HIV attacks the immune system by targeting and destroying CD4 cells. This leaves the body vulnerable to opportunistic infections over time. There are three stages of HIV infection: 1) Primary infection where viral levels peak as the immune system responds; 2) Clinical latency where the virus is controlled but active; 3) AIDS where immune function is lost and death will occur without treatment. A person's viral set point after primary infection predicts their rate of disease progression.
The human immunodeficiency virus (HIV) is a lentivirus (a subgroup of retrovirus) that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS).
The human immunodeficiency virus (HIV) is a lentivirus (a subgroup of retrovirus) that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS).
Secondary Immunodeficiency
By Dr. Usama Ragab Youssif
Reference: Included in Slides
Include causes of secondary immunodeficiency including AIDS and other viral infections
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
1. Pathogenesis of HIV Disease
and
Natural History of HIV Infection
Unit 3
HIV Care and ART: A Course for
Healthcare Providers by
Salahadin M.Ali
1
2. Learning Objectives
• Describe the characteristics of HIV
• Understand how HIV attacks the body’s
immune system
• Explain how the body’s immune system
responds to HIV infection
• Discuss the natural course of HIV disease and
its clinical implications
2
3. Characteristics of HIV
• HIV is a chronic viral infection with no cure
• HIV primarily affects the CD4 lymphocyte
• When CD4 cells are destroyed, a person’s
immunity is impaired
• As immune function decreases, opportunistic
infections increase
• HIV progresses over time to death, if no
treatment is given
3
4. Characteristics of HIV (2)
• HIV infects cells that express CD4 receptor
molecules
– T4-lymphocytes (T-helper cells)
– Monocyte-macrophage cell lines
• T4-lymphocytes are type of white blood cell
that ‘switch on’ the immune system to fight
disease
• HIV uses CD4 cells for reproduction
4
5. Characteristics of HIV (3)
• Successful entry of the virus to a target cell
also requires cellular co-receptors
• A fusion co-receptor is designated CXCR4 for
T-cell tropic strain and CCR5 for monocyte-
macrophage tropic strains
• The receptor and co-receptors of CD4 cells
interact with HIV’s gp-120 and gp-41 proteins
during entry into a cell
5
6. How does HIV disseminate?
• One of the cell types first encountered HIV-1 following sexual
transmission are dendritic cells (DC)
• DC capture HIV-1 through C-type lectin receptors, of which
the best studied example is DC-SIGN(CD209), which mediates
HIV-1 internalization
• DC can keep the virus infectious for several days and are able
to transmit HIV-1 to CD4 T cells.
• Subsequent transmission to T cells takes place via an
“infectious synapse,” but a virus that has not been
internalized can also be transmitted to T cells
6
7. Target Cells of HIV
• Numerous organ systems are infected by HIV:
– Brain: macrophages and glial cells
– Lymph nodes and thymus: lymphocytes and
dendritic cells
– Blood, semen, vaginal fluids: macrophages
– Bone marrow: lymphocytes
– Skin: Langerhans cells
– Colon, duodenum, rectum: chromaffin cells
– Lung: alveolar macrophages
7
8. General Mechanisms of HIV Pathogenesis
• Direct injury
– Nervous (encephalopathy and peripheral neuropathy)
– Kidney (HIVAN = HIV-associated nephropathy)
– Cardiac (HIV cardiomyopathy)
– Endocrine (hypogonadism in both sexes)
– GI tract (dysmotility and malabsorption)
• Indirect injury
– Opportunistic infections and tumors as a consequence
of immunosuppression
8
9. General Principles of
Immune Dysfunction in HIV
• All elements of immune system are affected
• Advanced stages of HIV are associated with
substantial disruption of lymphoid tissue
– Impaired ability to mount immune response to
new antigen
