1. Autoimmune diseases tend to be chronic conditions characterized by immune reactions against self antigens. Systemic lupus erythematosus is a chronic autoimmune disease involving almost any organ, characterized by a variety of autoantibodies and immune complex deposition causing tissue injury. 2. SLE commonly presents in women in their 20s and 30s, showing a variety of clinical manifestations including arthritis, renal disease, rashes and hematological abnormalities. The disease has a variable presentation and is defined by a set of clinical criteria established by the American College of Rheumatology. 3. The etiology of SLE involves genetic susceptibility factors like certain HLA alleles, environmental triggers like infections, and failures of immunological

2. • Introduction
• Examples
• Immunologic tolerance (self tolerance)
• Introduction
• Central tolerance
• Peripheral tolerance
• Mechanisms of autoimmunity
• Defective tolerance
• Abnormal display of self antigens
• Inflammation/innate immune response
• Pathogenesis
• Role of Susceptibility Genes
• Role of Infections
• General principles
• Systemic lupus erythematosus
• Introduction
• Spectrum of autoimmune antibodies
• Etiology and pathogenesis
• Morphology
• Clinical features
• Rheumatoid arthritis
• Sjogren’s syndrome
• Systemic sclerosis
• Inflammatory myopathies
• Mixed connective tissue diseases
• Polyarteritis nodosa
• IgG4 related diseases

3. Introduction • The presence of an immune reaction specific
for
some self antigen or self tissue
• Evidence that such a reaction is not
secondary to tissue damage but is of
primary pathogenic significance
• Absence of another well-defined cause of
the
disease

5. Introduction

6. • The antigen receptors of
lymphocytes are generated by
somatic recombination of genes
in a random fashion
• Hence lymphocytes with receptors
capable of recognizing self antigens
are generated constantly, and
these cells have to be eliminated to
prevent them from causing harm
• This phenomenon of eliminating
self reactive lymphocytes is
called self tolerance

7. Immunologic tolerance
(Self tolerance)
Mechanisms
Central
Tolerance

8. • In the central (or generative) lymphoid organs
(the thymus for T cells and the bone marrow
for B cells), immature self-reactive T and B
lymphocyte clones that recognize self antigens
are killed
• However, not all self antigens may be present in
the thymus, and hence T cells bearing
receptors for such autoantigens escape into the
periphery
• There is similar “slippage” in the B-cellsystem
• Self-reactive lymphocytes that escape
negative selection can inflict tissue injury
unless they are deleted or muzzled in the
peripheral tissues

9. • Developing B cells strongly
recognize self antigens in
the bone marrow
• Many of the cells reactivate
the machinery of antigen
receptor gene
rearrangement and begin
to express new antigen
receptors, not specific for
self antigens
Negative selection (In T cells)
• In developing T cells, random
somatic gene rearrangements
generate diverse TCRs
• TCR generation produces
many lymphocytes that
express high- affinity
receptors for self antigens
• When immature lymphocytes
encounter the antigens in the
thymus, many of the cells die
by apoptosis
Receptor editing (In B cells)
• If receptor editing does not
occur, the self reactive cells
undergo apoptosis

10. Anergy
Suppression
by regulatory
T cells
Deletion by
apoptosis
(of mature T
cells)

11. • Lymphocytes that recognize self antigens are
rendered functionally unresponsive by this
phenomenon
• Activation of antigen-specific T cells requires two
signals:
• Recognition of peptide antigen in association
with self
MHC molecules on the surface of APCs
• Aset of costimulatory signals (“second
signals”) provided by molecules such as
CD28
• If the antigen is presented to T cells without
adequate levels of costimulators, the cells
become anergic
• Because costimulatory molecules are not
expressed on dendritic cells in normal tissues,
the encounter between autoreactive T cells and
their specific self antigens displayed by these
dendritic cells may lead to anergy

12. • T cells that recognize self
antigens receive an
inhibitory signal from
receptors that are
structurally homologous to
CD28 but serve the
opposite functions
• Two of these
inhibitory receptors
are
• CTLA-4, which (like
CD28) binds to B7
molecules &
• PD-1 which binds to
PD L1

13. • CTLA-4 has higher affinity for B7 molecules than does
CD28
• CTLA-4 may be preferentially engaged when the levels
of B7 are low, as when APCs are presenting self
antigens
• Conversely, microbial products elicit innate immune
reactions, during which B7 levels on APCs increase
and the low-affinity receptor CD28 is engaged more

