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DISEASES OF

IMMUNE SYSTEM

NORMAL IMMUNE RESPONSE

IMMUNITY
refers to protection against infection.
THE IMMUNE SYSTEM
is the collection of cells, tissues and molecules that functions
to defend us against infectious microbes.
IMMUNE RESPONSE
is the coordinated reaction of the immune system against
infections and other foreign substances.
Abnormalities of the immune system that result in defective
immune responses make individuals susceptible to infections by
viruses, bacteria, fungi and parasites.
Many common diseases are caused by uncontrolled or excessive
immune response.

THE CONCEPT OF INNATE AND


ADAPTIVE IMMUNITY
1. Innate immunity (natural immunity) is
mediated by cells and proteins that are always
present and ready to fight against microbes and are
called into action immediately in response to
infection.
Fast

and nonspecific

Four

major components:

Epithelial barriers of skin, GIT and respi tract which


prevent microbe entry
Phagocytic leukocytes (neutrophil and macrophages)
Specialized cell type (NK cells)
Plasma proteins

Reactions of Innate Immunity

Due to Cytokines and products of


complement activation, and other mediators, which
triggers the vascular and cellular components of
inflammation. The recruited leukocytes destroy
microbes and ingest and eliminate damaged cells.

Inflammation.

defense. Type I interferons produced in


response to viruses act on infected and uninfected
cells and activate enzymes that degrade viral nucleic
acids and inhibit viral replication, inducing antiviral
state

Antiviral

Adaptive immunity is normally silent and


responds (or adapts) to the presence of infectious
microbes by becoming active, expanding and
generating potent mechanisms for neutralizing
and eliminating microbes.
Slow

response on first exposure but memory response


is faster and more robust

Components

are lymphocytes

CELLS AND TISSUES OF IMMUNE


SYSTEM
Cell type

Principal functions

T lymphocytes

Help for B cells and macrophages (CD4+ helper cells),


killing of infected and tumor cells (CD8 + cytotoxic T

B lymphocytes

lymphocytes)
Antibody production (B cells develop into plasma cells
which make antibodies)

Dendritic cells

Capture and display of foreign antigens

Macrophages

Phagocytosis and killing of microbes, antigen capture,


tissue repair

Neutrophils

Phagocytosis and killing of microbes

T-LYMPHOCYTES

Thymusderived,orT,lymphocytesaretheeffecto
rcellsofcellularimmunityandthehelpercells
for antibodyresponsestoproteinantigens

constitute60%to70%ofthelymphocytesin
peripheralbloodandarethemajorlymphocytepop
ulationinsplenicperiarteriolarsheathsandlym
phnode interfollicularzones

T-LYMPHOCYTES
Tcellsrecognizeonlypeptidefragmentsofprotein
antigensboundtoproteinsofthemajor
histocompatibilitycomplex(MHC)
Itisnowknownthatthenormalfunctionof
MHCmoleculesistodisplaypeptidesforrecognitionb
yTlymphocytes

B LYMPHOCYTES
BonemarrowderivedBlymphocytesarethecells
thatproduceantibodiesandarethustheeffecto
rcells ofhumoralimmunity
10%to20%ofthecirculatingperipherallympho
cytepopulation
presentinbonemarrowandinthefolliclesofp
eripherallymphoidtissues(lymphnodes,
spleen,tonsils,andothermucosaltissues

B LYMPHOCYTES
Afterstimulation,Bcellsdifferentiateintoplasmace
lls,whichsecretelargeamountsofantibodies,the
mediatorsofhumoralimmunity
Therearefiveclasses,orisotypes,ofimmunoglobulin
s:IgG,IgM,andIgA
constitutemorethan95%ofcirculatingantibodies

IgA

mucosal secretions
IgE attached at mast cells
IgD
-expressedonthesurfacesofBcellsbutisnotsecreted

TYPES OF ADAPTIVE IMMUNITY

Humoral immunity type

of host defence that is mediated by antibodies.


