Immunopathology lecture

1. The Immune Response
By
Prof. Dr. Gamal El-Din Abd El-Hamid

2. 2ANATOMY OF THE IMMUNE SYSTEM
 The immune system is
localized in several
parts of the body
◦ immune cells develop
in the primary organs
- bone marrow and
thymus (yellow)
◦ immune responses
occur in the

3. 3
PASSIVE IMMUNITY
Antibodies (Y) are also
found in breast milk.
The antibodies received
through passive immunity
last only several weeks.
While your immune system was developing, you were protected
by immune defenses called antibodies. These antibodies
traveled across the placenta from the maternal blood to the
fetal blood.

4. IMMUNE DEFENSES
Innate Immunity
- invariant (generalized)
- early, limited specificity
- the first line of defense
Adaptive Immunity
- variable (custom)
- later, highly specific
- ‘‘remembers’’ infection

5.  Internal defenses
v Innate, non-specific, immediate response
(min/hrs)
v Adaptive (Acquired) – attack a specific
pathogen (antigen)
Immune Defenses: Overview

6. Innate and Adaptive (Acquired) Immunity
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
Adaptive IMMUNITY
Slower responses to
specific microbes
External defenses Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic lymphocytes)
Invading
microbes
(pathogens)

7. Innate immunity
◦ Is present before any exposure to pathogens and is effective
from the time of birth
◦ Involves nonspecific responses to pathogens

8. External Defenses
I. Intact skin and mucous membranes
◦ Form physical barriers that prevents the entry of
microorganisms and viruses
.Certain cells of the mucous membranes produce
mucus. A viscous fluid that traps microbes and other
particles

9.  In the trachea, ciliated epithelial cells
◦ Sweep mucus and any entrapped microbes upward, preventing
the microbes from entering the lungs

10. II. Secretions of the skin and mucous membranes
◦ Provide an environment that is often hostile to microbes
◦ Give the skin a pH between 3 and 5, which is acidic enough to
prevent colonization of many microbes
◦ Also include proteins such as lysozyme, an enzyme that digests
the cell walls of many bacteria

11. 11
Cellular response
•
Nonspecific - the same response works against many
pathogens
•
This type of response is the same no matter how often it is
triggered
•
The types of cells involved are macrophages, neutrophils,
natural killer cells, and mast cells

12. Phagocytic Cells
 Phagocytes attach to their prey via surface receptors and
engulf them, forming a vacuole that fuses with a lysosome
Pseudopodia
surround
microbes.
1
Microbes
are engulfed
into cell.
2
Vacuole
containing
microbes
forms.
3
Vacuole
and lysosome
fuse.
4
Toxic
compounds
and lysosomal
enzymes
destroy microbes.
5
Microbial
debris is
released by
exocytosis.
6
Microbes
MACROPHAGE
Vacuole Lysosome
containing
enzymes

13. Adaptive immunity
(Acquired immunity)
◦ Develops only after exposure to inducing agents
such as microbes, toxins, or other foreign
substances
◦ Involves a very specific response to pathogens by
lymphocytes.

14. Innate Immune
System
Adaptive Immune
System
Repeated infections Do Not improve resistance Improve resistance
Cells PNLs, Macrophages,
Mast cells
NK cells
Lymphocytes
Soluble Factors C-reactive protein
Interferon
Complement
Antibodies
Cytokines

15.  It is a specific mechanism developing against particular
types of irritants in order to:
1. Get rid of the irritant
2. Increase the ability of the body to overcome it on
subsequent exposure
.Steps in Immune defense
◦ Detect invader/foreign cells
◦ Communicate alarm & recruit immune cells
◦ Suppress or destroy invader
Adaptive Immune Response

16.  Newly formed lymphocytes are all alike
◦ But they later develop into B cells or T cells, depending on
where they continue their maturation
Bone marrow
Lymphoid
stem cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T cell
Thymus

17. Lymphatic System:
Overview of Immune Defense Organs & Cells
 Bone marrow
 Thymus
 Lymph nodes
 Spleen
 Lymph vessels
 Leukocytes (white blood cells – WBCs)

