Download Diseases of Immunity

Diseases of Immunity
（免疫性疾病）
复旦大学上海医学院病理学系
Immune system:
A Two-edged sword
The Common Types of the Diseases
of Immunity
Transplant
Rejection
Hyperactive immunity：
Diseases of Autoimmunity
Immunodeficiency:
Immunodeficiency syndrome
Ⅰ. Transplant Rejection
1.
Host anti-donor allograft
(宿主抗移植物反应)
2.
Donor allograft anti-Host
(移植物抗宿主反应)
The mechanism of Transplant
Rejection
Immuno-reaction
Cell-mediated
Rejection
Antibody-mediated Rejection
The target of transplant rejection
Major Histocompatibility Complex
(MHC抗原)
also referred as to Human
Leukocyte Antigen (HLA抗原)
Characteristics: high variety
Classification of Transplant Rejection
Hyperacute Rejection(超急性排异反应)
Occurs within minutes to a few hours
after transplantation
Acute Rejection (急性排异反应)
Occurs within days, weeks, months
even years.
Chronic Rejection (慢性排异反应)
Occurs in months to years
Hyperacute rejection
Antibody-mediated (type II) hypersensitivity
circulating antibodies
rapidly bind to
endothelium of the grafted organ
complement fixation and vascular thrombosis
Antidonor antibodies are present in the
circulation of the host before transplant:
multiparous women who have anti-HLA
antibodies against paternal antigens shed
from a fetus.
exposure to foreign HLA from prior blood
transfusions.
host who has already rejected an organ
transplant.
Morphology
Gross:
swelling, cyanotic.
Microscope:
arteritis and arteriolitis
vessel thrombosis
ischemic necrosis.
Acute Rejection
The most common type of transplant
rejection
Can be treated with chemotherapy
It is mainly conducted by cell-mediated
rejection in the early stage. However,
antibody-mediated rejection also participate
in the later stage.
Cell-mediated
rejection:
(type Ⅳ hypersensitivity )
HLA stimulates CD4+、CD8+ T lymphocytes.
The morphologic characteristic is numerous
mononuclear cells invasion in the tissue.
antibody-mediated
rejection:
Also called as blood vessel type rejection.
(type II hypersensitivity)
The morphologic characteristic is fibrinoid
necrosis of the blood vessel wall. Immunofluorescence can prove there is immunocomplex precipitate in the necrosis tissue.
Chronic Rejection
It is usually the result from acute
rejection, and not respond to standard
immunosuppression therapy.
Gross:
shrunk kidney.
Microscope:
interstitial fibrosis, loss of
renal parenchyma, vascular changes
(smooth muscle cell proliferation and
extracellular matrix synthesis).
Ⅱ. Systemic Lupus Erythematosus
(系统性红斑狼疮)
Characteristics:
 Predominantly in young women.
 Mainly conducted by humoral
immunity.
 Variant Clinical manifestation.
 Multiple organs damage.
 Recurrence, with 90% and 80% 10year survive.
Etiology and Pathogenesis
The fundamental defect in SLE is a failure
to maintain self-tolerance.
1. It is mediated by antinuclear antibodies:




Anti-double-stranded DNA
Anti-histone
Anti-Sm
Anti-ribonucleoprotein
2. Genetic Factors
concordance:
25% in monozygotic twins
1% to 3% in dizygotic twins
family members have an increased risk
20% first-degree relatives reveal
autoAbs


association between SLE and HLA-DQ
3. Nongenetic Factors
 Most patients treated with
procainamide for more than 6 months
develop ANAs and 20% appear SLE.
 Sex hormones, especially estrogens.
 Exposure to ultraviolet light.
Morphology
LE body: ANAs attack the damaged cell’s
nuclear to produce so-called LE body.
The neutrophil or macrophage the LE
(LE cell)
 The Basic Morphologic Changes:
 Acute stage: Fibrinoid necrosis of blood
vessel wall.
 Chronic stage: perivascular fibrosis,
producing Onion-skin lesions.

Fibrinoid necrosis
Onion-skin lesions
Morphology of Common Involved Organs

Kidney: Lupus glomerolonephritis (60%)
all forms of glomerulonephritis
fibrinoid necrosis
wire loop(白金耳)
most common cause of death
fibrinoid
necrosis
Diffuse
hyperplasia
wire loop
 Skin:
involve in a vast majority of patients
erythematous eruption (butterfly
pattern)
(蝶形红斑)
liquefactive degeneration
edema (dermoepidermal junction)
mononuclear infiltrates
Ig and complement deposit
liquefactive degeneration
Ig and C deposit (狼疮带)

Heart: Nonbacterial verrucous endocarditis, pericarditis
Others:
more than 90% patients have joint
involvement.
CNS involvement is also very common.
CPC: The manifestations are extremely variable
because of multiple organs damaged.
AIDS
（acquired immuno-dificiency syndrom）
AIDS is a retroviral disease caused by the
human immunodeficiency virus (HIV)
and is characterized by profound
immunosuppression:
opportunistic infections
secondary neoplasms
neurologic manifestations.
The Situation of AIDS





Twenty-two million people have died of AIDS
till 2000.
Three million people died of AIDS only in
the year 2000 alone.
Another 3.5 million are infected with HIV.
Ninety-five percent of HIV infections are in
developing countries.
In USA, the people died of AIDS more than
in both Would Wars combined.
Epidemiology of AIDS
Five groups at risk for developing AIDS:





Homosexual or bisexual males
Intravenous drug abusers
Recipients of blood and blood components
Hemophiliacs
Heterosexual contacts of members of
other high-risk group
Three Major Transmission Routes



Sexual Transmission: accounting for more
than 75% cases in the world.
Parenteral Transmission: Including three
groups
(1) intravenous drug abusers
(2) hemophiliacs receiving factor Ⅷ or Ⅸ
(3) random recipients of blood transfusion
Mother-to-Infant Transmission.
Etiology of AIDS
 HIV 1
 HIV 2
USA, Europe, Central Africa
West Africa, Asia
Pathogenesis of AIDS
The CD4 molecule is a high-affinity receptor
for HIV infection. However, binding to CD4 is
not sufficient for infection. The virus should
bind to CXCR4 or CCR5 to entry the cells. And
then produce new virus in the CD4+ positive cell.
After infected cells were killed, the virus will
infect other CD4+ cells. At last, cause the loss of
CD4+ cells. The cytokines production reduced
so that the whole immuno-system break-down.
Coreceptor: CXCR4(LC), CCR5(MΦ)
Morphology of AIDS
 Lymphoid Tissue
follicles proliferating
T lymphocytes(Th) decreased
all kinds of lymphocytes decreased
 Opportunity infection
Pneumocystis(肺孢子虫)
cryptosporidium
(隐孢子虫)
Toxoplasmosis
(弓浆虫)
Candidiasis(白色念珠菌)
Aspergillus(曲菌)
Mucormysocic
(毛霉菌)
银染色
PAS染色
Cryptococcosis(隐球菌)
Histoplasmosis(组织胞浆菌)
银染色
粘卡、墨、PAS染色
Herpes simplex
virus(单纯疱疹)
Cytomegalovirus(巨细胞病毒)
Varicella-zoster virus
(带状疱疹)
 Secondary
malignant tumors:
Kaposi sarcoma
Lymphoma
Kaposi sarcoma
(卡波西肉瘤)