Transcript Diseases of Immunity

Diseases of Immunity
Dr . HALA Badawi
The Immune System
1.
2.
The immune system is composed of two
components:
Humoral immunity, mediated by soluble
antibody proteins.
Cellular immunity, mediated by
lymphocytes.
The Immune System
CELLULAR
T ymphocytes
HUMORAL
B lymphocytes
Cells of the Immune System
T- Lymphocytes
B- Lymphocytes
Macrophages
Dendritic Cells
Natural Killer (NK) Cells
Cells of the Immune System
T Lymphocytes

T lymphocyte constitute 60 to 70% of
the lymphocytes in circulating blood.
 Present in the periarteriolar sheaths of the
spleen
 and interfollicular zones of the lymph
nodes
Cells of the Immune System
T Lymphocytes

Each T cell has a
specific T-cell
receptor (TCR)

TCRs are linked to 5
clusters of polypeptide
chains, called the
CD3 complex
Cells of the Immune System
T Lymphocytes

In addition, T cells
express other
associated molecules,
(CD4 and CD8).
 These two molecules
are expressed on
distinct T-cell subsets
and serve as
coreceptors for T-cell
stimulation.
Cells of the Immune System
T Lymphocytes

CD4 is expressed on about
60% of mature T cells,
 Whereas CD8 is expressed on
about 30% of T cells.
 In normal healthy
individuals, the CD4/CD8
ratio is therefore about 2:1.
 During antigen recognition,
CD4 molecules on T cells
bind to class II MHC
molecules on selected APCs;
and CD8 binds to class I
MHC molecules.
Cells of the Immune System

CD4+ T cells are called "helper" T cells because
they secrete soluble molecules (cytokines) that
influence all other cells of the immune system.
 CD 4 T cells are divided into two types
(T- helper1 & T-helper 2)
 The CD 8 T cells are called cytotoxic cells.
They play an important role in directly killing
virus-infected or tumor cells.
Cells of the Immune System
2- B Lymphocytes
 B lymphocytes comprise 10% to 20% of the
circulating peripheral lymphocyte population. They
are also present in bone marrow, in peripheral
lymphoid tissues (lymph nodes, spleen, and tonsils)
 After stimulation, B cells form plasma cells that
secrete immunoglobulins, which in turn are the
mediators of humoral immunity.
 There are five basic immunoglobulin IgG, IgM,IgA
(95% of circulating antibodies) IgE and IgD.
•B cells recognize antigen via B-cell receptor (BCR)
•As with T cells, each BCR has a unique antigen specificity,
derived from somatic rearrangements of immunoglobulin genes
IgM, IgG, IgA,
IgE, IgD
B – Cell Receptors
Cells of the Immune System

Macrophages
•
Macrophages (along with dendritic cells, below) express class
II MHC and are therefore central players in the processing and
presentation of antigen to CD4+ helper T cells. Because T
cells (unlike B cells) cannot be triggered by free antigen,
presentation by macrophages or other antigen presenting cells
(APCs) is obligatory for induction of cell-mediated immunity.
Macrophages produce many cytokines that not only influence
T- and B-cell function but also affect other cell types,
including endothelium and fibroblasts.
Macrophages phagocytose (and ultimately kill) microbes
coated by antibody and/or complement ; consequently, they
are important effector elements in humoral immunity.
•
•
Cells of the Immune System
Dendritic Cells :
 They are the most potent antigen presenting cells
(APC), express high levels of MHC class II, and
presenting antigens to CD4+ T cells .
 They are widely distributed, occurring in lymphoid
tissues and in the interstitium of many non-lymphoid
organs, such as the heart and lungs.
 In the epidermis are also called Langerhans cells.
Cells of the Immune System
Natural Killer (NK) Cells
 NK cells are larger than small lymphocytes and
comprise 10 to 15% of peripheral blood lymphocytes.
 These cells are able to kill a variety of tumor cells,
virally infected cells, and some normal cells, without
previous sensitization.
 These cells are classified as part of the inborn
immune system that is the first line of defense against
a variety of attacks.
Major Histocompatibility Complex

They are genes located on chromosome 6
 They are present on all nucleated cells and are
classified into 3 classes
Major Histocompatibility Complex

Histocompatibility Molecules (MHC) are critical element in
inducing and regulating normal immune function.( also
known as the HLA complex).

They are responsible for presenting antigens for T cells,
as T cells (unlike B cells) can only recognize antigens,
through MHC molecules; (MHC restriction).

