Download Immune System and Natural History_2013

Immune System and Natural
History of HIV Infection
Vijay Kandula, MD MPH AAHIVS
Adjunct Assistant Professor
Division of Public Health, Department of Family and
Preventive Medicine
University of Utah, Salt Lake City
Components of the Immune System
• Organs
• Cells
• Molecules
•Immunoglobulins
•Complement system
Organs of the Immune System
Tonsils and adenoids
Lymph nodes
Lymphatic vessels
Thymus
Lymph nodes
Spleen
Peyer’s patches
Appendix
Lymph nodes
Bone marrow
Lymphatic vessels
Cells of the Immune System
Bone graft
Macrophage
Mast cell
Eosinophil
Marrow
Bone
Erythrocytes
Basophil
Monocyte
Megakaryocyte
Hematopoietic
stem cell
Multipotential
stem cell
Myeloid
progenitor Neutrophil
cell
Platelets
Lymphoid progenitor cell
Dendritic cell
T lymphocyte
Natural killer cell
B lymphocyte
B Cells
Antigen-specific B
cell receptor
Class II MHC and
processed antigen are
displayed
Antigen
Antibodies
B cell
Lymphokines
Antigen-presenting
bacteria
Plasma cell
Activated helper
T cell
B Cells produce Antibodies
• What do they do?
• Can be protective: E.g Hepatitis A and B, Varicella….
• Not protective: HIV, Hepatitis C
•How do we use them?
• To protect against infection: E.G Hep A Ig if travelling
• To diagnose
• Window period?
T Cells
Resting helper T cell
Activated helper T cell
CD-4 Cell
Resting cytotoxic T cell
Activated killer cell
CD-8 Cell
Phagocytes and Their Relatives
Monocyte
Eosinophil
Mast cell
Macrophage
Dendritic cell
Neutrophil
Basophil
Complement
C2
C3
C3a
C5a
C1
C6
C8
C5b
IgG
Antigen
C7
C4
Enzyme
C3b
C5
C5b
C9
Kinds of Immunity
Active immunity
Passive immunity
Naturally acquired
Naturally acquired
Artificially acquired
Artificially acquired
Immune System Disorder
• Though immune system defends the body
– Imbalance leads to problems
• Three common immune system disorders:
• allergies
• autoimmune diseases
• immunodeficiency diseases
Disorders of the Immune System:
Allergy
Interleukins
Allergen
IgE
Mediators
Symptoms
B cell
Mature
helper T
cell
Plasma cell
Mast cell
Disorders of the Immune System:
Autoimmune Disease
Pancreas
Cytotoxic T cell
Beta cell
Immunodeficiency Diseases
• weakened immune response.
• the immune system fails to develop normally.
• Affected by drugs and other diseases
• Infection: Acquired immunodeficiency disease is
AIDS.
– Allergies result when antigens from allergens bind
to
•
•
•
•
histamines.
pathogens.
mast cells.
T cells.
– An example of an autoimmune disease is
•
•
•
•
polio.
multiple sclerosis.
asthma.
smallpox.
403
– In Type I diabetes, antibodies attack
•
•
•
•
connective tissues around the joints.
neuromuscular junctions.
insulin-producing cells in the pancreas.
epinephrine-producing cells in the adrenal cortex.
– The retrovirus HIV causes
•
•
•
•
AIDS.
myasthenia gravis.
asthma.
polio.
– The principle targets of the HIV virus are the
body’s
•
•
•
•
red blood cells.
helper T cells.
connective tissue in the joints.
B cells.
T Helper cell also know as?
Why is natural history important?
• Helps to predict the progression of HIV infection
• This might help to identify the best moment to start
anti-retroviral therapy
• Helps targeted drug development to arrest the
infection at each of the various stages
• What is Public Health importance?