18. Lymphatic System

19. Cells of the immune system

20. T Lymphocytes: Cell Mediated
Immunity
T lymphocytes and NK cells

21. Antigen-
binding
sitesAntibody A
Antigen
Antibody B Antibody C
Epitopes
(antigenic
determinants)
 Antigen is any substance which when
introduced in body can evoke an immune
response.
 It may be exogenous or endogenous
 A lymphocyte actually recognizes and binds
to just a small, accessible portion of the
antigen called an epitope
 The plasma membranes of both B cells and T
cells have about 100,000 antigen receptor
that all recognize the same epitope
ANTIGEN

22.  MHC are molecules that mediate interactions of leukocytes
 They bind processed foreign proteins (phagocytosed
material)and present them on the cell surface to T-cells
 MHC determines compatibility of donors for organ transplant as
well as one's susceptibility to an autoimmune
disease via crossreacting immunization.
 They are two types: Class I antigns and Class II antigns
Major Histocompatibility Complex (MHC)
(Human Leukocyte Antigens – HLAs)

23. Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
(a) Cytotoxic T cell
CD8+
A fragment of foreign
protein (antigen) inside
the cell associates with
an MHC molecule and is
transported to the cell
surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
1
2
 Class I MHC molecules, found on almost all nucleated
cells of the body
◦ Display peptide antigens to cytotoxic T cells

24. Cytotoxic T cell
Perforin
Granzymes
CD8TCR
Class I MHC
molecule
Target
cell Peptide
antigen
Pore
Released
cytotoxic
T cell
Apoptotic
target cell
Cancer
cell
Cytotoxic
T cell
A specific cytotoxic T cell binds to a
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
1 The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis.
2 The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
3
1
2
3
 The activated cytotoxic T cell
◦ Secretes proteins that destroy the infected target cell

25.  Class II MHC molecules, located mainly on dendritic cells,
macrophages, and B cells
◦ Display antigens to helper T cells
1
2
Microbe Antigen-
presenting
cell
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
CD4+
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
(b)

26. Helper T Cells: A Response to Nearly All Antigens
 Helper T cells produce CD4, a surface protein
◦ That enhances their binding to class II MHC molecule–antigen
complexes on antigen-presenting cells
◦ Activation of the helper T cell then occurs
 Activated helper T cells
◦ Secrete several different cytokines that stimulate other
lymphocytes

27. The role of helper T cells in acquired immunity
After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Cell-mediated
immunity
(attack on
infected cells)
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Dendritic
cell
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
Cytokines
Cytotoxic T cell
B cell
1
2 3
1
2 3

28. Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
(a) Cytotoxic T cell
CD8+
A fragment of foreign
protein (antigen)
inside the cell
associates with
an MHC molecule and
is transported to the
cell surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
Microbe Antigen-
presenting
cell
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
CD4+
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
(b)
The activated cytotoxic T cell Secretes proteins that
destroy the infected target cell
Proliferation of the T cel gives rise to a clone of activated
helper T cells all with receptors for the same MHC–antigen
complex.

29. Cytokines
1. TNF (Tumor Necrosis Factor) alpha:
1. Attraction and activation of macrophages
2. Granuloma formation

30. Interferon 
1. Acts in a positive feedback signal activating T cells further
2. Activates Macrophages to be competent to contain
bacteria
3. Regulates APC function
4. B cell differentiation

31. Interleukins (IL)
 IL-12
§ Produced by macrophages.
§ It stimulates differentiation of T-cells in TH1 pathway

32. CD4+ (Th1) T cell help to the infected macrophages
T cell-
Macrophage
interaction can
take
several hours

33.  Acquired immunity includes two branches
1. Humoral immune response
◦.Involves the activation and clonal selection of B
cells, resulting in the production and secretion of
antibodies
2. Cell-mediated immune response
◦.Involves the activation and clonal selection of
cytotoxic T cells

34. Humoral immune response Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate Activate Activate
Gives rise to Gives rise to Gives rise to
B cell
Helper
T cell
Cytotoxic
T cell
Plasma
cells
Memory
B cells
Active and
memory
helper
T cells
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Defend against infected cells, cancer
cells, and transplanted tissues
Secreted
cytokines
activate

35. Antibody Classes
 The five major classes of antibodies, or immunoglobulins:
◦ They are produced by plasma cells
◦ They are γ globulins
◦ Differ in their distributions and functions within the body
◦ They are able to react specifically with Ag. that stimulate their