The MHC (HLA) system is highly polymorphic; that is,
there are several alternative forms of a gene at each locus.
Major Histocompatibility Complex
MHC gene products fall into three categories:

Class I MHC molecules are present on all nucleated cells, presenting
intracellular infection like viruses and can be detected by cytotoxic T
CD8 cells.

Class II MHC molecules expressed mainly on APCs (monocytes,
macrophages, and dendritic cells).

MHC II molecules bind to peptides derived from proteins (e.g., those
derived from extracellular bacteria) synthesized outside the cell.
which recognize CD4 cells..

Class III proteins include some of the complement components.
Significance of Histocompatibility Molecules.

The significance of MHC polymorphism is clear in
transplantation. MHC molecules of the graft evoke
both humoral and cell-mediated responses, eventually
leading to graft destruction.

Because the severity of the rejection reaction is in
large part related to the degree of donor and recipient
MHC (HLA) disparity, HLA typing is of clinical
significance in the selection of appropriate donorrecipient combinations.

Some diseases are related to HLA, e.g. ankylosing
spondylitis and several postinfectious arthropathies,
all associated with HLA-B27.
CYTOKINES,
The Soluble Mediators of the Immune System

Cytokines are polypeptides that are secreted mainly by
lymphocytes and APCs.
 Cytokines mediate their effects by binding to specific receptors
on their target cells. For example, IL-2 activates T cells by
binding to IL-2 receptors.
 Blockade of the receptor prevents T-cell activation.
 Cytokines induce their effects in three ways:
autocrine, paracrine and endocrine effects.
CYTOKINES,
The Soluble Mediators of the Immune System
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Many individual cytokines are produced by several different cell
types. For example, IL-1 and TNF can be produced by any cell.
The cytokines can act on many cell types, causing many different
effects. For example, IL-2 is a T-cell growth factor; however, it is
also regulate the growth and differentiation of B cells and NK
cells.
Multiple cytokines may induce similar effects, for example, IL-1
and TNF have very similar effectors profiles
HYPERSENSITIVITY REACTIONS
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Although immune activation are generally protective against
infections (and to some extent tumors), such responses may
also potentially damage host tissues
The term hypersensitivity is used to describe immune
responses which are damaging rather than helpful to the host
The hypersensitivity reactions are subdivided into four
types:
Type I disease : Allergy and Anaphylaxis

Type II disorders: Antibody Dependent.

Type III disorders: Immune complex diseases.
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Type IV disorders: delayed-type hypersensitivity
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Type I Hypersensitivity
(Allergy and Anaphylaxis)
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IgE-mediated hypersensitivity
Time: 2-30 mins
Mechanism: results from IgE antibodies bound to
mast cells, when these IgE molecules bind their
specific antigen (allergen), they are triggered to
release vasoactive mediators that in turn affect
vascular permeability and smooth muscle contraction
in various organs.
Examples: 1-Local reaction: (e.g., seasonal rhinitis, or
hay fever) andasthma)
2-Systemic disorder (anaphylaxis).
Type I
Hypersensitivity
Chemical mediators of
type I Hypersensitivity
Clinical Manifestations of Type I Hypersensitivity
Systemic anaphylaxis results from systemic (parenteral)
administration of protein antigens or drugs (e.g., bee venom
or penicillin).
 Within minutes of an exposure in a sensitized host, itching,
urticaria , skin erythema, followed by bronchoconstriction and
Laryngeal edema that cause respiratory obstruction.
 In addition, vomiting, abdominal cramps, and diarrhea.
 Without immediate intervention, there may be systemic
vasodilation (anaphylactic shock), and the patient may die
within minutes.
Local reactions occur when the antigen is confined to a
particular site by the route of exposure, such as
 Skin (contact), causing urticaria & eczema
 GIT (ingestion), causing diarrhea in food allergy
 Lung (inhalation), causing bronchoconstriction as in asthma
and hay fever.
Type II Hypersensitivity
(Antibody Dependent)

Antibody-mediated cytotoxic hypersensitivity
 Time: 5-8hrs
 Mechanism: is mediated by antibodies directed
against target antigens on the surface of cells
or other tissue components
 Examples: Blood transfusion reactions,
Haemolytic disease of the newborn,
Autoimmune Haemolytic anaemia
Type II, Complement dependent reaction that lead to cell
lyses or render them susceptible to phagocytosis
B - Antibody dependent cell mediated cytotoxicity (ADCC) IgG coated target
cells are killed by cell bear Fc receptor for IgG (NK cells)
C- Anti receptor antibodies, acetyle receptor antibodies, impair the
neuromuscular transmission in mythenia gravis
Type III Hypersensitivity
(Immune Complex-Mediated)

