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Pathology > Immunodeficiency and Immunosuppression > Flashcards

Immunodeficiency and Immunosuppression Flashcards

(60 cards)

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1
Q

What is a T cell immunodeficiency?

A

Cause susceptibility to infections by viruses and facultative intracellular pathogens: decreased function of individual T cells decreased cell-mediated immunity.

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2
Q

What is an inherited T cell immunodeficiency?

A

e.g thymic aplasia. Thymus is underdeveloped or involuted.

Predisposes to mTb

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3
Q

What is an acquired T cell immunodeficiency?

A

e. g loss of CD4+ T cells due to HIV/AIDS

e. g Herpes simplex virus, rotavirus

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4
Q

What clinical sign may someone with a T cell immunodeficiency show?

A

Delayed hypersensitivity skin test

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5
Q

What may B cell deficiencies increase susceptibility for?

A

Pyogenic infections

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6
Q

What is an inherited B cell immunodeficiency?

A

Agammaglobulinaemia (X linked) : Complete or near complete lack of proteins called gamma globulins, including antibodies.

Increased Sinusitis, sepsis, impetigo, pneumonia

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7
Q

Treatment for Agammaglobulinaemia?

A

Treatment includes intravenous infusion of Immunoglobulin and antibiotics.

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8
Q

What may a complement deficiency lead to infection with?

A

Streptococcus pneumoniae, Staphylococcus aureus.

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9
Q

What is Iatrogenic and therapeutic immunosuppression?

A

Complication of the use of cytotoxic drugs or irradiation in tumour therapy (neutropenic sepsis)

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10
Q

What are Calcineurium inhibitor?

A

Inhibit signal transduction in T cells and IL-2 secretion

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11
Q

What is the role of Rapamycin?

A

targets mTOR signalling pathway in dendritic cells preventing their maturation

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12
Q

What drugs can be given to induce therapeutic immunosupression?

A

Rapamycin, calineurium inhibitor, corticosteroids

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13
Q

Defective interferon alpha receptor likely to be seen with ?

A

Mycobacterial infections e.g TB

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14
Q

C3 deficiencies results in what type of infections?

A

Recurrent pyogenic infections e.g staph aureus

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15
Q

Splenectomy results in…

A

More prone to bacterial infections such as streptococcus pneumonia, Neisseria meningitidis

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16
Q

Defects in interferon gamma receptor predisposes to

A

Mycobacterial infections

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17
Q

Hypercacute rejection results from…

A

Preformed IgM antibodies from the recipient.

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18
Q

Histological features of hyperactute rejection are characterised by

A

Widespread capillary thrombosis and necrosis, PMN infiltrates

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19
Q

IPEX syndrome

A

Dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the Treg lineage.

Dysfunction of Treg cells and subsequent autoimmune disorders.

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20
Q

What disorders to individuals with IPEX get?

A

Autoimmune disorders E.g psoriasiform, excematous dermatitis, nail dystrophy, autoimmune endocrinopathies, alopecia universalis

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21
Q

Deficiencies in MAC are prone to what infections?

A

Prone to meningococcal infection.

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22
Q

Autografts are

A

Tissues derived from the patient themselves e.g. skin to treat life threatening burns

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23
Q

Isografts are

A

Tissues or organs harvested from an identical twin and for which immune intervention is not required

