Theme 2 Lecture 9: Immunodeficiency Flashcards

1
Q

Give 4 features of innate immunity

A
  • general, not antigen specific, but can recognise broad classes e.g bacteria
  • rapid speed of onset
  • does not alter on repeated exposure
  • no memory
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2
Q

Give 4 features of adaptive immunity

A
  • antigen specific
  • slower response, but more potent
  • subsequent exposure - more effective response
  • memory
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3
Q

What is immunodeficiency?

A

Clinical situations where the immune system is not effective enough to protect the body against infection

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4
Q

What is primary immunodeficiency?

A

inherent defect within the immune system - usually genetic

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5
Q

What is secondary immunodeficiency?

A

immune system affected due to external causes

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6
Q

What are 5 causes of secondary immunodeficiency?

A
  1. breakdown in physical barriers e.g in CF, there is a compromised mucosal barrier in the lung leading to recurrent infections
  2. protein loss e.g burns, malnutrition
  3. malignancy
  4. drugs - that suppress the immune system e.g for autoimmune conditions
  5. infection - HIV, TB
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7
Q

What are the two types of phagocytes?

A

neutrophils and macrophages

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8
Q

What is the difference between neutrophils and macrophages?

A
  • neutrophils are short lived, blood residents and can migrate when needed
  • macrophages are tissue residents
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9
Q

What do PRRs do?

A
  • pathogen recognition receptors
  • recognise conserved pathogen associated molecular patterns (PAMPs)
  • phagocytes use PRRs to detect pathogens
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10
Q

What is an example of PAMP?

A

Lipopolysaccharide

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11
Q

What effect might an IRAK4 or MyD88 deficiency have?

A
  • recurrent bacterial infection, pneumonia, meningitis, arthritis
  • poor inflammatory response
  • susceptibility to infection decreases with age
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12
Q

How does a phagolysosome kill bacteria?

A
  • NADPH complex - formed of several proteins including gp91phox
  • electron binds to oxygen producing superoxide
  • then becomes hypochlorous acid
  • hypochlorous acid is essentially bleach that kills fungi and bacteria
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13
Q

What is a granuloma?

A

collection of macrophages

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14
Q

Explain the genetic cause of chronic granulomatous disease

A
  • CGD is where there is an abnormality of gp91phox

- affects X chromosome so seen in males

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15
Q

What is the presentation of CGD?

A
  • Recurrent abscesses: lung, liver, bone, skin, gut

- unusual organisms e.g staphylococcus, klebsiella, aspergillus

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16
Q

what is the treatment for CGD?

A
  • Treatment: haemopoietic stem cell transplant, antibiotics

- patients typically need bone marrow transplant as they are prone to infection

17
Q

How do we test for CGD?

A
  • Neutrophil function test
  • tests rely on reduction (gain of electron)
  • measure dihydrorhodamine reduction (can be picked up on in neutrophils) using flow cytometry
  • in patients with CGD, patients were unable to reduce DHR
18
Q

Other than the neutrophil function test, how else can we diagnose CGD?

A

Nitro blue tetrazolium dye reduction

-healthy neutrophils should turn purple

19
Q

What are complement proteins important in the immune system for?

A
  • cell lysis (kill invading bacterium)
  • control of inflammation
  • stimulate phagocytosis
20
Q

What are the 3 complement pathways called?

A

classic, alternative and MBL

21
Q

what is the last event in the complement pathway?

A

Forming MAC complex, which lysis bacteria surfaces

22
Q

What is the function of complement?

A
  • should lyse foreign cells if the foreign cells are covered in antibody
  • will trigger the classical complement cascade
23
Q

A deficiency in which complement proteins might predispose to SLE, Infections and myositis?

A

C2, C4 (complements in the early classical pathway)

24
Q

A deficiency in which complement proteins presents with repeated episodes of bacterial meningitis?

A

C5-C9 (form membrane attack complex)

25
What do T helper cells do?
produce cytokines that effect B cells and the recruitment of other immune cells
26
Explain briefly how adaptive immunity works
- antigen binds to B cell and presents on an MHC II molecule to a Th cell - Th produce cytokines that stimulate B cells, so the B cells differentiate into memory and plasma cells which make antibodies
27
How does binding of antibodies to antigens inactivate the antigen?
- neutralisation (blocks viral binding sites; coats bacteria) - agglutination of microbes - precipitation of dissolved antigens - all of above enhances phagocytosis - activation of complement system ---> cell lysis
28
What is X linked agammaglobulinaemia?
- defect in Bruton's tyrosine kinase - this is needed for B cell signalling and B cell maturation - B cell maturation not completed in the bone marrow - antibodies not produced - occurs almost exclusively in males
29
Name 4 other B cell defects, other than X linked agammaglobulinaemia
- Common Variable Immune Deficiency (CVID) - IgA deficiency (most common antibody deficiency) - X linked hyper IgM syndrome - transient hypogammaglobulinaemia of infancy
30
Which drugs could potentially cause secondary antibody deficinecy?
rituximab, methotrexate
31
How do we treat antibody deficiency?
- antibiotics - immunoglobulin G replacement - IgG is most potent antibody and useful in clearing infection
32
What is SCID?
- Severe combined immunodeficiency - reduced T and NK cells - without T cells you don't get a sufficient B cell response either
33
How do we treat SCID?
-paediatric emergency, antibiotics, antivirals, antifungals, asepsis, haemopoietic stem cell transplant (only cure)
34
What are the causes of SCID?
- defect / absence of T cell - loss of communication - MHC II deficiency - metabolic - adenosine deaminase deficiency
35
Summarise the main potential immunodeficiencies
phagocyte: - PRR: IRAK4 --> recurrent pneumonia, poor inflammatory response - CGD - Complement - bacterial meningitis - antibodies - X linked agammaglobulinaemia - T cells - SCID