Immunodeficiency Flashcards
failures of the immune system
hypersensitive i.e. damaging overreaction
immunodeficiency i.e. fail to produced an adequate repose
types of immunodeficiency
primary immunodeficiency
secondary immunodeficiency
primary immunodeficiency
instrinsic genetic defects in the immune system affecting T and B cells (Ab production)
e.g. phagocytes affected
secondary immunodeficiency
external factors that an deleteriously affect the immune system e.g. drugs
specific vs non specific immunodeficiency
specific is the adaptive immune system i.e. B/T cells
non specific immunodeficiency is abnormalities of phagocyte or complement i.e. innate system
what categories do people with immunodeficiency fall into
1) Defects in Ig, C’ (complement) phagocytes
- susceptible to recurrent bacterial infections (H influenzae..)
- termed Pyogenic infections (pus formation)
2) Defects in cell mediated immunity (T cells)
- susceptible to commensal organisms eg candida, viruses
- opportunistic infections
B cell deficiens
X linked agammaglobulinemia
IgA deficency
X liked dominant gene
X linked B cell deficiency ( x linked agammaglobulinemia)
affects males(on X chromosome)
no B cells therefore little IgG in serum
defective btk gene so no maturation of B cell so no IgG
get pyogenic infections
therapy
- injection of gamma globulin throughout life
Hyper IgM immunodeficiency
B cell deficieny
- deficiency in IgG/A with hyper IgM
X linked recessive condition with mutations
succeptible to pyogenic infections and autoimmune disease Cd40 needed for Ig class switching
IgA deficiency
failure to terminal differentiation of B cells to plasma cells
Mainly affects IgA secretion
develop type III hypersensitivity
pyogenic infections
T cell deficiences
severe combined immunodeficiency
digeorge syndrome
MHC II deficiency
severe combined immunodeficiency.
no /poor T cell function
B cell function depends on T cell funciton
suffer from commensal organisms infections
digeorge syndrome
Affected thymus in foetal develoment
MHC II deficiency
failure to express MHCII antigens on APC
CD4 cells require MHC II for positive selection in thymus
lack of CD4 cells, Ab deficiency
complement deficienies lead to
pyogenic infections
most common condition is HAE
HAE
hereditary angioneurotic edmea
C1 inhibitor (first initiator of competent pathway)
inhibit complement activity and elements of kinin/clotting system
severe oedema due to plasma leakage, recurrent swelling
defects in phagocytes
can affect neutrophils or macrophages
genetic defetcs include:
1) Chronic granulomatous disease
2) Leukocyte adhesion deficiency
chronic granulomatous disease
defective NAPDH oxidase
phagocytes cannot form ROS to kill microbes
organisms alive in phagocytes
infection and granulomas form
how to diagnose chronic granulomatous
nitroblue tetraozlium die
remains yellow in CGD
goes purple in normal
leukocyte adhesion deficicieny types
LAD type 1
- deficient in cd18
LAD type 2
defective in CD15
LAD type 1
deficient in CD18
- lack of functional CD18 defective complete receptor 3 cannot phagocytose bactiera recurrent infections - immune cells also not able to extravate, can't leave blood stream
LAD type 2
defective receptors that bind selectors
phagocytes cannot leave BS as they can’t roll on endothelium
effects of corticosteroids on immune system
lymphocytopenia (can lead to opportunistic pathology)
monocytopenia
neutrophilia (due to release of neutrophils from bone marrow)
what does radiotherapy do
DNA strand breaks
cells cannot proliferate and repair
increased apoptos
targeted at high proliferation rates (so also affects the bone marrow and lymphoid tissue)
stops immune cell produce, proliferation and differentiatin
chemotherapy chemicals and what they do
cyclophospamde
- DNA stops proliferation and increases apoptosis
mainly affects lymphocytes (B cells mostly)
azathioprine
- stops DNA replication, therefore induced cell apoptosis
drugs used in organ transplantation
immunosuppressant drug used in transplants to reduce immune system
affects T cells via IL2 produciton
T cell and ag recognition
T cell binds to APC
IL2 secreated and binds to IL2R on T cells
leads to differentiation etc
what does malnutritiondo
damage lymphoid tissue
malnutrition affects
lymphoid atrophy ( T cell abornlaities, reduced CD4levels, reduced complement )
zinc effects
co factor involved in enzyme reactions
- reduction in delayed type IV hypersensivity (cell mediated)
- Low CD4 and CD8 numbers
- impaired Ab responses (low plasma cell numbers)
iron
needed for superoxide generation
vit B6 and folate deficiency
reduced cell mediated immunity
AIDS HIV replication
1) binds to CD4 in a complex with chemokine receptor (CCR5 or CXCR4)
2) once bound, can undergo conformational change and fusion
3) HIV gets injected into the cell
4) leads to replication
what does HIV bind to
CD4 and chemokine receptor to gain entry
1) X4 tropic – CXCR4 (coreceptor)with CD4
- mainly affects T cells
2) R5 tropic
- CD4 with CCRD
- mainly with macrophages
5 first, then 4 as infection carries on
