Immunodeficiency Diseases

TrMed 595
Block II - 2011

First Aid organizes immunodeficiency diseases by mechanism ..

A different organization .
Based on how you will see patients (infants) in Ob/Gyn and Pediatric clerkships (and USMLE I MCQs.)

What is the distinction between humoralimmunity and cell-mediated immunity?

What is the distinction between humoral- and cell-mediated immunity?

Humoral immunity is mediated by circulating Ab against extracellularly replicating bacteria. Cell-mediated immunity is mediated by T cells against intracellularly replicating bacteria, viruses, and fungi.

Why is this important?

Immunodeficiency Diseases (USMLE I MCQs found as of 4/20/11)

-Recurrent pyogenic infections: -Brutons agammaglobulinemia (3) -Hyper-IgM syndrome (1) -Selective IgA deficiency (3) -Complement deficiencies (3) -Common Variable Immunodeficiency (0) -Leukocyte Adhesion Deficiency (1) -Immobile Cilia Syndrome (1) -Chediak-Higashi Disease (2) -Recurrent fungal and viral infections: -DiGeorge Syndrome (2) -IL-12 Receptor Deficiency (1) -Chronic Granulomatous Disease (2) -Chronic Mucocutaneous Candidiasis (0) -Recurrent pyogenic and fungal/viral infections: -Severe Combined Immunodeficiency (3) -Other -Hyper-IgE syndrome (Job Syndrome) (1) -Wiscott-Aldrich Syndrome (2) -Ataxia telangiectasia (1)

What JABSOM PBL cases involve humoral immunity?

What PBL cases involve humoral immunity? -Streptococcus pyogenes (Ese Saipaia) -Staphylococcus aureus (Jordu Flaisek, Anna White, etc. -Hemophilus influenzae (Bob Coffman) -agent of pyelonephritis (Lina Flaisek) -agent of vesicoureter reflux (Mara Flaisek) -Helicobacter pylorii (Melanie Huang)

What PBL cases involve cellular immunity?

What PBL cases involve cellular immunity? -Mycobacterium tuberculosis (R. Domalagang) -HIV, Pneumocystis jiroveci (Charles Wilms) -HIV, Candida albicans (Darlene Walker) -Rotavirus (Jajo Ebon) -Hepatitis C (Frank Machado) -Hepatitis B (Juan Dela Cruz)

Generalization
Humoral immunity is invoked whenever extracellular replicating pathogens are involved. These usually are bacteria.
Cell-mediated immunity is invoked whenever intracellular replicating pathogens are involved. These are viruses, fungi, and some bacteria

Understanding Humoral vs Cellmediated Immunity - Passive Transfer Mouse Experiments

Passive Transfer Experiments

Do the following
Infect or immunize (vaccinate) mouse A After immunity develops, remove either serum (humoral Ab) or spleen (lymphocytes) Transfer into nave mouse Challenge with live pathogen. wait and see -If serum protects the nave mouse, humoral immunity is protective! -If spleen cells protect the nave mouse, cellmediated immunity is protective!

S. pyogenes? Ab or cells protective?

S. aureus? Ab or cells protective?

Hepatitis B? Ab or cells protective? (Tricky)

Hepatitis B (Juan Dela Cruz)

The hepatitis B vaccine is a recombinant S antigen mass produced in yeast. Vaccination will induce humoral antibodies which will neutralize hepatitis B virus upon infection. But

Ab can neutralize viral infectivity!

Hepatitis B
The hepatitis B vaccine is a recombinant S antigen mass produced in yeast. Vaccination will induce humoral antibodies which will neutralize hepatitis B virus upon infection. But once the virus enters and begins replicating within hepatocytes, cell-mediated immunity is necessary to eradicate the virus!

Humoral Immunity
Opsonization, Neutralization

Opsonization, Neutralization

2) Ab will opsonize S. pyogenes, S. aureus, and H. influenzae and initiate phagocytosis by PMNs.

Ab will neutralize bacterial toxins, e.g. S. pyogenes streptolysin O or S. aureus leukocidin,

Ab opsonization of bacterium .

Initiation of phagocytosis by PMNs (acute inflammation)

Ab can also neutralize viruses (block infectivity)!

Ab will neutralize bacterial toxins, e.g. S. pyogenes streptolysin O or S. aureus leukocidin,

Ab will neutralize bacterial toxins, e.g. S. pyogenes streptolysin O or S. aureus leukocidin,

MCQs

World 1. A 7-yr-old male injures his leg while playing in the yard. He has no significant PMH and all of his vaccinations are up-to-date. Several days after the injury, anaerobic cultures of a wound aspirate grow Clostridium tetani. The patient never develops tetanus because which of the following?
A) Sensitized CD8+ lymphocytes capable of killing the bacteria B) Activated macrophages capable of killing the bacteria C) Neutrophil infiltration of the wound with lysozomal enzyme release D) Circulating antibodies that activate complement E) Circulating antibodies that neutralize bacterial products

World 1. An outbreak of influenza A infection is reported in a small community with 70% of the adult population remaining uninfected despite prolonged and repeated exposure to ill contacts. Which of the following is the most important host factor in preventing influenza infection?
A) T-cell response against nucleocapsid proteins B) T-cell response against neuraminidase C) Circulating antibodies against RNA polymerase D) Circulating antibodies against hemagglutinin E) Antigen-nonspecific macrophage response

World 1. A 71-yr-old male who suffers from chronic obstructive pulmonary disease receives yearly shots of a killed viral vaccine. When he is subsequently exposed to this virus, which of the following is thought to happen?
A) Infective does of the virus is decreased B) Virus entry into cells in impaired C) Virus replication inside cells is impaired D) Viral progeny release from cells is impaired E) Infected cells are destroyed by sensitized Tlymphocytes

World 1. A 23-yr-old immigrant gives birth to a term newborn at home. The infants father cuts the umbilical cord with a kitchen knife. One week later, the infant develops rigidity and spasms. This childs condition could most likely have been prevented by which of the following
A) Infant vaccination at the time of birth B) Maternal vaccine during pregnancy C) Multivitamins during pregnancy D) Peripartum antibiotics to the mother E) Proper infant nutrition after birth

End