Infection and Altered Immunity

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Infection and Altered Immunity

• Chapter 8

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Hypersensitivity

• Heightened state of immune responsiveness
• Excessive reaction to an antigen that results in
  a pathologic response when re-exposed to the same
  antigen.
• In other words, the immune system has responded
  in such a way that it is not beneficial to the
  host.
• Examples allergy, autoimmunity, and alloimmunity
• Examples tissue damage, allergies, rashes,
  breathing problems, etc.

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Hypersensitivity

• The different types of hypersensitivity are
  classified in Types.
• Type I
• Type II
• Type III
• Type IV
• Some of the types will overlap in certain
  diseases.

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Type I Hypersensitivity

• Mast cell-bound IgE antibody reacts with antigen
  to release physically active substances
  (histamine, chemotactic factors, etc.).
• Individuals have an inherited tendency to respond
  to naturally occurring inhaled and ingested
  allergens with continual production of IgE.
• Symptoms allergic rhinitis, asthma, urticaria,
  food allergies, anaphylactic shock, diarrhea,
  and/or vomiting

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Type I Hypersensitivity
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Type I Hypersensitivity
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Type I Hypersensitivity
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Type I Hypersensitivity

• Treatment
• Depends on severity
• Antihistamines (Benedryl, Sudafed)
• Bronchodilators (Albuterol)
• Corticosteroids
• Epinephrine
• Hyposensitization (Building up of IgG blocking
  antibodies)

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Type II Hypersensitivity

• Cytotoxic, Tissue-specific Hypersensitivity
• Free antibody (IgG or IgM) reacts with antigenic
  determinants on cell membranes
• Phagocytosis
• Complement Activation (Which pathway?)
• Examples Immediate drug reactions, autoimmunity,
  alloimmunity

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Type II Hypersensitivity

• Types of Type II Hypersensitivity
• Transfusion Reactions
• Hemolytic Disease of the Newborn
• Autoimmune Hemolytic Anemia

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Type II Hypersensitivity
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Type III Hypersensitivity

• Antibody reacts with soluble antigen to form
  complexes that precipitate in the tissues.
• When soluble antigen combines with antibody,
  complexes precipitate out of the serum and
  deposit in tissues, bind/activate complement, and
  cause tissue damage.

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Type III Hypersensitivity

• Examples
• Serum Sickness (Result of passive immunization
  with animal serum to treat disease)
• Autoimmune diseases (Lupus and RA)
• Glomerulonephritis

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Type IV Hypersensitivity

• Delayed Hypersensitivity
• Sensitized T cells release lymphokines that
  recruit macrophages, neutrophils, produce edema,
  and enhance the inflammatory response
• Antibody and Complement are not directly involved
• Symptoms take several hours to develop

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Type IV Hypersensitivity

• Contact Dermatitis
• Poison Ivy, Poison Oak, topical anesthetics,
  antiseptics, and antibiotics
• Process takes days but effects last for years
  (blisters, peeling, weeping)
• TB Test and Graft Rejection

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Type IV Hypersensitivity
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Autoimmunity

• Autoimmunity is a breakdown of tolerance in which
  the bodys immune system begins to recognize
  self-antigens as foreign.
• Theories
• Exposure to a previously sequestered antigen
• Development of a neoantigen (tumor antigen)
• Complications of an infectious disease
• Alteration of suppressor T cells

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Autoimmunity

• Previously sequestered antigen
• Some antigens are hidden from the immune system
  and never come into contact with
  antigen-presenting cells, lymphoid organs, etc.
• These sequestered antigens can be released from
  damaged tissue and enter the lymphatics.
• Neoantigen
• Usually haptens that become immunogenic after
  binding to host proteins

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Autoimmunity

• Antigens from infectious diseases
• Closely resemble host antigens
• Form antigen-antibody complexes that initiate the
  immune response (hypersensitivity type III)
• Alterations of suppressor T cells
• If a specific cell-line of T suppressor cells is
  affected, a tissue specific autoimmune disease
  could result
• A general autoimmune reaction could occur if many
  cell populations were dysfunctional

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Autoimmunity

• Autoimmune diseases will commonly follow family
  lines (HLA antigens)
• Common autoimmune diseases
• Lupus
• Photosensitive facial rash
• Worsens with sun exposure
• Lupus (wolf-like)

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Common Laboratory Tests

• Fluorescent Antinuclear Antibody Test
• Animal cells are fixed to the slide

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Rheumatoid Arthritis

• Systemic autoimmune disorder affecting the
  synovial membrane of multiple joints.