14. Tumor
therapy and
Anergy
This realization has led to the
development of antibodies that
block CTLA-4 and PD-1 for
tumor immunotherapy
By removing the brakes on the
immune response, these
antibodies promote responses
against tumors

15. • Regulatory T cells functions to prevent immune reactions
against self antigens
• Develop mainly in the thymus, but they may also be
induced in peripheral lymphoid tissues
• Regulatory T cells are CD4+ cells that express high levels of
CD25, the
α chain of the IL-2 receptor, and a transcription factor of the
forkhead family, called FOXP3
• Clinical significance
• Foxp3 –
• Prevent immune reactions against fetal antigens that are inherited
from the father and therefore foreign to the mother and hence
acceptance of the fetus
• Possible defects in these cells are the basis for recurrent
spontaneous abortions??
• Mutations in FOXP3 result systemic autoimmune disease called
IPEX
(an acronym for immune dysregulation, polyendocrinopathy,
enteropathy, X-linked)
• CD25
• polymorphisms in the CD25 gene are associated with multiple
sclerosis

16. Deletion by apoptosis (of
mature Tcells)
• Two mechanisms of
deletion of mature T
cells which encounter
self antigens have
been proposed
• Bim pathway
• Fas-Fas ligand system
• Mutations in the
FAS (CD95) gene
leads to
autoimmune
lymphoproliferativ
e syndrome
(ALPS)
Encounter with
self antigens

17. Immune
privileged sites
• Some antigens are hidden (sequestered)
from the immune system, because the
tissues in which these antigens are
located do not communicate with the
blood and lymph
• As a result, self antigens in these tissues
fail to elicit immune responses and are
essentially ignored by the immune system
• Believed to be the case for the testis,
eye, and brain
• If the antigens of these tissues are
released, for example, as a consequence
of trauma or infection, the result may be
an immune response that leads to
prolonged tissue inflammation and injury.
This is the postulated mechanism for post-
traumatic orchitis and uveitis

18. Mechanisms of autoimmunity
Susceptibility
genes
Infections

19. • Susceptibility genes -
contribute to the breakdown of
self-tolerance
• Environmental triggers -
such as infections and tissue
damage -
promote the activation of self-
reactive
lymphocytes

20. Association of
HLA Alleles with
Disease
Association of
Non-MHC
Genes with
Autoimmune
Diseases

24. 1. Autoimmune diseases tend to be
chronic
• Epitope spreading - in which an
immune response against one self
antigen causes tissue damage,
releasing other antigens, and
resulting in the activation of
lymphocytes by these newly
encountered epitopes
2. Manifestations of an autoimmune
disease are determined by the nature
of the underlying immune response
• Whether caused by antibodies or T
cells

25. Definition Criteria Epidemiology
Spectrum of
autoantibodie
s
Etiology
Pathogenesis
Mechanism
of tissue
injury
Morphology
Clinica
l
feature
s
Variants

26. SLE is a chronic remitting and relapsing autoimmune
disease
Involving almost any organ of the body
Characterized by a vast array of autoantibodies,
particularly antinuclear antibodies (ANAs)
In which injury is caused mainly by deposition of immune
complexes and binding of antibodies to various cells and
tissues

27. SLE
• The clinical presentation
of SLE is so variable that
the American College of
Rheumatology has
established a complex set
of criteria for this disorder

28. • Arthritis - Non erosive, affecting two or more joints,
characterised by tenderness/swelling/effusion
• Renal disease (Persistent proteinuria >0.5 g/dL or >3 if quantitation not performed or
Cellular casts—may be red blood cell, hemoglobin, granular, tubular, or mixed)
• ANA (positive antinuclear antibody in the absence of drugs known to be
associated with drug-induced lupus syndrome)
• Serositis (pleurisy or pericarditis)
• Haematological disorders (Hemolytic anemia—with reticulocytosis, or Leukopenia—
<4.0 × 109 cells/L (4000 cells/mm3) total on two or more occasions, or
Lymphopenia—<1.5 × 109 cells/L (1500 cells/mm3) on two or more occasions, or
Thrombocytopenia—<100 × 109 cells/L (100 × 103 cells/mm3) in the absence of
offending drugs
• Photosensitivity (Rash as a result of unusual reaction to sunlight)
• Oral ulcers (Oral or nasopharyngeal ulceration)
• Immunological disorder (positive LE cell, anti-DNA, anti-Sm, false positive
serological test for syphilis)
• Neurological disorders (seizures or psychosis, in the absence of other causes)
• Malar rash (Fixed erythema, flat or raised, over the malar eminences, tending to
spare the nasolabial folds)
• Discoid rash (Erythematous raised patches with adherent keratotic scaling and

