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Immune Functioning
Major structures for immune
functioning
   Lymph nodes – small organs
    throughout the body designed to
    receive fluids from peripheral tissue
    sites. Clusters found in many areas

   Spleen – the largest lymphoid organ.
    Supports humoral immune response
    to blood-borne pathogens. Also
    assists in filtering for damaged RBCs
Major structures

   Thymus - contributed to the
    maintenance and functioning of
    T-cells
   Bone Marrow – generates
    pluripotent stem cells for cell
    generation including RBCs,
    WBCs, antibody production
   Blood – houses RBCs, WBCs
    and platelets
“Shift to the left”
is the release of
immature
neutrophills to
fight infection
WBC Functioning

   Granulocytes – neutrophils,
    eosinophils and basophils
   Nongranulocytes – lymphocytes
    and monocytes
Cellular WBC response as seen
on a CBC differential
   Neutrophils – one of the most
    plentiful along with lymphocytes
   55-70% of differential smear
   Most (90%) remain in the bone
    marrow for storage
   Neutrophils in circulation also adhere
    to endothelial lining of small blood
    vessels
   1st on the scene for inflammatory
    response (usually within 6-12 hrs)
Cellular WBC response
                         also trauma
   Elevated with acute  and surgery

    inflammatory reaction or acute
    infection
   Survive for only 24-48 hrs
   “segs” refer to mature cells
   “bands” refer to immature
mature



         immature
Lymphocyte activity

   Total lymphocytes accounts for
    20-40% of differential smear
   T-lymphocytes (mature in
    thymus)
   B-lymphocytes (mature in bone
    marrow)
   T Cytotoxic (CD8)
   T Helper (CD4)
   NK cells
Lymphocytes

   T-lymphocytes primarily involved in
    cell-mediated immunity, serve as NK
    cells and T4 helper cells
   B-lymphocytes primarily and humoral
    immunity
   The lymphocytes circulating in the
    blood are primarily responsible for
    fighting chronic bacterial and acute
    viral infections
       i.e. long
       standing       i.e. rhino virus
       pneumonia or
       celleulitis
Cellular WBC response

   Monocytes – triggered by
    chemotactic factors becoming a
    macrophage in lung, connective or
    lymphoid tissue to remove foreign
    substances by phagocytosis
   Arrives on site within 3-7 days
   4-8% of diff smear
   Elevated in long-standing
    infections
   Produces interferon, the body’s own
    immunostimulant
Cellular immune response

   Eosinophils – very small
    percentage seen in the WBC
    count (1-4% of diff smear)
   Elevated in parasitic
    infections and IgE-mediated
    allergic responses
   Do not respond to bacterial
    infections
Cellular immune response

   Eosinophils – house heparin,
    histamine and serotonin in the
    cytoplasm
   Eos infiltrate the tissue affected
    by allergy to further the
    inflammatory reaction
Cellular immune response

   Basophils – only 1-2 % of
    differential smear
   Also supports IgE-mediated
    allergic responses
Cells identified in the WBC
differential
leukocytosis=too
WBC differential        many white blood
                        cells



   Total WBCs (leukocytes)
    5000-11000/mm3
   Neutrophils 50-70%
   Lymphocytes 20-40%
   Monocytes 4-8%
   Eosinophils 0-4%
   Basophils 0-2%
Human Immunity

   Direct (active) immunity
   Indirect (inactive) immunity
    through intrauterine sources or
    other naturally and synthetically-
    generated immunoglobulins
    (antibodies)
                  see chapter 12
                  for active vs
                  passive
Active Immunity

   Humoral immunity (IgG, IgA, IgM)
    available in the blood
   Mucosal immunity (secretory IgA)
    available in the mucus of the GI,
    respi and urogenital tracts
   Cell-mediated immunity
    (T-lymphocytes)
   Type I hypersensitivity reactions (IgE
    response in mast cells found in
    respiratory and GI tracts)
                                 passive
                                 immunity is lost;
                                 active immunity
                                 last longer
Primary and Secondary
Antibody Response
Class and Function of
Immunoglobulins (Antibodies)
   IgG – 75%
   IgA – 15%
   IgM – 10%
   IgE - <1%
   IgD - <1%
Class and Function of
Immunoglobulins (Antibodies)

