Unit 4 Lec 3

Question 0

What factors suggest immunodeficiency?

Answer 0

Increased susceptibility to infection

• Autoimmune or Inflammatory Disease
• Increased susceptibility to Malignancy
• Syndrome complex

Question 1

What is the equation for risk of infection?

Answer 1

Dose x Virulence/Resistance

Epidemiology x Microbiology/ Anatomy x immunology
- Focus on denominators because of the impact these factors have on host immunity

Question 2

What can be one of the most important factors in suggesting immunodeficiency?

Answer 2

Family history is crucial

Question 3

What is the most common presenting manifestation of immunodeficient state?

Answer 3

Infection

• Recurrent
• Multiple sites over time
• Less virulent organisms

Unusual Severity
Difficult to treat

Question 4

What are some normally sterile sites of the body?

Answer 4

Lower respiratory tract
GU tract
Blood
CSF
Joint Fluid
Pleural and Peritoneal cavities

Question 5

What type of bacteria are found in skin and hair follicles?

Answer 5

Staphylococci and streptoococci

Question 6

What types of bacteria are found in the Oral Cavity?

Answer 6

Anaerobes, micro-aerophilics, streptococci, Grp A strep, Pneumococci, H. Influenzae, N. Meningitidis

Question 7

What type of bacteria are found in the GI tract?

Answer 7

Gram Neg. Rods
Anaerobes
MIcro-aerophilic Streptococci

Question 8

What type of bacteria are found in the vaginal vestibule?

Answer 8

Lactobacilli

Gram neg. rods

Question 9

What happens to the normal flora of immuno compromised patients?

Answer 9

Develop infections at sites that are normally colonized by these flora

example is erosive gingivitis in pts with PMN disorders

Question 10

What are primary or inherited immunodeficient states?

Answer 10

Not Rare
Can present at any age (childhood most common)
more than 50 percent due to antibody deficiency

Question 11

What is secondary/acquired immunodeficiency?

Answer 11

Due to another process
Underlying disease (AIDS)
Medications and chemotherapy can cause immunodeficient state also

Question 12

What provides the clinical picture of immunodeficiency?

Answer 12

Determined by functional impairment not taxonomic category

Question 13

What is the effector classification of immunodeficient state?

Answer 13

Antibody=B cell disorders > 50%

Cell mediated disorders = T cell

Phagocytic = PMNs and Macrophages (reticulo-endothelial system)

Complement

Combined B+T cell disorders

Question 14

What is the difference between Innate immune deficits and adaptive immune deficits?

Answer 14

Innate immune system is usually due to the a affected gene so easily intuited (i.e. functional impact0

Adaptive immune system requires three signals so the underlying functional response is not always easily apparent

Question 15

What is prematurity an example of?

Answer 15

example of developmental deficiency, can be severe

The more immature the greater the immunodeficiency

Question 16

What happens in newborns until age 2?

Answer 16

Since the maternal antibodies wear off by 6 months the baby becomes immunocompromised and is at risk for infections (meningisits i.e. encapsulated bacteria) until the baby regains immune function

This is why vaccines are so important (conjugate vaccines) showed a decrease in neonate meningitis by 100-1000 fold

Question 17

What are the three aspects of the triangle for immunodeficiency?

Answer 17

Host Defense
Organism
and Site of Infection

If know one than can predict the other two reasonably well
If know two can predict other one with high confidence

Question 18

What is the importance of anatomy in determining immune mechanism?

Answer 18

Recurrent infection at same anatomical location implicates immunodeficiency

• example would be an iV catheter that gets recurrent infections
• Main organism would be indigenous flora at site of infection

Question 19

What would antibody humoral immunity pattern recognition of immunodeficiency look like?

Answer 19

If antibody, Th2/B Cell axis

• see ENCAPSULATED BAC (S pneumonaie, N. Meningitis, Hib
• Also see Enterovirus, Giardia
• Site of infection: Sinopulmonary tree, meninges, Blood, GI

Question 20

What would you see in humoral immunity deficiency of complement?