29. • Prevalence as high as 1 in 2500
• Female-to-male ratio of 9 : 1
• Usually presents in the 20s and
30s

31. Spectrum of
autoantibodies
• Directed against
• Antinuclear
antibodies
• Other antibodies

34. Etiology Immunologic
Environmental

35. Genetic
HLA
• Specific alleles of the HLA-DQ locus
have been linked to the production of
anti– double stranded DNA, anti-Sm,
and antiphospholipid antibodies
• Inherited deficiencies of early
complement components, such as C2,
C4, or C1q
• Lack of complement may impair
removal of circulating immune
complexes by the mononuclear
phagocyte system, thus favouring
tissue deposition
Complement
system

36. • Failure of self-tolerance in B and T cells
• TLR engagement by nuclear DNA and RNA contained in immune
complexes may activate B lymphocytes, leading to increased production of
antinuclear antibodies
• Type I interferons play a role in lymphocyte activation in SLE
• Type I interferons are antiviral cytokines that are normally produced
during innate immune responses to viruses. It may be that nucleic
acids engage TLRs on dendritic cells and stimulate the production of
interferons

37. Environmental
• UV irradiation may induce
apoptosis in cells and may alter the
DNA in such a way that it becomes
immunogenic
• Sex hormones - Gender bias of
SLE is partly attributable to
actions of and partly related to
sex hormones and genes on the
X chromosome
• Drugs such as hydralazine,
procainamide, and D-penicillamine
can induce an SLE-like reaction

39. • DNA-antiDNA complexes (Type III hypersensitivity) Kidney
• DNA-anti-DNA complexes can be detected in the glomeruli
and
small blood vessels
• Antinuclear antibodies - Neutrophils and
macrophages (LE cell phenomenon)
• LE cell is any phagocytic leukocyte (blood neutrophil or
macrophage) that has engulfed the denatured nucleus
of an injured cell
• Nuclei of damaged cells react with ANAs, lose their
chromatin pattern, and become homogeneous, to
produce so-called LE bodies or haematoxylin bodies
• Readily seen when blood is agitated in vitro; was used as a
test in past for SLE
• Antiphospholipid antibodies - Blood vessels (Thrombosis)
• Patients with antiphospholipid antibodies may develop
venous and arterial thromboses, which may be associated
with recurrent spontaneous miscarriages
• Antibodies against clotting factors, platelets and endothelial
cells have all been proposed
• Neurons (antibodies that react with neurons or receptors for
various neurotransmitters)
• Neuropsychiatric manifestations

40. 1. Blood vessels
2. Kidney
1. Glomeruli
2. Tubules and
interstitium
3. Skin
4. Joints
5. Central nervous
system
6. CVS

41. • Acute necrotizing vasculitis
involving capillaries, small arteries
and arterioles
• Characterized by fibrinoid deposits in
the vessel walls

42. 2. Kidney
(Lupus
Nephritis)
(Immune
complex
deposition)
Minimal mesangial lupus nephritis
(class I)
Focal lupus nephritis
(class III)
Diffuse lupus nephritis
(class IV)
Membranous lupus nephritis
(class V)
Advanced sclerosing lupus
nephritis (class VI)

44. • Immunoflourescence and electron
microscopy - immune complex
deposition in the mesangium
• Lightmicroscopy - No structural
changes
A. Glomerulus without mesangial or basement membrane
changes by light microscopy (Jones silver stain).
B. B Mesangial lupus nephritis. Mesangial deposits are
present by immunofluorescence (anti-IgG)

45. • Mesangial cell proliferation, accompanied
by accumulation of mesangial matrix, and
granular mesangial deposits of
immunoglobulin and complement without
involvement of glomerular capillaries
A glomerulus shows mild mesangial hypercellularity