Antibodies are secreted into mucosal lumens, blood
and interstitial fluids. Effective against extracellular
microbes

Cell mediated immunity mediated

by T cells and is effective against


intracellular microbes.
Helper T Cells act on macrophages that have
ingested microbes and activate the macrophages to
kill these microbes
CTLs recognize microbes hiding in the cytoplasm of
infected cells (e.g. virus) and kill the infected cells

NATURAL KILLER CELLS


arelymphocytesthatarisefromthecommonlym
phoidprogenitorthatgivesriseto
TandBlymphocytes
theydonothavespecificitiesasdiverseasdoT
cellsorBcells

ANTIGEN PRESENTING CELLS


amongtheseAPCsaredendriticcells(DCs),the
majorcellsfor
displayingproteinantigenstonaiveTcellstoini
tiateimmuneresponses
capturemicrobesandotherantigens,transportt
hemtolymphoidorgans,anddisplay
themforrecognitionbylymphocytes
mostefficientAPCsareDCs,whicharelocatedi
n epitheliaandmosttissues.

Other APC Macrophages


Effector cells

Manydifferenttypesofleukocytesperformtheultim

atetaskoftheimmuneresponse,whichistoelimina
te infections

Lymphoid Tissues

Generative(Primary)Organs

peripheral(secondary)lymphoidorgans

OVERVIEW OF THE
NORMAL IMMUNE
RESPONSE

THEEARLYINNATEIMMUNERESP
ONSETOMICROBES

Theearlyreactiontomicrobesismediatedbythem
echanismsofinnateimmunity,whichare
readytorespondtomicrobes.Thesemechanismsincl
udeepithelialbarriers,phagocytes,NK
cells,andplasmaproteins(e.g.,ofthecomplementsys
tem).Thereactionofinnateimmunityis
oftenmanifestedasinflammation.

THECAPTUREANDDISPLAYOFMIC
ROBIALANTIGENS

EFFECTOR FUNCTIONS OF T
LYMPHOCYTES

HUMORALIMMUNITY

Main situations in which immune responses are


pathologic:
When

self-tolerance fails and the immune system


begins to attack individuals own tissues
(autoimmune diseases)
When the immune response becomes excessive or
uncontrolled, either against microbial antigens or
against normally harmless environmental antigens
As a part of an entirely normal reaction against some
microbes

HYPERSENSITIVITYREACT
IONS:MECHANISMSOFIM
MUNEMEDIATEDINJURY

HYPERSENSITIVITY:
IMMUNOLOGICALLY
MEDIATED TISSUE INJURY

Immune response that results in exaggerated or


inappropriate reactions that are harmful to the
host
Typically occur after the second contact with a
specific antigen (allergen)
First contact is a necessary preliminary event
that induces sensitization to that allergen
implies an excessive or harmful reaction to
antigen.

TYPES OF
HYPERSENSITIVITY

TYPE I HYPERSENSITIVITY
IMMEDIATE HYPERSENSITIVITY

anaphylactic hypersensitivity

induced by environmental antigens (allergens)


that stimulate strong TH2 subset of CD4+
helper T cells and IgE production in genetically
susceptible individuals
principal mediators are histamine, proteases,
and other granule contents, prostaglandins and
leukotrienes, and cytokines.

responsible

for the immediate vascular and smooth


muscle reactions and the late-phase reaction
(inflammation).

TYPE II HYPERSENSITIVITY
CYTOTOXIC HYPERSENSITIVITY

Occurs when antibody directed at


antigens of the cell membrane activates
complement
Generates

a membrane attack complex, which


damages the cell membrane
Leads to complement-mediated cell lysis

Attracts

phagocytes with consequent release of


enzymes that damage cell membranes

TYPE III HYPERSENSITIVITY


IMMUNE COMPLEX
HYPERSENSITIVITY

Immune complexes are composed of


antigen-antibody complexes
Persistence and deposition of immune
complexes in tissues activate the
complement system and attracts PMNs

Pathophysiology

IMMUNE COMPLEX FORMATION


Antigen triggers formation of antibodies
ABs react with antigen in circulation, forming ICs

IMMUNE COMPLEX DEPOSITION


Organs where blood is filtered at high pressure to
form other fluids are favored (glomeruli, joints)

INFLAMMATION AND TISSUE INJURY


Vasculitis (blood vessels), Glomerulonephritis (renal
glomeruli), arthritis (joints)

TYPE IV HYPERSENSITIVITY
CELL-MEDIATED
HYPERSENSITIVITY

Function of sensitized T lymphocytes


(not Abs)
Activate

macrophages to cause an
inflammation

Response is delayed and prolonged


Usually

starts 2-3 days after contact with the


antigen and often lasts for days

Pathophysiology

DELAYED-TYPE HYPERSENSITIVITY
CD4+ T cells interact with macrophages,
resulting in cytokine injury to tissue
May lead to granuloma formation

