Infectious Disease - Immunology - Immunodeficiencies; Immunomodulation; Transplants

Question 1

Which is much more common, primary or secondary immunodeficiencies?

Answer 1

Secondary

(due to malnutrition, drugs, infection, etc.)

Question 2

Name a few causes of secondary immunodeficiency.

Which is most common?

Answer 2

Malnutrition (most common);

drugs;

infection;

etc.

Question 3

An innate immune response against self is known as what?

An adaptive immune response against self is known as what?

Answer 3

Autoinflammation;

autoimmunity

Question 4

What disorders are characterized by failed immune responses?

Answer 4

Immunodeficiencies

Question 5

What are the top three warning signs for primary immunodeficiency in a neonate / child?

1. ____________
2. Need for _______ antibiotics
3. _______ to _______

Answer 5

1. Family history
2. Need for IV antibiotics
3. Failure to thrive

Question 6

____% of identified cases of primary immunodeficiency before puberty are in males.

Answer 6

83% of identified cases of primary immunodeficiency before puberty are in males (often X-linked).

Question 7

What general type of deficiency makes up the majority of cases of primary immunodeficiency?

Answer 7

Antibody deficiency / dysfunction

(~60% of cases)

Question 8

Is the following information true regarding secondary immunodeficiencies?

Antibody deficiency / dysfunction = 60% of cases

Combined B cell and T cell defects = 20% of cases

T cell defects = 10% of cases

Phagocytic defects = 10% of cases

Complement defects = 2% of cases

Answer 8

No, the following is true regarding primary immunodeficiencies.

Antibody deficiency / dysfunction = 60% of cases

Combined B cell and T cell defects = 20% of cases

T cell defects = 10% of cases

Phagocytic defects = 10% of cases

Complement defects = 2% of cases

Question 9

Recurrent bacterial infections (especially encapsulated) are typically indicative of dysfunction of ______ cells, ___________, and/or phagocytes.

Answer 9

Recurrent pyogenic bacterial infections (especially encapsulated) are typically indicative of dysfunction of B cells, complement, and/or phagocytes.

Question 10

Recurrent viral infections are typically indicative of dysfunction of ______ cells or ______ cells.

Answer 10

Recurrent viral infections are typically indicative of dysfunction of T cells or B cells.

Question 11

Recurrent fungal infections are typically indicative of dysfunction of ______ cells or ______ cells.

Answer 11

Recurrent fungal infections are typically indicative of dysfunction of T cells or phagocytic cells.

Question 12

Most maternal IgG transfer across the placenta begins _________ before birth, and peaks at __________, and is gone at _________ after birth.

Answer 12

Most maternal IgG transfer across the placenta occurs 6 mo. before birth, and peaks at birth, and is gone at 6 mo. after birth.

Question 13

Most maternal IgG transfer across the placenta occurs in which trimester?

Answer 13

The third

Question 14

The low-point for infant antibody levels is _____ months when maternal antibodies have waned, and the child’s antibody production is still ramping up (although Ig__ is already present; Ig__ lags for the first few years).

Answer 14

The low-point for infant antibody levels is 6 months when maternal antibodies have waned, and the child’s antibody production is still ramping up (although IgM is already present; IgA lags for the first few years).

Question 15

What is the most frequent primary immunodeficiency?

Answer 15

Selective IgA deficiency (~1/500)

Question 16

Selective IgA deficiency is diagnosed by serum IgA below what level?

How does it manifest?

Answer 16

< 10 mg/dL.

Typically asymptomatic, but may be recurrent GI infections and increased risk for autoimmune and endocrine disorders

Question 17

What is defective in Bruton’s X-linked agammaglobulinemia?

Answer 17

Bruton’s tyrosine kinase (BTK)

–>

no maturation from pre-B cells

–>

no antibodies produced

Question 18

What B cell type is found in Bruton’s X-linked agammaglobulinemia?

Answer 18

Pre-B cells

(no progression to mature cells)

Question 19

Which antibodies are decreased in Bruton’s X-linked agammaglobulinemia?

Answer 19

All of them

Question 20

In Bruton’s X-linked agammaglobulinemia, infections begin at ___________ of life (mostly bacterial pneumonia or otitis media but may also be viral GI issues).

Answer 20

In Bruton’s X-linked agammaglobulinemia, infections begin at 4 - 6 months of life (mostly bacterial pneumonia or otitis media but may also be viral GI issues).