Time: 2-8hrs
 Mechanism: is mediated by the deposition of antigenantibody (immune- complexes), followed by complement
activation and accumulation of polymorphonuclear leukocytes.
 PMN degranulation caused damages of tissue
 Immune complexes can involve exogenous antigens such as
bacteria and viruses or endogenous antigens such as DNA.

Examples: systemic when complexes are formed in the
circulation and are deposited in multiple organs or localized to
particular organs (e.g., kidneys, joints, or skin).
Type III Hypersensitivity
(Immune Complex-Mediated)
Type IV Hypersensitivity
(Cell-Mediated)
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Time: 24-72hrs

Mechanism: Type IV hypersensitivity is mediated by sensitized T
cells and is subdivided into two types:
1.
Delayed-type hypersensitivity, initiated by CD4+ T cells
2.
Direct cell cytotoxicity, mediated by CD8+ T cells.
Type IV Hypersensitivity
1- Delayed-type
hypersensitivity,
initiated by CD4+ T
cells, which secrete
cytokines, leading to
recruitment of
macrophages
forming granulomas
Granuloma
Type IV Hypersensitivity
(Cell-Mediated)
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Direct cell cytotoxicity, mediated by CD8+ T cells.
Mechanism:

Sensitized CD8+ T cells kill antigen-bearing target cells.
 Class I MHC molecules bind to intracellular viral peptides and
present them to CD8+ T lymphocytes to kill them.
 The CD8+ effector cells, called cytotoxic T lymphocytes (CTLs),
play a critical role in resistance to virus infections.

Examples: Contact dermatitis.
Type IV hypersensitivity,
Direct cell cytotoxicity,
Mediated by CD8+ T cells.
CTL Killing
Transplant Rejection

Rejection of organ transplants is involving both cell- and antibodymediated hypersensitivity responses of the host directed against
histocompatibility molecules on the donor graft.
Transplant Rejection
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Clinical Types of Rejection:
HYPERACUTE REJECTION: occurs within minutes to a few
hours after transplantation in a presensitized host (preformed
antibodies).
ACUTE REJECTION. Acute rejection may occur within days to
weeks of transplantation in a non-immunosuppressed host, acute
rejection is a combined process to which both cellular and humoral
mechanisms
CHRONIC REJECTION. chronic rejection presents late after
months to years with a progressive renal dysfunction and is
characterised by thickened BVs , fibrosis, and loss of renal tissue.
Caused by humoral and cell-mediated mechanisms. It is hard to
prevent and hard to treat.
Types of Organ Transplantation
Kidney
 Most common transplanted organ
 Diabetes, glomerulonephritis, congenital disorders
 Complications:
• Rejection
• post-transplant malignancy
Types of Organ Transplantation
Bone Marrow
 Leukemia, lymphoma
 Find living donor (easy) that matches (hard)
 Massive chemo/radiation first
 Complications: Graft versus host reaction (GVHD)
• Donor T cells see recipient as foreign!
• Attack skin, GI, liver
• Treat with immunosuppressives
• Or, partially deplete donor marrow of T cells
Immunologic Tolerance
and Autoimmunity
“Tolerance” = unresponsiveness to an antigen
 Selfe Tolerance:
Is a lack of immune responsiveness to one's own
tissue antigens.
 Autoimmunity implies loss of self-tolerance

