immunisation = direct transfer of antibodies to a non- immune person to provide temporary protection (anti-sera).

Question 7

There are Five Antibody classes (‘MADGE’)

Answer 7

IgM - serum - first response Ab

IgA - mucosae 
Secretory antibody (sweat, milk, intestinal fluid, saliva). Prevents pathogen attachment to epithelium. Provides protection to babies

IgD - B cell surface
B-cell antigen receptor

IgG - serum
Major serum Ab - most important Ab for vaccinations

IgE - cell membranes
Binds to mast cells and basophils. Allergenic antibody (histamine release)

Question 8

Humoral immunity: Antibody function

Answer 8

Extracellular pathogens are recognised by free antibodies in the bodies ‘humours’, i.e. fluids (blood, lymph, mucosa)

Bound antibodies :-

• inactivate toxins/pathogens and
• mark them for destruction (phagocytosis or complement)
• sensitise tissue resident mast cells => enhance inflammation

Very specifically neutralise and flag extracellular invaders
for destruction

Question 9

Adverse Events Following Immunisation - AEFI

Answer 9

Vaccine adverse events can be local or systemic:

Local: Injection site reactions
o occur at the site of vaccine administration, are the most frequent AEFI. o include pain, redness and swelling.
o most are mild and resolve without treatment within a few days.

Systemic adverse events most commonly include o fever, headache and lethargy.
o Allergic reactions can occur.
o Vaccination rarely causes anaphylaxis
(most severe form of allergic response)

Monitor patient for 15 minutes

Question 10

Colony stimulating factors - CSFs

Answer 10

Endogenous growth factors for blood cells

CSFs are glycoproteins

Released by many cell types

Stimulate 
- proliferation
- differentiation 
- activation
of neutrophils, macrophages / monocytes & other blood cells (depending on the version of CSF)

=> increase the power of the immune system

Question 11

G-Colony stimulating factor (G-CSF) as a drug

Answer 11

Examples:
Filgrastim and Lenograstim

Produced using recombinant DNA technology

Proteins => route of administration?

Effects:
Increases neutrophil production

Uses:
Neutropenia – low neutrophils (cancer chemo / radioT)
After bone marrow transplants

Question 12

Colony stimulating factors - adverse effects

Answer 12

• Bone pain
• GI tract effects
• Changes in blood cell levels (must be monitored!)
• Headache & fever