T CELL-MEDIATED CYTOLYSIS

CD8+ T cells interact with altered MHC class I


antigens on neoplastic, virus-infected, or donor
graft cells, causing cell lysis

AUTOIMMUNE DISEASES

AUTOIMMUNE DISEASES
Overactive

immune response against selfantigens due to loss of tolerance

Most

important steps is activation of selfreactive helper (CD4+) T cells


Self-reactive

Th-1 or Th-2 cells can induce cellmediated or antibody mediated reactions


Most are antibody-mediated

General

characteristics

Progressive course with sporadic, relapses and


remissions

Clinicopathologic manifestations determined


by nature of underlying immune response

Substantial clinical, pathologic, and serologic


overlaps between autoimmune diseases

IMMUNOLOGIC TOLERANCE

MECHANISMS OF AUTOIMMUNITY

CELIAC DISEASE

Mechanism
Gliadin

(wheat, barley, rye) stimulates a cytotoxic


attack on enterocytes, causing villous atrophy

Clinical Presentation
Diarrhea,

Treatment
Dietary

painful abdominal distention, steatorrhea

modification (gluten-free)

SYSTEMIC LUPUS ERYTHEMATOUS


autoimmune disease involving multiple organs
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.

O
N
U

C
L

A
R

SLE, SKIN

SLE, GLOMERULUS

TABLE 6-10 -- Clinical and Pathologic Manifestations of Systemic


Lupus Erythematosus
Clinical Manifestation

Prevalence in
Patients, %

Hematologic
Arthritis
Skin
Fever
Fatigue
Weight loss

100
90
85
83
81
63
50

Central nervous system


Pleuritis
Myalgia
Pericarditis
Gastrointestinal
Raynaud phenomenon
Ocular
Peripheral neuropathy

50
46
33
25
21
20
15
14

Renal

MORE SYSTEMIC
AUTOIMMUNE
DISEASES
RHEUMATOID

ARTHRITIS
SJGREN SYNDROME
SCLERODERMA (SYSTEMIC
SCLEROSIS) (PSS)


Destructive
Rheumatoid Synovitis
NORMAL Bi-Layered
Synovium

SJOGREN SYNDROME

Chronic disease
characterized by
Dry

eyes
(keratoconjunctivitis sicca)
Dry mouth (xerostomia)
Other S/Sx (e.g. arthritis)

Results from
immunologically mediated
destruction of the lacrimal
and salivary glands

SJGREN
SYNDROME

SYSTEMIC SCLEROSIS

Chronic inflammation
thought to be the result of
autoimmunity
Widespread damage to
small blood vessels
Progressive interstitial and
perivascular fibrosis in the
skin and multiple organs

SYSTEMIC SCLEROSIS
(SCLERODERMA)

SCLERODERMA
(SYSTEMIC SCLEROSIS)

MORE AUTOIMMUNE
DISEASES (LOCAL)
HASHIMOTO

microsome)

THYROIDITIS (anti-thyroglob, anti-

AUTOIMMUNE HEMOLYTIC ANEMIA (AHA) (anti-RBC)


MULTIPLE SCLEROSIS (anti-MBP)
AUTOIMMUNE ORCHITIS (Anti-germ cell)
GOODPASTURE SYNDROME (anti-GBM Abs)
AUTOIMMUNE THROMBOCYTOPENIA (ITP) (anti-plats)
PERNICIOUS ANEMIA (anti-IF, anti-parietal cell Abs)
INSULIN DEPENDENT DIABETES MELLITUS (I) (antiislets)
MYASTHENIA GRAVIS (anti-NM-junction)
GRAVES DISEASE (anti-TSHR-Abs cause activation)

DRUG-INDUCED LUPUS

Associated drugs
Hydralazine,

isoniazid, procalnamide, penicillamine

Distinguishing features
Anti-histone

antibodies
Low incidence of renal and CNS involvement
Disppearance of symptoms when drug is discontinued

MIXED CONNECTIVE TISSUE


DISEASE

Clinical features that are a mixture of the


feautres of SLE, systemic sclerosis and
polymyositis
High titers of antibodies to ribonucleoprotein
(anti-RNP)

REJECTION OF TISSUE
TRANSPLANTS

TYPES OF GRAFTS
1.