Answer 20

Organisms: Encapsulated Bacteria (MENINGOCOCCI and PNEUMOCOCCI)

Site of infection: SINOPULMONARY TREE, Meninges, Blood

Question 21

Why does humoral immunity play an important role against encapsulated bacteria?

Answer 21

Complement is important to break and opsonisize the bacterium to allow phagocytic cells to engulf them

Question 22

What is the most important part of complement system?

Answer 22

C3 is the most important component for both Phagocytic killing and serum bactericidal activity

Question 23

What would be some pattern recognizers for Cell mediated immunity (Th1/T cell axis)?

Answer 23

Organisms: Intracellular bacteria (salmonella, legionella, listeria, Tb)

• Fungi (cryptococcus)
• DNA Viruses (HSV, CMV)
• Protozoa (PCP, Giardia, Toxoplasmosis)
• Parasites (strongyloides)

Site of Infection: Lungs, Meninges, GI, Skin

Question 24

What would a PMN pattern recognition be?

Answer 24

If the numbers are low < 500 PMN/mm is bad - Organism: GNR, Pseudomonas, staphylococci, Fungi (candida, aspergillus) - Site is Blood Lungs Skin If the numbers are high (PMN count nl or increased) - Organism: Staph Aureus, GNR, Fungi Aspergillus - Site: SKin, Lungs, Blood

Question 25

What are two factors that are important in the risk of infection for patients suffering from leukemia?

Answer 25

The absolute number of PMN and the duration of neutropenia important determinants of RISK OF INFECTION and SEVERITY OF INFECTION

Question 26

What is the pattern recognition for Reticulo Endothelial System?

Answer 26

Depends on site - Spleen- Encapsulated bacteria (S. pneumoniae) - Site- Blood - Liver- Gram Neg Rods - Site - Blood

Question 27

What does cyclosporin do?

Answer 27

Binds cyclophilin inhibiting calcineurin and activation of NFAT mediated transcription in T cells therby inhibiting IL2 mediated expansion of T cell populaiton

Question 28

What are some classic examples of CEll mediated immune defects?

Answer 28

Adult AIDS Patients that need immunosuppressive drugs (cyclosporin) or immune mediators (TNF (infliximab or etanercept) - DiGeorge Syndrome - Certain T cell lymphomas and Leukemias - IFN gamma receptor deficiency - IL 12 receptor deficiency

Question 29

What are some classic examples of anatomic problems causing recurrent infections?

Answer 29

RIght Middle Lobe Syndrome Recurrent Cellulitis Kidney Stones Retained Foreign Bodies

Question 30

What are some classical examples of complement deficiency?

Answer 30

Individual component deficiencies Control protein problems

Question 31

What are some individual component deficiencies?

Answer 31

Classical pathway: infection with encapsulated bacteria (systemic lupus erythematous) Alternative Pathway: Meningococcal Disease Terminal Pathway: Recurrent Meningococcal Disease

Question 32

What are some control protein problems with the complement system?

Answer 32

Lead to unrestrained consumption of complement - C1 esterase inhibitor: Hereditary angio-edema (HAE) - Factors H and I (lead to C3 consumption): lead to infection with encapsulated bacteria (menigococci) and hemolytic uremic syndrome (without diarrhea) - CD 59: Paroxysmal Nocturnal Hemoglobinuria

Question 33

What are some problems with the RES dysfunction?

Answer 33

Spleen: Asplenia or surgically removed - Dysfunction is seen in sickle cell as blood gets trapped in spleen Liver: Cirrhosis is inability to filter organisms that enter the portal circulation

Question 34

What are some examples of antibody deficiency?

Answer 34

Brutons X linked agammaglobulinemia X linked Hyper IgM syndrome Common Variable Immunodeficiency Selective IgA deficiency