chapter 17

Question 1

host defenses

Answer 1

• Innate defense: properties of the normal host, non-specific defenses
  
  • Adaptative defense: induced by the infection, specific to the pathogen (based on antigens)
  • First barriers (innate defenses):
    1. CYLIA IN NASOPHARYNX: removal of particules
    2. SKIN: physical barrier and produces antimicrobial + produces antimicrobial FA and anti-bacterial peptides
    3. STOMACH ACIDITY (PH=2)
    4. FLUCHING OF URINARY TRACT
    5. EPITHELIAL CELLS
    6. RAPID PH CHANGE
    7. BLOOD AND LYMPH PROTEINS
    8. MUCUS, ANTIBACTERIAL, PEPTIDES
    9. MUCUS AND CILIA LINING TRACHEA
    LYZOZYMES in tears and other secretions

Question 2

innate defense of skin and mucous membrane

Answer 2

• Normal microbiome: competes for attachment sites and nutrients, secretes bacteriocin
  
  • Antimicrobial substances: FA, lysozymes, antimicrobial peptides (AMPs), antibodies (if the host is immune)
  • Skin: thick layer of dead cells
    Mucous membrane: mucus

Question 3

innate defense of the airways

Answer 3

Mucous membrane; mucus traps bacteria; ciliated cells remove mucus and trapped bacteria

Question 4

innate defense of tissues/internal fluids

Answer 4

• If a pathogens manages to overcome the first line of defences (skin, mucosa), it will encounter a second line of defenses:
  
  1. COMPLEMENT SYSTEM: set of proteins that creates pores in the pathogen membrane and induces lysis
  2. PHAGOCYTES: cells that take up and digest pathogens
     INFLAMMATION: general nonspecific response of the innate system to toxins, pathogens and tissue damage

Question 5

complement system

Answer 5

• Set of blood proteins= also present in tissues- known as complement because they complement the action of antibodies. Proteins: C1,C2,C3,C4,C5,C6,C7,C8,C9
  
  • 2 actions pathways:
    1. Activation by the classical pathway: antibodies
    2. Activation by the alternative pathway: microbial cell wall components (polysaccharides, lipopolysaccharides)
  • Activation of the complent results in the formation of a membrane attack complex (MAC, made of proteins C5b6789) that causes lysis of SOME gram-negatives, no effect on Gram-positives
    Pathogen sensitivity to complement: test by exposing pathogens to serum (blood without RBC)

Question 6

Membrane Attack Complex (MAC)

Answer 6

1. C5b binds C6 and C7
   
   2. C5b67 complexes bind to membrane via C7
   3. C8 binds to the complex and inserts into the cell membrane
   4. C9 molecules bind to the complex and polymerize
      1-16 molecules of C9 bind to form a pore in the membrane

Question 7

cells of the immune system

Answer 7

1. Hematopoietic stem cell: myeloid precursor, lymphoid precursor
   
   • Myeloid precursor: monocytes (dendritic cell, macrophage) or granulocytes (neutrophil, most cell)
     Lymphoid precursor (natural killer cell, T cell, or B cell = plasma cell)

Question 8

cells of the immune system

Answer 8

• White blood cells (leukocytes):
  
  1. MONOCYTES: circulate in the blood stream, differentiate into macrophages (and dendritic cells) in tissues, attracted to inflamed tissues, phagocytic. Macrophages are present in all tissues and take on different forms in different tissues
  2. GRANULOCYTES: their cytoplasm contains granules
     - Eosinophilsm basophilsm neutrophils, mast cells
     - Neutrophils are the most abundant, phagocytic, often called polymorphonuclear leucocytes (PMNs)
  3. LYMPHOCYTES:
     - B cells: antibodies
     T cells: T helper cells, cytotoxic T cells

Question 9

phagocytosis

Answer 9

1. Attachment of the organism to the membrane of the phagocyte
   
   2. INGESTION: the organism become enclosed in a phagosome
   3. A) granules (endosomes, lysosomes) containing hydrolytic enzymes fuse with the phagosomes, formation of the phagolysosomes.
      B) oxidative burst: production of reactive oxygen species (ROS)
   4. Killing and digestion of the microorganism
      Phagocytosis is crried primarly by neutrophils and macrophages

Question 10

generation of toxic reactive oxygen species (ROS)

Answer 10

• Oxidative burst: rapid increase in uptake of O2 = produces ROS (O2-,H2O2,OH-,Ocl-)
  
  • Important enzymes:
    1. Myeloperoxidase
    2. NADPH oxidase
    V-type ATPases (pumps H+ in)

Question 11

inflammation

Answer 11

• Inflammation is a non-specific response to tissue damage or the presence of microorganisms
  
  • Characteristics signs: redness, heat,swelling and pain
    1. Redness and heat are due to vasodilatation (enlargment of the blood vessels)
    2. Swelling is due to the passage of fluid (plasma) from blood vessels to the tissues from increased vascular permeability (vasodilatation). Plamsa contains antimicrobial proteins
    Function: inflammation allows the recruitment of immune cells to the site of infectipom (vascular permeability) and an increase concentration of molecules (complement subunits and antibodies)

Question 12

vasodilatation: increased permeability

Answer 12

• Complement proteins play an important role:
  
  1. C3a causes the release of histamine by mast cells = act to increase permeability of blood vessels
  2. C5a attracts phagocytes to infected tissues
     DIAPEDSIS: passage of white blood through the intact walls of the capillaries
• Role of Interleukin-1 (iI-1): increase movement of fluid and immune cells to the infection sites. Activates cells of the immune system (ex: increase phagocytosis)

Question 13

fever

Answer 13

• Macrophages can sense the presence of endotoxins (ex: LPS) they have specific receptors for it
  
