Immunopathology 2 Flashcards
how are females associated with autoimmune disease?
produce a higher titre of antibodies
produce more vigorous immune responses
have higher levels of CD4+ T cells and IgM
how are sex hormones associated with autoimmune disease?
oestrogens enhance immune response
testosterone reduces risk in animal models
sex steroids modulate gene transcription
how is prolactin associated with autoimmune disease?
immunoregulatory role? (immunosuppression following anterior pituitary removal, reversed by prolactin injection; PRL receptors on T and B cells
TH1 dominated responses
how is pregnancy associated with autoimmune disease?
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?
what is the difference between TH1 and TH2?
TH1 increases response
TH2 makes antibodies
what is the difference between monoclonal antibodies and polyclonal antiserum?
monoclonal antibody:
- Single epitope
- Single idiotype
- Single isotype
polyclonal antiserum:
-Multiple epitopes
how do you make monoclonal antibodies?
- inject volunteer with antigen with multiple epitopes
- cocktail of antibodies
- donate spleen
- spleen cells
- plasma cells
- stop dieing by getting mycloma cells
- hybridise
- dilute into multiwell plates
- 1 cell per well -> divide
what are the risks of monoclonal antibodies?
Type 1 hypersensitivity (immediate, anaphylactic)
Type 3 hypersensitivity (serum sickness, immune complex)
what 7 things are antibodies involved in?
- Antibody dependent cell-mediated cytotoxicity
- Neutralisation/blocking
- Complement fixation
- opsonisation
- Induced conformation change
- Immunomodulation
- Induced apoptosis
for cancer, what are examples of antibody targets?
abnormal molecules on tumour cells
normal molecules over-expressed on tumor cells
for cancer, what are the antibody modes of action?
(Abnormal molecules on tumor
cells / Normal molecules over-
expressed on tumour cells)
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
for cancer, what are examples of antibody targets?
proteins involved in formation of blood vessels that supply tumours with nutrients/oxygen
immune cells
for cancer, what is the antibody modes of action?
Proteins involved in formation of blood vessels that supply tumors with nutrients /oxygen. Immune cells
Starve cancer cells of nutrients /oxygen by inhibiting new blood vessel formation
Stimulate immune cells to kill tumor cells
for infectious disease, what are the examples of antibody targets?
infectious agent
immune cells
for infectious disease, what are the antibody modes of action?
Passive immunization (used to treat microbial infections in immunocompromised hosts)
Stimulate immune system to attack pathogen
for autoimmune disease, what are the examples of antibody targets?
Immune cells
Inflammatory cytokines that
participate in destruction of tissue
for autoimmune disease, what are the antibody modes of action?
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
for hypersensitivity conditions, what are examples of antibody targets?
IgE antibodies that trigger
symptoms of allergies and asthma
for hypersensitivity conditions, what are the antibody modes of action?
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.
for cardiovascular disease, what are examples of antibody targets?
Platelet molecules involved in
clot formation
for cardiovascular disease, what are the antibody modes of action?
Prevent platelets from binding each other and forming clots following angioplasty
what types of transplants are there?
autografts isografts allografts xenografts allografts are the most common clinical transplants
what are the characteristics of transplants?
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)
what is a hyperacute rejection?
(seconds/minutes)
caused by presence of anti-HLA antibodies from prior blood transfusions or rejection of a previous transplant
what is an acute rejection?
(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
what is a chronic rejection?
(weeks)
characterised by the walls of the blood vessels in the graft thickening and eventually becoming blocked
how do you prevent graft rejection?
Reduce graft immunogenicity
Immunosuppression of recipient
how do you Reduce graft immunogenicity?
Within families Tissue typing - serological techniques using B cells, class II more important than class I
how do you immunosuppress the patient?
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
what is neonatally-induced tolerance?
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
what is active enhancement?
transfusion of donor blood one week before transplantation can lead to long-term organ acceptance
what is passive enhancement?
anti-donor antibody given to the recipient at the time of transplantation
what are the characteristics of xenografts?
skin, blood vessels, valves
whole organs generally unsuccessful
‘humanised’ donor animals
shortage of human organs
problems with organ size, physiology, animal diseases, ethics
what is immunodeficiency?
Immunocompromised as a result of immunodeficiency
an antibody defect of immunodeficiency is most likely due to what infection?
Extracellular bacterial
a t cell defect of immunodeficiency is most likely due to what infection?
Viral, fungal, intracellular bacterial
what are the 2 classes of immunodeficiency?
Primary - congenital defect
Secondary - acquired, effects of external agents
what are the characteristics of primary immunodeficiency?
intrinsic defect
missing enzyme
missing cell type
nonfunctioning component
congenital/acquired
what are the characteristics of secondary immunodeficiency?
underlying disease
lymphoid malignancy
infection
malnutrition
immunosuppressive drugs
always acquired
what 3 examples of primary immunodeficiency are there?
Bruton’s agammaglobulinaemia
DiGeorge’s syndrome
Severe combined immunodeficiency disease (SCID)
what are the characteristics of Severe combined immunodeficiency disease (SCID)?
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
what are the characteristics of Bruton’s agammaglobulinaemia?
X-linked
no mature B cells, T cells normal
recurrent bacterial infection
what are the characteristics of DiGeorge’s syndrome?
maldevelopment of thymus gland
no cell-mediated response, normal antibody levels
recurrent viral, mycobacterial and fungal infections
what causes secondary immunodeficiency?
Malnutrition Loss of immune components Tumours Cytotoxic drugs/radiation Other diseases, e.g. diabetes Infections, e.g. malaria, HIV
what is the treatment for secondary immunodeficiency?
antibiotics, passive gamma-globulin, bone marrow transplant, foetal liver/thymus grafts, gene therapy
