Introduction to Microbiology

1. Introduction to Microbiology Anas Abu-Humaidan M.D. Ph.D. Lecture 13

3. Passive vs. active immunity • Acquired immunity is attained through either passive or active immunization. • Passive immunization refers to the transfer of  “ready-made” antibodies, from one individual to another. It can occur: • 1) naturally by transplacental transfer of maternal antibodies to the developing fetus, or through colostrum and breast milk rich in IgA. • 2) it can be induced artificially by injecting a recipient with exogenous antibodies targeted to a specific pathogen or toxin. • Examples: • Natural: Maternal antibodies protect against some diseases such as measles, rubella, and tetanus for the first few months of life. • Artificial: Pooled human immunoglobulins used intravenously (IVIG) can be used prophylactically in the case of immunodeficiency diseases, or specific antibodies used in the treatment of several types of acute infections such as rabies.

4. Passive vs. active immunity • Acquired immunity is attained through either passive or active immunization. • Active immunity refers to the process of exposing the body to an antigen to generate an adaptive immune response: the response takes days/weeks to develop but may be long lasting—even lifelong (unlike passive immunity). It can occur: • 1) Naturally through infection with a certain pathogen. • 2) Artificially through administration of vaccines containing weekend or inactive pathogen. • Examples: • Natural: Wild infection with hepatitis A virus (HAV) and subsequent recovery gives rise to an active immune response usually leading to lifelong protection. • Artificial: In a similar manner, administration of two doses of hepatitis A vaccine generates an acquired active immune response leading to long-lasting (possibly lifelong) protection.

5. Immunopathology Defects or malfunctions in either the innate or adaptive immune response can provoke illness or disease. Such disorders are generally caused by an overactive immune response (known as hypersensitivity reactions), an inappropriate reaction to self (known as autoimmunity) or ineffective immune responses (known as immunodeficiency).

6. Hypersensitivity Hypersensitivity reactions refer to undesirable responses produced by the normal immune system. There are four types of hypersensitivity reactions: Type I: immediate hypersensitivity Type II: cytotoxic or antibody-dependent hypersensitivity Type III: immune complex disease Type IV: delayed-type hypersensitivity

7. Type I: immediate hypersensitivity – Allergy • Immediate hypersensitivity reaction occurs when an antigen (allergen) binds to IgEon the surface of mast cells with the consequent release of several mediators. • This starts when an antigen induces the formation of IgE antibody, which binds firmly by its Fc portion to receptors on the surface of basophils and mast cells. • Reexposure to the same antigen results in cross-linking of the cell-bound IgE degranulation  release of pharmacologically active mediators within minutes (immediate phase).

9. Abdominal discomfort and diarrhea cough Runny nose and sneezing

10. Type I: immediate hypersensitivity – Allergy

11. Type I: immediate hypersensitivity – Allergy • The most severe form of type I hypersensitivity is systemic anaphylaxis, in which severe bronchoconstriction and hypotension (shock) can be life threatening. • The most common causes of anaphylaxis are foods such as peanuts and shellfish, bee venom, and drugs such as penicillin. Or latex used in gloves. • Drugs to counter the effect of mediators should be given like Epinephrine, antihistamines, corticosteroids, or cromolyn sodium, either singly or in combination, should be given.

12. Type II: cytotoxic or antibody-dependent hypersensitivity • Is an antibody mediated process in which IgG and IgM antibodies are directed against antigens on cells (such as circulating red blood cells) or extracellular material (such as basement membrane). • This subsequently leads to cell lysis, tissue damage or loss of function through mechanisms such as Complement activation and antibody –dependent cytotoxicity.

13. Type II: cytotoxic or antibody-dependent hypersensitivity An example is an acute haemolytic transfusion reaction following transfusion of ABO incompatible blood. Another example is Goodpasture's syndrome, where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies in a complement mediated fashion

14. Type III: immune complex disease • Occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response (e.g. Complement-mediated inflammation) causes injury and attraction of leukocytes. • Notable examples include: Systemic lupus erythematosus, poststreptococcal acute glomerulonephritis

15. Type IV hypersensitivity Also called delayed-type hypersensitivity. It is a cell-mediated immune reaction. The delay is the time required after initiation of a TH1 response for antigen to be processed, cytokines produced, and T cells to migrate and accumulate at the antigen site. The TH1 immune responses is can manifest in a microscopic structure called a granuloma, which is composed of lymphocytes, macrophages and fibroblasts in TB. Allergic contact dermatitis is another example, T cells that are activated in the skin by antigen captured cutaneous dendritic cells and produce various chemical mediators, which create antigen-specific inflammation.

16. Types of hypersensitivity reactions

17. Immunodeficiencies Immunodeficiency disorders result in a full or partial impairment of the immune system. Primary immunodeficiencies (PID) are the result of genetic defects, and secondary immunodeficiencies (SID) are caused by environmental factors, such as malnutrition, HIV/AIDS, and drugs. The abnormalities can involve absence or malfunction of blood cells (lymphocytes, granulocytes, monocytes) or soluble molecules (antibodies, complement components) Primary immunodeficiencies are rare but can be extremely serious. Secondary immunodeficiencies are more common and some of the primary causes of them are global health issues, Up to 50% of the poorest communities in the developing world are affected by malnutrition-related SID disorders.

21. Further reading and material: • Sherris Medical Microbiology, sixth edition • Chapter 2: Immune response to infection