Autograft

Self-to-self
Best survival rate

2.

Syngeneic Graft (Isograft)

3.

Allograft

4.

Between identical twins

Between different individuals of the same species

Xenograft

Between different species

REJECTION OF TISSUE
TRANSPLANTS

HYPERACUTE REJECTION
Occurs

within minutes to hours


Due to performed antibodies
Type II hypersensitivity reaction
Morphology

Thrombotic occlusion of capillaries, and fibrinoid necrosis


occurs in arterial walls

Example

Blood group A person receives a blood group B heart

REJECTION OF TISSUE
TRANSPLANTS

ACUTE REJECTION
most

common transplant rejection


Reversible reaction that occurs within weeks to
months after transplant
Two components

Acute cellular rejection


Associated with interstitial mononuclear cell infiltrate
Acute humoral rejection
Associated with vasculitis

Acute

cellular rejection

Within months after transplant


Type IV hypersensitivity
Clinical and biochemical signs of renal failure
Morphology
Extensive interstitial mononuclear cell infiltration and
edema
Injury to vascular endothelial cells

Treatment: immunosuppressives

Acute

humoral rejection

Within months after transplant


Type II hypersensitivity
Mediated by antidonor antibodies
Morphology
Necrotizing vasculitis with endothelial cell necrosis,
neutrophilic infiltration, deposition of Ig, complement,
fibrin

Treatment: B cell-depleting agents

REJECTION OF TISSUE
TRANSPLANTS

CHRONIC REJECTION
Occurs

over months to years


Type IV hypersensitivity
Progressive renal failure manifested by a rise in
serum creatinine over 4 to 6 months
Morphology

Vascular changes, interstitial fibrosis and tubular atrophy


with loss of renal parenchyma

GRAFT-VERSUS-HOST DISEASE
(GVHD)

Immunologically competent cells are


transplanted into immunologically crippled
recipients
Usual setting: bone marrow or liver transplant

Acute GVHD
Occurs

within days to weeks after BMT


Clinical manifestations
Desquamating skin rash
Bile duct necrosis
Bloody diarrhea

Chonic GVHD
May

follow acute GVHD or occur insidiously


Clinical manifestations
Dermal fibrosis (resembles sleroderma)
Chronic liver disease (cholestatic jaundice)
Esophageal strictures
Recurrent and life-threatening infections

IMMUNODEFICIENCY
State in which the immune systems ability to
fight infectious disease is compromised
Can occur if any of the four major components of
the immune system are compromised:

cells (antibody)
T cells
Phagocytes
complement

TYPES OF IMMUNODEFICIENCY
Primary

Immunodeficiency

Genetic susceptibility to infections since childhood


Examples: IgA deficiency, Brutons XLA

Secondary

Immunodeficiency

Acquired susceptibility to infection to infection as a result of


external processes or diseases
Examples: malnutrition. Aging, drugs, AIDS

IMMUNODEFIENCY
SYNDROMES (-IDS)
PRIMARY

(GENETIC) (P-

IDS?)
SECONDARY

(ACQUIRED) (A-IDS)

PRIMARY

CHILDREN with repeated, often severe infections,


cellular AND/OR humoral immunity problems,
autoimmune defects
BRUTON (X-linked agammaglobulinemia)
COMMON VARIABLE
IgA deficiency
Hyper -IgM
DI GEORGE (THYMIC HYPOPLASIA) *22q11.2
SCID (Severe Combined Immuno Deficiency)
.with thrombocytopenia and eczema (WISKOTTALDRICH)
COMPLEMENT DEFICIENCIES

PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS

X-linked Hypogammaglobulinemia (Brutons


Aggammaglobulinemia)

Mechanism
Very low levels of all immunoglobulins

Virtual absence of B cells due to tyrosine kinase mutation

Cell-mediated immunity is normal


Clinical manifestation
Male infants at about 6 months of age
Recurrent pyogenic bacterial infections

Streptococcus pneumoniae
Haemophilus influenzae

Recurrent enteroviral infections


Treatment: pooled gamma globulin

PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS

Selective IgA Deficiency


Mechanism

Failure of isotype switching

Clinical

Presentation

Recurrent bacterial sinus and lung infections

Treatment

Do not treat with gamma globulin preparations


Form antibodies against foreign IgA
Cross-reaction depletes their already low IgA or may
cause anaphylaxis

PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS

Common Variable Immunodeficiency (CVID)


Mechanism

Defect in B-cell maturation to plasma cells

Clinical

Presentation

Diagnosis of exclusion
Recurrent pyogenic bacterial infections
Most common form of severe antibody deficiency affecting
both children and adults

Treatment

Pooled gamma globulin

PRIMARY IMMUNODEFICIENCIES

T CELL DISORDERS

diGeorge Syndrome
Mechanism

Profound deficit of T cells


Failure of development of thymus and parathyroids
Due to a defect in 3rd and 4th pharyngeal pouches
Humoral immunity is normal

Clinical

Presentation

Tetany due to hypocalcemia


Severe viral, fungal, or protozoal infections during infancy

Treatment

Transplant of fetal thymus

PRIMARY IMMUNODEFICIENCIES

T CELL DISORDERS

Chronic Mucocutaneous Candidiasis


Mechanism

Specific T-cell deficiency for Candida albicans


Other T-cell and B-cell functions are normal

Clinical

presentation

Recurrent candidiasis (skin, mucous membranes) in chidren

Treatment

Azole antifungal drugs

PRIMARY IMMUNODEFICIENCIES

COMBINED B & T CELL


DISORDERS
Severe Combined Immunodeficiency (SCID)
Mechanism

X-linked: mutation in gene encoding common gamma


chain/IL-2 receptor gamma
Autosomal: ADA deficiency

Clinical

Presentation

Recurrent bacterial, viral, fungal and protozoal infection in


early infancy (3 months of age)

Treatment

Enclosure in plastic bubble


Bone marrow transplant

PRIMARY IMMUNODEFICIENCIES

COMBINED B & T CELL


DISORDERS

Wiskott-Aldrich Syndrome
Mechanism

X-linked (affects male infants)


Inability to mount IgM response
Mutation in WASP gene for actin filament assembly

Clinical

Presentation

Recurrent pyogenic infections, eczema and bleeding due to


thrombocytopenia

Treatment

Bone marrow transplant

PRIMARY IMMUNODEFICIENCIES

COMBINED B & T CELL


DISORDERS

Ataxia-telangiectasia
Mechanism

Autosomal recessive disease


Mutations in DNA repair enzymes
IgA deficiency

Clinical

Presentation

Ataxia, telangiectasia, recurrent infections by 2 years of age

Treatment

Supportive management

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Chronic Granulomatous Disease


Mechanism

Lack of NADPH oxidase activity


Failure of oxidase burst
Normal B- and T-cell activity

Clinical

Presentation

Recurrent infections with:


Catalase-positive bacteria
Fungi (A. fumigatus)
Widespread granulomas of unknown etiology

Treatment

Antibiotic chemoprophylaxis

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Chediak-Higashi Syndrome
Mechanism

Autosomal recessive disease


Failure of phagolysosomal fusion
Faulty microtubules impair neutrophil chemotaxis

Clinical

presentation

Recurrent pyogenic infections caused by staphylococci and


streptococci

Treatment

antibiotics

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Leukocyte Adhesion Deficiency


Mechanism

Autosomal recessive disease


Mutation in integrins
Defective adhesion (LFA-1) proteins in the surface of
phagocytes

Clinical

Presentation

Severe pyogenic infections in infancy


Delayed separation of umbilical cord

Treatment

Antibiotics, bone marrow transplant

PRIMARY IMMUNODEFICIENCIES

COMPLEMENT DISORDERS

Hereditary Angioedema
Mechanism

Autosomal dominant disease


Deficiency of C1 inhibitor leads to increased C3a and C5a

Clinical

presentation

Widespread angioedema
Fatal laryngeal edema

Treatment

corticosteroids

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Early Complement Deficiency


C2

DEFICIENCY

Most common complement defect


Usually asymptomatic but may develop septicemia or SLE

C3

DEFICIENCY

Recurrent pyogenic ifections due to Staphylococcus aureus

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Terminal Complement Deficiency


Mechanism

Complement-mediated hemolysis
Deficiency of decay-accelarating factor (DAF)
Occurs at night due to lower RBC oxygen concentration
during sleep