  • Induce production of fever-producing (pyrogen) signaling molecule: the cytokine interleukin-1 (iI-1)
  • iI-1 acts on the thermoregulatory center of the brain, which in turn causes the body temperature to increase.
  • Temp. Higher than 37degree reduce the growth of some pathogens. Death if temp. Reaches 44degree.
    iI-1 also activates phagocytes and other cells of the immune system, also cause inflammation

Question 14

innate defenses

Answer 14

• The innate system might be able to contain the infection and clear the microorganisms
  
  1. Complement
  2. Antimicrobial proteins
  3. Phagocytes (neutrophils, macrophages)
     Inflammation (and fever)

Question 15

adaptative defense

Answer 15

• During infection, the adaptative defenses are being primer. If the infection is prolonged, adaptative immunity will be called upon to help in the fight against the invading microorganisms
  
  • Adaptative defense rely on the detection and response to FOREIGN ANTIGENS, molecules of the microorgansisms that can be recognized by the immune system
    Cells of the adaptive immune system: B cells, T cells and antigen presenting cells (APCs: macrophages, dendritic cells; important for activation of the adaptative defenses)

Question 16

3 characteristics B and T cells

Answer 16

1. SPECIFICITY: immune cells have surface receptors that interact with individual antigens
   
   • Population of T and B cells. Each cell is specific for one antigen
   • At the population level, T and B cells recognize billions of antigens
     2. MEMORY: the first antigen exposure induce multiplication of antigen-reactive cells, resulting in multiple copies, or clones. After a subsequent exposure to the same antigen, the immune response is fater and stronger due to the large number of responding cells
     ** once activated by the antigen they recognize, T and B cells grow and produce copies of themselves. A cell that is specific to antigen X will produce more cells specific for antigen X. some cells will differentiate into memory cells. Their role is to remember the antigen X
     3. TOLERANCE: immune cells are not able to react with self antigen. Self-reactive cells are destroyed during development of the immune response
     Antigen specificity is randomly generated during development of T and B cells. Cells that recognize host antigen are destroyed

Question 17

T cells

Answer 17

There are 2 types of T cells:
1. T helper cells (Th): activate B cells and macrophages
2. Cytotoxic T cells (Tc): kill host cells that display foreign antigen on their surfaces
- Population of T cells in the body, each T cell is specific for one antigen
APCs present antigen to T cells. If the T cell is specific for this antigen, the T cell will become activated and produce interleukin 2 (iI-2). This induces multiplication and differentiation into effector T cells and memory T cells

Question 18

presentation of antigen

Answer 18

• The major histocompatibility complex (MHC): an antigen-presenting molecular complex
  
  • All cells have MHC I
  • APCs only: have MHC II : macrophages, dendritic cells, b CELLS
  • Professionnal APCs also have MHC I
  • MHC I: expressed by all cells, presents antigen that come from inside the cell (important during infection by viruses/intracellular pathogens). Recognized by Tc
    MHC II: expressed by APCs and B cells, presents antigen process in the phagolysosomes (from microorgnisms that were phagocytosed). Recognized by Th

Question 19

cytotoxic T cells

Answer 19

• Cells that display foreign antigens on MHC 1 are killed by Tc are specific for this antigen
  
  • The Tc releases perforins and granzymes that kill the cell
    Very useful against the infection by viruses/intracelullar pathogens

Question 20

activation of macrophages: helper T cells

Answer 20

• Once activated, the Th cell can activate macrophages (TNF-a) that are presenting antigens for which the T cell is specific
  
  • Activated macrophages have increased phagocytic acitivty and produce much higher levels of hydrolytic enzymes. Often referred to as angry killer cells
    Very important roles against bacterial pathogens (especially against intracellular pathogens of microphages)

Question 21

activation of B cells

Answer 21

• The B cell siplays its antibody on its surface. Act as a receptor to pick up the foreign antigen it recognizes. This antigen will be processed and displayed on its surface by MHC II
  
  • A pre-activated T cell specific for the antigen recognized this complex (MHC II- antigen), and activates the B cell (II-4). The T cell was previously activated by APC
    The B cell multiplies and differentiates into plasma cells (produce the antibody) and memory cells (waiting for the next exposure to the antigen)

Question 22

antibodies

Answer 22

• Group of related proteins - immunoglobulins
  
  • Antigen binding sites (Fab) highly variable
  • Constant region (Fc_ binds to receptor on macrophages and activates complement (classical pathway)
    Types of antibodies: IgA, IgG, IgM, IgE

Question 23

4 types antibodies

Answer 23

1. IgG: major circulating body, most abundant. Found in lymph, blod and extracellular fluid
   
   2. IgML first antibody to appear. Found in blood and lymph only. Causes aggregation of antigens and helps early complement activation
   3. IgA: secretory antibody, found in extracellular body fluids and in mucus. Main mediators of mucosal immunity
      IgE: least abundant, main function is immunity to parasites. Essential role in hypersensitivity and various allergies (ex: food allergies)

Question 24

3 roles antibodies

Answer 24

1. Antibodies functions as opsonins, which increase phagocytosis efficiency
   
   2. Bind to toxins, which prevents binding of toxin tohost cells
      Bind to adhesins, which prevents adhesion of microorganisms to host cells

Question 25

natural immunity

Answer 25

Natural immunity (species resistance): humans are naturally resistant to many infectious diseases of lower animals and vice versa:
1. ACTINOBACILLUS PLEURPNEUMONIAE cause pleuropneumoniae in pigs but does not cause disease in humans
2. SALMONELLA TYPHY cause typhoid only in humans
Natural immunity may be explained in part by the absence or presence of the appropriate receptors in the animal for the adhesins expressed by the pathogen