Immunology Lecture

Question 1

When to think of primary immunodeficiency?

Answer 1

• SPUR
• Serious
• Persistent
• Unusual
• Recurrent

Question 2

How primary immunodeficiency may present

Answer 2

• 4 or more new ear infections <1 yr
• Two or more serious sinus infections <1yr
• 2 or more months on abx with little effect
• Two or more pneumonia <1yr
• Failure of infant to gain weight or grrow
• Recurrent deep skin/organ abscess
• Persistent thrush in the mouth/fungal infection on skin
• Need for IV abx to clear infections
• 2 or more deep seated infections inc septicaemia
• FH of PI

Question 3

Key things to ask re infection history

Answer 3

• Site - if localised site may be something wrong specifically there
• Frequency
• Need for admission/IV abx?
• Microbiology?
• Immunisation status (then do response status)

Question 4

FH to ask about for ?Primary immunodeficiency

Answer 4

• Infections
• Autoimmune disease - immune dysregulation
• Neonatal deaths
• Consanguinity - increase risk of genetic disease

Question 5

Types of primary immune deficiency

Question 6

Two portions of immune system

Answer 6

• Innate - non specific, rapid, macrophages/neutrophils/complement, does not remember
• Adaptive - pathogen specifc, slower onset, B cells (antibodies), T cells

Question 7

Categories of PID

Answer 7

• Antibody deficiency (B cells)
• Combined (T cells +)
• Complement
• Phagocyte disorders
• Those associated with sydnromes

Question 8

Example of type of antibody deficiency

Answer 8

• X linked agammaglobulinaemia
• Problem with maturation of B cells
• Affect boys

Question 9

Common variable immunodeficiency

Answer 9

• Type of antibody deficiency
• Many different mutations
• Most common in adults

Question 10

Selective IgA deficiency

Answer 10

• Type of antibody deficiency
• Often asymptomatic and never diagnosed
• Tendency for recurrent mucous membrane infections
• Come across when testing for coeliac disease

Question 11

IgG role

Answer 11

• Main one in blood
• Multiple subtypes
• Memory response

Question 12

IgA

Answer 12

• In mucosa
• Most abundant overall

Question 13

IgM

Answer 13

Early response
Binds complement
Limited memory response

Question 14

IgE role

Answer 14

• Mast cell activation
• Allergy and parasitic response

Question 15

Immunoglobulin levels in child

Answer 15

• Get maternally transferred IgG at term - flu and whooping cough vaccine
• IgG dips at 4 months
• Mature over time

Question 16

When and how to antibody deficiency infections manifest?

Answer 16

• Around 6 months - after maternal antibody has waned
• Sinopulmonary infections - hospital admissions, CXR changes
• Recurrent OM with discharge
• Giardia more often

Question 17

Management of antibody deficiency

Answer 17

XLA and severe:
* IgG replacement - SC (preffered) or IV
* Others - prompt and prolonged courses of abx as needed, consider prophylaxis

Question 18

Effect of combined immune deficiencies

Answer 18

• T cell defects
• Complex interaction of T cells and B cells means other antibodies response also impacted (B cells)

Question 19

What do T cells do?

Answer 19

• CD4 cells - helper cells, activate macrophages and B cells
• CD8 T cells - killer cells, anti-viral, induce apoptosis, anti-tumor (increased rate malignancy if immunodeficiency)
• TRegs - immunoregulatory, self vs non self, loss –> autoimmunity

Question 20

Types of combined immune deficiency

Answer 20

• Severe combined immunodeficiency
• Hyper IgM syndrome (can’t make IgG)
• Complete DiGeorge (no thymus, can’t mature T cells)

Also: Hyper IgE, ataxia telangiectasia, wiscott aldrich

CID can be B+ve or -ve, NK+ve or -ve

Question 21

Infections in combined immune deficiency

Answer 21

• Anything and everything - recurrent bacterial, viral, mycobacteria, candida, aspergillus, cryptosporidium, PJP
• Chronic diarrhoea and faltering growth

Question 22

Investigation for CID

Answer 22

• Lymphocytes - under 2.8 /L if under 1 yr

Question 23

Management of CID

Answer 23

• Severe - bone marrow transplant, before significant morbidity
• Prophylactic abx and antifungals
• Immunoglobulin replacement - B cells not working properly
• Infection prevention
• CMV neg and irradiated blood products
• Avoid ALL live vaccines (non live won’t work but won’t cause harm)

Question 24

Functions of complement

Answer 24

• Innate immune system
• Opsonisation - flags cells for phagocytosis
• Chemoattraction to recruit more phagocytes
• Membrane attack complex creates holes in certain types of bacteria - encapsulated

Question 25

Infections in complement disorders

Answer 25

* Recurrent invasive bacterial disease - meningitis, pneumonia * Due to: meningococcal, pneumococcal, Hib * Usual, but frequent sinopulmonary infection in early pathway defects

Question 26

Management of complement disorders

Answer 26

* Penicillin prophylaxis daily * Additional immunisations - Men ACWY, Men B, pneumovax * Check green book if in doubt

Question 27

What do neutrophils do?

Answer 27

* Phagocytosis * Primarily bacteria - but also fungi * Also act as antigen presenting cells - co-ordinate rest of response * Normal neutrophils numbers in disorders but functional tests abnormal

Question 28

Phagocyte disorders

Answer 28

* Chronic granulomatous disease - problem with pathogen fusing with lysosome to kill pathogen - failure of chemical reaction Also leucocyte adhesion defects (problems with bouncing along BV walls, slow it down, higher levels of WCC in blood, delayed seperation of cord) and severe congenital neutropenia

Question 29

Infections associated with phagocyte disorders

Answer 29

* Recurrent abscesses * Fungal chest infection - aspergillus * Liver abscess * Osteomyelitis * BCG itis * Early onset inflammatory bowel disease

Question 30

Management of phagocyte disorders

Answer 30

* Consider BMT - esp with early diagnosis * Antifungal and abx prophylaxis * Avoid fungal spores - compost, leaf mulch * Avoid BCG

Question 31

Syndromes associated with immune deficiency

Answer 31

* DiGeorge * Ataxia telangiectasia - DNA repair disorder, malignancy (no radiation) * CHARGE - similar to DiGeorge

Question 32

Management of complete DiGeorge

Answer 32

* Same SCID urgency * Same prophylaxis * Thymic transplant - donor thymus matures own babys T cells

Question 33

Investigations for ?PID

Answer 33

* FBC * Lymphocyte subsets - T cells, B cells, NK cells * Total antibodies - immunoglobulins (myeloma screen) Other further: * Specifc antibodies - vaccination history eg tetanus, pneumococcus, Hib * Neutrophil oxidative burst - for CGD, see if neutrophils can be activated * Complement - CH50, AP50 (not C3/C4) * HIV - don't forget, can be born with and presents similarly

Question 34

5 year old girl presents with second culture positive episode of pneumococcal meningitis - likely cause

Answer 34

Terminal pathway complement deficiency

Question 35

Young boy with previous boils needed I&D, presented with liver abscess - likely underlying cause

Answer 35

X linked chronic granulomatous disease

Question 36

Multiple ear and chest infections needing IV abx, well until 6 months age - likely cause

Answer 36

X linked agammaglobulinaemia

Question 37

Newborn screening for SCID

Answer 37

* Pilot started in 2021 * Test for T cell development - TRECs produced as T cells mature * Early discovery = less morbidity * Delay BCG until after screen so now have outside of hospital