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Rheumatoid Arthritis Progression

• Malaise, fever, weight loss, and joint pain
• Joint pain lasting longer into the day
• Progression from small joints to large joints in
  a symmetric fashion
• Muscle spasms leading to joint deformity
• Nodules (necrotic areas) on the bones

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Other Autoimmune Related Diseases

• Hashimotos Thyroiditis Graves Disease (thyroid)
• Insulin-dependent Diabetes (pancreas)
• Multiple Sclerosis (myelin sheath)
• Myasthenia Gravis (muscles in the face)
• Goodpastures Syndrome (kidney)
• Autoimmune thrombocytopenia
• Pernicious anemia
• Ulcerative colitis

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Alloimmune Graft Rejection

• Alloimmunity occurs when an individuals immune
  system reacts against antigen of the tissue of
  other members of the same species.
• Transplants are complicated by an alloimmune
  response to donor HLA antigens.
• Classified as hyperacute, acute, or chronic
  depending on activation time.

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Alloimmune Graft Rejection

• Hyperacute
• Patient has preexisting IgG or IgM antibody to
  the tissue.
• Antibody binds to the tissue and activates an
  inflammatory response.
• This results in the cessation of blood flow to
  the graft.

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Alloimmune Graft Rejection

• Acute
• The rejection is a cell-mediated immune response
  that occurs approximately 2 weeks after the
  transplant.
• Chronic
• Can occur after months or years of normal
  function
• Signs and Symptoms slow progressive organ
  failure and damage to endothelial cells of the
  blood vessels

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Infectious Agents

• Symbiosis two organisms living together in
  close association
• Commensalism neither organism is harmed
• Mutualism association is beneficial to both
• Parasitism (pathogenicity) one benefits and the
  other is harmed

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Infectious Agents

• Pathogens cause cellular injury because they
  circumvent defensive barriers.
• Pathogens directly damage cells, interfere with
  cellular metabolism, and limit the functionality
  of the cell.
• Virulence
• Ability of a pathogen to cause disease
• Presence of enzymes, toxins, number, capsules,
  intracellular invasion

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Modes of Disease Transmission

• Contact Transmission
• Direct (touching, kissing, intercourse, etc.)
• Indirect (fomites - shared objects)
• Droplet (distance lt 1 meter)
• Common Vehicle Transmission
• Contaminated food, water, blood, vector, etc.
• Carrier
• People who are carrying the pathogen but do not
  appear to be ill.

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Size Comparison
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Bacteria

• Unicellular
• Aerobic
• Anaerobic
• Bacteria can live as opportunists, commensals,
  and intracellular and extracellular parasites.

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Bacterial Shapes

• Bacteria are characterized by their shape and
  size.
• Before specific culture information is available,
  physicians use location and appearance
  characteristics to begin antibiotic therapy

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Bacterial Shapes

• Cocci
• Spherical, non-motile bacteria
• Subcategories
• Diplo (pair)
• Strepto (chain)
• Staphylo (irregular cluster)
• Tetra (group of four)

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Bacterial Shapes

• Bacilli
• Rod-shaped bacteria
• Spirillia
• Rod-shaped, rigid, spiral organisms
• Spirochetes
• Non-rigid, spiral rods
• Pleomorpic
• Cells that do not fit in any of the above
  categories (no defined shape)

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Bacteria

• Cell Wall
• The cell wall is composed of peptidoglycan
• Peptidoglycan is a large molecular network of
  glucose and amino acids.
• Based on cell wall characteristics, bacteria are
  classified as gram () or gram (-).

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Gram Positive
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Gram Negative
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Identifying a Specific Bacterium
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Gram Stain
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Bacterial Toxins

• Gram bacteria produce exotoxins
• Exotoxins are released from the bacterium during
  its life cycle.
• Exotoxins cause symptoms specific to the disease.
• Examples Botulism, tetanus, staph food
  poisoning, Toxic Shock Syndrome
• Gram bacteria produce endotoxins
• Endotoxins are released from the cell when it
  dies
• Produce generalized symptoms
• Example Salmonella food poisoning

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Sporulation

• Sporulation is the formation of endospores.
• When nutrients become scarce and conditions are
  unfavorable, certain bacteria (Bacillus,
  Clostridium, etc.) will form endospores.
• Endopores help the DNA of the bacteria survive
  extreme temperatures, radiation, and chemicals.

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Viruses

• A virus is not technically living. It can not
  perform any metabolic activity.
• A virus must replicate inside a host cell.
• The virus provides the RNA and DNA to replicate,
  and the host cells provide the energy and
  resources.
• Components
• Nucleic acid, capsid, and an envelope (optional)

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Viruses

• Viral replication depends on absorption,
  penetration, uncoating, replication, assembly,
  and ability to release new virons.
• Effects
• Cell protein synthesis cessation, release the
  cells own lysosomal enzymes causing cell death,
  fusion of host cells, alteration of antigenic
  properties causing the immune system to attack
  the host cell, and transformation of host cells
  into cancerous cells.