   IgG – present in circulation
    and tissue, first Ig produced
    in secondary response,
    crosses placenta
   IgA – present in circulation of
    mucous secretions; prevents
    adherence on mucosal surface
     deficiency leads to a lot of skin
     infections and mucous
     membrane infections. secreted
     through breast milk
Class and Function of
Immunoglobulins
   IgM – present in circulation; first
    Ig of primary immune
    response. Large and cannot
    move to tissues
   IgE – present in mast cells,
    mediates hypersensitivity
    reactions
   IgD – lymphocytes
Active, Acquired Immunity

   A result of invasion by a foreign
    substance OR through
    inoculation of a less virulent
    antigen
   Subsequent reinvasion
    generates a greater response
Types of Acquired, Specific
Immunity
   Active (Natural) – contact with
    antigen through clinical infection
   Active (Artificial) – immunization
    with live or killed antigen
   Passive (Natural) –
    transplacental transfer of
    antibodies (lost at 3-6months)
   Passive (Artificial) – injection of
    serum from immune globulin
Human Hypersensitivity
Reactions
   Type I – immediate or
    anaphylactic
   Type II – cytolytic or cytotoxic
   Type III – immune complex
   Type IV – cell-mediated,
    delayed         1&2 are immediate
                    3 is associated
                    with chronic
                    disease
                    4 is delayed
Human Hypersensitivity
Reactions
   Type I – Immediate/anaplylactic
   IgE initiated
   Mast cell degranulation →
    histamine and leukotriene
    release
   Reaction includes anaphylaxis,
    atopic diseases such as
    allergies and asthma, skin
    reactions     asthma is a type of
                  allergic disease under
                  sub category atopia
Causes of Anaphylaxis

   Drugs
   Foods
   Insect sting
   Allergy
   Latex allergy
Causes of Anaphylaxis

   Drugs – PCN, sulfonamides,
    insulins, ASA, TCN, tetracycline
    cephalosporins,     (antibiotic)


    chemotherapeutic agents,
    NSAIDs
   Insects – wasps, bees, hornets,
    ants
Causes of Anaphylaxis

   Foods – eggs, nuts, shellfish,
    fish, chocolate, strawberries
   Animal Sera – tetanus, rabies,
    diptheria, snake venom
    antitoxins
   Therapeutic Treatments – blood
    products, Iodine-based media
S & S of Anaphylaxis

              Hives, wheal-and-flare reaction,
               itching
              Angioedema
              Dyspnea, wheezing
fainting      Syncope, ↓ BP, flushing
              N & V, diarrhea, abd pain
              Onset generally 5-30 mins after
               antigen
              See Fig. 14-11 on p. 226
Treatment for Anaphylactic
Shock
   Epinephrine (SC, IM or IV) 0.5ml
    1:10,000 IV for severe
   Remove antigen
   02 non rebreather mask best
    source with out intabation
   Maintain vascular volume by ↑
    legs, fluid resuscitation with NS
    or LR
   Vasopressive agents such as
    dopamine (Intropin)
Latex Allergy (Type I)

   Common in the U.S. population
   Incidence higher among HCWs
   An allergy to the natural latex
    proteins and occurs within
    minutes of exposure
Latex Allergy (Type I)

   Apparent relationship with
    allergy to certain medications
    including bananas, avocado,
    apricot, papaya, kiwi
   S & S include dermatitis, itching,
    urticaria, sneezing/coughing,
    wheezing, vascular collapse
Latex Allergy
Other Type I Hypersensitivities

   Atopic conditions – a broad
    category used to describe many
    conditions that are IgE
    stimulated. Includes hay fever,
    asthma, and all conditions cited
    hereafter
   To repeat, allergic rhinitis fits
    here
Atopic Conditions (cont.)

