Lecture 27

Question 1

1. What is the purpose of the immune system?
2. What is innate immunity? What does it function to do?
   
   1. What cells carry out this ability?
   2. What does it also function to do?
3. What is adaptive immunity? Is it specific or non-specific?
4. What is the basic idea of these systems?

Answer 1

1. Recognizes and destroys pathogens that get through the non-specific defenses of the body.
2. A pre-existing, non-specific ability. An immediate response to invasion by a pathogen.
   
   1. Carried out by phogocytes (cells that engulf, kill, and digest bacteria and engulf and digest other foreign particles, cell debris, etc.).
   2. Functions to activate the adaptive immune response.
3. Activated when a pathogen, due to its virulence, gets through the non-specific defense and survives the innate immune response. A specific response to an individual pathogen. It’s an aquired ability (takes time to work). The response is directed at unique pathogen molecules, called antigens.
4. Basic Idea: Phagocytes injest and digest pathogens and present their antigens to lymphocytes, which interact with the antigens via specific receptors; this interaction activates the lymphocyte to produce pathogen-specific antibodies, which bind to the pathogen and mark it for destruction.

Question 2

1. Innate immune system
   
   1. What type of organisms have this?
   2. Is it specific or non-specific?
   3. Is it an immediate or delayed response?
   4. Does it have memory?
2. Adaptive immune system
   
   1. What type of organisms have this?
   2. Is it specific or non-specific?
   3. Is it an immediate or delayed response?
   4. Does it have memory?
3. Are these two systems linked?
4. What immune system is activated first?

Answer 2

1. Innate immune system
   
   1. Vertebrates and invertebrates
   2. Non-specific response
   3. Immediate maximal response
   4. No memory
2. Adaptive immune system
   
   1. Vertebrates only
   2. Pathogen-specific (antigenic specific) response.
   3. Delayed maximal response.
   4. Develops memory (rapid response upon second exposure to a pathogen).
3. The innate and adaptive immune responses are linked.
4. When an infection begins and the innate system starts responding, components of the innate system communicate with and activate the adaptive system.

Question 3

1. What is immunity carried out by?
2. What does blood consist of?
   
   1. What are RBCs?
   2. What are WBCs?
3. What is plasma?
4. What is serum?
5. What are antibodies?
6. What is lymph?

Answer 3

1. Carried out by cells and proteins that circulate throughout the body, primarily in the blood and lymph.
2. Cells plus plasma
   
   1. RBCs = erythrocytes, not nucleated, carry oxygen.
   2. WBCs = leukocytes, nucleated, two kinds. Myeloid cells (phagocytes, innate immune system). Lymphocytes (T cells, B cells, adaptive immune system).
3. Liquid portion of the blood, containing proteins and other solutes.
4. Blood without cells and without fibrin (protein, clotting factor), but does contain antibodies.
5. Proteins of the immune system (also called immunoglobulins), produced by B lymphocytes, bind to antigens.
6. Similar in composition to blood but lacks RBCs.

Question 4

1. What is the lymph system composed of?
2. How does lymph fluid enter the blood?
3. What can the cells of the immune system do?
4. What kind of cells do lymph nodes contain?
5. What pumps lymph through the body?

Answer 4

1. Bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT)
2. Lymph fluid from the thoracic duct drains into the blood via the left subclavian vein.
3. They can move from the blood to the lymph and back.
4. Has plasma cells, T cells, APCs, and B cells.
5. Contraction of the body’s other muscles exercise is important for activity of the lymph system.

Question 5

1. What are the primary lymph tissues? What do they do?
2. What are the secondary lymph tissues? What do they do?

Answer 5

1. Primary Lymph Tissues:
   
   1. Bone marrow: produces cells of the immune system.
   2. Thymus: site of T cell maturation.
2. Secondary Lymph Tissues:
   
   1. Lymph Nodes: high concentrations of lymphocytes and phagocytes; interacts with antigens and pathogens from the lymph.
   2. Spleen: site of antibody synthesis (and other function)
   3. MALT: like lymph nodes, high concentrations of lymphocytes and phagocytes; interacts with antigens and pathogens from the intestinal and bronchial mucous membranes and other muscosal membrane.

Question 6

1. What does the lymph transports?
2. What is a lymph node?
3. What does the lymph also carry?

Answer 6

1. Transports antigens, pathogens, and antigen presenting cells to the lymph nodes where an immune response is stimulated.
2. An organized collection of lymphoid tissue through which lymph passes on its way to returning to the blood. The node is composed of a dense collection of lymphocytes and phagocytes, and its size can expand significantly when a foreign antigen is present.
3. Also carries lymphocytes and antibodies from the efferent duct, exiting the lymph nodes, to travel around the body via the lymphatic system.