Clinical

Presentation

Hemoglobinuria upon arising

Treatment

Iron replacement, corticosteroids

PRIMARY IMMUNODEFICIENCIES

PHAGOCYTE DISORDERS

Paroxysmal Nocturnal Hemoglobinuria


Mechanism

Complement-mediated hemolysis
Deficiency of decay-accelerating factor (DAF)
Occurs at night due to lower RBC oxygen concentration
during sleep

Clinical

Presentation

Hemoglobinuria upon arising

Treatment

Iron replacements. corticosteroids

SUMMARY OF THE PRIMARY


IMMUNODEFICIENCIES
Defect

Disease

Bacterial

B Cell

Brutons XLA
IgA deficiency
CVID
DiGeorge

S. pneumoniae
H. influenzae
S. aureus

B and T Cell

SCID
Wiskott-Aldrich

Macrophage

CGD
Chediak-Higashi

Complement

C6-C9 deficiency

S. pneumoniae
H. influenzae
S. aureus
P. aeruginosa
S. aureus
P. aeruginosa
M. tuberculosis
B. cepacia
N. meningitidis
N. gonorrhoeae

T Cell

Defect

Viral

B Cell

Entorovirus
HBV
EBV
CMV
VZV
EBV
CMV
VZV

T Cell

B and T Cell

Macrophage
Complement

Fungal

Parasitic
G. lamblia

C. albicans
P. jiroveci
C. albicans
P. jiroveci
A. fumigatus
C. albicans

G. lamblia

ADA=

ADENOSINE
DEAMINASE

Examples of Infections in Immunodeficiencies


Pathogen Type
Bacteria

T-Cell-Defect
Bacterial sepsis

Granulocyte
B-Cell Defect
Defect

Streptococci, Staph,
Neisserial
staphylococci, Pseudomo infections,
Haemophilus nas
other
pyogenic
infections

Viruses

Enteroviral
Cytomegalovirus,
Epstein-Barr virus, encephalitis
severe varicella,
chronic infections
with respiratory and
intestinal viruses

Fungi and
parasites

Candida, Pneumocystis Severe intestinal


carinii
giardiasis

Special features Aggressive

Complement Defect

disease with Recurrent


opportunistic pathogens, sinopulmonary
failure to clear infections infections, sepsis,
chronic meningitis

Candida,
Nocardia,
Aspergillus

(A)IDS
Etiology:

(SECONDARY IDS)

HIV
Pathogenesis: Infection, Latency,
Progressive T-Cell loss
Morphology: MANY
Clinical

Expressions: Infections,
Neoplasms, Progressive Immune Failure,
Death, HIV+, HIV-RNA (Viral Load)

SECONDARY
IMMUNODEFICIENCIES

Acquired Immune Deficiency Syndrome (AIDS)


Disease

caused by the retrovirus humaln


immunodeficiency virus (HIV)
Characterized by profound immunosuppression that
leads to opportunistic infections, secondary
neoplasms and neurologic manifestations

Human Immunodeficiency Virus


Spherical

RNA virus
Contains an electron- dense, cone-shaped core
surrounded by a lipid envelope
Major capsid protein p24
Nucleocapsid preotein p7/p9
Two copies of genomic RNA
Three viral enzymes
Protease
Reverse transcriptase
integrase

AIDS: Pathogenesis
Preferentially

lymphocytes

Main

infects and kills helper (CD4+) T

immune response consists of cytotoxic (CD8+)


lymphocytes

AIDS: SEROLOGIC TESTING


Test

Use

Comments

ELISA

Screening test
(sensitivity ~100%)
Confirmatory test
(~100% specificity)
Monitoring immune
status

Anti-gp120
antibodies
p24 antigen and gp41
antibodies
Guide for initiating
treatment and
administering
prophylaxis
Most sensitive test
for diagnosis of acute
HIV before
seroconversion

