Immunopathology 2

Question 1

how are females associated with autoimmune disease?

Answer 1

produce a higher titre of antibodies
produce more vigorous immune responses
have higher levels of CD4+ T cells and IgM

Question 2

how are sex hormones associated with autoimmune disease?

Answer 2

oestrogens enhance immune response
testosterone reduces risk in animal models
sex steroids modulate gene transcription

Question 3

how is prolactin associated with autoimmune disease?

Answer 3

immunoregulatory role? (immunosuppression following anterior pituitary removal, reversed by prolactin injection; PRL receptors on T and B cells
TH1 dominated responses

Question 4

how is pregnancy associated with autoimmune disease?

Answer 4

need to tolerate a foreign graft
in pregnacy TH2 responses predominate (rather than TH1)
SLE (TH2-like, antibody-mediated) exacerbated during pregnancy
RA and MS (TH1-like, inflammatory, cell-mediated) ameliorated during pregnancy
role of long-lived foetal cells in maternal circulation?

Question 5

what is the difference between TH1 and TH2?

Answer 5

TH1 increases response

TH2 makes antibodies

Question 6

what is the difference between monoclonal antibodies and polyclonal antiserum?

Answer 6

monoclonal antibody:

• Single epitope
• Single idiotype
• Single isotype

polyclonal antiserum:
-Multiple epitopes

Question 7

how do you make monoclonal antibodies?

Answer 7

1. inject volunteer with antigen with multiple epitopes
2. cocktail of antibodies
3. donate spleen
4. spleen cells
5. plasma cells
6. stop dieing by getting mycloma cells
7. hybridise
8. dilute into multiwell plates
9. 1 cell per well -> divide

Question 8

what are the risks of monoclonal antibodies?

Answer 8

Type 1 hypersensitivity (immediate, anaphylactic)

Type 3 hypersensitivity (serum sickness, immune complex)

Question 9

what 7 things are antibodies involved in?

Answer 9

1. Antibody dependent cell-mediated cytotoxicity
2. Neutralisation/blocking
3. Complement fixation
4. opsonisation
5. Induced conformation change
6. Immunomodulation
7. Induced apoptosis

Question 10

for cancer, what are examples of antibody targets?

Answer 10

abnormal molecules on tumour cells

normal molecules over-expressed on tumor cells

Question 11

for cancer, what are the antibody modes of action?

(Abnormal molecules on tumor
cells / Normal molecules over-
expressed on tumour cells)

Answer 11

prevent cells from dividing by blocking signalling molecules

induce apoptosis by binding and triggering molecules involved in cell suicide

kill cells through ADCC

antibodies conjugated with cytotoxic substances bring payload to tumor cells

Question 12

for cancer, what are examples of antibody targets?

Answer 12

proteins involved in formation of blood vessels that supply tumours with nutrients/oxygen

immune cells

Question 13

for cancer, what is the antibody modes of action?

Proteins involved in formation of blood vessels that supply tumors with nutrients /oxygen. Immune cells

Answer 13

Starve cancer cells of nutrients /oxygen by inhibiting new blood vessel formation

Stimulate immune cells to kill tumor cells

Question 14

for infectious disease, what are the examples of antibody targets?

Answer 14

infectious agent

immune cells

Question 15

for infectious disease, what are the antibody modes of action?

Answer 15

Passive immunization (used to treat microbial infections in 
immunocompromised hosts)

Stimulate immune system to attack pathogen

Question 16

for autoimmune disease, what are the examples of antibody targets?

Answer 16

Immune cells

Inflammatory cytokines that
participate in destruction of tissue

Question 17

for autoimmune disease, what are the antibody modes of action?

Answer 17

Prevent immune cells from entering tissue by blocking surface proteins that cells use to pass from blood into tissues

Interfere with activities
mediated by inflammatory
cytokines, which include:    
 -destruction of tissue     
 -recruitment of immune cells that mediate tissue damage

Question 18

for hypersensitivity conditions, what are examples of antibody targets?

Answer 18

IgE antibodies that trigger

symptoms of allergies and asthma

Question 19

for hypersensitivity conditions, what are the antibody modes of action?

Answer 19

Prevent release of substances by mast cells that cause the symptoms of allergies /asthma. Antibodies that bind IgE inhibit
mast cell binding of IgE and the release of mast cell substances.

Question 20

for cardiovascular disease, what are examples of antibody targets?

Answer 20

Platelet molecules involved in

clot formation

Question 21

for cardiovascular disease, what are the antibody modes of action?