46. • Involvement of fewer than 50% of all
glomeruli
• The lesions may be segmental (affecting
only a portion of the glomerulus) or global
(involving the entire glomerulus)
• Affected glomeruli may exhibit swelling and
proliferation of endothelial and mesangial
cells
associated with leukocyte
accumulation,
capillary necrosis, and hyaline
thrombi
• Clinical presentation ranges from mild
hematuria and proteinuria to acute
renal insufficiency
• Red cell casts in the urine are
common
Focal proliferative glomerulonephritis, with two focal
necrotizing lesions at the 11 o’clock and 2 o’clock
positions (H&E stain

47. Diffuselupus
nephritis (class
IV)
• Most common and severe form
• Half or more of the glomeruli are affected
• Lesions may be segmental (IV-S) or
global (IV-G)
• Involved glomeruli show proliferation of
endothelial, mesangial and epithelial
cells, with the latter producing cellular
crescents that fill
Bowman’sspace
• Subendothelial immune complex deposits
may create a circumferential thickening of
the capillary wall, forming “wire loop”
structures on light microscopy
Diffuse proliferative glomerulonephritis. Note the marked increase in
cellularity throughout the glomerulus
(H&E stain).
Lupus nephritis showing a glomerulus with several “wire loop”
lesions representing extensive subendothelial deposits of
immune complexes (periodic acid-Schiff stain).

48. • Diffuse thickening of the capillary walls due
to deposition of subepithelial immune
complexes, similar to idiopathic
membranous nephropathy
• The immune complexes are usually
accompanied by increased
production of basement membrane-
like material
• This lesion is usually accompanied by
severe proteinuria or nephrotic
syndrome, and may occur concurrently
with focal or diffuse lupus nephritis

49. • Sclerosis of more than 90% of the
glomeruli
• Represents end-stage renal disease

50. Discrete immune
complexes similar to
those in glomeruli are
present in the tubular or
peritubular capillary
basement membranes
There are well organized
B- cell follicles in the
interstitium, with plasma
cells that may be sources
of autoantibodies

51. • Characteristic erythema affects the face along
the bridge of the nose and cheeks (the “butterfly”
rash)
• Exposure to sunlight incites or
accentuates the erythema
• Histologically the involved areas show vacuolar
degeneration of the basal layer of the epidermis. In
the dermis, there is variable edema and
perivascular inflammation. Vasculitis with fibrinoid
necrosis may be prominent.
• Immunofluorescence microscopy shows
deposition of immunoglobulin and complement
along the dermoepidermal junction

52. 4. Joints
• Non erosive
synovitis
• The changes are
usually reversible
since they are due
to tendon
involvement rather
than synovial
damage and so
the patient does
not usually require
or benefit from
joint surgery
X-ray of hands of lupus patient
showing non-erosive arthropathy
including Z thumbs

53. • Neuropsychiatric symptoms of SLE have been attributed to noninflammatory occlusion
of small vessels by intimal proliferation is sometimes

54. • Pericardium
• The mesothelial surfaces are sometimes covered with fibrinous exudate
• Later they become thickened, opaque, and coated with a shaggy fibrous tissue
• Endocardium and valves
• Primarily the mitral and aortic valves are affected
• Manifest as stenosis or regurgitation
• Libman-Sacks endocarditis was more common prior to the widespread use of steroids.
This nonbacterial verrucous endocarditis takes the form of single or multiple 1- to3-mm
warty deposits on any heart valve, distinctively on either surface of the leaflets
• Coronary artery disease
• increasing number of patients have clinical evidence of coronary artery disease (angina,
myocardial infarction) owing to coronary atherosclerosis. This complication is particularly
notable in young patients with long-standing disease, and especially in those who have
been treated with corticosteroids.

56. • Diagnosis is based on criteria as discussed
earlier
• Typically SLE presents as
• A young woman with some, but not
necessarily all, of the following features:
• Butterfly rash over the face
• Fever
• Pain but no deformity in one or more
peripheral joints (feet, ankles, knees,
hips, fingers, wrists, elbows,
shoulders)
• Pleuritic chest pain
• Photosensitivity.

