Autoimmune

@ peripheral
Normal function = Self Tolerance
: do not response to self-antigens, so Mechanism for T(CD4), B cell self-tolerance
1.Clonal deletion by apoptosis
living in harmony. 2.Clonal anergy by unresponsive to antigens challenge
Why become autoimmune d. ? 3.Clonal suppression by other immunity cells& cytokines
There is genetic factors, but environmental factors 4.Immune-privlleged sites (testis, eye, brain)
trigger to become sick
-Hormones (estrogen, prolactin), -infection agents,
- drugs, - UV – Psychological stress
- Dietary substances

@ peripheral
7 theories of Mechanisms
1.Release sequestered antigens = endogenous self antigens:only tissue injury
2.Abnormal Tcell function/ forbidden clone Theory: loss of suppressor T cells-> activation of non-
tolerant clones
3.Polyclonal B cell activation: parasites, viral, drugs act as B cell mutagents = Bystander Effect.
Too much activated B cells
4.Genetic factors (class 2 MHC, only APC has)
5.Cross reaction with infectious agent/ Molecular mimicry: Strucualy similar self-protain and
microbial peptide
6.Antigen modification: mutation of immunocompetent cells forming anoantibodies
7.Hormonal factors: X-Y linked genes, estrogen, prolactin
 1. Systemic Lupus Erythematosus
B-cell hyperactivity

Autoimmune
Deseases
3. Systemic sclerosis (Scleroderma)
2. Sjogren syndrome Anti DNA topoisomerase 1
T-cell (lymphatic )infiltration antinuclear-autoantibodies
Antibodies to ribonuclear proteins, Collagen, fibrosis
antinuclear-autoantibodies
 No. 1 Systemic Lupus Erythematosus
Connective tissue
disorder
-Multisystem, inflammatory disease
-Any organ -> Skin, Joints, Kidneys, serous
membranes
-Chronic, remitting and relapsing
Who gets this…?
-Females (9:1)
-Reproductive year (10-50)
Etiology + Pathogenesis
-a lack of self-tolerance -> a failure of the regulatory
circulating immune complexes = Antinuclear
antibodies(ANAs)
Genetic factors (Monozygotic twins< dizygotic twins)
Environment factors/ Drugs , Ultraviolet light, sex
hormones
Immunologic factors/ Production of autoantibodies
against nuclear antigens. Tissue damage by type 2
hypersensitivity (immune complexes) or type3
hypersensitivity,(antibody-mediated: autoantibodies+
RBC/WBS/platelets
Viruses maybe … Epstein-Barr virus
Morphology/ Pathology
Skin: Butterly malar rash, Ulceration, Perivascular lymphoid infiltrate,
lopapuurticaria, bullae, maculopaplar lesions, liquefactive
degeneration of basal cells
Joints: 90% have polyarthralgias. Difference from RA= nonerosive
synovitis with little deformity. (RA= little joints with erosive synovitis)
Kidneys: 75% have renal involvement(e.g. Glomurulonephritis), 40-
50% have the diffuse proliferative glomerulonephritis
(immunosuppressive therapy is worked)
CNS: acute vasculitis with occlusion of small vessels by intimal
proliferation -> focal neurologic symptoms
Spleen: forcal hyperplasia + capsular thickening -> moderately
enlarged spleen
Lungs: 50% has pleuritis, pleural effusions
Clinical Features (4 out of 11 = SLE)
1.Malar rash: Fixed erythema, flat or raised, over the malar
eminences
2.Discoid rash: Erythematous raised patches with adherent
keratotic scaling and follicular plugging
3.Photosensitivity: UV light -> Skin rash
4.Oral ulcers: Oral or nasopharyngeal ulceration
5.Arthritis: Nonerosive arthritis involving ≥2 peripheral
joints, characterized by tenderness, swelling, or effusion
6.Serositis: Pleuritis: or Pericarditis: (Documented by ECG
or rub) both evidence of pericardial effusion
7.Renal disorder (A)proteinuria >0.5 g/d or >3+ or (B)
Cellular casts
Systemic Lupus Erythematosus
 No. 2 Sjogren Syndrome
Connective tissue
Inflammatory exocrine Morphology
disorder
glands dysfunction
The periductal and perivascular lymphocytic infiltraion by
Inflammatory glands destruction: Lacrimal cellular debris, fibrosis, hyalinization and later replaced by fat
Dry- corneal epithlium -> inflamed, eroded, ulcerated
and salivary (parotid) glands - oral mucosa atropies with inflamed fissuring, ulceration
keratoconjunctivitis sicca(dry eyes), - nose crusting -> ulceration, perforation of the nasal septum
xerostomia(dry tongue) with Other organs dysfunction 25%
Kidney, lungs, skin, CNS, muscles
Who gets this…? Extremely rare: Glomerular lesions (common in SLE)
-Females 35-45 yrs
-2ndary form with RA, SLE, Clinical Features
Polymyositis, thyroiditis Chronic, progressive
Karatoconjunctivitis -> blurring of vision,
Etiology + Pathogenesis burning/itching/thick secretions
Xerostomia with dental caries(->difficulty in swallowing
Sicca syndrome: Dry eye and mouth due to lymphocytic
solid foods, !taste) and stomatitis(inflammation of lining in
infiltration and fibrosis of 2 glands -> heavy infiltration of T
the mouth)
helper cells (some B, plasma cells)-> glandular destruction
Mikulicz syndrome: lacrima and Paratid (salivary) gland
(cellular debris, fibrosis, hyalinization, later replacement
enlargement. And narrowing of palpebral fissures
with fat) ->! Tears and saliva
Dry- nose, throat, pharynx, vagina
Antinuclear autoantibodies 75%,Rheumatoid factor 75%
S. Disorder- kidney, lung, skin, CNS, muscle
Antibobodies to ribonuclear protein 90%
^ risk of Lymphoma (x 40): any neoplastic disorder of
POINT! lymphoid tissue. Due to polyclonal lymphocytic
Sjogren s.-antibodies to ribonuclear protein , proliferation
antinuclear autoantibodies, 60% have other autoimmune disease.
Systemic Sclerosis- anti DNA topoisomerase 1 Confirmed by Minor salivary gland (by biopsy)
(anti-Scl70), antimuclear autoantibodies,
 Systemic Sclerosis (Scleroderma)
Multisystem progressive d. Morphology/ Pathology Clinical Features
Excessive systemic/collagen fibrosis deposition in the 100%- antinuclear antibodies, anti DNA topisomerase 1
skin -> internal organs (anti-SCL 70)
4types of scleroderma Skin: edema, induration(doughy)-> diffuse sclerotic
Localized: most common, 3F(Finger, forearm, face)-> atrophy. Calcinosis cutis(Subcutaneous calcification).
viscera Ulceration, gangrene (exposed finger bone)
Blood vessels: thickening and fibrosis of vessel wall with
Diffuse: skin+ internal organ (wide spread)
thrombosed lumen, nodular morphone
Overlap/ Mixed: combination of SSC,RA,SLE, GI tract: Esophageal dysfunction
polymyositis Kidneys: Focal haemorrhage, cortical infarcts
CREST variant Lungs, heart