   Atopic dermatitis – often
    complaints of itchy skin. May be
    dry. Lesions may develop.
    Treatment includes ↓exposure
    and the response. Cool
    compresses, lubricants, avoid
    scratching
Eczema – a form of atopic
dermatitis
   Tx:
   topical corticosteroids
   avoid triggers


Gel sticks better
than creams or
lotions
Other Type I Hypersensitivities

   Urticaria – (hives) a systemic
    response because of an
    allergen
   Histamine → localized
    vasodilation, transudation, and
    flaring
Type I Hypersensitivities -
Urticaria
   Papules that tend to develop on
    face, neck, ant. aspect of arms,
    and abdomen, back
   Many causative agents
   Avoidance
   Cool compresses,
    antihistamines
Urticaria
Type I Hypersensitivities
   Angioedema – similar to
    urticaria but involves deeper
    layers of skin and mucosa
   Areas affected are significant
    and include eyelids, lips, tongue,
    larynx, hands, feet, GIT, and
    genitalia
Meds used for Allergies

   Antihistamines – H1 receptor
    binding agents to ↓ sneezing,
    rhinitis, itching. (Zyrtec, Allegra,
    Claritin). Non-blood brain barrier
    crossing.
   Benadryl (diphenhydramine)
    does cross BBB if it crosses
                        BBB causes
                        drowsiness
Meds. cont

   Decongestants – relieve nasal
    congestion to ↓ alpha-
    adrenergic response at entrance
    to venous plexus of turbinates.
    (Sudafed, phenylephrine)
   Corticosteroids – topical, nasal
    (Nasocort, Rhinocort)
Meds. cont.

   Inhaled steroids – fundamental
    treatment for asthma. (Flovent,
    Advair, Azmacort, Vanceril)
   Beta-agonists for bronchospasm
    (Albuterol, salmeterol)
Meds. cont.

   Antipruritic Drugs: may be
    applied topically such as
    calamine lotion, camphor and
    menthol
   Mast Cell-Stablizing Drugs:
    inhibit the release of histamines
    and leukotrienes (Cromolyn).
    Used to treat allergic rhinitis and
    asthma
Meds. cont

   Leukotriene inhibitors –
    Leukotrienes contribute airway
    edema, smooth ms. contraction
    and inflammation. (Accolate,
    Singulair)   used for
                allergic
                rhinitis and
                allergies
Type II Hypersensitivity
reactions
   Cytolytic or Cytotoxic
   IgG or IgM mediated
   Complement activated and cell
    destruction occurs
   Examples of include hemolytic
    anemia, Rh disease,
    autoimmune hyperthyroidism,
    myasthenia gravis, and blood
    transfusion reactions
Blood Transfusion Reactions

   Occurs as a result of intravascular
    hemolysis or RBCs and includes; H/
    A, back pain, chest pain, N & V, ↑
    HR, ↓ BP, hematuria, urticaria
   Probably IgM-based reaction
   Stop the blood and all the tubings
    including blood               death by kidney
   Notify the MD and the lab cloggingdue to
                                  failure
                                          by dead
   Maintain vascular             RBC

   Fluid resuscitation access with new
    bag of NS
   Save the urine
Type III Hypersensitivity
Reactions
   Immune Complex reactions
   Antigens and antibodies bind and
    occlude capillaries causing urticaria,
    arthritis, arteritis, glomerulonephritis
   Reactions can be localized or
    systemic
   Systemic Lupus Erythmatosus
   Acute glomerulonephritis
SLE
Type IV Hypersensitivity
Reactions
   Cell-mediated, or Delayed
   Requires effective T-cell
    functioning
                    TB testing
   Used with PPD testing - edema
    and fibrin result in induration.
    Also responsible for caseous
    lesions that develop with
    tubercle bacillus
Type IV Hypersensitivity
Reactions
   Contact dermatitis – a result of
    contact with an allergen such as
    lanolin, adhesive, topical
    medications or plant toxins.
    Latex allergy due to contact fits
    here.
   Antibodies are formed with first
    exposure; hypersensitivity
    reactions occur with later
    exposure
Hypersensitivity Reaction
Prevention
   Good assessment and health
    history. Attending to all food,
    medication and environmental
    allergies
   Controlling the environment
Immunodeficiency Disorders