57. • Skin plaques on face and scalp
• Systemic manifestations are rare
• ANA is positive but antibodies to double-stranded DNA are rarely
present
• Immunofluorescence studies of skin biopsy specimens show deposition
of immunoglobulin and C3 at the dermoepidermal junction similar to
that in SLE

58. • Also presents with predominant skin involvement and can be
distinguished from chronic discoid lupus erythematosus by
• Skin rash in this disease tends to be widespread, superficial, and
nonscarring
• Mild systemic symptoms consistent with SLE
• Strong association with antibodies to the SS-A antigen and with the
HLA-DR3
genotype

59. • Lupus erythematosus-like syndrome may develop in patients receiving a
variety of drugs, including hydralazine, procainamide, isoniazid, D-
penicillamine and anti TNF therapy for RA
• Associated with the development of ANAs
• Multiple organ systems are involved but renal and central nervous
system involvement is distinctly uncommon
• High frequency of antibodies specific for histones
• The disease remits after withdrawal of the offending drug

60. Majority of manifestations of
this autoimmune disease are
in joints

62. Definition
• Chronic disease characterized by
• dry eyes
(keratoconjunctiviti
s sicca) and
• dry mouth (xerostomia)
• resulting from
immunologically mediated
destruction of the lacrimal
and salivary glands
• Types
• Primary form - Sicca syndrome
• Secondary form –
associated with other
disorders like
• Rheumatoid arthritis
• SLE
• Polymyositis
• Scleroderma,
• Vasculitis
• Mixed connective
tissue disease
• Thyroiditis

63. Viral infection of the salivary
glands
Local cell death and release of tissue self antigens
(cytoskeletal protein called α-fodrin is a candidate
autoantigen)
Aberrant T-cell and B-cell
activation
Antibodies directed against two ribonucleoprotein antigens,
SS-A (Ro) and SS-B (La) can be detected in as many as
90% of patients
Tissue damage, and, eventually,
fibrosis

64. Women
between the
ages of 50
and 60
Keratoconjunctivitis - blurring of vision, burning, and itching; thick
secretions accumulate in the conjunctival sac
Xerostomia - difficulty in swallowing solid foods, a decrease in the ability to
taste,
cracks and fissures in the mouth, and dryness of the buccal mucosa
Glandula
r
disease
Diffuse pulmonary fibrosis Peripheral
neuropathy Tubulointerstitial nephritis
Extraglandul
ar
disease

65. Labdiagnosis
andprognosis
• Biopsy of the lip (to examine minor salivary
glands) is essential for the diagnosis of
Sjögren syndrome
• In early stages of the disease, this
immune infiltrate consists of a mixture of
polyclonal T and B cells
• However, if the reaction continues
unabated there is a strong tendency
over time for individual clones within the
population of B cells to gain a growth
advantage, presumably because of the
acquisition of somatic mutations.
• Emergence of a dominant B-cell clone is
usually indicative of the development of a
marginal zone lymphoma (also a feature
of other autoimmune disorders like
Hashimoto’s)

66. Morphology
• Lacrimal and salivary (both major and minor) glands
• Periductal and perivascular lymphocytic infiltration
• Lymphoid follicles with germinal centers
• Atrophy of the acini, fibrosis, and hyalinization
• Replacement of parenchyma with fat

67. • Definition
• Pathogenesis
• Clinical
features
• Lab Diagnosis
• Morphology

68. Definition and
Types
• Chronic inflammation thought to be the result of
autoimmunity
• Widespread damage to small blood vessels
• Progressive interstitial and perivascular fibrosis in the
skin and organs like gastrointestinal tract, kidneys, heart,
muscles, and lungs
Type
s
• Diffuse scleroderma
• widespread skin involvement at onset
• rapid progression
• Early visceral involvement (renal failure, cardiac
failure, pulmonary insufficiency, or intestinal
malabsorption)
• Limited scleroderma
• skin involvement is often confined to fingers, forearms,
and
face
• Slow progression
• Visceral involvement occurs late

69. • Some patents with the limited disease
also develop a combination of
• Calcinosis
• Raynaud phenomenon
• Esophageal dysmotility
• Sclerodactyly
• Telangiectasia

71. Clinical Features
• Female; 50-60 years
• Striking cutaneous changes, notably skin thickening
• Raynaud phenomenon - episodic vasoconstriction
of the arteries and arterioles of the extremities
• Dysphagia attributable to esophageal fibrosis and
its resultant hypomotility
• Abdominal pain, intestinal obstruction, or
malabsorption syndrome with weight loss and
anemia reflect involvement of the small intestine
• Respiratory difficulties caused by the pulmonary
fibrosis may result in right-sided cardiac
dysfunction, and myocardial fibrosis may cause
either arrhythmias or cardiac failure
• Proteinuria or nephrotic syndrome
• Malignant hypertension

