Chapter 15

 

Host Defenses II

 

 

Third Line of Defense

  Initiated when host barriers and nonspecific defenses fail to control an infectious agent

  4 important aspects:

  Antigen-specific

  Has memory

  Tightly regulated and complex

  Must be able to discriminate between self and nonself

 

 

Lymphocyte Development

  Major histocompatibility complex (MHC) a marker found on nearly all cells that allows for recognition of self

  Clonal Selection lymphocytes undergo extensive gene rearrangements that generate millions of different clones, each specific for a particular antigen

  those that react to self are destroyed

 

 

Presentation of Antigens

  Antigen-presenting cell (APC) - engulfs the antigen and breaks it into fragments

  APCs can be dendritic cells, macrophages, and B cells

  Antigen fragments merge with MHC proteins on the surface of the APC

  APC goes to nearest lymphoid organ and presents antigen to T cells via MHC proteins

 

 

Third Line of Defense

  There are 2 types of specific immunity in the Third Line of Defense:

  Cell-mediated immunity

  Antibody-mediated immunity

 

 

Cell-Mediated Immunity

  Mediated by T-cells that recognize antigen only when presented in association with MHC

  Activated T cells divide and differentiate into 4 types of cells:

  cytotoxic T cells (CD8) - induce death in virus-infected cells or cancer cells similar to NK cells

use perforin and granzymes

produce cytokines that activate neighboring cells

recognize endogenous antigens presented on MHC class I molecules

  helper T cells (CD4) - release cytokines that activate other T cells, B cells, NK cells, and phagocytes

further differentiate into Th1, Th2 or Th17 cells depending on cytokines

recognize exogenous antigens presented on MHC class II molecules

  regulatory T cells - control the inflammatory response to prevent autoimmunity

  memory T cells - recognize specific antigens in case of repeated exposure

 

 

Antibody-Mediated Immunity

  Mediated by B-cells

  B-cells recognize and internalize antigen and present it to helper T cells

  use MHC class II molecules

  Helper T cells stimulate B cell division and differentiation into 3 types of cells:

  plasma cells - produce and secrete antibodies

  memory B cells - long lived for repeated exposure

  regulatory B cells suppress helper T cells to prevent autoimmunity

 

 

Antibodies

  Variable regions (Fab regions) - bind antigen

  form antigen-antibody complex

  Constant region (Fc region) - binds other cells of immune system

 

 

Antibodies: 5 Classes

  IgM - first class produced in response to antigen

  IgG - second class produced in response to antigen

  provides long-term protection

  can cross placenta to protect baby

  IgA - secreted from mucous membranes

  passed to infants in breast milk

  IgD - triggers B cell activation

  IgE - found on basophils and mast cells

  causes allergic reactions

 

 

Antibodies Inactivate Antigen

  Neutralization

  bind to toxins or virus and prevent them from binding to host cells

  Immobilization

  bind to flagella and pili to inhibit motility and attachment

  Agglutination of antigens

  aids in phagocytosis

  Opsonization

  similar to complement

  Complement activation

  Antibody-dependent cellular cytotoxicity (ADCC)

  helps target cells for destruction by NK cells

 

 

 

Types of Immunity

  Naturally acquired acquired through normal exposure in the environment

  Artificially acquired acquired through medical procedures

  Active immunity the individual makes their own antibodies after exposure to the antigen

  Passive immunity the individual receives antibodies that were produced by another individual

 

 

Examples of Immunity

  Naturally acquired-active immunity

  natural exposure to an antigen causes the person to produce their own antibodies

  ex. getting over a cold

  Naturally acquired-passive immunity

  individual provided with antibodies that someone else made after natural exposure to the antigen

  ex. antibodies transferred from mother to child via breast milk or the placenta

  Artificially acquired-active immunity

  deliberate exposure to the antigen via an injection causes the person to make their own antibodies to the antigen

  ex. immunization for measles

  Artificially acquired-passive immunity

  deliberate introduction of antibodies made by some other individual into the body of the patient

  ex. antivenom, antitoxin, gamma globulin

 

 

Immunization

  Deliberately exposing a person to antigens in order to protect against a disease

  Herd immunity - the inability of an infection to spread because of the lack of susceptible hosts

  mass immunization confers indirect protection on the non-immune members

 

 