– Impaired ability to maintain memory responses
– Loss of containment of HIV replication
– Susceptibility to opportunistic infections
9
10. Mechanisms of CD4
Depletion and Dysfunction
• Direct
– Elimination of HIV-infected cells by virus-specific
immune responses
– Loss of plasma membrane integrity because of viral
budding
– Interference with cellular RNA processing
• Indirect
– Syncytium formation
– Apoptosis
– Autoimmunity
10
11. Syncytium Formation
• A mass of protoplasm containing several
nuclei
• Observed in HIV infection, most commonly in
the brain
• Uninfected cells may then bind to infected
cells due to viral gp 120
• This results in fusion of the cell membranes
and subsequent syncytium formation
• These syncytium are highly unstable, and die
quickly. 11
13. Role of Cellular Activation in Pathogenesis
of HIV
• HIV induces immune activation
– Which may seem paradoxical because HIV
ultimately results in severe immunosuppression
• Activated T-cells support HIV replication
– Intercurrent infections are associated with
transient increases in viremia
– The magnitude of this increase correlates
inversely with stage of HIV disease
– Accounts for why TB worsens underlying HIV
disease
13
14. Role of Cytokine Dysregulation in
Pathogenesis of HIV
• HIV is associated with increased expression of
pro-inflammatory cytokines
– TNF-alpha, IL-1,IL-6, IL-10, IFN-gamma
– Associated with up-regulation of HIV replication
• HIV results in disruption and loss of
immunoregulatory cytokines
– IL-2, IL-12
– Necessary for modulating effective cell-mediated
immune responses (CTLs and NK cells)
14
15. Consequence of Cell-mediated
Immune Dysfunction
• Inability to respond to intracellular infections
and malignancy
– Mycobacteria, Salmonella, Legionella
– Leishmania, Toxoplama, Cryptosporidium,
Microsporidium
– PCP, Histoplamosis
– HSV, VZV, JC virus, pox viruses
– EBV-related lymphomas
15
17. Transmission
• Modes of infection
– Sexual transmission at genital or colonic mucosa
– Blood transfusion
– Mother to infant
– Accidental occupational exposure
• Viral tropism
– Transmitted viruses are usually macrophage-tropic
– Typically utilizes the chemokine receptor CCR5 to gain
cell entry
– Patients homozygous for the CCR5 mutation are
relatively resistant to transmission
17
18. Cell free
HIV
Skin or
mucosa
24 hours 48 hours
1. HIV co-receptors,
CD4 + chemokine
receptor CCR5
Immature
Dendritic cell
3. Mature Dendritic cell in
regional LN undergoes
a single replication,
which transfers HIV to
T-cell
Via lymphatics or
circulation
T-cell
PEP
Burst of HIV
replication
2. Selective of
macrophage-
tropic HIV
Early Phases of HIV Infection of Mucosal
Surfaces
18
19. Laboratory Markers of HIV Infection
• Viral load
– Marker of HIV replication rate
– Number of HIV RNA copies/mm3 plasma
• CD4 count
– Marker of immunologic damage
– Number of CD4 T-lymphocytes cells/mm3 plasma
– Median CD4 count in HIV negative Ethiopians is
significantly lower than that seen in Dutch controls
• Female 762 cells/mm3 (IQR 604-908)
• Male 684 cells/mm3 (IQR 588-832)
19
21. 0
100
200
300
400
500
600
700
800
900
1000
0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11
weeks years
CD4+ cells
modified after Pantaleo et al., NEJM, 1993
Primary HIV infection
Acute HIV Syndrome
(Acute RetroviralS~)
clinical
latency*
constitutional
symptoms
plasma
viremia
AIDS
very
early disease
early disease
advanced disease
* high rate of replication
in lymphoid tissue
steady state
21
HIV Disease Progression
22. Primary HIV Infection
• The period immediately after infection characterized by
high level of viremia (>1 million) for a duration of a few
weeks
• Associated with a transient fall in CD4
• Nearly half of patients experience some mononucleosis-
like symptoms (fever, rash, swollen lymph glands)
• Primary infection resolves as body mounts HIV-specific