   Inadequate protection of the
    body at the cellular, enzyme or
    humoral level
   Primary – inadequate immune
    cells with mostly genetic causes.
    Apparent at birth. Most common
    hypogammaglobulinemia
                      i.e. bubble boys
Immunodeficiency Disorders

   Secondary – obtained through
    other causes such as
    medication use and disease;
    medication use by far the most
    common cause i.e. steroids, chemo,
                       antibiotics, radiation,
                       spleenectomy

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Immune

  • 2.
  • 3. Major structures for immune functioning  Lymph nodes – small organs throughout the body designed to receive fluids from peripheral tissue sites. Clusters found in many areas  Spleen – the largest lymphoid organ. Supports humoral immune response to blood-borne pathogens. Also assists in filtering for damaged RBCs
  • 4. Major structures  Thymus - contributed to the maintenance and functioning of T-cells  Bone Marrow – generates pluripotent stem cells for cell generation including RBCs, WBCs, antibody production  Blood – houses RBCs, WBCs and platelets
  • 5. “Shift to the left” is the release of immature neutrophills to fight infection
  • 6. WBC Functioning  Granulocytes – neutrophils, eosinophils and basophils  Nongranulocytes – lymphocytes and monocytes
  • 7. Cellular WBC response as seen on a CBC differential  Neutrophils – one of the most plentiful along with lymphocytes  55-70% of differential smear  Most (90%) remain in the bone marrow for storage  Neutrophils in circulation also adhere to endothelial lining of small blood vessels  1st on the scene for inflammatory response (usually within 6-12 hrs)
  • 8. Cellular WBC response also trauma  Elevated with acute and surgery inflammatory reaction or acute infection  Survive for only 24-48 hrs  “segs” refer to mature cells  “bands” refer to immature
  • 9. mature immature
  • 10. Lymphocyte activity  Total lymphocytes accounts for 20-40% of differential smear  T-lymphocytes (mature in thymus)  B-lymphocytes (mature in bone marrow)  T Cytotoxic (CD8)  T Helper (CD4)  NK cells
  • 11. Lymphocytes  T-lymphocytes primarily involved in cell-mediated immunity, serve as NK cells and T4 helper cells  B-lymphocytes primarily and humoral immunity  The lymphocytes circulating in the blood are primarily responsible for fighting chronic bacterial and acute viral infections i.e. long standing i.e. rhino virus pneumonia or celleulitis
  • 12. Cellular WBC response  Monocytes – triggered by chemotactic factors becoming a macrophage in lung, connective or lymphoid tissue to remove foreign substances by phagocytosis  Arrives on site within 3-7 days  4-8% of diff smear  Elevated in long-standing infections  Produces interferon, the body’s own immunostimulant
  • 13. Cellular immune response  Eosinophils – very small percentage seen in the WBC count (1-4% of diff smear)  Elevated in parasitic infections and IgE-mediated allergic responses  Do not respond to bacterial infections
  • 14. Cellular immune response  Eosinophils – house heparin, histamine and serotonin in the cytoplasm  Eos infiltrate the tissue affected by allergy to further the inflammatory reaction
  • 15. Cellular immune response  Basophils – only 1-2 % of differential smear  Also supports IgE-mediated allergic responses
  • 16. Cells identified in the WBC differential
  • 17. leukocytosis=too WBC differential many white blood cells  Total WBCs (leukocytes) 5000-11000/mm3  Neutrophils 50-70%  Lymphocytes 20-40%  Monocytes 4-8%  Eosinophils 0-4%  Basophils 0-2%
  • 18. Human Immunity  Direct (active) immunity  Indirect (inactive) immunity through intrauterine sources or other naturally and synthetically- generated immunoglobulins (antibodies) see chapter 12 for active vs passive
