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 MCQ’s….)

What is the distinction between humoral-

immunity 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 MCQ’s found as of 4/20/11)

-Recurrent pyogenic infections:

-Bruton’s 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 Cell-

mediated 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 naïve mouse

– Challenge with live pathogen…. wait and see

-If serum protects the naïve mouse, humoralimmunity is protective!

-If spleen cells protect the naïve mouse, cell-mediated 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 PMN’s.

Ab will “neutralize” bacterial toxins, e.g. S. pyogenes

streptolysin O or S. aureus leukocidin,

Ab opsonization of bacterium ….

Initiation of phagocytosis by PMN’s (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,

MCQ’s

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 lysozomalenzyme 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 T-

lymphocytes

World 1. A 23-yr-old immigrant gives birth to a

term newborn at home. The infant’s father cuts the

umbilical cord with a kitchen knife. One week later,

the infant develops rigidity and spasms. This child’s

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