72. LabDiagnosis
• Two ANAs strongly associated
with systemic sclerosis
• DNA topoisomerase I (anti-Scl
70)
• More likely to have
pulmonary fibrosis and
peripheral vascular disease
• Anticentromere antibody
• Found in 20% to 30% of
patients, who tend to have
the CREST syndrome
• Have relatively limited
involvement of skin, often
confined to fingers,
forearms, and face

73. Morphology
• Begins in the fingers and
distal regions of the upper
extremities and extends
proximally to involve the
upper arms, shoulders,
neck, and face
• Edema and perivascular
infiltrates containing CD4+
T cells, together with
swelling and degeneration
of collagen fibres, which
become eosinophilic
• Extensive deposition of
dense collagen in the
dermis with virtual
absence of appendages
(e.g., hair follicles) and foci
of inflammation

74. 2)In appropriate immune response
1. Transplant rejection, organs transplantation used to treat irreversible diseases of kidney, liver, heart, lung and
bone marrow. The action of immune system destroy the transplanted tissue by HI and CMI directed against the
MHC Ag (HLA) of donor graft endothelial cells are rich with MHC (HLA) Ag and blood group Ag.
Types of transplant rejection:
1-Hyper acute rejection: Occur within minutes to few hours. There is wide spread thrombosis, focal necrosis, it formed due to
reaction of preformed Abs against graft Ags. TheseAbs developed either by:
1. Previous rejection of previous graft.
2. Women who develop anti HLA Abs against paternal Ags.
3. Prior blood transfusion.
2-Acute rejection: Occur within days or weeks, when stop immunosuppressive drugs also occurred by HI and CMI against
donor graft Ag. Particularity MHC class II Ag. So renal failure with infiltration of CD4+,CD8+vasculitis endothelial necrosis, neutrophils
infiltration, damage of B.V.
3-Chronic rejection: Occur slowly during months and years of graft transplant. It is slowly breakdown of self-tolerance to graft
due to inadequate immune suppression. So increase creatinine level (renal dysfunction). Antimal fibrosis lead to ischemic damage
hyalinization, loss of glomeruli, tubular necrosis, atrophy and interstitialfibrosis.
Transplantation of other organ liver, heart, lungs, pancreas unlike of kidney it can preformed with:
1. ABO blood grouping.
2. Absence of preformed Abs.
3. Body habitus example child not receive heart of adult.

75. 1)In adequate immune response:
Result from immunodeficiency states there are 2classes of immunodeficiency
syndrome:
1.Primary immunodeficiency at birth due to genetic disorders.
2.Secondary immunodeficiency during the life (acquired).

76. 1-Transient hypogammaglobinemia this occur in infants during 3-6month of birth, in which
breakdown of maternal IgG it is considered physiological hypogammaglobinemia, and occur
when infants unable to synthesize IgG level so child become susceptible to recurrent pyogenic
infection.
2-X-linked a gammaglobulinemia (Bruton disease) it is a genetic disorder in which failure of B
cells maturation result in absence of antibodies, the disease mostly occur in males so suffering
from recurrent bacterial infection.
3 Isolated IgA deficiency:
There is reduction in IgA level but other antibodies are normal level.
4 Hyper IgM syndrome:
In normal condition IgM and IgD produced first against protein antigen (Ag), followed by IgG,
IgA and IgE antibodies (Ab). Patient with this syndrome have normal level of IgM or abnormal
level of IgM Abs but fail to produce other Abs suchas IgG, IgA, IgE, although IgM important for
the fixation of complement for activation and opsonizationbacteria.