Question 21

What might be some physical or laboratory signs of Bruton’s X-linked agammaglobulinemia?

How is it treated?

Answer 21

Abesent tonsils,

no B cells in serum;

IV Ig

Question 22

What is the diagnosis?

What is another name for it?

Answer 22

Hyper-IgM syndrome;

CD40L deficiency

Question 23

What inheritance pattern does hyper-IgM syndrome (CD40L deficiency) show?

Answer 23

X-linked

Question 24

Besides impaired antibody class switching, hyper-IgM syndrome also leads to decreased ____________ secretion and ____________.

Answer 24

Besides impaired antibody class switching, hyper-IgM syndrome also leads to decreased chemokine secretion and phagocytosis.

Question 25

Hyper-IgM syndrome is characterized by decreased _________ count and recurrent _________ infections.

Answer 25

Hyper-IgM syndrome is characterized by decreased **_neutrophil_** count and recurrent **_bacterial_** infections.

Question 26

How is hyper-IgM syndrome treated?

Answer 26

Bone marrow transplant or IV Ig replacement

Question 27

How common are complement deficiencies?

Answer 27

Very rare

Question 28

Complement deficiencies are very rare. - A deficiency of ______________ leads to hereditary angioedema. - A deficiency of ______________ are associated with autoimmunity. - A deficiency of ______________ leads to recurrent *Neisseria spp.* infection (especially recurrent meningitis from *N. meningitidis*).

Answer 28

Complement deficiencies are very rare. - A deficiency of **_C1 inhibitor_** leads to hereditary angioedema. - A deficiency of **_early complement_ (C1 - C4)** are associated with autoimmunity. - A deficiency of **_late complement_ (C5 - C9)** leads to recurrent *Neisseria spp.* infection (especially recurrent meningitis from *N. meningitidis*).

Question 29

Complement deficiencies are very rare. - A deficiency of C1 inhibitor leads to \_\_\_\_\_\_\_\_\_\_\_\_\_\_. - A deficiency of early complement (C1 - C4) are associated with \_\_\_\_\_\_\_\_\_\_\_\_. - A deficiency of late complement (C5 - C9) leads to recurrent ____________ infection (especially recurrent meningitis from \_\_\_\_\_\_\_\_\_\_\_\_).

Answer 29

Complement deficiencies are very rare. - A deficiency of C1 inhibitor leads to **_hereditary angioedema_**. - A deficiency of early complement (C1 - C4) are associated with **_autoimmunity_**. - A deficiency of late complement (C5 - C9) leads to recurrent ***_Neisseria spp._*** infection (especially recurrent meningitis from ***_N. meningitidis_***).

Question 30

\_\_\_\_\_\_\_\_ _______ deficiencies result in impaired ability for leukocytes to get to the site of infection due to defective leukocyte \_\_\_\_\_\_\_\_\_.

Answer 30

**_Leukocyte_** **_adhesion_** deficiencies result in impaired ability for leukocytes to get to the site of infection due to defective leukocyte **_integrins_**.

Question 31

Leukocyte adhesion deficiencies are characterized by the following: Recurrent _______ \_\_\_\_\_\_\_ (tissue type) infection. Delayed _______ \_\_\_\_\_\_\_ separation. Severe _____________ (body location) disease. No ________ formation despite high WBC counts.

Answer 31

Leukocyte adhesion deficiencies are characterized by the following: Recurrent **soft tissue** infection. Delayed **umbilical cord** separation. Severe **periodontal** disease. No **pus** formation despite high WBC counts.

Question 32

Which is the more common form of primary immunodeficiency, Chediak-Higashi or chronic granulomatous disease?

Answer 32

**Chronic granulomatous disease** (Chediak-Higashi is very rare)

Question 33

You find out that besides his staphylococcal infections, this boy has had *Nocardia* and *Aspergillus* cutaneous infections as well. Upon further examination, you notice he has granulomas of his liver, lungs, and lymph nodes. What confirmatory test can you use to diagnose his underlying condition?

Answer 33

Nitroblue tetrazolium OR chemiluminescene test (chronic granulomatous disease)

Question 34

Why do patients with Chediak-Higashi syndrome often have partial albinism?

Answer 34

Melanin deficiency | (defects in granules)

Question 35

What is the underlying cause of chronic granulomatous disease?

Answer 35

NADPH oxidase deficiency

Question 36

What is the underlying cause of Chediak-Higashi syndrome?

