Immunodeficiency and Immune Deficiency Diseases

Question 1

What is primary immunodeficiency?

Answer 1

Defective immunity due to and inherited or acquired gene defect

Question 2

What are the consequences of primary immunodeficiency?

Answer 2

There are opportunistic infections and the type of infection reflects the defect

Question 3

Which immune cell is responsible for the largest percentage of primary immunodeficiencies?

Answer 3

B cells/antibodies

Question 4

A patients immune system is able to fight off viruses but not most bacterial infections. Which immune cell is not affected by this patients immunodeficiency?

Answer 4

T cells

Question 5

Regarding complement defiencies, when there is a defective gene C1q, C1r, C1s, C2, C3, C4, Factor 1, what is a typical infection

Answer 5

Pyogenic bacteria

Question 6

Discuss paroxysmal nocturnal hemoglobinuria (PNH)

Answer 6

There is a mutation in the PIG-A gene, resulting in an inability to synthesize glycosyl phosphatidylinositol (GPI) anchors. A lack of these GPI anchors mean that complement control proteins CD55 and CD59 are absent from the surface of erythrocytes, so these erythrocytes are susceptible to complement mediated lysis.

Question 7

What is hereditary angiodema?

Answer 7

A rare genetic condition that causes swelling under the skin and lining of the guts and lungs. It’s due to a C1 inhibitor deficiency which is required to regulate the uncontrolled activation of the coagulation system, in its absence there is excessive clotting

Question 8

Patients with C9 deficiency are particularly prone to infection with?

Answer 8

Neisseria meningitidis

Question 9

Why are RBC that are devoid of GPI anchors on their cell surface prone to complement mediated lysis?

Answer 9

GPI anchors attaches CD55 and CD59 to the cell surface, which inhibit complement mediated lysis by inhibiting C3 convertase and insertion of the membrane attack complex

Question 10

What are the gene defects that can affect phagocytic cells and what are their disorders?

Answer 10

• defective genes for components of the NADPH oxidase: chronic granulomatous disease (CGD)
• CD18beta-subunit: leukocyte adhesion deficiency 1
• GDP-fucose transporter: leukocyte adhesion deficiency 2
• Kindlin-3: leukocyte adhesion deficiency 3
• LYST: Chédiak-Higashi syndrome

Question 11

Chronic granulomatous diseases (CGD) is due to?

Answer 11

In most patients, a defect in subunits of NADPH oxidase. Monocytes, macrophages and neutrophils fail to produce reactive oxygen intermediates tyatvare required to kill engulfed organisms. The X linked form is most common

Question 12

Chédiak-Higashi syndrome leads to dysfunction of which cells?

Answer 12

Neutrophils, NK cells and cytotoxic T cells

Question 13

What is Familial Mediterranean Fever (FMF)?

Answer 13

An autoinflammatory disorder: pyrin mutations; inflammasome regulator that’s expressed in neutrophils and monocytes; inflammasomes generate active caspase-1, converts pro-IL-1beta into active IL-1beta

Causes recurrent episodes of fever usually accompanied by pain in abdomen, chest or joints.

Question 14

What are the primary immunodeficiencies affecting B cells?

Answer 14

• common variable immunodeficiency
• X-linked agammaglobulinemia
• selective IgA deficiency

Question 15

What is autoimmune disease?

Answer 15

A disease in which the body’s immune system attacks healthy cells

Question 16

What are AIRE genes required in the thymus to ensure?

Answer 16

Central tolerance of T cells

Question 17

Defective lymphocyte apoptosis was seen in autoimmune lymphoproliferative syndrome due to?

Answer 17

Fas(CD95) or Fas ligand(CD95L)

Question 18

What is SCID?

Answer 18

Severe Combined Immunodeficiency, affects both T and B cells. There is a complete and total failure of T cell development.

Question 19

What are some tests done in diagnosis of primary immunodeficiency?