Vaccine Preparation: Whole Cells or Viruses

  Attenuated vaccine a weakened, live form of the pathogen

  Manipulated to remove virulence factors

  multiply to produce infection and induce an immune response, but unable to cause disease

  a single dose may be enough to induce long-lasting immunity

  can spread from an immunized individual to non-immunized people, inadvertently immunizing the contacts

  because they can spread, they have the potential of causing disease in immunosuppressed people

  some can revert or mutate back into the disease-causing form

  attenuated strains can cross the placenta

  Include mumps, measles, and rubella vaccines

  Inactivated vaccines killed organisms unable to replicate but still cause an immune response

  they cannot cause infection or revert to dangerous forms

  the magnitude of the immune response by inactivated vaccines is very limited

  usually necessary to give booster doses to enhance the immune response

  include Hepatitis A and Influenza vaccines

 

 

Vaccine Preparation: Subunit Vaccines

  Used when the exact antigens that stimulate immunity are known

  Composed of key antigens of the infectious agent

  Bacterial capsules polysaccharide conjugage vaccines

  Streptococcus pneumoniae, Haemophilus influenzae

  Toxoids inactivated exotoxins

  diphtheria, tetanus, pertussis

  Surface proteins

  Hepatitis B, anthrax, HPV

 

 

 

Chapter 17

 

Diagnosing Infections

 

 

Phenotypic Methods for Diagnosing Infections

  Microscopic Observation

  can identify cell size, shape, and arrangement

  can use fresh or stained specimen (i.e. gram stain, acid-fast stain)

  Isolation Media

  can compare texture, size, shape, pigment, speed of growth, or patterns of growth in broth or agar

  can use selective and differential media for mixed cultures

  ex. Blood agar, Mannitol Salt Agar, MacConkey agar

  Biochemical Testing

  determine the presence of specific enzymes and to assess nutritional and metabolic activities

  ex. catalase test, urease test, sugar fermentation tests, antibiotic sensitivity tests

 

Genotypic Methods for Diagnosing Infections

  Nucleic acid probes

  labeled strands of known DNA are used to determine if those sequences are present in the specimen

  complementary sequences will become fixed to each other (hybridize)

  Nucleic Acid Sequencing and ribosomal RNA analysis

  comparing the sequence of 16S ribosomal RNA can determine the relatedness of organisms

  can be used to identify at the species level

  Polymerase chain reaction

  used for a variety of bacteria, viruses, protozoa, and fungi

  used for rapid identification of pathogens even in tiny amounts

 

 

Immunologic Methods for Diagnosing Infections

  Serology use of serum antibodies to detect antigens or use of known antigens to detect antibodies

  Often easier than testing for the microbe itself, especially for viral infections

  Show high degree of specificity and sensitivity

  Individuals exposed to an antigen for the first time usually do not have detectable antibodies in the blood serum until about 7-10 days after infection

  Titer - measures the amount of specific antibody in serum and a rise in titer suggests an active infection

 

 

Examples of Immunologic Tests

  Precipitation and Agglutination reactions - antibodies combine with soluble antigens to form a visible insoluble precipitate

  used in ABO blood typing and Rh testing

  have also been developed for Salmonella, Mycoplasma, Rickettsia, Treponema and other microbes

  Complement Fixation - antibody/antigen complexes are identified using complement proteins and sheep RBCs as indicators of hemolysis

  used to diagnosis influenza, polio, various fungi, and streptococcal infections

  Fluorescent Antibody tests - fluorescent dyes are attached to known antibodies and then used to detect antigen

  used to diagnose syphilis, gonorrhea, chlamydiosis, whooping cough, meningitis, and other infectious diseases

  Radioimmunoassay (RIA) - antibodies or antigens labeled with a radioactive isotope are used to identify minute amounts of antibody or antigen

  used to measure insulin and other hormones and to diagnose allergies

  Enzyme-Linked Immunosorbent Assay (ELISA) - an enzyme-antibody complex is used as a color tracer for antigen-antibody reactions

  enzymes release a dye (chromogen) when exposed to their substrate

  common screening test for HIV, rickettsial disease, Hepatitis A and C, cholera, Helicobacter, and others

  Western Blot - cell proteins separated on a gel and transferred to a blot are identified using labeled antibody or antigen

  used to rule out false positive HIV tests