Infectious Disease - Immunology - Immunodeficiencies; Immunomodulation; Transplants Flashcards
Which is much more common, primary or secondary immunodeficiencies?
Secondary
(due to malnutrition, drugs, infection, etc.)
Name a few causes of secondary immunodeficiency.
Which is most common?
Malnutrition (most common);
drugs;
infection;
etc.
An innate immune response against self is known as what?
An adaptive immune response against self is known as what?
Autoinflammation;
autoimmunity
What disorders are characterized by failed immune responses?
Immunodeficiencies
What are the top three warning signs for primary immunodeficiency in a neonate / child?
- ____________
- Need for _______ antibiotics
- _______ to _______
- Family history
- Need for IV antibiotics
- Failure to thrive
____% of identified cases of primary immunodeficiency before puberty are in males.
83% of identified cases of primary immunodeficiency before puberty are in males (often X-linked).
What general type of deficiency makes up the majority of cases of primary immunodeficiency?
Antibody deficiency / dysfunction
(~60% of cases)
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
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
Recurrent bacterial infections (especially encapsulated) are typically indicative of dysfunction of ______ cells, ___________, and/or phagocytes.
Recurrent pyogenic bacterial infections (especially encapsulated) are typically indicative of dysfunction of B cells, complement, and/or phagocytes.
Recurrent viral infections are typically indicative of dysfunction of ______ cells or ______ cells.
Recurrent viral infections are typically indicative of dysfunction of T cells or B cells.
Recurrent fungal infections are typically indicative of dysfunction of ______ cells or ______ cells.
Recurrent fungal infections are typically indicative of dysfunction of T cells or phagocytic cells.
Most maternal IgG transfer across the placenta begins _________ before birth, and peaks at __________, and is gone at _________ after birth.
Most maternal IgG transfer across the placenta occurs 6 mo. before birth, and peaks at birth, and is gone at 6 mo. after birth.
Most maternal IgG transfer across the placenta occurs in which trimester?
The third
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).
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).
What is the most frequent primary immunodeficiency?
Selective IgA deficiency (~1/500)
Selective IgA deficiency is diagnosed by serum IgA below what level?
How does it manifest?
< 10 mg/dL.
Typically asymptomatic, but may be recurrent GI infections and increased risk for autoimmune and endocrine disorders
What is defective in Bruton’s X-linked agammaglobulinemia?
Bruton’s tyrosine kinase (BTK)
–>
no maturation from pre-B cells
–>
no antibodies produced
What B cell type is found in Bruton’s X-linked agammaglobulinemia?
Pre-B cells
(no progression to mature cells)
Which antibodies are decreased in Bruton’s X-linked agammaglobulinemia?
All of them
In Bruton’s X-linked agammaglobulinemia, infections begin at ___________ of life (mostly bacterial pneumonia or otitis media but may also be viral GI issues).
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).
What might be some physical or laboratory signs of Bruton’s X-linked agammaglobulinemia?
How is it treated?
Abesent tonsils,
no B cells in serum;
IV Ig
What is the diagnosis?
What is another name for it?
Hyper-IgM syndrome;
CD40L deficiency
What inheritance pattern does hyper-IgM syndrome (CD40L deficiency) show?
X-linked
Besides impaired antibody class switching, hyper-IgM syndrome also leads to decreased ____________ secretion and ____________.
Besides impaired antibody class switching, hyper-IgM syndrome also leads to decreased chemokine secretion and phagocytosis.
Hyper-IgM syndrome is characterized by decreased _________ count and recurrent _________ infections.
Hyper-IgM syndrome is characterized by decreased neutrophil count and recurrent bacterial infections.
How is hyper-IgM syndrome treated?
Bone marrow transplant or IV Ig replacement
How common are complement deficiencies?
Very rare
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).
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).
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 ____________).
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).
________ _______ deficiencies result in impaired ability for leukocytes to get to the site of infection due to defective leukocyte _________.
Leukocyte adhesion deficiencies result in impaired ability for leukocytes to get to the site of infection due to defective leukocyte integrins.
Leukocyte adhesion deficiencies are characterized by the following:
Recurrent _______ _______ (tissue type) infection.
Delayed _______ _______ separation.
Severe _____________ (body location) disease.
No ________ formation despite high WBC counts.
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.
Which is the more common form of primary immunodeficiency, Chediak-Higashi or chronic granulomatous disease?
Chronic granulomatous disease
(Chediak-Higashi is very rare)
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?
Nitroblue tetrazolium
OR
chemiluminescene test
(chronic granulomatous disease)
Why do patients with Chediak-Higashi syndrome often have partial albinism?
Melanin deficiency
(defects in granules)
What is the underlying cause of chronic granulomatous disease?
NADPH oxidase deficiency
What is the underlying cause of Chediak-Higashi syndrome?
Lack of lysosome + phagosome fusion
(i.e. poor phagolysosome formation)
T cell deficiencies can lead to an increased susceptibility to what infection types?
All types.
Intracellular infections
Viruses
Fungi
Protozoa
Mycobacteria
Extracellular infections
Other bacteria
What is the most common cause of SCID?
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)
What enzymes are the only available methods for ‘cleaning up’ purine metabolism waste products in leukocytes?
(Other cell types have more enzymes.)
Adenosine deaminase;
purine nucleotide phosphorylase
What is the diagnosis?
SCID
True/False.
There are clearly defined methods of determining the specific molecular cause of SCID.
True.
What might be indicated by infections that are either too too severe, too invasive, too frequent, too protracted, or caused by unusual organisms?
Immunodeficiency
What immunodeficiency is represented here?
Common variable immunodeficiency
Name a few causes of secondary immunodeficiency.
The degree of transplant rejection is correlated with what?
MHC polymorphisms and genetic disparity
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.
Type III hypersensitivity reaction (antigen-antibody complexes block up / prevent angiogenesis and vascularization of graft)
This is an example of second-set rejection.
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?
This is an example of primary-set rejection.
TC cells
Describe the following host v. graft outcomes for a small graft without vascular anastomoses:
___________-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.
Describe the following host v. graft outcomes for a small graft without vascular anastomoses:
Primary-set rejection — destruction of graft after 10–20 days by TC 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.
Describe the various types of transplant rejection.
What are some common mechanisms of action by which immunosuppressive medications given for transplants work?
IL-2 downregulation
