Imunodefisiensi

Evy Yunihastuti

Immunodeficiency and
Autoimmunity
Evy Yunihastuti

Immunodeficiency
3

Immunodeficiency
Primary
Immunodeficiency

Neutrophil defects
Humoral: B cell
defects
Humoral:
Complement
Cell-mediated: T
cells
Severe combined
immunodeficiency

Secondary
Immunodeficienc
y
AIDS
Neutropenia

Post-transplant
BMT
chemotherapy

Splenectomised
patient

Immunodeficiency in adults
Infectious
disease: HIV
Environmental
stress
Age extremes:
old age

malnutrition

Adaptive &
innate
IMMUNITY

INFECTION

IMMUNODE
FICIENCY

Surgery & trauma,

splenectomy
Genetic and
metabolic
disease
*20 mg or more per day of prednisone, 14 days or longer
NOT aerosols, alternate day, short courses, topical
Immunosuppresive
drugs *

TUMOR

Chinen J, Shearer.WT. Secondary immunodeficiency. J Allergy Clin Immunol 2010; 125: S195-202 , Epidemiology
and Prevention of Vaccine-Preventable Diseases. National Center for Immunization and Respiratory Diseases. CDC.

Body surfaces and their resident

microbial flora

The immunodeficient host

Virulent infection with common organism
(e.g. TB)
Infection with opportunistic pathogen
virus (cytomegalovirus - CMV)
bacteria (Mycobacterium avium
intracellulare)
fungi (aspergillus, candida, pneumocystis)
protozoa (cryptosporidia, toxoplasma)

Immunodeficient patients
are

More susceptible to infection and disease

More likely to develop persistent infection
More likely to develop multiple infections
may develop unusual clinical
manifestations, i.e. which are not seen in
immunocompetent patients

Acquired Immunodeficiency
Cytotoxic
Neutropenia
Neutro
phils
X 109/l

Onset
maximum risk

0.5
0.1
Time
(days)
Timely admission in cyclical chemotherapy
2

10

12

<0.5 x 109/l risk of infection

<0.1 x 109/l high risk of septicaemia

Major clue
categories in
suspected
infection in
patients who
are
immunocompr
omised.

Pattern of opportunistic
infections of newly
diagnosed HIV-infected
patients in
Ciptomangunkusumo
hospital 2008-2009

Karjadi TH, Yunihastuti E , Pramundita R, Aziza S, Lie

S, Imran D, et al.
Presented at 2010 PDPAI Clinical Research Meeting

Opportunistic Infection

Percentage (%)

Candidiasis oral

50

Pulmonary TB

37

Pneumonia

16.5

Extra pulmonary TB

13.8

Toxoplasma encephalitis

12.1

Chronic Diarrhea

11.2

Seborrheic dermatitis.

5.3

CMV retinitis

3.4

Candidiasis esophageal

3.3

Persistent Fever

3.2

Herpes zoster

3.2

EPP

1.6

Wasting syndrome

1.2

Herpes simplex

0.6

Cryptococcal Meningitis

0.4

ITP

0.2

Toxocariasis

0.1

PCP

Defects in immunity suggested by

infection
Non Specific
immunity
Defence system
Infectious
complication

Common
microorganism

Less common

Phagocytes
Lymphadenitis
Skin infection
Liver, lung abscess
GI disease, UTI
Bacteria
Staphylococci, E colli
Klebsiella
Fungi: candida,
aspergillus
Bacteria:
salmonella, proteus

Complement
Classic-alternate
Systemic bacterial
infection
Autoimmune disease
Pyogenic bacteria:
Staphylococci
Neisseria

Virus: CMV, HSV

Defects in immunity suggested by

infection
Specific immunity
Defence system
Infectious
complication

Common
microorganism

Less common

B cells antibody

T cells cellular immunity

Respiratory tract
sespis
GI tract sepsis

Viral infection
Gastroenteritis
Lymphoproliferation

Pyogenic bacteria
Staphylococci
Streptococci
Haemophilus

Virus: CMV, adeno, HSV

Pyogenic bacteria
Fungi: candida,
aspergilus, PCP
Protozoa: cryptospora

Enterovirus
Other bacteria:
salmonella

Other bacteria

Opportunistic infection and CD4 cell

count

Temporal relationship of stemcell transplantation with

complications

Timeline of posttransplant infections

following solid organ transplantation

Management of
immunodeficiency

Managing the cause

Treatment and prevention of infection
Supportive

17

HIV preferentially infect CD4+ T

cells

HIV replicates in CD4

ds DNA

HIV

DNA

2
RNA

vpr Integrase
3

Genomic RNA

Proviral DNA

RT
Transcription

4
mRNA
Spliced mRNA

Polyprotein
Protein

Protease

Type of HIV progression

A model of HIV pathogenesis

HIV-1 infection and
replication

Main target CCR5+ activated CD4+ T

cell

Anti-HIV
immune
response

Cellular and
humoral

Massive CD4+ T cell

depletion

In particular mucosal CD4+ T cell

Production of
HIV proteins
Gp120, nef

Bacterial
Translocati
on
Incl. TLR
ligand

Viral
reactivation

In particular CMV

Systemic immune activation

Adaptive and innate

Systemic immune activation

Adaptive and innate

Sustained T-cell
apoptosis
Turn over and
senescence

Homeostatic
mechanism
Cellular renewal
hematopoesis

Exhaustion of
immune response

HIV
replication

Decline of regenerative
capacity loss of effective
anti-HIV immunity

=
Immunosenescence?

Secretion of
proinflammatory
cytokines
e.g. IL-6, TNF, IL-1

Damage
To
Lymphoid Inflammation-related
tissue
disorders
Osteoporosis
Atherosclerosis
Neurocognity deterioration
Frailty

= inflammationageing?

Persistence of this process

=> Collapse of immune system / AIDS

Prinsip penatalaksanaan
HIV
Supo
rtif

Infeksi
oportu
nistik

Antiret
roviral
(ARV)

02-2007

LSU SVM PBS

25