Who gets this…? CREST

Female x 4, 264 in 100,000 /45-65yrs Calcinosis
Raynaud’s phenomenon
Etiology + Pathogenesis Esophageal dysfunction
Both hypotheses are involved Mast cells, Sclerodactyly
macrophages release- cytokines IL-1, Telangiectasias
fibroblast growth factor, PDGF ->
^collagen -> fibrosis
Immunologic hypothesis: Tcell->
fibroblast-> ^collagen
Vascular hypothesis: Endothelial cell
injury -> ischemia -> ^collagen
 1. Amyloidosis

Other Immune
Diseases
Immunodeficiency disease
2. Acquired immunodeficiency syndrome
(AIDS)
 Amyloidosis
Systemic disease Morphology
-deposition of abnormal proteinaceous
substance at extracellulary
2types of amyloidosis
1. Primary(immune-derived): excessive imunogloblin light
chain- myeloma
2. 2ndary cmyloidosis excessive prolonged inflammatory
activity, non-Ig, and acute phase reactant protein Clinical Features
Neuropathies
Carpal tunnel syndrome (median nerve)
Alzheimer’s disease- amyloid plaques

Who gets this…?

Etiology + Pathogenesis
 Acquired immunodeficiency syndrome (AIDS)
Profound immunosuppression of T-cell Morphology
mediated immunity leads… Opportunistic
infections, 2ndary neoplasms, Neurologic
manifestations
Who gets this…?
-homosexual/ bisexual men (57%)
-Intravenous drug abusers (25%)
-haemophiliacs, recipients of blood, Acute, self-
heterosexual contacts
limited illness
-breath milk, birth canal
Common transporters: Blood, semen, CSF,
Breast milk (Not: saliva, tears, sweat,
urine, feces)
Sexual transmission (75%)- the virus is Clinical Features
carried in semen of lymphocytes or cell- -Fever
free state -Weight loss
-Diarrhoea
-Generalized lymphadenopathy
Etiology + Pathogenesis -Multiple opportunistic infections
Common targets of HIV -Neurologic d.
1. Immune system, 2. CNS -2ndary neoplasms

HIV-1 targets CD4+ lymphocyte

: binding -> internalization -> DNA synthesis ->
viral integration -> viral replication ->
viral dissemination