Diseases of the Immune System IV Flashcards
cellular rejection
T cell response to transplant
CD8 and CD4
direct pathway of cellular rejection
T cells recognize antigens on donor MHC on APCs in graft
CD4 and CD8 response
**acute rejection
indirect pathway of cellular rejection
T cells recognize antigens of donor on own APCs
CD8 response not generated
-bc these CTLs recognize graft antigens presented by hosts APCs
**chronic rejection
humoral rejection
B cell response to transplant
hyperacute humoral rejection
preformed antidonor antibodies present in recipient
-ex/ multiparous women against paternal antigens from fetus
or blood transfusions
acute humoral rejection
exposure to antigens of donor graft stimulate antibody production
often attack vessels first - vasculitis
hyperacute rejection
within minutes or hours
in kidney - glomeruli have thrombi occlusion and fibrinoid necrosis
acute rejection
within days
in kidneys - vasculitis (humoral) and interstitial mononuclear infiltrate (cellular)
acute cellular rejection
CD4 and CD8
kidney - mononuclear cells in capillaries, glomeruli, tubules
endothelitis
respond well to immunosupressive therapy (cyclosporine)
acute humoral rejection
kidney - mainly damage to vessels
-proliferation of smooth muscles
deposition of C4d (from classical complement pathway)
chronic rejection
kidney - progressive renal failure with rise in creatinine over period of 4-6 months
dense obliterative intimal fibrosis in cortical arteries
increasing graft survival
unless identical twins - immunosuppressive therapy necessary
cyclosporine azathioprine steroids monoclonal anti-T-cell antibodies rapamycin mycophenolate mofetil
also, attempt to prevent costimulatory signals
-interrupt B7 CD28 interaction
cyclosporine
blocks NFAT
-no IL-2 production
transplantation of hematopoietic cells
from bone marrow
problems:
graft-versus host disease
immunodeficiency
graft-versus host disease
immune competent cells transplanted to immune crippled recipient
-transferred cells recognize host antigens
often with bone marrow transplant
depleting T cells in donor bone marrow can help to eliminate disease
acute GVH
within days or weeks
-involve immune system, skin epithelia, liver, intestines
rash, jaundice, bloody diarrhe
chronic GVH
cutaneous injury
fibrosis of dermis (may resemble scleroderma)
liver problems - jaundice
esophageal strictures
graft-versus-leukemia effect
T cells in bone marrow transplant control leukemic cells
primary immunodeficiency
genetic
most manifest in infancy
- 6 months to 2 years
- with recurrent infection
secondary immunodeficiency
due to infection, cancer, malnutrition, therapy, etc.
X-linked agammaglobulinemia
failure of B cell precursors to develop to mature B cells
heavy change rearranged first
-induce light chain rearrangement
mutation in Btk - no light chain rearrangement
seen mostly in males - around 6 months of age
-infections - haemophilis influenza, streptococcus pneumoniae, traphylococcus auresu
also susceptible to viral infections
Btk
mutated in X-linked agammaglobulinemia
-no light chain formation in B cells
clinical features of X-linked agammaglobulinemia
B cells decreased
-serum antibodies are all decreased
-pre-B cells in normal numbers
underdeveloped germinal centers
absent plasma cells
T cell responses normal
Tx of x-linked agammaglobulinemia
immunoglobulin replacement therapy
-allows most to reach adulthood
common variable immunodeficiency
hypogammaglobulinemia
-sometimes only IgG
normal B cells in blood - with no plasma cells
**contrast with X-linked agammaglobulinemia
clinical features of common variable immunodeficiency
childhood or adolescence
hyperplastic B-cell areas of lymphoid tissues (no negative feedback by antibodies)
recurrent sinopulmonary pyogenic infection
recurrent herpesvirus infection
isolated IgA deficiency
low levels of serum and secretory IgA
mucosal defense weakened
-infection of respiratory, GI, GU tracts
if transfused with normal IgA - can develop anaphylactic reaction to IgA
hyper IgM syndrome
high IgM
no IgM, IgA, IgE
defect in ability of helper T cell to activate B cells
- no class switching
- mutation in CD40
hemolytic anemia
thrombocytopenia
neutropenia
recurrent pyogenic infections
class switching
CD40 on B cells with CD40L on activated helper T cells
Digeorge syndrome
T cell deficiency
failure development of 3rd and 4th pharyngeal pouches
- no thymus (no T cells), parathyroid (tetany)
- defects in heart and great vessels
22q11 deletion syndrome
leads to Digeorge syndrome
severe combined immunodeficiency
SCID
defects in humoral and cell-mediated immunity
infants with thrush, diaper rash, failure to thrive
recurrent infections - candida albicans, P. jiroveci, pseudomonas
Tx - bone marrow transplant necessary
X-linked SCID
more common in boys
- mutation in cytokine receptor (gamma-c)
- defect in T cell development
- defect in B cells - no helper T cells
also deficiency of NK cells
autosomal recessive SCID
deficiency of adenosine deaminase (ADA)
hassall corpuscles
seen in thymus of SCID with ADA deficiency
lobules of undifferentiated epithelial cells resembling fetal thymus
seen in thymus of SCID with gamma-c deficiency (X-linked)
Tx of SCID
bone marrow transplant
also gene therapy - retroviral gamma-c gene introduction
wiskott-aldrich syndrome
immunodeficiency with thrombocytopenia and eczema
X-linked recessive
recurrent infections
progressive decrease of T cells
IgM low, IgG normal, IgE and IgA elevated
mutation in WASP
Tx bone marrow transplant
genetic deficiency in complement
most common - C2
-SLE -like autoimmune disease
C3 - susceptible to infection
neisseria infection
have thin cell walls
-recurrent infections with deficiency of C5,6,7,8,9
hereditary angioedema
deficiency of C1 inhibitor
parenteral
intravenous