Western Blot
CD4 count

HIV viral load

Detection of active
replication
Marker of
progression

OPPORTUNISTIC INFECTIONS IN
AIDS
CD4
<500

<200

<50

ETIOLOGY

CLINICAL SYNDROME

M. tuberculosis

Disseminated tuberculosis

HSV

HSV esophagitis

C. albicans

Esophageal candidiasis

HHV-8

Kaposis sarcoma

P. jiroveci

PCP pneumonia

T. gondii

Cerebral toxoplasmosis

C. neoformans

Meningoencephalitis

C. immitis

Coccidioidomycosis

C. parvum

Chronic diarrhea

M. avium

Invasive pulmonary disease

H. capsulatum

Histoplasmosis

CMV

CMV retinitis

AIDS

Lymph Nodes
Early

stages of AIDS

Marked follicular hyperplasia


Viral DNA in the nuclei of CD4 cells

Late

stages of AIDS

burnt-out lymph nodes


Follicle depletion
Disruption of organized network of follicular dendritic
cells

EPIDEMIOLOGY
HOMOSEXUAL

(40%, and

declining)
INTRAVENOUS DRUG
USAGE (25%)
HETEROSEXUAL SEX
(10% and rising)

ETIOLOGY

PATHOGENESIS

ATTACHING

BUDDING

PATHOGENESIS

EARLY BUDDING

PATHOGENESIS

LATE BUDDING

PATHOGENESIS

MATURE NEW VIRIONS

REVERSE TRANSCRIPTASE
The

enzyme reverse transcriptase


(RT) is used by retroviruses to
transcribe their single-stranded
RNA genome into single-stranded
DNA and to subsequently
construct a complementary strand
of DNA, providing a DNA double
helix capable of integration into
host cell chromosomes.

PATHOGENESIS

PATHOGENESIS

1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) ACUTE SYNDROME 4-8
weeks)
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS

GENERAL IMMUNE
ABNORMALITIES
LYMPHOPENIA
DECREASED

T-CELL

FUNCTION
B-CELL ACTIVATION,
POLYCLONAL
ALTERED
MONOCYTE/MACROPHAGE
FUNCTION

INFECTIONS

Protozoal/Helminthic:

Cryptosporidium, PCP
(Pneumocystis Carinii (really
Jiroveci) Pneumonia),
Toxoplasmosis
Fungal: Candida, and the usual 3
Bacterial: TB, Nocardia, Salmonella
Viral: CMV, HSV, VZ (Herpes Family),
HPV

PCP

CRYPTOSPORIDIUM

CASEATING GRANULOMA

CANCERS OF AIDS
KAPOSI

SARCOMA (Herpes-

8)
B-CELL LYMPHOMAS
CNS LYMPHOMAS
CERVIX CANCER,
SQUAMOUS CELL (HPV)

AMYLOIDOSIS
BUILDUP

AL

AA

OF AMYLOID PROTEIN

(Amyloid Light Chain)

(NON-immunoglobulin protein)
A (Alzheimers)

WHERE? BLOOD VESSEL WALLS, at first


KIDNEY

SPLEEN
LIVER

HEART

CONGO RED STAIN, WITHOUT, and WITH, POLARIZATION

AMYLOID ASSOCIATIONS
PLASMA

CELL DYSCRASIAS, i.e.,


MULTIPLE MYELOMA
CHRONIC GRANULOMATOUS
DISEASE, e.g., TB
HEMODIALYSIS
HEREDOFAMILIAL
LOCALIZED
ENDOCRINE MEAs (Multiple Endocrine
Adenomas-2)
AGING

AMYLOIDOSIS

Amyloid

Pathologic

proteinaceous substance
Deposited in extracellular space in various tissues

Apple green-colored birefringence in polarized


light with Congo red

TYPES OF AMYLOIDOSIS
Type

Protein

Derived from

Mnemonic

Primary

AL

AL=light chain

Secondary

AA

Senile cardiac

Transthyretin

IgG light chains


(multiple
myeloma)
SAA protein
(inflammatory)
AF

T2 DMassociated
Medullary
thyroid CA
Alzheimers
Disease
Dialysisassociated

Amylin

AE

AE = Endocrine

A-CAL

Calcitonin

B-amyloid

APP

A-CAL
CALcitonin

B2-microglobulin

MHC Class I
proteins

AA = Acute phase
reactants
AF = old Folks

AMYLOIDOSIS

Renal amyloidosis
Most

common and most serious form


Nephrotic syndrome

Massive splenomegaly
Tapioca-like

granules in the splenic follicles (sago

spleen)
Map-like areas in walls of spenic sinuses (lardaceous
spleen)

Marked hepatomegaly
Due

to amyloid deposits in space of Disse

AMYLOIDOSIS

Heart

Subendocardial

Other organs
Adrenals,

and myocardial deposits

thyroid, and pituitary


Macroglassia (tumor-forming amyloid of the tongue)