adaptive immune response
– Cell-mediated response (CTL) followed by humoral
– Patient enters “clinical latency”
22
23. Window Period: Untreated Clinical Course
23
--------------------------------------------PCR
P24
ELISA
0 2 3 4
Weeks since infection
a b Time from a to b is the window period
viremia
antibody
Asymptomatic
Acute HIV syndrome
Primary
HIV
infection
Source: S Conway and J.G Bartlett, 2003
years
25. Relative Control of HIV: Viral Set Points
25
Year 1
Predictor for:
-Disease progression
-Risk of transmission
Low set point = slower
disease progression
High set point = faster
disease progression
26. HIV RNA Set Point Predicts
Progression to AIDS
• HIV RNA viral loads after infection can be used
in the following ways:
– To assess the viral set point
– To predict the likelihood of progression to AIDS in
the next 5 years
• The higher the viral set point:
– The more rapid the CD4 count fall
– The more rapid the disease progression to AIDS
26
27. CD4 T-cell Count and Progression to AIDS
• In contrast to VL, baseline CD4 is not a good
predictor of time to progression to AIDS
– Unless CD4<321 cells/ml
• However, as the CD4 count declines over time,
patients will develop opportunistic infections
– Develop in a sequence predictable according to
CD4 count
– WHO Staging system
27
28. Patterns of HIV Disease Progression
28
HIV
Infection
Long-term
Non-progressors
Rapid Progressors
Typical Progressors
<3 years
7-10 years
>10-15 yrs
Normal, Stable CD4
90 %
<5 %
<10 %
29. Immune Response in Children
• Absolute CD4 cell count age-dependent (disease
progression expressed as CD4%)
• Variability in disease progression similar to adults
• Viral set point is higher in children
25-30 % die within 1 year (rapid progressors)
• 50-60 % die within 3 to 5 years
• 5-25 % live beyond 8 years (slow
progressors)
29
30. Acute Retroviral Syndrome
Clinical
• Non-specific ‘flu-like’ symptoms, which do
not lead directly to the diagnosis of HIV
infection and which are not present in all
patients
• Fever
• Fatigue
• Pharyngitis
• Lymphadenopathy
• Rash
30
31. Acute Retroviral Syndrome
Lab markers
31
• HIV test May be Negative
• HIV RNA levels (usually >50 000 copies)
Period of extreme infectiousness
Be aware of false negatives
• Using rapid tests >95% of patients will
test positive within 6 months
32. Acute Retroviral Syndrome:
Management
32
• Clinical management is primarily
symptomatic, unless serious and prolonged
seroconversion illness (e.g. meningitis):
HAART
• Goal is to give appropriate counseling and
education to prevent further spread
• Issues to consider:
• Patient’s self-reproach
• Implication for patient’s lifestyle
• Patients are most likely to transmit HIV during
the early stage of infection
34. Clinical Latency
• At CD4 cell counts over 500 cells/ml, many
complications overlap with conditions found in
the general population (malaria, bacterial
pneumonia, tuberculosis, minor skin
conditions) although they may be more
frequent
• At CD4 counts between 200 and 500 cells/ml,
other conditions, or opportunistic infections,
begin to appear (Kaposi’s sarcoma, oral or
vaginal candidiasis, herpes zoster, etc.)
34
35. Key Points
• HIV is a retrovirus, capable of integrating into host genome
and establishing chronic infection
• The important steps in the lifecycle of HIV include cell entry,
reverse transcription, integration, and maturation/assembly
• Cell-mediated immunity is critical for containment of HIV
infection and other intracellular infections
• HIV evades host immunity by a variety of mechanisms
• HIV activates the immune system initially to increase its own
replication
• CD4 count declines by both direct and indirect mechanisms
• HIV RNA set point predicts rate of progression to AIDS
• CD4 count decline is associated with a predictable sequence
of opportunistic infections
35