Question 7

Myeloid Cells

1. What immune system are these cells active in?
2. What are monocytes?
   
   1. What are the two monocytes?
3. What are granulocytes?
   
   1. What are the two groups?

Answer 7

1. Active in the innate immunity, all are phagocytic.
2. Develop into antigen presenting cells (APCs) (phagocytose antigens, digest them, and present parts of them to lymphocytes).
   
   1. Macrophages and Dendritic cells.
3. Contain granules of toxin or enzymes (phagocytose target cells, release toxins or enzymes to kill the engulfed cells or other target cells).
   
   1. Neutrophils and Mast cells.

Question 8

1. What is innate immunity mediated by?
2. What are PAMPs?
   
   1. What are some examples?
3. What is PRR?
4. How do phagocytes interact with pathogens?
5. What are cytokines?

Answer 8

1. Mediated by phagocytes. (e.g. macrophages and neutrophils) via PRRs that recongnize (bind to) PAMPs.
2. Pathogen-associated molecular pattern. Molecules with repeating structural subunits. Shared among related pathogens. Highly conserved with a pathogen group.
   
   1. Lipopolysaccharide (gram negative bacteria), Flagellin (protein of bacterial flagellum), Double stranded RNA (some viruses), Lipoteichoic acid (Gram positive bacteria).
3. Pattern recognition receptor. A preformed receptor for each PAMP. Many different PRRs on each phagocyte. Found in all multicellular organisms.
4. Interact by recognizing (binding to) PAMPs via PRRs. The interactions activate the phagocyte to ingest and destroy the pathogen and to produce cytokines that attract and activate other cells.
5. Small proteins involved in inflammation and immunity.

Question 9

1. Does innate immunity require activation?
2. What is it carried out by?
3. What is it directed against?
4. What is innate immunity activated by?

Answer 9

1. Does not require activation by prior exposure to a pathogen.
2. Carried out by phagocytes, cells that can recognize, engulf, kill, and digest pathogens.
3. The first line of defense when physical and chemical barriers to infection are breached by a pathogen. Directed against common features of pathogens.
4. Activation:
   
   1. Alarm signals sent out by damaged, injured, or stressed cells.
   2. PRRs - recognize components found in or on broad groups of microbes.

Question 10

1. What purpose does inflammation serve?
2. What does plasma do?
3. What does inflammation and clotting do?
4. How quick is the onset of inflammation?
5. What is inflammation produced by?
6. What do these alarm signals function to do?

Answer 10

1. An early, protective response to infection; tissue redness, heat, swelling, and pain caused by increased flow of blood and leukocytes from the blood to damaged/infected tissue.
2. Brings fibrin (blood clotting protein) to the damaged tissue.
3. Forms a physical barrier blocking the spread of infection, and it promotes healing of damaged tissue after pathogens have been removed.
4. Has a rapid onset of minutes or hours, with a duration of a few days.
5. Response is produced by eicosanoids and cytokines that are released by infected or injured cells.
6. Alarm signals function to stimulate blood flow and recruit immune cells to the site of infection and to enhance healing of damaged tissues. The signals attract phagocytes, especially neutrophils, which then release factors that recruit other leukocytes and other immune system cells to the site of infection.

Question 11

1. What are eicosanoids?
2. What are cytokines?

Answer 11

1. Derived from fatty acids
   
   1. prostaglandins - produce fever and increase blood flow.
   2. leukotrienes - attract leukocytes to the injured tissue.
2. Proteins, Peptides, or Glycoproteins
   
   1. interleukins - mediate communication among white blood cells.
   2. chemokines - stimulate chemotaxis of immune system cells to the site of injury.
   3. interferons - shut down protein synthesis in infected cells (antiviral effect).

Question 12

1. What are neutrophiles?
2. What are neutrophiles activated by?
3. What else ingest and destroy a pathogen?
4. What is the overall effect

Answer 12

1. A granulocyte kind of myeloid cell. First responders, attracted to a site of infection or tissue damage by chemokines (chemotactic cytokines) released by damaged host cells.
2. Activated by chemokines, migrate to and ingest damaged cells and pathogens and release other chemokines, which attract macrophages (a monocyte kind of myeloid cell) to the site of infection.
3. Macrophages also ingest and destroy the pathogen and damaged cells, and they release cytokines, which with chemokines, stimulate swelling, reddening, and localized heating of the damaged phage.
4. Rapid localization of the infection/damage and destruction of the pathogen or injured host cell by the recruited neutrophils and macrophages.

Question 13

Phagocytes and pathogen killing

1. How do phagocytes find pathogens?
2. What does it do to the pathogen?
3. What do lysosomes do?
   
   1. What do they contain?
   2. At what pH do these enzymes work well?
4. What is an example of a phagocyte?

Answer 13

1. Phagocytes (myeloid type leucocytes) move around the body looking for pathogens, and can be called to a site of infection by cytokines.
2. Engulf pathogen in intracellular vesicle (phagosome) that then fuses with another vesicle (lysosome) to form a phagolysosome.
3. Release toxic oxygen species (hydrogen peroxide, superoxide anions, hydroxyl radicals, singlet oxygen; these are reactive oxygen species) by activating a “respiratory burst”.
   
