Immune Defense and Deficiency Flashcards Preview

Infectious Disease: Unit 2 > Immune Defense and Deficiency > Flashcards

Flashcards in Immune Defense and Deficiency Deck (21):
1

Definition of immunity & relationship to immunology

  • Derived from Latin word "immunitas" = "exemption"
  • Protection against disease, but not necessarily infection
  • More rapid & greater response to subsequent exposure
  • "Natural" and acquired immunity exist
  • Immunology = study of mechanisms of immunity against infection and adverse effects of immune response

2

4 components of immune function

  1. Anatomic
    1. Skin
    2. Mucosal barriers
  2. Phagocytes
    1. PMNs
    2. Macrophages
  3. Cellular immunity
    1. CD4+ T cells
    2. CD8+ T cells
    3. NK cells
  4. Humoral immunity
    1. Antibodies from B cells
    2. Complement

3

Immunodeficiency: clinical clues

  • History: childhood infections, family history, behavior, prescribed medications
  • Infections: increased frequency, increased severity, increased duration, poor response to therapy, unusual pathogens (including opportunistic pathogens)
    • Respiratory infections will be more frequent
    • More severe: bacteremia, increased tissue injury
  • References for # of infxns/year:
    • Age 0-10: 6-8 URI/year
    • Age 0-3: < 6 episodes of otitis media + 2 episodes of gastroenteritis/year

4

Immunodeficiency: clinical clues

  • Detect decreased number/function of cells
  • Neutrophils (PMNs)
    • Nitroblue tetrazolium (NBT) - doesn't turn blue with CGD
    • < 500 PMNs = neutropenia --> increased risk of infection
  • T cells
    • CD4 for HIV
    • CBC simply gives B cells vs T cells - doesn't break down constituents of each group
  • Antibody
    • Assay Ig levels or other immunoglobulins

5

Primary immunodeficiency

  • Rare (1/10,000 live births) 
  • > 100 defects
  • 70% humoral
  • Most are single gene defects
  • Most present in childhood - SCID, etc.
  • Adults:
    • IgA deficiency
    • CVID
    • IgG subclass deficiency
    • Hyper IgE (Job's syndrome)

6

Secondary immunodeficiency 

  • Developing countries
    • Malnutrition: most common worldwide
    • HIV-1/AIDS: significant cause of disease worldwide
    • Measles
    • Age: extremes are risk factors, many affect young and elderly
  • Developed countries
    • Chronic steroids
    • HIV-1/AIDS
    • Cancer therapy
    • Transplantation

7

Consequences of immunodeficiency

  • Increased incidence and severity of:
    • Infection
    • Malignancy
    • Autoimmunity

8

Anatomic immunodeficiency: types and associated bugs

  • Skin
    • Primary: eczema
    • Secondary: burns, IV
    • Bugs: S. aureus, P. aeruginosa
  • Lung
    • Primary: Cystic fibrosis
    • Secondary: post-viral
    • Bugs: P. aeruginosa, S. pneumoniae, S. aureus
  • GI/Oral
    • Primary: n/a
    • Secondary: chemo drugs
    • Bugs: E. coli, Candida, Enterococcus

9

Phagocytic immunodeficiency: neutropenia

  • Neutropenia = < 500 PMNs/uL
    • Particularly when < 100 PMNs/uL
  • Intestinal:
    • Gram (-) rods: E. coli, Candida, Enterococcus
  • Periodontal anaerobic abscesses: oral Streptococci
  • Skin/catheters: MRSA, Strep, Pseudomonas

10

Phagocytic immunodeficiency: CGD

  • Sufficient # but decreased function of phagocytes
    • ​Defect in NADPH oxidase (ROS decrease)
  • Risk for catalase (+) organisms that destroy O2 radicals
  • Specific bugs: S. aureus, Serratia, Nocardia, Salmonella, Aspergillus
  • Recurrent skin abscesses, severe prolonged pneumonia, bone infections

11

Diagnosis of CGD

  • Labs:
    • Nitroblue tetrazolium (NBT) test
    • Tests PMN production of reactive oxygen species (ROS)
    • Applied clear
    • If reduced by ROS --> cells turn blue
      • Blue = ROS 
  • Clinically:
    • Family history

12

Cell-mediated immunodeficiency

  • WBC x % lymphocytes = lymphocyte number
    • Should be 1500-4000 in adults
  • Most common cause: malnutrition
  • HIV: associated with combined immune defects
    • Low CD4+ number and decreased function
    • NK dysfunction
    • Decreased memory B cells, decreased response to new antigens, high rates of autoimmunity
    • PMNs and macrophage functions preserved

13

Cell-mediated immunodeficiency: bacterial infections

  • Let My Legion Never Surrender:
    • Listeria
    • Mycobacteria
    • Legionella
    • Nocardia
    • Salmonella

14

Cell-mediated immunodeficiency: fungal infections

  • Cryptococcus
  • Pneumocystis
    • Can prevent with TMP/SMX
  • Aspergillus
  • Candida
  • Cocci immitis

15

Cell-mediated immunodeficiency: viral infections

  • HSV
  • Varicella
  • CMV
  • Adenovirus

16

Cell-mediated immunodeficiency: protozoal and helminth infections

  • Protozoan
    • Toxoplasma
    • Cryptosporidium
  • Helminths
    • Strongyloides

17

Humoral mediated immunodeficiency

  • Hypogammaglobulinemia 
  • Serum protein electrophoresis: used to visualize Ig deficient states
  • Selective IgA deficiency
  • Common variable immunodeficiency (CVID)

18

Selective IgA deficiency

  • Most common primary immunodeficiency
  • Little increase in infection rate unless also IgG2 deficient
  • Increased autoimmunity +/- malignancy

19

Common variable immunodeficiency (CVID)

  • Recurrent sinopulmonary infections
  • Chronic diarrhea
  • Decreased levels of IgG, IgM, and IgA
  • Normal # of B cells
  • "Normal" T cells 
  • Increased risk of non-Hodgkins lymphoma and gastric cancers

20

Gammaglobulins

  • Represent all antibodies - IgM + IgG + IgD + IgA + IgE
  • IgG1 
    • Recognize proteins
    • 70% of IgG
  • IgG2
    • Recognize polysaccharides (e.g. capsules of S. pneumo and H. influenzae)
    • 20% of IgG
  • IgM
    • Blood/mucosal
    • Very opsonic
  • IgA1,2
    • Mucosal > blood

21

Complement

  • 3 activation pathways, all converge on C3 - C5-9 forms membrane attack complex
    • Classical
    • Alternative
    • Lectin
  • Acts in concert with Ab to opsonize bacteria and facilitate killing of Gram (-) organisms by lysis or phagocytosis
  • Several complement deficiencies possible
  • C2 complement deficiency most common
  • C1-4 deficiencies --> pyogenic infetions
  • C5-9 deficiencies --> Neisseria infections