36. 1. Most abundant Ig class in blood; also presents in
tissue fluids
2. Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
3. Promotes opsonization, neutralization, and
agglutination of antigens
4. Less effective in complement activation than IgM
IgG

37. 1. First Ig class produced after initial exposure to antigen;
then its concentration in the blood declines
2. Promotes neutralization and agglutination of antigens
3. Very effective in complement activation
IgM

38. 1. Present in secretions such as tears, saliva, mucus,
and breast milk
2. Provides localized defense of mucous membranes
by agglutination and neutralization of antigens
IgA

39.  Triggers release of histamine and other chemicals
from mast cells and basophils in allergic
reactions
IgE

40.  Presents primarily on surface of naive B cells that have
not been exposed to antigens
 Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells.
IgD

41. Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Bacterium
Virus Bacteria
Soluble
antigens Foreign cell
Complement
proteins
MAC
Pore
Enhances
Phagocytosis
Leads to
Cell lysis
Macrophage

42. Acquired Immunity: Antigen-Specific Responses
Functions of antibodies

43.  It is a system of plasma proteins that exists in an
inactive form and constitutes about 10% of serum
globulins.
 The proteins of the system form 2 inter-related
enzyme cascades, termed The Classical and
Alternative Pathways, providing 2 routes for cleavage
of C3, the central event in the complement system
The Complement System

44.  The proteins of the classical pathway are numbered
C1 - C9. Most components are β globulin
 The bulk of the plasma complement components are
made in hepatic cells except C1 which is synthesized
mainly in the epithelium of GIT and urogenital tracts

45.  Both classic and alternative pathways generate C3
convertase which converts C3 into C3b
 The classic pathway represents an adaptive immune
mechanism while the alternative pathway represents
a non-specific innate immunity

46.  Complement activation is associated with the release
of active mediators; the most important are C3a and
C5a
 Effects of C5a
1. Major chemotactic factor
2. Activation of PMNs
3. Increase of vascular permeability
4. Mast cell degranulation
5. Membrane attack complex (C6, 7,8, 9) helping in
Effects of Complement Activation

47.  Hypersensitivity reactions are exaggerated
(hypersensitive) responses to certain antigens called
ALLERGENS
◦ They are classified into :
• Type I (Anaphylactic) Reactions
• Type II (Cytotoxic) Reactions
• Type III (Immune Complex) Reactions
Those associated with
Humoral Antibodies
• Type IV (Cell-Mediated) Reactions
Those associated with
Cell-mediated Immune
Response

48.  In localized allergies such as
§ hay fever,
§ atopy, or
§ bronchial asthma
Type I (Anaphylaxis, Atopy)

49.  The allergic response
IgE antibodies produced in
response to initial exposure
to an allergen bind to
receptors or mast cells.
1 On subsequent exposure to the
same allergen, IgE molecules
attached to a mast cell recog-
nize and bind the allergen.
2 Degranulation of the cell,
triggered by cross-linking of
adjacent IgE molecules,
releases histamine and other
chemicals, leading to allergy
symptoms.
3
1
2
3
Allergen
IgE
Histamine
Granule
Mast cell

50.  An acute allergic response sometimes leads to
anaphylactic shock
◦ A whole-body, life-threatening reaction that can
occur within seconds of exposure to an allergen

51. ACUTE ANAPHYLAXIS ATOPIC DERMATITIS

52. ◦ Involve activation of complement by IgG or IgM
binding to an antigenic cell.
◦ The antigenic determinants may be:
1. Intrinsic to the cell membrane or matrix, or
2. Extrensic, such as a drug metabolite, that is
adsorbed on a cell surface or matrix.
◦.In either case, the hypersensitivity reaction results
from the binding of antibodies to normal or
Type II (Cytotoxic) Reactions

54. Opsonization of cells by antibodies and complement
components and ingestion by phagocytes.
It occurs in Transfusion Reactions

55. ◦ Transfusion reactions:
 ABO Blood group system: Type O is
universal donor. Incompatible
donor cells are lysed as they enter
bloodstream.
 Rh Blood Group System: 85% of
population is Rh positive. Those
who are Rh negative can be
sensitized to destroy Rh positive
blood cells.
 Hemolytic disease of newborn: Fetal
cells are destroyed by maternal anti-
Rh antibodies that cross the placenta.