Autoimmune Diseases

Autoimmune diseases range from:
 1-Localized: specific immune responses against one
particular organ or cell type and result in localized
tissue damage.
 Examples:
1. Hashimoto thyroiditis,
2. Autoimmune hemolytic anemia,
3. Autoimmune atrophic gastritis,
4. Myasthenia gravis
5. Graves disease
Autoimmune Diseases
2-Multisystem diseases: characterized by lesions in many
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1.
2.
3.
4.
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organs and associated with a multiplicity of auto-antibodies or
cell-mediated reactions.
Examples,
Systemic lupus erythematosus,
Rheumatoid arthritis,
Sjogren syndrome
Inflammatory myopathy
In these diseases, the pathologic changes occur principally
within the connective tissue and blood vessels of the various
organs involved, and called collagen vascular diseases or
connective tissue diseases
Autoimmune Diseases
Lupus Erythematosus
 Typical patient: young woman with butterfly rash
 Symptoms unpredictable (relapsing/remitting)
 Multisystem effects:
 Kidney (renal failure)
 Skin (“butterfly rash”)
 CNS (focal neurologic deficits)
 Joints (arthritis)
 Heart (peric
Autoimmune Diseases
Lupus Erythematosus
Etiology and Pathogenesis.
 The main defect in SLE is a failure to maintain self-tolerance.
 There is generation of a wide array of autoantibodies that can
damage tissue either directly or in the form of immune complex
deposits
1- Antinuclear Antibodies (ANAs).
2- Anti-double-stranded DNA antibodies
SLE, butterfly rash
Discoid lupus
Autoimmune Diseases
Rheumatoid Arthritis
•Female patient with aching, stiff joints, especially in
morning
•Symmetric joint swelling (mostly small joints)
•Fingers: ulnar deviation and swan-neck deformities
•Rheumatoid skin nodules
•Systemic symptoms (skin, heart, vessels, lungs)
Autoimmune Diseases
Rheumatoid Arthritis
Rheumatoid factor:
• Circulating IgM antibody
• Directed against patient’s OWN IgG!
• Forms IgM-IgG immune complexes, which
deposit in joints and cause badness
•Present in 80% of patients
Autoimmune Diseases
Rheumatoid Arthritis
•Chronic synovitis with
pannus formation
•synovial cell
proliferation
•Inflammation
•granulation tissue
Autoimmune Diseases
Rheumatoid Arthritis
Autoimmune Diseases
Sjögren syndrome
• Inflammatory disease of salivary and lacrimal
glands
•Female between 35-45
•T cells react against some Ag (self? viral?) in
gland; gland gets destroyed
• Dry eyes (Keratoconjunctivitis sicca)
•Dry mouth (Xerostomia )
• Increased risk of lymphoma
Autoimmune Diseases
Sjögren syndrome
Immune Deficiency Diseases
Congenital Immune Deficiency Diseases
X-linked agammaglobulinemia
Common variable immunodeficiency
Isolated IgA deficiency
Hyper-IgM syndrome
DiGeorge syndrome
Severe combined immunodeficiency
Acquired Immune Deficiency Disease (Aids)
ACQUIRED IMMUNODEFICIENCY SYNDROME
AIDS is a retroviral disease characterized by
profound immunosuppression that leads to:
1. Opportunistic infections,
2. Secondary neoplasms,
3. Neurologic manifestations
ACQUIRED IMMUNODEFICIENCY SYNDROME
Five groups of adults are at risk for developing AIDS:
1. Homosexual or bisexual men (57% of cases)
2. Intravenous drug abusers (25% of cases)
3. Hemophiliacs, who received large amounts of infected
factor VIII concentrates (0.8% of cases)
4. Recipients of blood and blood components , who
received transfusions of HIV-infected whole blood or
components (e.g., platelets, plasma) (1.2% of cases)
ACQUIRED IMMUNODEFICIENCY SYNDROME

In approximately 6% of cases, the risk factors cannot
be determined
 Close to 2% of all AIDS cases occur in pediatric
population
 In this group, more than 90% have resulted from
transmission of the virus from mother to child. The
remaining 10% are hemophiliacs and others who
received infected blood or blood products
ACQUIRED IMMUNODEFICIENCY SYNDROME
Aetiology:
 AIDS is caused by human immunodeficiency virus (HIV

Two genetically different but related forms of HIV, called
HIV-1 and HIV-2, have been isolated from patients with
AIDS

HIV-1 is the most common type associated with AIDS in the
United States, Europe, and Central Africa

HIV-2 causes a similar disease principally in West Africa
ACQUIRED IMMUNODEFICIENCY SYNDROME


Aetiology:
The HIV-1 virion is spherical and
contains an electron-dense, coneshaped core surrounded by a lipid
envelope derived from the host
cell membrane
 The virus core contains
1. The major capsid protein p24
2. Nucleocapsid protein p7/p9
3. Two copies of genomic RNA,
and
4. The three viral enzymes
(protease, reverse transcriptase,
and integrase)
ACQUIRED IMMUNODEFICIENCY SYNDROME