  • 19. Active Immunity  Humoral immunity (IgG, IgA, IgM) available in the blood  Mucosal immunity (secretory IgA) available in the mucus of the GI, respi and urogenital tracts  Cell-mediated immunity (T-lymphocytes)  Type I hypersensitivity reactions (IgE response in mast cells found in respiratory and GI tracts) passive immunity is lost; active immunity last longer
  • 21. Class and Function of Immunoglobulins (Antibodies)  IgG – 75%  IgA – 15%  IgM – 10%  IgE - <1%  IgD - <1%
  • 22. Class and Function of Immunoglobulins (Antibodies)  IgG – present in circulation and tissue, first Ig produced in secondary response, crosses placenta  IgA – present in circulation of mucous secretions; prevents adherence on mucosal surface deficiency leads to a lot of skin infections and mucous membrane infections. secreted through breast milk
  • 23. Class and Function of Immunoglobulins  IgM – present in circulation; first Ig of primary immune response. Large and cannot move to tissues  IgE – present in mast cells, mediates hypersensitivity reactions  IgD – lymphocytes
  • 24. Active, Acquired Immunity  A result of invasion by a foreign substance OR through inoculation of a less virulent antigen  Subsequent reinvasion generates a greater response
  • 25. Types of Acquired, Specific Immunity  Active (Natural) – contact with antigen through clinical infection  Active (Artificial) – immunization with live or killed antigen  Passive (Natural) – transplacental transfer of antibodies (lost at 3-6months)  Passive (Artificial) – injection of serum from immune globulin
  • 26. Human Hypersensitivity Reactions  Type I – immediate or anaphylactic  Type II – cytolytic or cytotoxic  Type III – immune complex  Type IV – cell-mediated, delayed 1&2 are immediate 3 is associated with chronic disease 4 is delayed
  • 27. Human Hypersensitivity Reactions  Type I – Immediate/anaplylactic  IgE initiated  Mast cell degranulation → histamine and leukotriene release  Reaction includes anaphylaxis, atopic diseases such as allergies and asthma, skin reactions asthma is a type of allergic disease under sub category atopia
  • 28. Causes of Anaphylaxis  Drugs  Foods  Insect sting  Allergy  Latex allergy
  • 29. Causes of Anaphylaxis  Drugs – PCN, sulfonamides, insulins, ASA, TCN, tetracycline cephalosporins, (antibiotic) chemotherapeutic agents, NSAIDs  Insects – wasps, bees, hornets, ants
  • 30. Causes of Anaphylaxis  Foods – eggs, nuts, shellfish, fish, chocolate, strawberries  Animal Sera – tetanus, rabies, diptheria, snake venom antitoxins  Therapeutic Treatments – blood products, Iodine-based media
  • 31. S & S of Anaphylaxis  Hives, wheal-and-flare reaction, itching  Angioedema  Dyspnea, wheezing fainting  Syncope, ↓ BP, flushing  N & V, diarrhea, abd pain  Onset generally 5-30 mins after antigen  See Fig. 14-11 on p. 226
  • 32. Treatment for Anaphylactic Shock  Epinephrine (SC, IM or IV) 0.5ml 1:10,000 IV for severe  Remove antigen  02 non rebreather mask best source with out intabation  Maintain vascular volume by ↑ legs, fluid resuscitation with NS or LR  Vasopressive agents such as dopamine (Intropin)
  • 33. Latex Allergy (Type I)  Common in the U.S. population  Incidence higher among HCWs  An allergy to the natural latex proteins and occurs within minutes of exposure
  • 34. Latex Allergy (Type I)  Apparent relationship with allergy to certain medications including bananas, avocado, apricot, papaya, kiwi  S & S include dermatitis, itching, urticaria, sneezing/coughing, wheezing, vascular collapse
  • 36. Other Type I Hypersensitivities  Atopic conditions – a broad category used to describe many conditions that are IgE stimulated. Includes hay fever, asthma, and all conditions cited hereafter  To repeat, allergic rhinitis fits here
  • 37. Atopic Conditions (cont.)  Atopic dermatitis – often complaints of itchy skin. May be dry. Lesions may develop. Treatment includes ↓exposure and the response. Cool compresses, lubricants, avoid scratching
  • 38. Eczema – a form of atopic dermatitis Tx: topical corticosteroids avoid triggers Gel sticks better than creams or lotions