56. Table 43.1

57. Inflammation induced by antibody binding to Fc receptors of
leukocytes and by complement breakdown products.
It occurs in some forms of:
Glomerulonephritis
Vascular rejection in organ grafts,
Acute rheumatic fever

58. Antireceptor antibodies disturb the normal function of receptors.
In these examples, antibodies against the thyroid stimulating
hormone (TSH) receptor activate thyroid cells in Graves disease,
and acetylcholine (ACh) receptor antibodies impair
neuromuscular transmission in myasthenia gravis.

59.  Antibody-mediated destruction of cells may occur by
another process called antibody-dependent cellular
cytotoxicity (ADCC).
 This form of antibody-mediated cell injury Does Not
involve fixation of complement but instead requires
the cooperation of leukocytes (monocytes,
neutrophils, eosinophils, and NK cells).
Antibody-dependent cellular
cytotoxicity (ADCC)

60. T Cell-Mediated Cytotoxicity
 Sensitized CD8+ T cells kill antigen-bearing target
cells. Such effector cells are called cytotoxic T
lymphocytes (CTLs).
 CTLs directed against cell surface histocompatibility
antigens play an important role in graft rejection.
They also play a role in resistance to virus infections

61. TYPE III HYPERSENSITIVITY
(Immune Complex Reactions)
◦ Involves reactions against SOLUBLE antigens circulating in serum.
◦ Usually involve IgA antibodies.
◦ Antibody-Antigen immune complexes are deposited in organs, activate
complement, and cause inflammatory damage.
◦ Two general types of antigens cause immune complex-mediated injury:
(1) Exogenous, such as a foreign protein, a bacterium, or a virus; or
(2) Self-components-endogenous antigens. This can be circulating
antigens present in the blood or, more commonly, antigenic components
of one's own cells and tissues.

63.  Examples:
 SLE
 Serum Sickness: Generalized disease caused by antibody
produced to horse or bovine serum used in antitoxins.
Aggregates of IgG activate complement.
 Glomerulonephritis: membranous or post-streptococcal
 Polyarteritis nodosa

64. ◦ Involve reactions by T memory cells.
 First contact sensitizes person. Subsequent contacts elicit a
reaction.
◦ Reactions are delayed by one or more days (delayed type
hypersensitivity).
 Delay is due to migration of macrophages and T cells to site of
foreign antigens.
 Examples are:
 Contact dermatitis
 Rheumatoid artheritis
Type IV (Cell-Mediated) Reactions

65. Allergic Contact Dermatitis
Reactions are frequently
displayed on the skin:
itching, redness, swelling,
pain.
Tuberculosis skin test
Poison ivy
Metals
Latex in gloves and
condoms

66. CONTACT DERMATITIS

68.  Immune reactions against self-antigens causes damage to
organs.
 Loss of self-tolerance leads to production of antibodies or T
cells that react against one’s own antigens.
 Three types of autoimmune disorders:
1. Cytotoxic (Type II reactions)
2. Immune complex (Type III reactions)
3. Cell-mediated (Type IV reactions)
Autoimmune Diseases

69. Involve antibody reactions to cell surface molecules, without
cytotoxic destruction of cells.
◦ Grave’s Disease:
 IgG Antibodies attach to receptors on thyroid gland and stimulate
production of thyroid hormone.
 Symptoms: Goiter (enlarged thyroid) and thyrotoxicosis.
◦ Myasthenia gravis:
 Progressive muscle weakness. Antibodies block acetylcholine
receptors at neuromuscular synapse.
A. Type II (Cytotoxic) Autoimmune Reactions

70. ◦ Systemic Lupus Erythematosus:
 Autoantibodies react against DNA, blood cells, neurons, and other
tissues.
 When cells die, immune complexes form and deposit under skin,
joints, in kidneys, blood vessels, and central nervous system.
 Inflammation interferes with normal function of these sites
(arthritis, rash, kidney damage).
 Most patients die from renal failure.
 No cure. Symptoms treated with anti-inflammatory and
immunosuppressive drugs.
B. Type III (Immune Complex) Autoimmune Reactions

71. ◦Rheumatoid Arthritis:
Cause unknown, but microbial mimicry may be
involved.
IgM autoantibodies (rheumatoid factors) against
IgG form complexes in joint, leading to inflammation
and cartilage damage.
Often causes finger and joint deformities.
No cure. Symptoms treated with anti-
inflammatory (aspirin) and immunosuppressive
drugs. Physical therapy keeps joints movable.
Surgical replacement of joints may be necessary.