Aetiology:
 p24 is the most readily detected
viral antigen and, as such, is the
target for the antibodies that are
used for the diagnosis of HIV
infection by (ELISA)
 The viral core is surrounded by
a matrix protein called p17,
which lies underneath the virion
envelop
 Studding the viral envelope are
two viral glycoproteins, gp 120
and gp 41, which are critical for
HIV infection of cells
ACQUIRED IMMUNODEFICIENCY SYNDROME
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PathogenesisThere are two major targets of HIV:
The immune system and the central nervous system
Initially, HIV-1 infects T cells and macrophages directly or is
carried to these cells by Langerhans cells

CD4 molecule is, a high-affinity receptor for HIV. This explains
the selective tropism of the virus for CD4+ T cells and other
CD4+ cells, particularly monocytes /macrophages and
Langerhans cells/dendritic cells

Binding to CD4 is not sufficient for infection, however HIV
gp120 must also bind to other cell surface molecules for entry
into the cell

After fusion, the virus core containing the HIV genome enters
the cytoplasm of the cell
ACQUIRED IMMUNODEFICIENCY SYNDROME

Pathogenesis
There are two major targets of HIV:
The immune system and the central nervous system

It is important to note that although HIV-1 can infect resting T
cells, the initiation of productive infection occurs only when the
infected cell is activated by an exposure to antigens or cytokines

It is obvious therefore that physiologic stimuli that promote
activation and growth of normal T cells lead to the death of HIVinfected T cells

So the productive infection of T cells is the mechanism by which
HIV causes lysis of CD4+ T cells
ACQUIRED IMMUNODEFICIENCY SYNDROME

Pathogenesis

There continues a gradual erosion of CD4+ cells by
productive infection

Ultimately, CD4+ cell numbers decline, and the patient
develops clinical symptoms of full-blown AIDS

Macrophages are also parasitized by the virus early; they are
not lysed by HIV-1, and they may transport the virus to
tissues, particularly the brain
ACQUIRED IMMUNODEFICIENCY SYNDROME
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Pathogenesis
HIV infection of macrophages has three important
significans:
They act as virus factory and reservoir.
Macrophages provide a vehicle for HIV to be transported to
various parts of the body, particularly the nervous system.
In late stages of HIV infection, when the CD4+ T-cell
numbers decline greatly, macrophages may be the major site
of continued viral replication.
MAJOR ABNORMALITIES OF IMMUNE FUNCTION IN AIDS
1.
Lymphopenia
2.
Decreased T-Cell Function
3.
Polyclonal B-Cell Activation
4.
Altered Monocyte or Macrophage Functions
Natural History of HIV Infection
Three phases reflecting the dynamics of virus-host interaction
can be recognized:
1. An early, acute phase
2. A middle, chronic phase
3. A final, crisis phase

In the absence of treatment, most but not all patients with
HIV infection progress to AIDS after a chronic phase lasting
from 7 to 10 years
Natural History of HIV Infection

Exceptions to this typical course are:
–
Long-term nonprogressors: patient remains asymptomatic
for 10 year or more, with stable CD4+ counts and low
level of plasma viremia.
–
Rapid progressors. in those the middle, chronic phase is
shortened to 2 to 3 years after primary infection
Infection & Neoplasms

Protozoal and Helminthic Infections
– Pneumocytosis Carnii (pneumonia or
disseminated infection)
– Toxoplasmosis (pneumonia or CNS infection)
 Fungal Infections
– Candidiasis (esophageal, tracheal, or pulmonary)
– Cryptococcosis (CNS infection)
– Coccidioidomycosis (disseminated)
– Histoplasmosis (disseminated)
Infection & Neoplasms
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Bacterial Infections
–
Mycobacteriosis (atypical, e.g., M. avium-intracellulare,
disseminated or extrapulmonary; M. tuberculosis,
pulmonary or extrapulmonary)
Nocardiosis (pneumonia, meningitis, disseminate)
Salmonella infections (disseminated)
–
–
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Viral Infections
–
–
–
–
Cytomegalovirus (pulmonary, intestinal, retinitis, or CNS
infections)
Herpes simplex virus (localized or disseminated)
Varicella-zoster virus (localized or disseminat)
Progressive multifocal leukoencephalopathy
Infection & Neoplasms
Neoplasms
 Kaposi sarcoma
 B-cell non-Hodgkin lymphomas
 Primary lymphoma of the brain
 Invasive cancer of uterine cervix
Can there be a cure ??