   1. Contain hydrolytic enzymes (lysozyme, proteases, phosphatases, nucleases, lipases) that digest the proteins, carbohydrates, lipids of the pathogen.
   2. At low pH inside the lysosome, approx. pH 5, these enzymes work well.
4. Neutrophils (in blood, a major kind of leukocyte) and macrophage (in tissue).

Question 14

1. What are PRRs?
2. When were they discovered?
3. What do they recognize?
4. What do leukocytes (e.g. macrophages) and cells of the adaptive immune system (T cells, B cells) have?
5. What do TLRs (PRRs) function in?
6. How many TLRs are there?

Answer 14

1. Membrane-bound proteins on phagocytes, recognize specific classes of pathogen structural components; example LPS.
2. Discovered in 1985 in Drosophila and called “Toll receptors), called TLRs in humans.
3. Recognize molecules that are broadly shared by pathogens but are distinguishable from host molecules; the pathogen molecules are referred to as PAMPs; interaction between the PRR and a PAMP activates the phagocyte to ingest and destroy the targeted pathogen.
4. TLRs on their cytoplasmic membranes.
5. Function in detecting infections.
6. 13 or more TLRs, each of which binds to a characteristic kind of pathogen molecule, such as LPS, lipoprotein, flagellin (surface components of bacteria) and to kinds of DNAs and RNAs that typically are released by bacteria and viruses.

Question 15

Evading the innate immune systems

1. What species of bacteria block phagolysosome formation?
2. What species of bacteria form a protective capsule?
3. What species of bacteria inhibit phagocytosis by blocking receptors used by phagocytes?
4. What species of bacteria kill the phagocyte?
5. What species of bacteria forms a biofilm?
6. What species of bacteria neutralize toxic products of the phagocyte?

Answer 15

1. Salmonella (prevents fusion of the phagosome with the lysosome and then grows within the host cell).
2. Streptococcus pneumoniae (prevents phagocytosis and prevents complement binding and lysis).
3. Bacteroids fragilis (not seem as “foreign, non-self”)
4. Streptococcus pyogenes (produces protein called leukocidin, which kills the phagocyte)
5. Pseudomonas aeruginosa (block access of cells and proteins of the immune system).
6. Staphylococcus aureus (produces carotenoids which neutralizes toxic oxygen species).

Question 16

1. How is adaptive immunity activated?
2. What is cell-mediated immunity?
3. What is antibody-mediated immunity?
4. What is an antigen?
5. What is antigenic epitope?

Answer 16

1. When a pathogen overwhelmes or evades the innate immune response. A stronger response than innate immunity directed at individual, pathogen-specific macromolecules (antigens). Each pathogen is “remembered” by its specific antigen(s).
2. Killing of pathogen-specific cells by recognition of pathogen antigens presented on the surfaces of these cells.
3. Effective against extracellular pathogens and their products (e.g. toxins).
4. A molecules (e.g., component of the cell of a pathogen) that interacts with the immune system.
5. Also called antigenic determinant. That portion of an antigen that interacts with (bind to) an antibody (soluble protein, immunoglobin) or to a T cell receptor..

Question 17

1. What is special about adaptive immunity?
2. What is it mediated by?
3. What does it produce?
4. What happens during the first exposure to an antigen?
5. What happens during secondary exposure to the same antigen?

Answer 17

1. The aquired ability to recognize and destroy individual specific pathogens AND the acquired inability to respond against self antigens (tolerance). Also called antigen-specific immunity.
2. Mediated by lymphocytes (antigen-reactive lymphocytes). T cells, B cells.
3. Produce antigen-specific proteins.
   
   1. T cells - T cell receptors (TCRs).
   2. B cells - anitbodies
4. Stimulates the reproduction of these antigen-reactive cells, creating clones: large numbers of identical antigen-reactive cells. The clones of this primary adaptive immune response persist for months to years.
5. Activates these clones (immune memory), yielding a faster and stronger secondary adaptive immune response. The pathogen is quickly targeted and destroyed.

Question 18

1. How does adaptive immunity show specificity?
2. Memory?
3. Tolerance?

Answer 18

1. The response is directed against a specific pathogen by recognition of unique molecular features of antigens; takes some days to develop; based on specific antigen-antibody or antigen-immune cell (T cell) interactions.
2. Secondary exposure to an antigen stimulates rapid production of antigen-reactive T cells or antibodies; allows host to specifically and strongly resist previously encountered pathogens; immunization against a disease (vaccination) is based on immune specificity and memory.
3. The acquired inability to make an adaptive immune response to one’s own antigens; immune system discriminates between antigens that are foreign (non-self, dangerous) and host (self, not dangerous); tolerates (does not attack and destroy) self.