Answer 36

Lack of lysosome + phagosome fusion | (i.e. poor _phagolysosome_ formation)

Question 37

T cell deficiencies can lead to an increased susceptibility to what infection types?

Answer 37

_All_ types. ## Footnote Intracellular infections Viruses Fungi Protozoa Mycobacteria Extracellular infections Other bacteria

Question 38

What is the most common cause of SCID?

Answer 38

X-linked SCID due to **gamma chain deficiency** (T cells no longer make interleukin receptors --\> No T cells made --\> B cells don’t function well without T cells)

Question 39

What enzymes are the only available methods for 'cleaning up' purine metabolism waste products in leukocytes? (Other cell types have more enzymes.)

Answer 39

Adenosine deaminase; purine nucleotide phosphorylase

Question 40

Why do adenosine deaminase deficiencies selectively damage B cells and T cells?

Answer 40

B cells and T cells have no back-up methods of purine metabolism waste cleanup (most cells do)

Question 41

What causes autosomal recessive SCID?

Answer 41

Issues in **VDJ recombination** (e.g. RAG defects)

Question 42

What is the diagnosis?

Answer 42

SCID

Question 43

**True/False**. There are clearly defined methods of determining the specific molecular cause of SCID.

Answer 43

True.

Question 44

# Fill in the blanks for **DiGeorge syndrome**: Variable __________ cells Diagnosed by absence of _______ \_\_\_\_\_\_\_ on CXR Hypocalcemia, congenital heart disease, thymic aplasia, characteristic facies (low, rotated ears + broad nasal bridge + abnormal \_\_\_\_\_\_\_\_), sometimes mental retardation *\_\_\_\_\_* gene (chromosome 22) involved in cell migration  pouches 3 and 4 Treatment: ________ transplant

Answer 44

# Fill in the blanks for **DiGeorge syndrome**: Variable **B** and **T** cells Diagnosed by absence of **thymic shadow** on CXR Hypocalcemia, congenital heart disease, thymic aplasia, characteristic facies (low, rotated ears + broad nasal bridge + abnormal **philtrum**), sometimes mental retardation ***TBX*** gene (chromosome 22) involved in cell migration  pouches 3 and 4 Treatment: **Thymic** transplant

Question 45

Wiskott-Aldrich syndrome is characterized by **actin** defects in _________ and \_\_\_\_\_\_\_\_\_.

Answer 45

Wiskott-Aldrich syndrome is characterized by **actin** defects in **_leukocytes_** and **_platelets_**.

Question 46

What mnemonic is useful for remembering the features of Wiskott-Aldrich syndrome?

Answer 46

**WATER** **W**iskott **A**ldrich **T**hrombocytopenia **E**czema **R**ecurrent infection (also, elevated Ig**A** and Ig**E**)

Question 47

What infection type is increased by a deficiency of any of the following? ## Footnote **IFN-Gamma receptor** **IL-2 receptor** **IL-12 receptor deficiencies**

Answer 47

Mycobacterial infection

Question 48

When is proper T cell function assessed during perinatal / childhood development?

Answer 48

Newborn screening: Bloodspot (Guthrie) card (T cell receptor excision circles --- excised DNA from recombination during T cell development)

Question 49

What might be indicated by infections that are either too too severe, too invasive, too frequent, too protracted, or caused by unusual organisms?

Answer 49

Immunodeficiency

Question 50

What is the molecular cause of all common variable immunodeficiencies?

Answer 50

Many, many genetic causes

Question 51

When does common variable immunodeficiency (late-onset hypogammaglobulinemia) present? How common is it?

Answer 51

2nd or 3rd generation of life; fairly common (~1/5000)

Question 52

What immunodeficiency is represented here?

Answer 52

Common variable immunodeficiency

Question 53

Name a few causes of secondary immunodeficiency.

Answer 53

Question 54

How can you check a patient's ability to produce antibodies / mount an immune response?

Answer 54

Check their response to their past vaccinations

Question 55

What two tests can be used to determine the number / type of WBCs in the blood?

Answer 55

CBC; flow cytometry

Question 56

How can an antibody deficiency be treated? How can a complement deficiency be treated?

Answer 56

IV Ig; plasma transfusion

Question 57

Why did we stop using the live polio vaccine in the U.S.?

Answer 57

It caused actual polio in immunocompromised children

Question 58

How do vaccines prevent infection?