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Fungi

• Fungi are important for the decomposition and
  recycling of organic material.
• Fungi are divided into two groups, yeasts and
  molds
• Examples Candida Albicans (yeast infection) and
  Tenia Corporis (ringworm)

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Fungi

• Fungi release mycotoxins and enzymes that damage
  connective tissues
• Diseased caused by fungi are called mycoses.
• Fungi can cause superficial and deep infections
• Some fungi are part of the normal body flora and
  act as opportunists

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Ascaris

• Ascaris lumbricoides

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Pinworms

• Life cycle
• Fecal/oral
• Diagnosis
• Use of pinworm paddles

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Immunodeficiencies

• Immune deficiencies occur because of the
  impairment of one or more components of the
  immune or inflammatory response.
• Usually manifested by the tendency to develop
  unusual or recurrent infections.
• Can be unsafe to administer immunizing agents.
• At risk for graft-versus-host disease
• White cells in transfused blood can are
  immunologically active, but the host cells
  arent.

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Graft-Versus-Host Disease
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Immunodeficiencies

• Primary Immune Deficiency (Congenital)
• Occurs during leukocyte development in the fetus
  or embryo.
• Can affect one or more white cell lines
• If the T and B cell lines are affect, the patient
  will have normal number of the other leukocytes,
  but they will have low number of T cells, and
  diminished levels of antibodies.

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Immunodeficiencies

• Di George Syndrome
• Lack or partial lack of the thymus
• Lymphopenia and decreased T cell function
• Bruton agammaglobulinemia syndrome
• Failure of B cell precursors to become mature B
  cells.

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Immunodeficiencies

• Wiskott-Aldrich Syndrome
• X-linked recessive disorder
• IgM production is depressed
• Selective IgA deficiency
• Produce other types of antibody but not IgA
• Can cause chronic intestinal candidiasis and
  increased allergen uptake, and more severe
  allergen responses

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Acquired or Secondary Immune Deficiencies

• Develop after birth and not related to genetic
  defects
• Nutritional deficits
• T cell number and function
• Enzyme cofactor deficiency
• Chemotherapeutic agents
• Corticosteroids
• Burn victims
• Emotional stress

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HIV

• In 1981, a cluster of young men, with no known
  immune dysfunction, developed opportunistic
  infections with Pneumocystis carinii.
• The only link was that they were homosexual.
• In 1982, it was discovered in hemophiliacs.
• The virus HIV-1 was identified in 1983
• HIV-2 was discovered in 1986

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HIV

• HIV is a retrovirus
• Retroviruses infect cells by binding to a surface
  receptor and inserting their RNA into the target
  cell
• A viral enzyme reverse transcriptase converts the
  RNA to DNA and inserts the viral genetic material
  into the host cell.
• The genetic material can begin replicating
  immediately or remain latent for a period of time
  (up to 10 years).

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HIV
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HIV

• HIV is of course spread primarily through contact
  with blood or body fluids containing the virus.
  It is also speculated that ulcerations from other
  sexually transmitted diseases provide
  opportunities for the virus to enter the host.
• Concentrations of HIV
• High blood and semen
• Low vaginal fluid, tears, sweat, breast milk
• Has also been transmitted through infected tissue

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HIV

• Pathology
• Latent period may last up to 10 years
• Virus infects cells utilizing the CD4 antigen
  receptor
• The virus replicates in the T4 cell until the
  cell dies.
• Other cells have CD4 receptors (monocytes,
  macrophages, and some brain and skin cells)
• The number of T4 cells continues to diminish
  until the patient is prone to opportunistic
  infections.

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Testing for HIV

• Presentation at time of diagnosis
• Serologically negative, serologically positive
  but asymptomatic, early stages of HIV, or AIDS
• Window Period
• Laboratory Tests
• Antigen Tests
• Antibody Tests (most common)

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Testing for HIV

• FYI
• Western Blot
• Confirmation
• Antigen must be pure

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Testing for HIV

• Treatment (antiviral agents)
• Interferons
• Azidothymidine (AZT), Dideoxycytidine (ddC), and
  Dideoxyinosine (ddI)
• HIV Cocktail
• Reverse transcriptase and protease inhibitors
• New AIDS vaccine
• How to test?
• Genetic variants

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Treatment of Immune Deficiencies

• Administration of gamma globulin
• Administration of fresh-frozen plasma
• Antibodies and complement
• Bone marrow transplants
• Graft-versus-host, and HLA antigens
• Gene therapy