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24
Q

Allografts

A

Tissues or organs taken from unrelated members of the same species

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25
Xenografts
Organs harvested from an unrelated species e.g. the use of replacement heart valves harvested from pigs
26
What is the major immunological basis of allograft rejection?
Polymorphism in the MHC
27
How many genes encode MHC ?
6
28
How are maternal and paternal MHC alleles expressed?
Maternal and paternal alleles are co-dominantly expressed
29
What defines a unique haplotype?
An individual’s immunological identity - based on the MHC alleles they express from their parents
30
What assures that no two individuals express the same HLA phenotype?
Polymorphism
31
Why is it advantageous for each individual to have a unique haplotype?
Can detect when there is foreign antigens
32
What underpins the direct pathway of rejection?
Dendritic cells in transplanted organ carried into host
33
Who's DCs are involved in the direct pathway?
Donor APC
34
How do donor APC leave the transplanted organ? Why?
Lymphatics not joined so leave organ via vasculature
35
Where does direct pathway occur?
Spleen
36
What happens when DC reach the spleen (direct pathway)?
Present foreign MHC to foreign T cell repertoire in the spleen. 10% of T-cells often respond and are activated, leading to destruction of the organ
37
Why is the direct pathway transient?
Controlled by DCs with limited lifespans (1-2weeks) not being replaced by recipient bone marrow.
38
What happens in the indirect pathway of rejection?
When DCs die, release the alloantigens (foreign MHC), these are acquired by recipients own APCs. Activates a different set of alloreactive T-cells.
39
Who's DCs are involved in the indirect pathway?
Host
40
Does direct or indirect produce a larger T cell response
Indirect less destructive as less T-cells (one in 10^6) will respond compared to 10% in direct
41
Is direct or indirect rejection pathway more long lasting?
Indirect permanent chronic response - alloantigen can be released through the full lifespan of organ.
42
What are minor Histocompatibility (mH) Antigens? (5)
ABO blood group antigens Epitopes from naturally-occurring polymorphic proteins Retrovirally-encoded antigens Mitochondrial proteins Male-specific gene products encoded on the nonrecombining arm of the Y chromosome (women are not tolerant of these - women reject tissues from male donors)
43
Who is the best transplant donor and why?
Identical twin is the best source of tissues since all HLA loci and mH antigens are shared, avoiding transplant rejection
44
How good are sibling donors?
Siblings are ‘haploidentical’ since they share approximately half of their HLA loci and are the next best option
45
Effector Mechanisms in Allograft Rejection
CD4+ Th cells CD8+ Cytotoxic T cells (all cells express MHC I) NK cells (inhibitory NK receptors) Alloantibodies and complement Activated macrophages (release pro-inflammatory cytokines and ROS, largely responsible for damage which leads to the positive feedback in rejection)
46
What is a hyperacute rejection time span?
Hours
47
What does a hyperactue rejection involve?
Involves pre-formed or ‘natural’ antibodies of the IgM isotype Binding to endothelial cells causes formation of thrombi in small vessels and organ infarcts.
48
Why do you get RBC lysis in hyperacute rejection?
Natural antibodies specific for ABO blood group antigens can fix complement causing RBC lysis
49
What is an acute rejection time span?
2-3 weeks
50
What is acute rejection driven by?
Driven by the direct pathway of alloantigen presentation The high precursor frequency of alloreactive T cells inflicts rapid and significant tissue damage (polyclonal response)
51
What is a chronic rejection time span?
Occurs over months or years (full lifespan)
52
What is chronic rejection driven by?
Driven by the indirect pathway of alloantigen presentation
53
What is Graft vs Host Disease (GvHD)?
Rejection of host tissues by mature T cells from the donor carried over in the graft e.g. liver
54
Why is GvHD so dramatic?
Up to 10% of donor T cells are recipient’s own MHC resulting in a dramatic polyclonal response and cytokine storm
55
When is GvHD most frequently seen?
Most frequently observed following bone marrow transplantation for the treatment of haematological malignancy: bone marrow contains mature donor T cells.
56
Infection most likely to show increased incidence in an immunodeficient child suffering from CGD
Staph aureus infection
57
Infection most likely to show increased incidence in an immunodeficient child suffering from defective interferon-gamma receptor
TB
58
Infection most likely to show increased incidence in an immunodeficient child suffering from inability to synthesise IgA
E. coli gastro-enteritis
59
Infection most likely to show increased incidence in an immunodeficient child suffering from congenital thymic aplasia
TB
60
Infection most likely to show increased incidence in an immunodeficient child suffering from inability to make complement C3
Staph aureus infection

Pathology (21 decks)

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