Answer 58

They don't; they just increase the speed with which the body responds

Question 59

**True/False**. While vaccines save millions of lives, it is worth noting that most cases of vaccine-preventable diseases do not cause _severe disease_.

Answer 59

**True**. E.g. most polio infections do not result in paralysis, most measles cases do not result in encephalitis, etc.

Question 60

**Acute** inflammation leads to tissue \_\_\_\_\_\_\_. **Chronic** inflammation leads to tissue \_\_\_\_\_\_\_.

Answer 60

**Acute** inflammation leads to tissue **_repair_**. **Chronic** inflammation leads to tissue **_damage_**.

Question 61

What antibody suffix characterizes murine (mouse) antibodies?

Answer 61

-**Mo**mab (**mo**use)

Question 62

What antibody suffix characterizes chimeric antibodies?

Answer 62

-**Xi**mab (**chi**meric)

Question 63

What antibody suffix characterizes humanized monoclonal antibodies?

Answer 63

-**Zu**mab (humani**z**ed)

Question 64

What antibody suffix characterizes fully human monoclonal antibodies?

Answer 64

-**Mu**mab (**mu**man = **hu**man)

Question 65

\_\_\_\_\_\_\_\_\_ _________ can be used in many diseases to disrupt many aspects of the immune system (bind IgE and their receptors, leukotrienes and their receptors; bind TNF and its receptors; bind IL-2, IL17, and other ILs; etc.).

Answer 65

**_Monoclonal_** **_antibodies_** can be used in many diseases to disrupt many aspects of the immune system (bind IgE and their receptors, leukotrienes and their receptors; bind TNF and its receptors; bind IL-2, IL17, and other ILs; etc.)

Question 66

What is CAR T cell therapy?

Answer 66

**C**himeric **a**ntigen **r**eceptor T cell modification --\> cancer treatment

Question 67

What process can be used to take antibodies or other non-chelatable substances out of the blood?

Answer 67

Plasmapheresis

Question 68

Specific _________ can be given after toxin exposure (e.g. tetanus or botulinum) to provide passive immunity.

Answer 68

Specific **_immunoglobulins_** can be given after toxin exposure (e.g. tetanus or botulinum) to provide passive immunity.

Question 69

What proportion of transplants are in women? And in men?

Answer 69

1/3 2/3

Question 70

The MHC (HLA) region is on what chromosome?

Answer 70

Chromosome 6

Question 71

There are ___ total MHC alleles per person (these are what are compared for transplant matching). \_\_\_ MHC class I (2 HLA-A, 2 HLA-B, 2 HLA-C) \_\_\_ MHC class II (2 HLA-DP, 2 HLA-DQ, 2 HLA-DR)

Answer 71

There are **12** total MHC alleles per person (these are what are compared for transplant matching). **6** MHC class I (2 HLA-A, 2 HLA-B, 2 HLA-C) **6** MHC class II (2 HLA-DP, 2 HLA-DQ, 2 HLA-DR)

Question 72

Which MHC class is made of an α-heterodimer and a β-heterodimer? Which MHC class is made of an α-homotrimer and a β2-microglobulin?

Answer 72

MHC class II MHC class I

Question 73

In transplants, T cells bind foreign _____ which triggers an immune response.

Answer 73

In transplants, T cells bind foreign **_MHCs_** which triggers an immune response (positive selection ensured that T cells ‘know’ the difference between self and foreign MHC).

Question 74

What is the main APC that is present in nearly every tissue?

Answer 74

Dendritic cells

Question 75

A graft to one's own self is called what?

Answer 75

An autograft (autogeneic)

Question 76

A graft from one monozygotic twin to the other is called what?

Answer 76

An isograft (syngeneic)

Question 77

A graft from one member of a species to another is called what?

Answer 77

An allograft (allogeneic)

Question 78

A graft from one species to the other is called what?

Answer 78

A xenograft (xenogeneic)

Question 79

The degree of transplant rejection is correlated with what?

Answer 79

MHC polymorphisms and genetic disparity

Question 80

A patient has received a small skin graft from a donor who also donated this patient a graft several months ago. Two days later you inspect the graft and notice that it is bright white. **What type of hypersensitivity reaction is this?** **This is an example of \_\_\_\_\_\_\_\_\_\_\_-set rejection.**

Answer 80

**Type III hypersensitivity reaction** (antigen-antibody complexes block up / prevent angiogenesis and vascularization of graft) This is an example of **second**-set rejection.