77. 5 IgG subclassesdeficiency :
Selective of IgG (IgG1, 2,3,4)are easily missed because IgG1 contribute 70-of total IgG-IgG2
predispose the individuals to respiratory infections and meningitis. IgG2 deficiency occur
together with IgG4 and IgA. Similarly IgG1 and IgG3 are commonly seen deficiency
together.
6 Thymic hypoplasia (diGoeorge syndrome)
Affective Tcells due to hypoplasia of thymus glands occur together with hypoplasia of
parathyroid gland so hypocalcemia, tetany, cardiac malformation, facial abnormalities.
7-Severe combined immunodeficiency:
This inherited either autosomal or x-linked occur due to failure of development of Band T
cells, therefore thymus is small and body lymphoid tissue are also small so children are
susceptible to candida thrush, pneumonia, diarrhea.
8-Defects in neutrophils and complementsystem.
Continued

78. More common than primary, it occur during life, caused by:
1 Protein loss (nephrotic syndrome).
2 Impaired protein synthesis, malnutrition.
3Lymph proliferative disease: lymphoma, leukemia.
4- Multiple myeloma.
5 Immunosuppressive drugs.
6 Spleenectomy, tonsillectomy.
7Infections suchas cytomegalovirus. Measles, rubella, infectious
mononucleosis, viral hepatitis.

79. It is retrovirus disease caused by human immunodeficiency virus (HIV)
characterized by:
1- Immunosuppression leading to opportunistic infections.
2- Secondary tumors.
3- Neurological manifestations
The diseases is worldwide, about 20years ago discovered and more than 22
million people died.
Three major routes for the transmission of virus:
1 Sexual contact.
2Parenteral inoculation drugs, hemophilia, blood transfusion.
3- Infected mother to newborn.
Cause: retrovirus belong to lenti virus family (HIV 2types) HIV-1 in USA, Europe,
central Africa where HIV-2 in West Africa.

80. Two major targets for HIV immune system and central nervous system:
*In immune system:
Aids lead to impair cell mediated immunity. It distruct CD4+lymphocytes and decrease
helper suppressor Tcells ratio.
Virus has selective tropism for CD4+and macrophages and dendritic cells. Whereas viral
envelope bind to other cells to enhance cell entry. The virus core enter the cytoplasm have
genes undergoes for reverse transcriptase in which complementary DNA making and enter
nucleus of cells as a latent provirus DNA transcribed to from complete virus, bud from the
cell membrane and death of the cells.
HIV colonizes the spleen, lymph node, tonsils. The Tcells, macrophages and dendritic cells
represent reservoir of infection.
*In central nervous system:
Virus carried into brain by infected monocytes in brain microglia (equivalent macrophages)
is the target for HIV. In brain the neurological deficit is caused by indirect viral products,
cytokines produced by macrophage/ microglia.

81. 1 Primary infection:
At the beginning when viral replication in body organs, an immune
response developed with increase virus infected CD8+to replace
dying Tcells, followed by decrease CD4+/ CD8+ratio, resulted in
influenza, skin rash, lymphadenopathy.
2 Asymptomatic phase (incubation period):
In this phase the immune system is intact but viral replication
continued, this stage may still for years, patients have AbS and
transmit the disease.

82. Copyrights
©
2017
l
Aliraqia
University
l
Dentistry
l
Pathology
l
Prof.Dr.
Khalil
Hassan
Zenad
Aljeboori.
3 Aids related complex:
In this CD4+infected cells increased, their function impaired, their
number in blood fall to 400cell/ ULSo malaise, fever, night sweating
weight loss, diarrhea and lymphadenopathy. Impaired CMI and
CD4+so fungal infection, salmonella and hemophilus are sever.
4 Aids (crisis phase):
In which fully developed immune deficiency so fatigue, fever,
weight loss, lymphadenopathy and diarrhea, CD4+cells is below
200/UL.So most of opportunistic infection, secondary tumors and
neurological manifestations occurred and death.

83. Responsible for 80%of aids patients death it include:
1- Pneumocystis carinii pneumonia.
2- Recurrent candidiasis.
3 Cytomegalovirus infection mainly retinitis, enteritis.
4Herpes simplex infection in mouth, perianal infection. 5-
Mycobacterium infection.
6 Toxoplasmosis.
7 Cryptococcus meningitis.
8 Cryptosporidium- enteritis.
Patients with aids have high incidence of Neoplasms (Tumors): due to defects in Tcells so;
1 Kaposi sarcoma occur in association with human herpes virus (KS) infect skin, lung,
lymph node, GIT.
2 Non-Hodgkin's lymphoma occur in association with (EBV)Epstein bar virus. It affect
brain, lymphoid tissue.
3 Cervix-uterus carcinoma tissue it occur with papilloma virus.

84. THANK YOU