  • 39. Other Type I Hypersensitivities  Urticaria – (hives) a systemic response because of an allergen  Histamine → localized vasodilation, transudation, and flaring
  • 40. Type I Hypersensitivities - Urticaria  Papules that tend to develop on face, neck, ant. aspect of arms, and abdomen, back  Many causative agents  Avoidance  Cool compresses, antihistamines
  • 42. Type I Hypersensitivities  Angioedema – similar to urticaria but involves deeper layers of skin and mucosa  Areas affected are significant and include eyelids, lips, tongue, larynx, hands, feet, GIT, and genitalia
  • 43. Meds used for Allergies  Antihistamines – H1 receptor binding agents to ↓ sneezing, rhinitis, itching. (Zyrtec, Allegra, Claritin). Non-blood brain barrier crossing.  Benadryl (diphenhydramine) does cross BBB if it crosses BBB causes drowsiness
  • 44. Meds. cont  Decongestants – relieve nasal congestion to ↓ alpha- adrenergic response at entrance to venous plexus of turbinates. (Sudafed, phenylephrine)  Corticosteroids – topical, nasal (Nasocort, Rhinocort)
  • 45. Meds. cont.  Inhaled steroids – fundamental treatment for asthma. (Flovent, Advair, Azmacort, Vanceril)  Beta-agonists for bronchospasm (Albuterol, salmeterol)
  • 46. Meds. cont.  Antipruritic Drugs: may be applied topically such as calamine lotion, camphor and menthol  Mast Cell-Stablizing Drugs: inhibit the release of histamines and leukotrienes (Cromolyn). Used to treat allergic rhinitis and asthma
  • 47. Meds. cont  Leukotriene inhibitors – Leukotrienes contribute airway edema, smooth ms. contraction and inflammation. (Accolate, Singulair) used for allergic rhinitis and allergies
  • 48. Type II Hypersensitivity reactions  Cytolytic or Cytotoxic  IgG or IgM mediated  Complement activated and cell destruction occurs  Examples of include hemolytic anemia, Rh disease, autoimmune hyperthyroidism, myasthenia gravis, and blood transfusion reactions
  • 49. Blood Transfusion Reactions  Occurs as a result of intravascular hemolysis or RBCs and includes; H/ A, back pain, chest pain, N & V, ↑ HR, ↓ BP, hematuria, urticaria  Probably IgM-based reaction  Stop the blood and all the tubings including blood death by kidney  Notify the MD and the lab cloggingdue to failure by dead  Maintain vascular RBC  Fluid resuscitation access with new bag of NS  Save the urine
  • 50.
  • 51. Type III Hypersensitivity Reactions  Immune Complex reactions  Antigens and antibodies bind and occlude capillaries causing urticaria, arthritis, arteritis, glomerulonephritis  Reactions can be localized or systemic  Systemic Lupus Erythmatosus  Acute glomerulonephritis
  • 52. SLE
  • 53. Type IV Hypersensitivity Reactions  Cell-mediated, or Delayed  Requires effective T-cell functioning TB testing  Used with PPD testing - edema and fibrin result in induration. Also responsible for caseous lesions that develop with tubercle bacillus
  • 54. Type IV Hypersensitivity Reactions  Contact dermatitis – a result of contact with an allergen such as lanolin, adhesive, topical medications or plant toxins. Latex allergy due to contact fits here.  Antibodies are formed with first exposure; hypersensitivity reactions occur with later exposure
  • 55.
  • 56. Hypersensitivity Reaction Prevention  Good assessment and health history. Attending to all food, medication and environmental allergies  Controlling the environment
  • 57. Immunodeficiency Disorders  Inadequate protection of the body at the cellular, enzyme or humoral level  Primary – inadequate immune cells with mostly genetic causes. Apparent at birth. Most common hypogammaglobulinemia i.e. bubble boys
  • 58. Immunodeficiency Disorders  Secondary – obtained through other causes such as medication use and disease; medication use by far the most common cause i.e. steroids, chemo, antibiotics, radiation, spleenectomy

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