Antiretroviral drugs:
Virus persists in the lymphoid tissue
 Vaccination:
High degree of polymorphism
At present, therefore,
prevention and effective public health measures
remain the mainstay in the fight against AIDS
Amyloidosis

Amyloidosis is the term used for the abnormal
deposition of proteinaceous material in tissues
interstitium

Can occur in a spectrum of clinical disorders

with progressive accumulation, it encroaches on and
produces pressure atrophy of adjacent cells
Amyloidosis
Nature Physical nature
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Amyloid is composed largely of non-branching fibrils
7.5 to 10 nm in width
Arranged in a characteristic crossed B-pleated sheet
conformation
this structural organization is seen regardless of the
clinical setting or the chemical composition
is responsible for the distinctive staining and optical
properties of amyloid
Amyloidosis
Nature Chemical nature

Three distinct forms of amyloid proteins are most
common:
1.
2.
3.
AL (amyloid light chain) is derived from plasma
cells and contains immunoglobulin light chains
AA (amyloid-associated) is a unique non-immuno
globulin protein synthesized by the liver
Aft amyloid is found in the cerebral lesion of
Alzheimer disease
Amyloidosis
Nature Chemical nature

The AL protein is made up of complete
immunoglobulin light chains, the terminal fragments of
light chains, or both
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AL type is produced by immunoglobulin-secreting cells

its deposition is associated with some form of
monoclonal B-cell proliferation
Amyloidosis
Nature Chemical nature

The AA amyloid fibril is composed of a protein that
derive from a larger serum precursor synthesized in
the liver called SAA (serum amyloid-associated) protein

AA proteins are typically deposited in the setting of
chronic inflammatory states
Amyloidosis
Nature Chemical nature
Other forms:
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Transthyretin (TTR)
B2-microglobulin, a component of the MHC class I
molecules and a normal serum protein
Pathogenesis
Amyloidosis
Classification
SYSTEMIC
On clinical
grounds
PRIMARY
SECONDARY
LOCALIZED
FAMILIAL/HEREDITARY
Amyloidosis
Primary Amyloidosis

usually systemic in distribution and is of the AL type
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this is the most common form of amyloidosis

The best example in this category is amyloidosis
associated with multiple myeloma, a malignant
neoplasm of plasma cells
Amyloidosis
Reactive Systemic Amyloidosis (Secondary Amyloidosis)
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Systemic in distribution and is of the AA type
Cell injury occurring in a spectrum of infectious and
non-infectious chronic inflammatory conditions
Tuberculosis, bronchiectasis, and chronic osteomyelitis
Rheumatoid arthritis, ankylosing spondylitis, and
inflammatory bowel disease
Chronic skin infections
Renal cell carcinoma and Hodgkin disease
Amyloidosis
Heredofamilial Amyloidosis

The best characterized is an autosomal recessive
condition called familial Mediterranean fever

It is associated with widespread tissue involvement
indistinguishable from reactive systemic amyloidosis
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The amyloid fibril proteins are made up of AA proteins
Amyloidosis
Localized Amyloidosis
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Amyloid deposits are limited to a single organ or tissue
without involvement of any other site in the body
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The deposits may produce grossly detectable nodular
masses or be evident only on microscopic examination

Nodular (tumor-forming) deposits of amyloid are most
often encountered in the lung, larynx, skin, urinary
bladder, tongue, and the region about the eye
Amyloidosis
Morphology
No specific findings for the previous categories, however:
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Secondary amyloidosis more often involves: kidneys,
liver, spleen, lymph nodes, adrenals, and thyroid, as
well as many other tissues are typically affected
Primary amyloidosis, more often involves the heart,
gastrointestinal tract, respiratory tract, peripheral
nerves, skin, and tongue
cannot reliably be distinguished by its organ distribution
Amyloidosis
Morphology
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Grossly: Organ is enlarged, grayish in color, waxy firm
in consistency
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Microscopically: amyloid appears as deposition of an
amorphous, eosinophilic, hyaline extracellular
substance
Amyloidosis
Kidney
Heart
Amyloidosis
Diagnosis

Diagnosis is by Congo red stain; apple green
birefringence upon examination under polarized light

Confirmation can be obtained by electron microscopy,
which reveals amorphous non-oriented thin fibrils
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AA, AL, and transthyretin amyloid can also be
distinguished by specific immunohistochemical staining
Amyloidosis
Morphology