CHAPTER 10 Infection and Immunity

1. CHAPTER 10Infection and Immunity

2. Outline • 10.1 Infection • 10.2 Non-specific immunity • 10.3 Specific immunity • 10.4 Medical Immunology

3. 10.1 Infection • Infection is the invasion of a host organism's bodily tissues by disease-causing organisms, their multiplication, and the reaction of host tissues to these organisms and the toxins they produce.

4. 10.1.1 Bacterial pathogenesis • Pathogen: A microorganism capable of causing disease. • Non-pathogen:A microorganism that does not cause disease. It may be part of the normal flora. • Opportunistic pathogen:An agent capable of causing disease only when the host’s resistance is impaired (e.g. the patient is immunocompromised).An agent capable of causing disease only when spread from the site with normal bacterial microflora to the sterile tissue or organ.

5. Pathogenicity and Virulence • Pathogenicity and virulence are terms that refer to an organism's ability to cause disease. Technically, pathogenicity is used with respect to differences between microbial species whereas virulence denotes differences between strains of the same species. In practice they are often used interchangeably. • Pathogenicity: The ability to cause disease; usually used to describe the difference in disease causing capability between two different species. • Virulence: The ability to cause disease; usually used to describe the difference in disease causing capability between two different strains of the same species.

6. To cause disease, an organism must: • 1. Maintain a reservoir before and after infection (humans, animals, environment, etc.), • 2. Leave the reservoir and gain access to the new host, • 3. Colonize the body, and • 4. Harm the body. • Whether or not a person actually contracts an infectious disease after exposure to a particular potentially pathogenic bacterium depends not only on the microorganism, but also on the number of bacteria that enter the body and the quality of the person's innate and adaptive immune defenses.

7. Quorum sensing • The production, release, and community-wide sensing of molecules called autoinducers that modulate gene expression in response to the density of a bacterial population.

8. Development of a Biofilm by Pseudomonas aeruginosa • Planktonic Pseudomonas aeruginosa use their polar flagella and chemotaxis to swim towards host mucous membranes. Pili then bind to host cell receptors for initial bacterial attachment.

9. Development of a Biofilm by Pseudomonas aeruginosa • The pili retract and bacterial cell wall adhesins enable a more intimate attachment of the bacterium.

10. Development of a Biofilm by Pseudomonas aeruginosa • As the bacteria replicate, quorum sensing genes trigger production of an extracellular polysaccharide called alginate to begin biofilm formation as well as exoenzymes and toxins that damage host cell membranes.

11. Development of a Biofilm by Pseudomonas aeruginosa • Enzyme- and toxin-induced damage to host cell membranes supplies the bacteria within the biofilm with nutrients. The bacteria continue to replicate as the biofilm continues to develop and mushroom up.

12. Development of a Biofilm by Pseudomonas aeruginosa • As the bacteria replicate, the biofilm continues to mushroom up. Water channels form within the biofilm to deliver water and nutrients to the growing population of P. aeruginosa.

13. Development of a Biofilm by Pseudomonas aeruginosa • As the population begins to overgrow the area, quorum sensing genes trigger some of the P. aeruginosa in the biofilm to again produce flagella.

14. Development of a Biofilm by Pseudomonas aeruginosa • Planktonic P. aeruginosa leave the biofilm and move to a new location to begin new biofilms.

15. Toxin • Exotoxin: A soluble protein toxin usually secreted from a living bacterium. Not all exotoxins are necessarily produced to harm humans. Some may be designed to play a role in bacterial physiology, such as resisting bacteriophages, regulating cellular function, or quorum sensing. Other toxins may be produced primarily to target protozoa, insects, and smaller animals and harming human cells becomes an accidental side effect. • Endotoxin: A heat-stable toxin present in the intact bacterial cell but not in cell-free filtrates of cultures of intact bacteria. Endotoxins are lipopolysaccharide complexes that occur in the cell wall; they are pyrogenic and increase capillary permeability.

16. Comparison of Bacterial Exotoxin and Endotoxin

17. Detection of endotoxin • The Limulus lysate test

18. Toxoid • A toxoid is a bacterial toxin (usually an exotoxin) whose toxicity has been inactivated or suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained.

19. 10.1.2 Other microbial pathogenesis • Smallpoxwas an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. Transmission occurs through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. In ordinary type smallpox the bumps are filled with a thick, opaque fluid and often have a depression or dimple in the center. Girl infected with smallpox. Bangladesh, 1973.

20. Smallpox • The smallpox virus, looking like an oil painting. The protein coat of each virus is coloured yellow; DNA genetic material is red. Magnification: ×28,500.

21. Smallpox • Looking uncannily like a collection of sushi, in fact this is a closeup of Smallpox viruses. The virus consists of genetic material (red), DNA (deoxyribonucleic acid), enclosed by a protein capsid (coat, yellow).

22. Smallpox • After vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest, which was declared eradicated in 2011. The last known person in the world to have smallpox of any kind. Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia CDC.

23. 10.1.2 Other microbial pathogenesis • Poliomyelitisoften called polio or infantile paralysis, is an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route. Child with polio sequelae.

24. Poliomyelitis • Polio viruses: RNA genetic material occurs in the core of each virus, surrounded by a protein coat (blue). There are three types of polio viruses, type 1 being the cause of most polio epidemics. Magnification: × 90,000.