72. ◦ Insulin-dependent (Type I or Juvenile) Diabetes
Mellitus:
Insulin Dependent (Type I or Juvenile) Diabetes:
Makes up 10% of diabetes cases.
Characterized by insufficient insulin production due
to immunological destruction by T cells of insulin-
secreting cells of the pancreas. Usually develops
before the age of 15.
C. Type IV (Cell-Mediated) Autoimmune Reactions

73.  Immunodeficiencies can be divided into:
 1) Primary immunodeficiency disorders, which are
almost always genetically determined
 2) Secondary immunodeficiency states, which may
arise as complications of infections; malnutrition;
aging; or side effects of immunosuppression,
irradiation, or chemotherapy for cancer and other
autoimmune diseases.
Immunologic Deficiency Syndromes

74. Acquired Immunodeficiency
Syndrome (AIDS)
 AIDS is a disease caused by the retrovirus:
Human Immunodeficiency Virus (HIV) and
characterized by:
 Profound immunosuppression that leads to
opportunistic infections,
 Secondary neoplasms, and
 Neurologic manifestations.

75. HIV and AIDS
Acquired Immunodeficiency Syndrome
•
Disease caused by an infectious agent:
A Retrovirus

76. HIV and AIDS
The Cellular Picture
In advanced disease: the loss of another cell type
CD8+ cytotoxic killer cells
Loss of one cell type throughout the course of the disease
CD4+ T4 helper cells
A fall in the CD4+ cells always precedes disease

77. •
AIDS is therefore the end point of an infection that is
continuous, progressive and pathogenic
AIDS Definition
•
AIDS is the presence of one of 25 conditions
indicative of severe immunosuppression
OR
•
HIV infection in an individual with a CD4+ cell
count of <200 cells per cubic mm of blood

78. Female sex partners of AIDS
Not just in the Gay community
Different ways of getting a similar syndrome
•
Blood transfusions
•
Intravenous drug use
•
Hemophilia (clotting factor)
HIV and AIDS

79.  Mothers who are HIV infected can pass the
virus on to their fetuses in utero or to infants
via breast milk.
 Infection is aided by the presence of other
sexually transmitted diseases that can produce
mucosal ulceration and inflammation.

80.  HIV infection is aided by Langerhans
cells in mucosal epithelial surfaces
which can become infected.

81.  When HIV infects a cell, it must use its reverse
transcriptase enzyme to transcribe its RNA to host cell
proviral DNA.
 It is this proviral DNA that directs the cell to produce
additional HIV virions which are released.

85. Types of HIV
 HIV-1 is the most common type and is the infectious
agent that has led to the worldwide AIDS epidemic.
ØIt has a number of subtypes (A through H and O)
which have differing geographic distributions but all
produce AIDS similarly.
 HIV-2 that is much less common and less virulent,
but eventually produces clinical findings similar to
HIV-1.

86. Acquired Immunodeficiency Syndrome (AIDS)
 When the CD4 lymphocyte count drops below
200/microliter, then the stage of clinical AIDS has been
reached. This is the point at which the characteristic
opportunistic infections and neoplasms of AIDS appear.
 The organ involvement of infections with AIDS represents
the typical appearance of opportunistic infections in the
immunocompromised host--that of an overwhelming
infection--that makes treatment more difficult.

87.  Pneumocystis carinii is the most frequent opportunistic
infection seen with AIDS.
 It produces a pulmonary infection, called Pneumocystis
carinii pneumonia (PCP), but rarely disseminates
outside of lung. The most common clinical findings in
patients with PCP are acute onset of fever, non-
productive cough, and dyspnea.
Pneumocystis carinii (jiroveci)

90.  Cytomegalovirus (CMV) is the most frequent
disseminated opportunistic infection seen with AIDS.
 It causes the most serious disease as pneumonia.
 It can also cause serious disease in the brain and
gastrointestinal tract. It is also a common cause for
retinitis and blindness in persons with AIDS.
Cytomegalovirus (CMV)