Answer 19

Enumeration, assessment of in vitro functioning, assessment of in vivo functioning

Question 20

The ability of phagocytic cells to mount a respiratory burst can be measured using?

Answer 20

Nitroblue tetrazolium

Question 21

Which test would be used to assess in vivo functioning of T cells?

Answer 21

Measuring the delayed hypersensitivity reaction to purified protein derivative of M.tuberculosis

Question 22

In patients with neutropenia, the bone marrow can be stimulated to produce more neutrophils using?

Answer 22

G-CSF

Question 23

Viral vectors can be used as a treatment for immunodeficiencies by inserting functional genes into?

Answer 23

CD34+ hematopoietic stem cells

Question 24

What is secondary immunodeficiency?

Answer 24

Immunodeficiency caused by an external agent unlike primary immunodeficiencies that are caused by gene defects.

OR

defective immunity caused by an external factor

Question 25

What are some causes of secondary immunodeficiency?

Answer 25

Cytotoxic drugs 
Radiation
Immunosuppressive drugs
Malnutrition, metabolic and other diseases
Tumors 
Immaturity 
Pregnancy 
Aging
Infection

Question 26

Protein-calorie malnutrition and deficiency of micronutrients particularly affects immune response mediated by?

Answer 26

T cells

Question 27

The receptor that transfers IgG across the placenta from the mother to the fetus is called?

Answer 27

FcRn

Question 28

Transient hypogammaglobulinemia occurs in neonates because?

Answer 28

Placentally transferred maternal IgG is metabolized while the neonate produces their own IgG

Question 29

At what age do babies have innate immunoglobulins at about the same concentration as adults?

Answer 29

1 year old

Question 30

What is immunosenescense?

Answer 30

The gradual deterioration of the immune system brought upon by age. The adaptive immune system is affected more than the innate immune system.

Question 31

Which disease causes secondary immunodeficiency produces hemozoin which inhibits dendritic cell function?

Answer 31

Malaria

Question 32

What does the HIV retrovirus infect?

Answer 32

It can affect CD4+T cells, macrophages and dendritic cells

Question 33

In HIV there is a depletion of CD4+ cells due to?

Answer 33

• direct cytopathic effect of virus
• HIV gp120-mediated cytotoxicity
• activation-induced apoptotic cell death
• CD8+ T cell killing of infected CD4+ cells due to recognition of pMHC1

Question 34

What does gp120 stand for?

Answer 34

Glycoprotein with the molecular weight of 120,000 daltons

Question 35

A cell surface receptor for HIV is?

Answer 35

CXCR4

Question 36

Give the progression of HIV infection

Answer 36

1. Acute phase: death of memory CD4+T cells
2. Viral dissemination: viremia
3. Latency
4. Chronic phase: activation of T cells, extensive death of CD4+T cells
5. AIDS

Question 37

During the clinical course of HIV what during the primary infection stage?

Answer 37

• acute HIV syndrome
• wide dissemination of virus
• seeding of lymphoid organs

Question 38

What occurs after clinical latency?

Answer 38

Constitutional symptoms, opportunistic diseases, CD4+ T cells rapidly decline, without medical intervention=death

Question 39

What does an extremely high mutation rate of HIV lead to?

Answer 39

• evasion of host immune responses

- anti retroviral drug resistance

Question 40

During the acute HIV disease phase what are the clinical features?

Answer 40

Fever, headache, sore throat with pharyngitis, generalized lymphadenopathy, rashes

Question 41

During the acute clinical latency period what are the clinical features?

Answer 41

Declining blood CD4+ T cell count

Question 42

During the AIDS phase what are the clinical features?

Answer 42

Opportunistic infections (protozoa, bacteria, fungi, viruses), tumors (lymphomas, Kaposi’s syndrome, cervival carcinoma), encephalopathy, wasting syndrome

Question 43

Discuss post-exposure prophylaxis (PEP)

Answer 43

A combination of 2-3 anti retroviral drugs that must begin within 72 hours of exposure to HIV and taken for 28 days following exposure to HIV