Defense Against Infectious Diseases

Topic 11.1

Assessment Statements11.1.1 Describe the process of blood clotting.

11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity.

11.1.3 Define active and passive immunity.

11.1.4 Explain antibody production.

11.1.5 Describe the production of monoclonal antibodies and their use in diagnosis and in treatment.

11.1.6 Explain the principle of vaccination.

11.1.7 Discuss the benefits and dangers of vaccination.

Blood Clotting

0Bruising0 Braking small blood vessels (capillaries, arterioles,

venules) allowing blood to escape the closed circulatory system

0 Allows entry point for pathogens0Clots

0 Seals damaged blood vessels0 Prevents excessive blood loss and entering pathogens

Blood Clotting

0Within blood, 0 Plasma proteins

0Prothrombin and fibrinogen0 Always present in blood plasma, remain inactive unless needed

0 Platelets0Form in bone marrow, one large cell breaks into many

fragments

Blood Clotting

0Damaged blood vessel0 Release chemicals which stimulate platelets to adhere to

damaged area0 Other platelets adhere to those platelets forming a

‘plug’0 Damaged tissue and platelets release chemicals to

convert prothrombin thrombin0 Thrombin (active enzyme) catalyzes conversion of

soluble fibrinogen into insoluble fibrin0 Fibrin (fibrous protein) forms a mesh-like network that

stablizes the platelet plug

Blood ClottingDamaged blood vessel

Chemicals released

Platelets adhere to damaged area

Chemicals which convert

Prothrombin

Thrombin (enzyme)

Fibrinogen Fibrin (forms mesh)

Immune Response

0Body recognition of foreign cells0 ‘self ’: normal body cells

0All body cells have common set of cell membrane proteins0 ‘not-self ’ (aka antigens): pathogens, transplanted

organs, etc.0Different cell membrane proteins

Antibody Production

0Leucocytes0 B lymphocytes (B cell)

0Synthesizes and secretes a specific antibody which binds to a specific antigen

0 Represent roughly 1% of all cells in bloodstream0No one type of B cell is found in high numbers0Cloning occurs to make enough antibodies to combat

antigens

Antibody Production

1. Macrophage (phagocytic cell) – first to encounter an antigen2. Macrophage engulfs ‘not-self’ antigen by phagocytosis and

only partially digests it3. Molecular pieces of antigen are displayed on cell membrane

of macrophage (antigen presentation)4. Helper T-cells chemically recognize antigen and become

activated5. Helper T-cells turn immune response from non-specific

(‘not-self’) to antigen-specific (identity of pathogen)6. Helper T-cells chemically communicate with (activate)

specific B cell type (able to produce the antibody needed)

Cell Cloning

0Activated B cell begins cell divisions (aka cell cloning)0 Antibody-secreting plasma cells

0Secrete antibodies immediately0Help fight off the first (primary) infection

0 Memory cells0Do not secrete antibodies during primary infection0Long-lived cells, remain circulating in bloodstream awaiting

secondary infection

Fundamental Principles of True Immunity

0 Challenge and Response0 Immune system must be challenged by antigen (primary infections) in

order to develop immunity0 All cellular events (macrophages, helper T-cells, B cells) are part of

response0 Clonal Selection

0 Identification of leucocytes (particular plasma B cell) help with specific pathogen

0 Multiple cell divisions which occur to build up numbers of that cell type0 Memory Cells

0 Provide long-term immunity0 Must experience a pathogen in order to produce these cells0 Have true immunity to that specific pathogen

Antibody Production

Production of more antibodies in less time

Active and Passive Immunity

0Active0 Always leads to the production of memory cells long-

term immunity0Passive

0 One organism acquires antibodies which were produced in another organism

0 Only short-term benefits0 Examples:

0Mother to fetus: placenta, colostrum 0 Injection of antibodies in antisera (antivenoms)

Polyclonal and Monoclonal Antibodies

0Polyclonal Response0 Primary immune response by an organism0 Pathogen is recognized as many antigens (not just one)

0Ex: capsid (protein coat) of a virus will have several types of protiens

0 Each protein/antigen can cause an immune response causing several types of B cells to be made

0Monoclonal0 Production of the same type of antibodies

Production of Monoclonal Antibodies

1. Inject an antigen into a laboratory mouse0 Choice of antigen extremely important

2. Animal goes through primary immune response0 Polyclonal response

3. Spleen of animal is ‘harvested’ – gain access to many blood cells

4. Some of those cells will be leucocytes from recent immune response

0 Problems:0 Keeping B cells alive for extended period of time0 Identification of B cells that produces the desired antibody

Production of Monoclonal Antibodies

5. B cells are fused with myeloma (cancerous) cells hybridoma6. Hybrid cells have characteristics of both cells

0 Produce antibodies0 Long lived (as are all cancer cells

7. Entire mix is transferred to environment to where the hydridoma cells are sole survivors

8. Hybridomas are cultured in separate containers9. ELISA (enzyme-linked immunosorbent assay) test is

performed to identify which B cells are producing desired antibodies

10. Antibody is purified from cell culture when needed

Uses of Monoclonal Antibodies

0Diagnosis0 Pregnancy testing

0Embryo produces hormone HCG (human chronic gonadotropin)

0Small amounts will be present in mothers bloodstream and urine

0Hybridomas can be produced by injecting animal with HCG0B cells produce antibodies that recognize HCG as an antigen0Antibodies bind to HCG causing a color change pregnant!

Uses of Monoclonal Antibodies

0Treatment0 Cancer

0Cancerous body cells produce specific antigens on their membranes

0One possible treatment is to produce monoclonal antibodies that target the cancer cell antigens

0Monoclonal antibody could be modified to carry a toxin specific for that cancer cell, or

0Attach radioisotope for pin-point radiation therapy0Advantage: direct target to cancer cells

Vaccinations

0Reminder: you CANNOT be immune to a pathogen prior to being exposed to it

0Vaccines0 Act as the first exposure to pathogen0 Developed by weakening pathogen, then injecting the

pathogen into the body0 Methods of production:

0Selecting a particularly ‘weak’ strain0Heating the pathogen0Chemical treatment

Vaccinations

0 Immune response0 Leucocytes recognize the weakened pathogen as ‘not-

self ’ and primary immune response ensues0 Formation of memory B cells which means long-term

immunity0Vaccine DOES NOT prevent infection, but allows

secondary immune response to occur0 Much quicker and more intense

VaccinationsBenefits Dangers

Possible total elimination of disease• Small pox, polio, measles

Prior to 1999, many vaccines contained thimerosal, a Hg-based preservative.• Hg shown to be a neurotoxin

Decrease in spread of epidemics and pandemics

Perception exists that multiple vaccines given to children over short period will ‘overload’ their immune system

Preventative medicine is typically the most cost-effective approach to healthcare

Anecdotal evidence suggested that MMR vaccine may have a link to autism

Each vaccinated individual benefits because the full symptoms of the disease are not experienced

Cases have been reported of vaccines leading to allergic reactions and autoimmune responses