9. Immunological Disorders and Vaccines

• immune system evolved to protect the host
• imperfect, has detrimental aspects =
• hypersensitivity
• autoimmune diseases
• immunodeficiency diseases

• immediate - happens within 15 minutes
• immunogens are usually non-infectious substances
• antibody (IgE) mediated, mast cell is key =
• - antibody is produced on first exposure
• - on next exposure antigen is reconized by IgE bound to a mast cell, histamine is released
• causes allergies

• cytotoxic, antibody dependent
• many types of antigens
• IgG and IgM mediated
• can take up to 8 hours
• example = Rh + and - compatibility

• immune complex disease
• microorganisms can be antigen - antigen must be soluble to circulate
• response mediated by IgG
• initial response within 8 hours, but reaction can go on for years
• antigen-antibody complexes are formed, deposit in tissues causing inflammation
• example: farmer's lung

• delayed type hypersensitivity
• antibody independent
• immunogens may be infectious or not
• different, CMI is involved
• response time is 24-48 hours
• example: dermatitis, tuberculosis

• autoimmunity is an acquired immune reactivity to self antigens - disease occurs when the autoimmune response leads to tissue damage or abnormal regulation of an organ
• genetic factors important
• mechanisms = molecular mimicry, breakdown of sequestration, failure to delete self-reacting cells

• host is infected with a microorganism containing an immunogenic epitope that is similar to an epitope on a host tissue
• immune response against the microbes reacts to host tissue and causes damage

• some self antigens are sequestered from the immune system during development
• later in life, antigens get exposed to immune system, which reacts as if they are foreign

• grave's disease - excessive thyroid activity
• type I diabetes - destruction of insulin-producing cells of pancreas
• rheumatoid arthritis - destruction of membrane of joints
• multiple sclerosis - destruction of myelin sheath of nerves
• systemic lupus - reaction against DNA of all cells
• coeliac disease - inflammation in small intestine caused by cross-reaction with gliadin

• primary immunodeficiency - genetic basis =
• - C3 deficiency
• - lack of B cells
• - lack of T cells
• - lack of B and T cells

• secondary immunodeficiency - acquired =
• - infectious agent
• - immunosuppressive drugs
• - radiation treatment
• - malnutrition
• - aging
• - overwhelming infection

• the enhancement of the immune response, usually by artificial means
• two types = active and passive

• when an immune response is mounted by the host
• occurs as a result of =
• being infected with an organism
• administration of vaccines

• the enhancement of the immune response by providing the host with preformed antiboddies to the antigen
• of interest

a molecule that is recognized by the immune system and can combine with a product of the immune system

a type of antigen that is able to induce an adaptive immune response

the smallest unit of an antigen to which the immune system responds

• biochemical nature - proteins highest response
• molecular weight - larger = more
• physical form - particulate > soluble
• foreignness
• route of exposure - intravenous > intramuscular > oral
• dose - larger dose = more
• presence of adjuvant - substance given with antigen

• effective
• safe
• inexpensive
• stable

• live attenuated
• killed whole organism
• subunit
• DNA

• microorganisms cultivated so that they lose the ability to cause disease, but still generate an immune response
• used mainly against viral diseases
• stimulate both humoral and CMI
• advantage - stimulates CMI
• disadvantage - may cause disease in an immunocompromised host

• made from preparations of the microorganisms inactivated chemically or by heat
• used to protect against diseases caused by extracellular bacteria and some viruses
• humoral stimulated, not CMI
• main disadvantage - side effects

• can be purified directly from microorganisms, but usually recombinant
• recombinant form - the most important epitope of the microorganism for generation of an immune reponse
• gene for the epitope is inserted into yeast or bacteria
• humoral stimulated, not CMI
• limited side effects

• toxoid = an exotoxin which has been altered to eliminate its toxicity while retaining its immunogenicity
• humoral stimulated, not CMI
• very safe, rarely any side effects

• naked cDNA injected into muscle
• acts as templates for transcription of mRNA and translation of the desired antigenic protein
• experimental in humans
• potential advantages = stimulates CMI, no risk of disease, easy storage

• IgG cross the placenta and enter fetus
• antibodies (especially IgA) in colostrum and breast milk

• antibodies are derived form donor humans or animals who have high levels
• used in diseases where - rapid immune protection is needed, no vaccine available, host is immunocompromised

the protection of a susceptible individual by virtue of the fact that the vast majority of the population is immune to the disease and cannnot get infected and spread the microorganisms

toxoid vaccines cannot help because people can get infected and still spread

• identify high-risk people, don't vaccinate
• safer vaccines
• informed consent
• national compensation program