Immunodeficiency

Question 1

what is the difference between primary and secondary autoimmune disease

Answer 1

primary - inherent defect usually genetic

secondary - immune system affect due to external causes or disease

Question 2

describe the hierarchy of the immune system

Answer 2

immune syetem - innate and adaptive

innate - barrier and chemical, pathogen recognition, cellular (phagocytes and NK), complement

adaptive - hunoral (antibodies and B cells0 and cellular (B and T cells)

Question 3

what are 5 causes of immunodeficiency

Answer 3

breakdown of physical barriers - CF (lack of lung secretion) 
protein loss 
malignancy 
drugs 
infection (HIV/TB)

Question 4

give 5 examples of drugs that have a secondary association with autoimmune disease

Answer 4

steroids - suppress immune system 
DMARDS - anti rheumatic
Rituximab - against B cells 
anti-convulsants 
myelosuppressive

Question 5

what is the role of neutrophils and macrophages in the innate immunity

Answer 5

neutrophils are short lived
macrophages are long lasting (start as monocytes then mature in bone marrow to macrophages)
east bacteria and fungi

Question 6

what type of acid is found din a lysosome to form phagolysosome complex

Answer 6

hypochlorous acid

Question 7

what quality about neutrophils and macrophages allow them to recognise pathogens associated molecular patterns (PAMPS)

Answer 7

the innate cells have pathogen recognition receptors unique to pathogens to differentiate from human cells

Question 8

give an example of a PAMP

Answer 8

liposaccharide

Question 9

give an example of a type of PRR and examples within that subset of recognition

Answer 9

TLR - toll like receptors are PRR

TLR3 - recognise viral RNA
TLR4 - liposacchrides
TLR5 - recognises flagellum

Question 10

what is the role of MyD88 and IRAK4

Answer 10

released on phagocytosis after PRR activation on innate cells which release more inflammatory mediators

Question 11

why is it strange to have normal levels of WBC’s during bacterial infection

Answer 11

should have increases in WBC to attack infection

which shows deficiency in B cell recruitment or activation which may infer an innate system issue

Question 12

what is the clinical presentation of IRAK4 deficiency and how do you treat it

Answer 12

can recognise the bug but cannot cause an inflammatory response - recurrent infection strep/staph

prophylactic antibiotics or IV immunoglobin if severe

Question 13

how do you differentiate between MyD88 deficiency and IRAK4

Answer 13

genetic testing

Question 14

how do you create hypochlorous acid in the lysosome

Answer 14

O2 - superoxide via reduction (electron donation to O2)

Question 15

what is a granuloma

Answer 15

collection of macrophages

Question 16

what is the common problem associated with cells which causes chronic granulomatous disease

Answer 16

macrophages will eat pathogen but can’t destroy and NADPH complex can donate electron to produce lysosome acid

Question 17

what genetically in chronic granulomatous disease

Answer 17

X linked - affects men mainly

Question 18

what is the treatment of chronic granulomatous disease

Answer 18

haemopoitic stem cell transplant and prophylactic antibiotics

Question 19

how do you test to see if a phagocyte is dysfunction in producing effective hypochlorous acid

Answer 19

relays on reduction
eg test neutrophils - nitro blue tetrazolium reduction - healthy neutrophils go clear but purple mean they are dysfunctional

Question 20

which part of the immune system is complement within

Answer 20

innate

Question 21

what are the three types fo complement pathways

Answer 21

classical

alternative / MBL

Question 22

describe in terms of C proteins the classical compliant pathway

Answer 22

antibody dependant (adaptive help)
antibody attaches to microbe 
C1 binds to this and cleaves C4 into C4a/b + C2 into C2a/b 

then C4b and C2a bind to C4a2b (c3 convertase)

this cleaves C3 into C3a/b

C3a causes inflammation
C3b contends with c3 convertase = C4b2a3b (C5 convertase)

this cleaves c5 in c5a/b

c5b recruits c6/7/8 which then binds with C9 in microbe membrane

Question 23

what is the role of C3a C4a and C5a in complement

Answer 23

dilation of arterioles, release of histamine from mast cells and chemotaxis of phagocytes

Question 24

what is the role of C3b in complement

Answer 24

opsonisation of microbes to help phagocytosis

Question 25

what is the role of c5b C6 C7 C8 C9

Answer 25

form MAC complex which causes cytolysis of cell via perforation

Question 26

how do you test complement function

Answer 26

patients serum should Clyde sheep erythrocytes via classical pathway

Question 27

what would a deficiency in C2 or C4 cause

Answer 27

autoimmunity SLE or myositis

Question 28

what would a deficiency in MAC complex cause

Answer 28

repeated bacterial meningitis (N. meningitis)

Question 29

what Th cell tends to cause more atopic diseases

Answer 29

TH2 | makes a lot of IgE

Question 30

what three ways to antibodies neutralise toxins

Answer 30

neutralise them clump together opsonise activate complement

Question 31

what would a defect in Brutons tyrosine kinase cause

Answer 31

no b cell maturation in the bone marrow so no antibodies are made

Question 32

name 4 types of B cell defects

Answer 32

CVID IgA deficiency X linked hyper IgM syndrome transient hypogammaglobulaemia of the infant

Question 33

``` how do these drugs affect the immune system riturximab methotrexate ciclosporin/azathiprine prednisolone ```

Answer 33

antibody against cd20 for B cell cancers hits fast growing cells like neutrophils and macrophages work of B/T cells works on large part of immune

Question 34

what type of cell does HIV kill

Answer 34

CD4 cells

Question 35

what is SCID and what causes it

Answer 35

no T cells defect in critical T cell receptors loss of communication - MHC2 deficiency in B cells metabolic - adenosine deaminase deficiency

Question 36

``` what do problems in these types of cells cause phagocyte complement antibodies T cells ```

Answer 36

PRR - IRAK4 - recurrent pneumonia recurrent bacterial meningitis recurrent sinopulmonary infection SCID, and HIV causes some complications with T cells