25. Protozoan parasite Plasmodium 10.1.2 Other microbial pathogenesis • Malaria isa mosquito-borne infectious disease of humans and other animals caused by protists of the genus Plasmodium. This disease is characterized by severe chills, fever, sweating, fatigue and great thirst. • One way to reduce human deaths (2.7 million annually) from Malaria is to control the mosquito populations. Without the mosquito host, the Plasmodium protozoan can not complete their life cycle. Malaria is usually cured with a drug derived from the Cinchona tree, which is called Quinine.

26. The Life Cycle of the Plasmodium

27. 10.1.2 Routes of pathogen transmission • intestinal infections, respiratory infections, wound infectons, contact infection, animal bites infections.

28. 10.1.3 Patterns of infection • Inapparent infection: subclinical infection that has no detectable clinical symptoms • Carrier state: The continued presence of an organism (bacteria, virus, or parasite) in the body that does not cause symptoms, but is able to be transmitted and infect other persons. • Apparent infection: When an infection causes pathological changes leading to disease, it is often accompanied by a variety of signs and symptoms. Infections that come on rapidly, with severe but short-lived effects, are called acute infections. The infection persists several months to several years called chronic infection.Localized infection stands for the case that the microbe enters the body and remains confined to a specific tissue.

29. Systemic infection • Toxemia: the presence of microbial toxins in the blood. • Bacteremia: a transitory disease in which bacteria present in the blood are usually cleared from the vascular system with no harmful effects. • Septicemia: a disease in which the blood serves as a site of bacterial multiplication as well as a means of transfer of the infectious agent from one site to another. • Pyemia: the presence of pyogenic bacteria in the blood as they are being spread from one site to another in the body.

30. 10.2 Non-specific immunity • Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. • The immune system is composed of two major subdivisions, the innate or non-specific immune system and the adaptive or specific immune system. • The innate immune system is our first line of defense against invading organisms while the adaptive immune system acts as a second line of defense and also affords protection against re-exposure to the same pathogen.

31. 10.2 Non-specific immunity • Nonspecific immune response is the first and second line of defense when a foreign object tries to enter or enter the body. • This response will attack anything (specific immune response will only attack certain infections) that it comes in contact with. • Parts of nonspecific immune response are: Skin, Mucous membranes, Phagocytic (cells that eat foreign particles) cells, Antimicrobial proteins, and the inflammatory response.

32. 10.2.1 Anatomical barriers to infections • Anatomical barriers are tough, intact barriers that prevent the entry and colonization of many microbes.

33. Skin and mucous membranes • The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents. Thus, the skin acts as our first line of defense against invading organisms.

34. Blood-brain barrier and blood-embryo barrier • The blood–brain barrier is a separation of circulating blood from the brain extracellular fluid in the central nervous system.

35. Normal microbiota of the human body • The mixture of microorganisms regularly found at any anatomical site is referred to as the normal microbiota, the indigenous microbial population, the microflora, or the normal flora.

36. 10.2.2 Humoral barriers to infection • The anatomical barriers are very effective in preventing colonization of tissues by microorganisms. However, when there is damage to tissues, the anatomical barriers are breached and infection may occur. • Once infectious agents have penetrated tissues, another innate defense mechanism comes into play, namely acute inflammation. • Humoral factors play an important role in inflammation, which is characterized by edema and the recruitment of phagocytic cells. These humoral factors are found in serum or they are formed at the site of infection.

37. Interferon • Interferons are proteins that can limit virus replication in cells. Antiviral action of interferon

38. Lysozyme • Lysozyme breaks down the cell wall of bacteria. Streptococcus pneumoniae

39. 10.2.3 Cellular barriers to infection • Part of the inflammatory response is the recruitment of polymorphonuclear eosinophiles and macrophages to sites of infection. These cells are the main line of defense in the non-specific immune system.

40. Basophil granulocyte Neutrophil granulocyte Eosinophil granulocyte Monocyte agranulocyte Lymphocyte agranulocyte Defense Cells in the Blood: The Leukocytes

41. A Macrophage with Pseudopods Defense Cells in the Tissue: Macrophages, Dendritic Cells and Mast Cells A Macrophage Phagocytosis of E. coli Dendritic Cell Mast cell

42. The process of phagocytosis

43. 10.2.4 Inflammation • A process in which blood vessels dilate and become more permeable, thus enabling body defense cells and defense chemicals to leave the blood and enter the tissues. Acute inflammation is usually a localized, protective response to tissue injury. Excessive or chronic inflammation, however, may lead to tissue destruction.

44. Diapedesis During InflammationStep-1 A normal capillary prior to inflammation.

45. Diapedesis During InflammationStep-2 Integrins on the surface of the leukocyte bind to adhesion molecules on the inner surface of the vascular endothelial cells.

46. Diapedesis During InflammationStep-3 The leukocytes flatten out and squeeze between the endothelial cells to leave the blood vessels and enter the tissue. The increased capillary permeability also allows plasma to enter the tissue.

47. Diapedesis During InflammationStep-4 External view of leukocytes squeezing between the endothelial cells, leaving the blood vessels, and entering the tissue.

48. Diapedesis During Inflammation

49. 10.3 Specific immunity • The specific immune system of vertebrates has three major functions: to recognize anything that is foreign to the body (“nonself”), to respond to this foreign material, and to remember the foreign invader. • There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity. • Humoral immunity involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes. • Cell-mediated immunity involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen and is mediated by T-lymphocytes.

50. 10.3.1 Immune system:immune organ, immune cell and immune molecule Central immune organ: Thymus