Primary Immunodeficiency Part I

Question 1

2 pathways that pluripotent haematopoietic Stem cells in bone marrow differentiate through into immune cells

Answer 1

myeloid or lymphoid pathways

Question 2

2 things immune cells use to migrate from blood circulation into the tissues, which regulate the inflammatory response

Answer 2

cell adhesion molecules, chemotactic factors and complement proteins

Question 3

what do phagocytic cells do to pathogens when they enter tissues

Answer 3

engulf them by phagocytosis and destroy them with lots of different microbicidal agents

Question 4

What cells deal with intracellular infections as phagocytes, complement, and antibodies cannot access pathogens once inside the cell

Answer 4

Natural Killer cells

Question 5

how do natural killer cells differ to T cells

Answer 5

they do not need to be activated by specific antigens

Question 6

what immunity provides back-up to the innate response

Answer 6

adaptive immunity

Question 7

how is adaptive immunity different to innate immunity

Answer 7

It’s developed over time in response to exposure to specific pathogens. Unlike innate immunity, adaptive immunity can recognize and remember specific pathogens, for a more targeted and effective response upon re-exposure.

Question 8

cytotoxic T cells

Answer 8

type of T cell in the adaptive immune response. They have the ability to kill infected or abnormal cells directly.

They are activated when they recognize antigens. Then they release toxic substances that can destroy the target cell.

Question 9

What can cytotoxic t cells secrete that helps to coordinate the immune response and stimulate other cells to take action

Answer 9

cytokines

Question 10

what is immunodeficiency disease

Answer 10

group of disorders that impair the function of the immune system, making it less able to fight off infections and diseases

Question 11

what infections are those who are affected with severe immunodeficiency at risk of

Answer 11

Opportunistic infections which are caused by microorganisms that healthy individuals can easily get rid of, but that cause disease and even death in those with significantly impaired immune function.

Question 12

many people with what virus develop opportunistic infections

Answer 12

HIV

Question 13

what are Primary immunodeficiencies (permanent)

Answer 13

Inherited conditions that affect the development or function of the immune system - caused by a genetic defect producing defective protein or glycoprotein.

Question 14

how rare are primary immunodeficiencies

Answer 14

1 in 10,000

Question 15

what sex is 1y immunodeficiency more common in and why

Answer 15

More common in males as several 1y immunodeficiencies are x-linked. Males only have one x chromosome

Question 16

main immunodeficiency syndrome that are caused by mutations of genes located on the x chromosome

Answer 16

x linked agammaglobulinemia

Question 17

adaptive immunity

Answer 17

immunity to infection caused by an adaptive immune response (response of antigen-specific lymphocytes to antigen, the development of immunological memory)

Question 18

innate immunity

Answer 18

innate resistance mechanisms that are encountered first by a pathogen, before adaptive immunity is induced (anatomical barriers, antimicrobial peptides, complement system and macrophages and neutrophils carrying non-specific pathogen-recognition receptors)

Question 19

how many functional groups of primary immunodeficiencies are there

Answer 19

8 (over 350 immunodeficiencies)

Question 20

what makes immunodeficiencies more severe

Answer 20

how early image defects happen in hematopoietic cell development as they affect everything downstream

Question 21

IgA deficiency

Answer 21

low levels of or no IgA in your blood - sinopulmonary (lung) and gastrointestinal infections as plays role in immune function of mucous membranes

most common inherited form of immunolglobulin deficiency in populations of european origin - 1 in 700

Question 22

Reticular dysgenesis

Answer 22

the most severe form of severe combined immunodeficiency (SCID). Rare genetic disorder of the bone marrow resulting in complete absence of granulocytes and decreased number of abnormal lymphocytes

Question 23

XLA (X-Linked Agammaglobulinemia)

Answer 23

Inherited immune disorder caused by an inability to produce B cells or the immunoglobulins (antibodies) that the B cells make. (due to a defect in the gene encoding the tyrosine kinase BTK)

1 in 200,000

Question 24

what is IFN-γ and whats it secreted by

Answer 24

is the main cytokine that activates macrophages

secreted by NK cells (innate immunity) and TH1 CD4+* and cytotoxic CD8+* cells (*adaptive immunity)

Question 25

what happens when IFN-γ binds to IFN-γ Receptor

Answer 25

it causes increased phagocytosis and bacterial killing by activating JAK1 and JAK2 pathways

Question 26

What mutations cause IFN-γ receptor deficiency

Answer 26

recessive mutations of IFN-γ R1 genes - no R1 polypeptides on the cell surface, so cannot respond to IFN-γ

Question 27

what do Dominant mutations of IFN-γ R1 cause so they are unable to bind and activate JAK1 signalling

Answer 27

truncated cytoplasmic tails

Question 28

what form of IFN-γ receptor deficiency is more severe

Answer 28

Dominant mutation as 25% of receptors are normal, so blood monocytes still respond to IFN-γ (only need one mutant allele for a dominant condition)

Question 29

What reoccurs in patients with antibody deficiency until given antibiotics

Answer 29

pyogenic infections

Question 30

what are pyogenic bacterial infections

e.g

Answer 30

Infections caused by bacteria that can lead to the formation of pus

e.g. pneumonia, impetigp

Question 31

why do Encapsulated pyogenic bacteria need to be bound by specific antibody and complement first before being ingested and killed by phagocytes

Answer 31

as they are not recognized by phagocytic receptors of macrophages and neutrophils,

Question 32

what was the 1st immunodeficiency identified

Answer 32

XLA

Question 33

what gene, when mutant, causes the B-cells to be arrested at the pre-B-cell stage in XLA

Answer 33

Bruton’s tyrosine kinase (Btk)

Question 34

why are boys with XLA initially protected by passive immunity during their first few months life

Answer 34

due to transfer of maternal IgG antibodies via placenta

Question 35

what pyogenic bacteria do
Individuals with XLA have lots of infections

Answer 35

staphylococcus aureus

Question 36

why are viral infections still easily dealt with in people with XLA

Answer 36

as cell-mediated immunity is normal

Question 37

2 XLA treatments

Answer 37

Antibiotics
Intravenous Ig administration (passive immunity) against all common pathogens every 3-4 weeks to maintain adequate concentrations of circulating Ig to prevent tissue damage caused by recurrent infections (problematic in lungs)

Question 38

what causes the rare genetic disorder X-linked hyper IgM syndrome (XHIM)

Answer 38

mutations in the CD40L gene,

Question 39

why is XHIM more common in males

Answer 39

as mutations in the CD40L gene are located on the X chromosome and males only have one X chromosome.

Question 40

what does CD40L mutation cause in XHIM, leading to an increased susceptibility to pyogenic infections

Answer 40

no memory cells
no B cell activation, so inability of B cells to produce immunoglobulin class switching, leading to a selective deficiency of IgG, IgA, and IgE,

Question 41

what immunoglobulin antibody is abnormally high in XHIM

Answer 41

IgM

Question 42

how can Ig deficiencies be detected

Answer 42

Measure the antibody level to see whether they are below the normal level - blood test

screen serum for natural antibodies

Attempt to induce active immunity but NOT using live vaccines - use diphtheria, tetanusus, pertussis

Enumerate B cells by immunophenotyping - CD19, CD20 , and CD22 are the 3 main B cell markers