Immunopathology 2 Flashcards by Amy Thomas

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

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how are sex hormones associated with autoimmune disease?

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

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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

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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?

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what is the difference between TH1 and TH2?

TH1 increases response

TH2 makes antibodies

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what is the difference between monoclonal antibodies and polyclonal antiserum?

monoclonal antibody:

Single epitope
Single idiotype
Single isotype

polyclonal antiserum:
-Multiple epitopes

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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

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what are the risks of monoclonal antibodies?

Type 1 hypersensitivity (immediate, anaphylactic)

Type 3 hypersensitivity (serum sickness, immune complex)

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what 7 things are antibodies involved in?

Antibody dependent cell-mediated cytotoxicity
Neutralisation/blocking
Complement fixation
opsonisation
Induced conformation change
Immunomodulation
Induced apoptosis

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for cancer, what are examples of antibody targets?

abnormal molecules on tumour cells

normal molecules over-expressed on tumor cells

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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

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for cancer, what are examples of antibody targets?

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

immune cells

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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

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

infectious agent

immune cells

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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

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

Immune cells

Inflammatory cytokines that
participate in destruction of tissue

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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

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for hypersensitivity conditions, what are examples of antibody targets?

IgE antibodies that trigger

symptoms of allergies and asthma

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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