Answer 21

Prevent platelets from binding each other and forming clots following angioplasty

Question 22

what types of transplants are there?

Answer 22

autografts
isografts
allografts
xenografts
allografts are the most common clinical transplants

Question 23

what are the characteristics of transplants?

Answer 23

Autografts or allografts
Transplantation antigens = major histocompatibility (MHC) antigens
MHC locus in man is known as HLA (human leukocyte antigen) locus
Four separate HLA subregions:
HLA A, B & C (MHC class I)
HLA D (MHC class II)

Question 24

what is a hyperacute rejection?

Answer 24

(seconds/minutes)

caused by presence of anti-HLA antibodies from prior blood transfusions or rejection of a previous transplant

Question 25

what is an acute rejection?

Answer 25

(minutes/hours)
due to the primary response of T cells and the consequent triggering of various effector mechanisms. If the patient has been pre-sensitised to antigens on the organ, a secondary T cell response occurs, leading to accelerated cell-mediated rejection

Question 26

what is a chronic rejection?

Answer 26

(weeks)

characterised by the walls of the blood vessels in the graft thickening and eventually becoming blocked

Question 27

how do you prevent graft rejection?

Answer 27

Reduce graft immunogenicity

Immunosuppression of recipient

Question 28

how do you Reduce graft immunogenicity?

Answer 28

Within families
Tissue typing - serological techniques using B cells, class II more important than class I

Question 29

how do you immunosuppress the patient?

Answer 29

corticosteroids cytokine gene transcription blocker (e.g. IL-1), danger of general immunodeficiency
azathiaprine, metabolic toxin, stops lymphocyte maturation
cyclosporin A, IL-2 gene transcription blocker
FK506, as above but less nephrotoxic

Question 30

what is neonatally-induced tolerance?

Answer 30

deliver a persistent source of antigens before mature T cells are first exported from the thymus (16 - 20 weeks) reactive T cells do not develop

Question 31

what is active enhancement?

Answer 31

transfusion of donor blood one week before transplantation can lead to long-term organ acceptance

Question 32

what is passive enhancement?

Answer 32

anti-donor antibody given to the recipient at the time of transplantation

Question 33

what are the characteristics of xenografts?

Answer 33

skin, blood vessels, valves

whole organs generally unsuccessful

‘humanised’ donor animals

shortage of human organs

problems with organ size, physiology, animal diseases, ethics

Question 34

what is immunodeficiency?

Answer 34

Immunocompromised as a result of immunodeficiency

Question 35

an antibody defect of immunodeficiency is most likely due to what infection?

Answer 35

Extracellular bacterial

Question 36

a t cell defect of immunodeficiency is most likely due to what infection?

Answer 36

Viral, fungal, intracellular bacterial

Question 37

what are the 2 classes of immunodeficiency?

Answer 37

Primary - congenital defect

Secondary - acquired, effects of external agents

Question 38

what are the characteristics of primary immunodeficiency?

Answer 38

intrinsic defect

missing enzyme
missing cell type
nonfunctioning component

congenital/acquired

Question 39

what are the characteristics of secondary immunodeficiency?

Answer 39

underlying disease

lymphoid malignancy
infection
malnutrition
immunosuppressive drugs

always acquired

Question 40

what 3 examples of primary immunodeficiency are there?

Answer 40

Bruton’s agammaglobulinaemia

DiGeorge’s syndrome

Severe combined immunodeficiency disease (SCID)

Question 41

what are the characteristics of Severe combined immunodeficiency disease (SCID)?

Answer 41

autosomal recessive and X-linked forms
defect at stem cell level
defective T and B cell response
virtually absent lymphoid tissue
early death from opportunistic infections

Question 42

what are the characteristics of Bruton’s agammaglobulinaemia?

Answer 42

X-linked
no mature B cells, T cells normal
recurrent bacterial infection

Question 43

what are the characteristics of DiGeorge’s syndrome?

Answer 43

maldevelopment of thymus gland
no cell-mediated response, normal antibody levels
recurrent viral, mycobacterial and fungal infections

Question 44

what causes secondary immunodeficiency?

Answer 44

Malnutrition
Loss of immune components
Tumours
Cytotoxic drugs/radiation
Other diseases, e.g. diabetes
Infections, e.g. malaria, HIV

Question 45

what is the treatment for secondary immunodeficiency?

Answer 45

antibiotics, passive gamma-globulin, bone marrow transplant, foetal liver/thymus grafts, gene therapy