HIV Life Cycle Videos
1st thisBasic
http://www.youtube.com/watch?v=6gGEU6vw
4J0&feature=related
second
http://video.about.com/aids/How-AIDSAffects-the-Body.htm
thrid
http://www.youtube.com/watch?v=RO8MP3w
Mvqg&feature=related
How HIV infects the body
Natural History of HIV Infection
CD4 Count, Viral Load and Clinical Course of Untreated HIV Infection in Adults
Primary
Infection
Seroconversion
10,000,000
Intermediate Stage
AIDS
1,000,000
1,000
100,000
Plasma
HIV
Viral
Load
10,000
Viral Load
1,000
AIDS
100
CD4 Cells
CD4
500 Cell
Count
200
10
1
4-8 Weeks
5-10 Years to AIDS
Natural History of HIV Infection
Survival with
AIDS 1 Year
18
Time to Death from Diagnosis of AIDS
1981-1987
Proportion surviving
1.0
0.8
0.6
0.4
0.2
0
0
10 20 30 40 50 60
Months after OI diagnosis
Source : National AIDS case surveillance data,27CDC
Primary HIV Syndrome - Rash
Cerebral Toxoplasmosis
Swollen Posterior Cervical Lymph
Nodes
Seborrheic Dermatitis
Natural History of HIV Infection
32
Folliculitis
Oral HSV Ulcer and
Angular Cheilitis
Aphthous Ulcers
Dermatomal Herpes (Varicella)
Zoster
Dermatomal Herpes (Varicella)
Zoster
Oral Candidiasis
Oral Hairy Leukoplakia
Pulmonary Tuberculosis
With mild –moderate
immunosuppression
(CD4 > 200)
usually presents
with typical
upper lobe
cavitary disease
Bacterial Pneumonia
Streptococcus pneumoniae
Kaposi’s Sarcoma
Usually,
multiple dark
raised
lesions.
Lesions
themselves
are not itchy
and are rarely
painful.
Kaposi’s Sarcoma
Lymphedema from Kaposi’s
Sarcoma
Involvement of
regional lymph
nodes with distal
edema is
common.
Node disease
and swelling
may be painful.
Oral
Kaposi’s
Sarcoma
Implies
involvement of
internal organs
such as
gastrointestinal
tract
Severe Chronic
Herpes Simplex Ulcers
Persistence for
> 1 month is an
AIDS-defining
condition
Umbilicated
papules of
Molluscum
contagiosum
and
Cryptococcus
have the same
appearance
Pneumocystis carinii (jiroveci)
Pneumonia or PCP
Subacute or acute illness of more than one week, with fever, severe shortness of
breath and cough with little or no sputum
Breath sounds may be
normal.
Bilateral interstitial
infiltrates on
x-ray are typical.
Oesophageal Candidiasis
HIV infected patient with oral
candidiasis and chest (sub-sternal)
pain with swallowing has presumed
Candida oesophagitis.
Endoscopy would prove the
diagnosis but is unnecessary if the
patient responds to antifungal
therapy.
Cryptococcal Meningitis
Spinal fluid: may
have increased
lymphocytes, may
have increased
protein.
Budding yeast seen
in spinal fluid in
60-80% with India
ink preparation.
Enhancing Mass Lesion of the Brain
Single ring
enhancing lesion
with oedema
on brain CT scan
Primary brain
lymphoma versus
Toxoplasmosis
versus
Tuberculoma
CNS Toxoplasmosis
Response to empiric
therapy
Cytomegalovirus Retinitis
Afebrile patient;
reduced vision in one or
both eyes;
painless; external eye
exam normal
Retinal exudate and
hemorrhage follow retinal
vessels
Natural History of HIV without Treatment:
10,000,000
1,000,000
100,000
Acute
HIV
800
Virologic set-point varies
from patient to patient
HIV antibodies
asymptomatic
Minor HIV-related
symptoms
500
10,000
Opportunistic
infections
1,000
200
100
100
50
10
HIV Viral Load
(copies/mL)
Months
1 3 about 6mths //
Years
5
0
10 yrs CD4
(cells/mL)
HIV in plasma (“viral load”)
CD4 (T Cell) count
Typical course of HIV infection in an untreated person
Acute HIV
800
HIV antibodies
CD4
count
cells/ul
10^6
Minor HIV-related
symptoms
Virologic set-point varies
from patient to patient
HIV
RNA
copies
/ml
200
10^2
1 3 about 6mths //
Time
5
10 yrs
†
Outcome with Treatment: low viral load, normal CD4
800
10,000,000
1,000,000
500
100,000
10,000
1,000
200
100
100
50
Months
10
HIV Viral Load
(copies/mL)
1 3 about 6mths //
HIV in plasma (“viral load”)
Years
5
10 yrs
0
CD4
(cells/mL)
CD4 (T Cell) count
Match the disease with CD4 level at which they are
likely to occur
Opportunistic Infections
CD4 Threshold
level
CMV Retinitis
<50 cells/µl
Cryptococcus Meningitis
<100 cells/µl
Pneumocystis pneumonia
<200 cells/µl
Cerebral toxoplasmosis
<200 cells/µl
Oral Candida
<200 cells/µl
Persistent generalized adenopathy
>500 cells/µl
Herpes zoster
>=500 cells/µl
Pulmonary Tuberculosis
Any CD Count