Question 81

A patient has received a small skin graft from a donor who also donated this patient a graft several months ago. Twelve days later, you inspect the graft and notice that it is necrotic. **This is an example of \_\_\_\_\_\_\_\_\_\_\_-set rejection.** **What type of cell mediates this process?**

Answer 81

This is an example of **primary**-set rejection. **T_C cells**

Question 82

**Describe the following host v. graft outcomes for a small graft without vascular anastomoses:** ## Footnote \_\_\_\_\_\_\_\_\_\_\_-set rejection --- **destruction** of graft after 10–20 days by _______ cells due to immunological memory (MUST BE A SECOND GRAFT). \_\_\_\_\_\_\_\_\_\_\_-set rejection --- no **vascularization** of graft after ______ days due to immunological memory (MUST BE A SECOND GRAFT). This is a type III hypersensitivity reaction that prevents ____________ by occluding the new vessels.

Answer 82

**Describe the following host v. graft outcomes for a small graft without vascular anastomoses:** ## Footnote **_Primary_**-set rejection --- **destruction** of graft after 10–20 days by **_T_C_** cells due to immunological memory (MUST BE A SECOND GRAFT). **_Secondary_**-set rejection --- no **vascularization** of graft after **_2_** days due to immunological memory (MUST BE A SECOND GRAFT). This is a type III hypersensitivity reaction that prevents **_angiogenesis_** by occluding the new vessels.

Question 83

Soon after a liver is grafted into a patient, it rapidly turns white over the course of the next hour. What has occurred?

Answer 83

Hyperacute rejection (preformed antibodies against organ endothelium)

Question 84

Describe the various types of transplant rejection.

Answer 84

Question 85

What mediates hyperacute transplant rejection?

Answer 85

Preformed antibodies

Question 86

What mediates acute transplant rejection?

Answer 86

CD8+ T cells | (Type IV)

Question 87

What transplant rejection is characterized by interstitial fibrosis and vascular narrowing?

Answer 87

Chronic

Question 88

What are some common mechanisms of action by which immunosuppressive medications given for transplants work?

Answer 88

IL-2 downregulation

Question 89

After bone marrow is taken, how is it grafted into the recipient?

Answer 89

Via IV (grafted bone marrow cells home back to the bone medulla)

Question 90

**True/False**. Graft v. host disease occurs commonly with bone marrow and liver transplants.

Answer 90

**True**. It goes away eventually --\> death of grafted leukocytes and growth of new self leukocytes from grafted bone marrow.

Question 91

How does graft v. host disease resolve?

Answer 91

The **death of grafted leukocytes** + **growth of new self leukocytes** from grafted bone marrow

Question 92

What cell types mediate graft v. host disease?

Answer 92

Donor T_H and T_C cells

Question 93

The severity of graft v. host disease depends on the size of the _______ disparity.

Answer 93

The severity of graft v. host disease depends on the size of the **_MHC_** disparity.

Question 94

**True/False**. Cross-presentation plays a major role in graft v. host disease.

Answer 94

True.

Question 95

Cross-presentation plays a role in graft v. host disease --- In this process, ___________ antigens are displayed on APC MHC I to activate T_C cells.

Answer 95

Cross-presentation plays a role in graft v. host disease --- In this process, **_exogenous_** antigens are displayed on APC MHC I to activate T_C cells (usually, MHC I displays ****_endogenous_**ly** synthesized antigens).

Question 96

\_\_\_\_\_\_\_\_\_ \_\_\_\_\_recognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes (typically presented by donor-derived ‘passenger’ dendritic cells) are recognised directly by **recipient** **T** **cells**.

Answer 96

**_Direct_** **_allo_**recognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes (typically presented by donor-derived ‘passenger’ dendritic cells) are recognised directly by **recipient** **T** **cells**.

Question 97

In ________ \_\_\_\_recognition, the alloantigens derived from graft are internalized, processed and presented in form of peptides by recipient’s **APCs** on their MHC II molecules.

Answer 97

In **_indirect_** **_allo_**recognition, the alloantigens derived from graft are internalized, processed and presented in form of peptides by recipient’s **APCs** on their MHC II molecules.

Question 98

**Direct** allorecognition involves recognition of alloantigens by what? **Indirect** allorecognition involves recognition of alloantigens by what?

Answer 98

Recipient **T cells**; recipient **APCs**