91.  Mycobacterial infections are frequently seen with
AIDS. Mycobacterium tuberculosis has been
increasing in frequency since the start of the AIDS
epidemic.
 The appearance of M tuberculosis with AIDS is
similar to that of non-AIDS patients, with
granulomatous pulmonary disease, though the
infection may be more extensive or may be
disseminated to other organs.
Mycobacterium tuberculosis

92.  There are many types of fungi that can complicate the
course of AIDS.
 One of the most frequent (though uncommonly life-
threatening) is Candida.
 Oral candidiasis is often seen with HIV infection and may
presage the progression to AIDS. Candida can occasionally
produce invasive infections in esophagus, upper respiratory
tract, and lung.
Fungus Infection

94.  Toxoplasma gondii is
a protozoan parasite
that most often leads
to infection of the
brain with AIDS.
 The lesions are
usually multiple and
Toxoplasma

95.  Herpes simplex virus infection with AIDS is most likely
to involve the gastrointestinal tract, mainly the
esophagus and the perianal region.
 Herpes zoster infection of the skin can also occur prior
to the onset of clinical AIDS.
Herpes virus

96.  Cryptosporidium, Microsporidium, and
Isospora are all capable of producing a
voluminous watery diarrhea in patients with
AIDS.
Protozoal Infections

97. Malignant Neoplasms
 Kaposi's sarcoma (KS) produces reddish
purple patches, plaques, or nodules over
the skin and can be diagnosed with skin
biopsy.
 Visceral organ involvement eventually
occurs in 3/4 of patients with KS.
 Malignant lymphomas seen with AIDS are
typically of a high grade and extranodal,
often in the brain. They are very
aggressive and respond poorly to therapy.

98. Amyloidosis

99. Amyloidosis
 A disease characterized by Extracellular Deposition
of pathologic insoluble fibrillar proteins in organs
and tissues.
 Amyloid is especially deposited around the
supporting fibers of blood vessels and basement
membranes

100. Linear non branching aggregated
fibrils with a diameter of 8-10nm
Fibrillar nature and sheet
configuration described by
electron microscopy in 1959.

101. Amorphous homogenous, hyalin-like
eosinophilic appearance of amyloid under
light microscopy.
Amyloid protein is either:
a) Amyloidogenic itself or
b) Can be modified to
become amyloidogenic

103.  Detection:
1. Lugol’s iodine
Deep brown color
Blue color
H2SO
4

104. 2) Methyl violet
Red color

105. 3) Congo red
Red orange color
Apple Green Fluorescence
Polarized light

106. 4) Thioflavin -T
Strong Fluorescence
Ultraviolet
light

107. Distribution
Systemic
Primary (AL)
Multiple Myeloma
Plasmacytoma
Some B-cell Lymphomas
Secondary (AA)
T.B.
Lepromatous Leprosy
Chronic Osteomyelitis
Chronic suppurative lung
diseases
Localized
β-amyloid
Prealbumin
Senile brain
Medullary thyroid
carcinoma

108. Effects
Around blood
vessels
Increased
Permeability
Narrowing
Pressure on
adjacent cells
Atrophy

110. v
May present with rapid and progressive onset of CHF.
v
Characteristically, features of right sided CHF.
v
Concentrically thickened ventricles with normal-small cavity
CARDIAC

111. RENAL
 Nephrotic syndrome
present in 30-50% at
diagnosis.
 Renal failure develops
only rarely during course
of the illness.
Pale, waxy, and firm kidney

112. Effects
Around blood vessels
Increased
Permeability
Narrowing
Pressure on adjacent cells
Atrophy
Proteinuria
Degeneration
of tubules
Renal Failure

113. v
Involvement of liver is common.
v
Hepatomegaly may be striking at
presentation
v
Patients may present with severe
intrahepatic cholestasis
v
Presence of jaundice is a bad
prognostic factor
Liver is enlarged, firm, and waxy
HEPATIC

114.  Sago Spleen
Deposit is limited to splenic
follicles
 Diffuse (Lardaceous)
Spleen
Deposit is present in the
follicles and red pulp
SPLENIC

115. v
Atrophy of intestinal mucosa
v
The patient may present with:
1. Malabsorption
2. Diarrhea
3. Protein loss
4. Electrolyte imbalance
The intestinal mucosa is
pale and atrophic
GIT