Immunopathology Flashcards
Tolerance: Gut
M cells process antigen
taken up by gut dendritic cells
travel to mesenteric lymph nodes- make IL-10, favors Treg development
What is autoimmunity?
immune response to self antigen and a loss of tolerance
Is autoimmunity an autoimmune disease?
No! But it is a cause of inflammation and when the damage from inflammation exceeds the body’s ability to repair you get DISEASE!
General characteristics of autoimmune disease
idiopathic-except when drug induced, suspected that infection/virally induced
multiple factors involved-genes, sex, age, infection
most HLA associated diseases are autoimmune
multiple immune mechanisms
inability to avoid immunogen
Mechanisms of autoimmune disease
failure to delete autoreactive clone in thymus
breakdown of peripheral tolerance (loss of anergy)
antigen-nonspecific lymphocyte activation (superantigens)
molecular mimicry-infectious immunogens cross react w/ self
abnormalities in lymphocyte interactions
ideal immune response
directed only against harmful immunogens
completely effective and totally eradicates harmful immunogen
completely protective, with no host tissue damage
Latrogenic
adverse response to therapy
Mechanisms of tolerance
not inherited but acquired=active process
developed during fetal life
requires continued presence of immunogen
induced in adult animals under some conditions
Est. of tolerance as clinical goal: allergy therapy, est of allografts
Central tolerance
immunogen-induced apoptosis of double positive T cells (negative selection in thymus)
immunogen-induced apoptosis of IgM-expressing B cells
Peripheral tolerance
immunogen-induced anergy in absence of costimulation (during antigen presentation there is no B7-CD28 costimulation)
Induction of tolerance in mature immunogenic reactive cells
Treg are distinct helpers, can be antigen specific, produce primarily immunosupressive cytokines-inhibit autoimmune cell function
M2 macrophages and NKreg cells involved
TGFbeta and IL10
induction of tolerance in mature cells, clinically
oral tolerance to proteins
high dose tolerance to aq. proteins (system. adm)
low dose tolerance- repeated, low doses (systemic)
alloantigen
foreign antigen from same species
ex: ABO blood groups, Rh factors, HLA complex, minor blood group system
Alloimmunity in pregnancy
results when mother and fetus have different Rh factors.
1st pregnancy=sensitizing event
2nd+ pregnancies=secondary immune response, lots of high affinity IgG transctosed to fetal circulation causing massive destruction of fetal erythrocytes triggered by anti-Rh IgG
Results in anemic newborn
What medication is used to treat mom with anti-Rh IgG?
RhoGAM
What are the hazards associated with blood and blood derivatives?
transfusion reactions- hemolytic and febrile
Infection disease- CMV, Hep C, HIV, Hep B
Which blood type is the universal donor?
O-
Which blood type is the universal acceptor?
AB+
What is the most important thing to match correctly for a blood transfusion?
ABO group then RH, minor blood groups and HLA
When transplanting an organ or tissue what is most important to match?
HLA complex (class 1 > 2)»_space; ABO
Why treat a transplant patient with CSA and glucocorticoids?
to induce tolerance by suppressing the normal immune response
How does cyclosporine work?
Cyclosporin works by inhibiting the production of IL-2 which is made by Th1 cells and induces T cell proliferation and promotes cell growth. IL-2 also enhances cytotoxic activities of NK cells and CTL which is seen in graft rejection. Inhibition of IL-2 will lead to a decrease in T-cell proliferation and cytotoxic activities
Hyper acute organ rejection
preexisting antibody- antibodies against donor blood group antigens bind vascular endothelium of graft, initiating inflammatory response that occludes blood vessels and rapidly causing it to fail.
Acute Organ rejection
T-cell mediated due to HLA differences
When donor organ is transplanted into recipient some donor dendritic cells are present. After the transplant they migrate to the spleen, activate effector T cells which recognize the Class I and II MHC as foreign and then they migrate to the transplanted organ, inflammation sets in and eventually destroys it.
Alternate mechanism for acute organ rejection
Direct: CD4 and CD8 effector T cells recognize the nonself MHC on donor DC and attacks
Indirect: antigen is presented to donor DC, processed and present on the surface by foreign MHC and then CD4 recognizes that it isn’t right and attacks!
Chronic organ rejection
antibody mediated causing decreased perfusion
Increase in inflammatory cells enables immune effectors to enter the tissue
How can pregnancy lead to anti-HLA phenotype?
mother and father have different HLA
during birth mother and fetal cells mix and stimulates the production of antibodies against paternal HLA
transplant rejection
when T cells attack the transplant
graft vs host disease
when the T cells in the donor tissue/organ attack the recipient’s tissue
Coombs and Gel Hypersensitivity reaction: Type 1
IgE mediated (anaphylactic or immediate)
soluble antigen cross links IgE on mast cells to cause degranulation
(Atopy and rhinitis)
Early phase products of Mast cell degranulation
Histamine, heparin and TNFa
Late phase procucts of mast cell degranulation
leukotrienes, PAF, IL-4, IL-13
What kind of response is a mast cell degranulation associated with?
Th2 response geared to fighting off parasites
What receptor binds IgE to Mast cells
FceRI
What other cells can bind IgE?
eosinophils and basophils
Coombs and Gel Hypersensitivity reaction: Type II
Cytotoxic Allergy
complement activation and ADCC IgG and IgM
How does penicillin cause a Type II rxn?
it modifies proteins on RBC creating foreign epitopes
What are the basics of complement activation?
Ab binds to the cell
Ab binds to the Ag
Complement binds to Ab
Complent kills cell
How does antibody dependent cellular cytotoxicity work?
(NK cells and Macs)
anti-CD20 Ab binds to CD20 on surface of B-cell lymphoma cell
Fc receptors on NK recognize bound anti-CD20 ab
cross-linked Fc receptors signal NK cell to kill the B-cell lymphoma cell
B-cell lymphoma dies by apoptosis
Coombs and Gel Hypersensitivity reaction: Type III
Immune Complex Disease (IgG)
Highly immune person exposed to high dose of classical complete immunogen
Tissues effected by Type III hypersensitivity and type of lesion
those w/ small vessels-kidneys, joints, lungs, skin
vasculitis
Coombs and Gel Hypersensitivity reaction: Type IV
Cell-mediated allergy (delayed hypersensitivity or tuberculin type)
CD4+ T cells- Th17 (promote inflammation response by macs)
CD8+ T cells (tissue rejection)
Tissues effected by type IV hypersensitivity
skin very common but can be any
allergen ex: nickel, poison ivy, latex
Which types of hypersensitivity involve inflammation?
Types I, III and IV
What is atopy?
Inherited tendency for IgE mediated allergy to common environmental allergens, commonly inhalants and ingestants
