MHAM

COLLEGE OF MEDICINE CLASS 2024

Diseases of the Immune System (Part 3)
Abelardo Alera, M.D. | September 20, 2021
GENERAL PATHOLOGY

Outline 5. New viral RNA is used as genomic RNA and to

I. Immunodeficiency make viral proteins
A. HIV 6. New viral RNA and proteins move to the cell
B. Primary Immunodeficiency surface, and a new, immature HIV forms.
C. Amyloidosis
7. Virus is released. Viral protease cleaves new
D. Secondary Immunodeficiency
E. HIV Discussions polyproteins to create mature infectious viruses.

Statistics
LEGENDS
Presentations remember lecturer previous
DOH on HIV
exams

I. IMMUNODEFICIENCY
Know which type of autoimmune disorder is more
common. Is it primary or secondary?
Know the most common primary and secondary
types of autoimmune disorders.

A. HIV
Mechanism of Action

→ As of July 2021, we have 1000+ new cases

→ Majority is males
→ Majority are young individuals
→ Signs and symptoms + exposure (especially
unprotected anal sex) = high probability of being
HIV positive
HIV in the Philippines

→ Fast growing
→ July 2021 = 89,153 cases
→ Our country is part of the top 9 countries that has
contributed TB to the world
→ In the Ph, the rate of HIV infection is going up,
while in the other parts of the world, it is going
Figure 1 Propagation of HIV in the Body down
1. Fusion of HIV to the host cell surface
2. HIV, RNA, reverse transcriptase, integrase, and
other viral proteins enter the host cell
3. Viral DNA is formed by reverse transcription
4. Viral DNA is transported across the nucleus and
integrates into the host DNA.

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 DOH on HIV Q&A
1. HIV kills a person directly
Answer: False
2. Everyone infected with HIV eventually gets AIDS
Answer: False
AIDS is the terminal event of HIV infection. If the
patient takes antiretroviral (ARV) drugs, most
likely the said patient will not reach the terminal
→ 95% = sexually transmitted stage (AIDS) of the infection.
→ >50% of the cases are 24-35 years old 3. HIV infected people who get early treatment by
→ Three (3) were less than 15 years old an HIV specialist live longer
→ Median age = 28 (1-67 years old) Answer: True
A lot of HIV positive patients are still alive
Table 1 Number of HIV cases diagnosed by MOT, July 2021 because of ARV drugs.
4. What is the difference between HIV and AIDS?
Answer: HIV is the infection. It starts from the
asymptomatic stage and then to the final stage,
which is AIDS.
5. Effectiveness of antiretroviral therapy is
measured by:
A. A fall in the plasma viral load and an increase
in the CD4 count
B. A rise in RBC count and hemoglobin level
C. A rise in plasma HIV antibodies level
D. A reduction in opportunistic infections
Answer: A
CD4 is the basis. Normal count ranges from 500-
Issues Seen in Patients with HIV 1,600 cells/mm3. If the patient started with 20,
1. AMs are hard and the patient will now have 1200, then that is
2. Check for the rashes/bumps a good sign.
3. I never meet their eyes
4. Emotional torment/stigma may end me 6. The decision to begin antiretroviral therapy is
5. Praying for a false positive based on:
6. Family has no clue A. The CD4 cell count
7. Hoped that ex-BF is going to be supportive B. The plasma viral load
8. Pray for false positive C. The intensity of the patient’s clinical
9. I talk to God crying symptoms
10. My illness has cost me my relationship and D. AOTA
sanity Answer: Before, it is based on the CD4 count.
But now, it is only based on the patient’s positive
11. I am afraid - future, rejection, SE
HIV test result. Therefore, the patient needs the
12. Help me find beauty
AVR drug as soon as the pt. tests positive.
13. Awareness and stigma, help others
14. I am alone 7. Which is most important in cases of a patient
15. Bargain live tomorrow week month year diagnosed as AIDS and who is expressing death
16. 2 years wishes?
A. Immediately send the patient for HIV
confirmation tests
B. Immediately start antiretroviral therapy (ART)
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 C. Send the patient for CD4 count testing → Cellular immunity deficiency
D. Treat the patient for depression and suicidal → Combined immunodeficiency disease
thoughts → Non-specific immunodeficiency diseases
Answer: D

8. Oral candidiasis in AIDS is treated with:

A. Trimethoprim + sulfimethaxazole
B. Fluconazole
C. Acylovir
D. Zidovudine
Answer: B

Learning Objectives
1. Explain the normal response of the body to
external forces that can cause infection
2. Differentiate the innate and adaptive immunity
3. Describe the difference between a cellular and
humoral response Figure 2 Primary Immune Deficiency Disorders

4. Discuss the role of the cytokines in the immune

This is one way of looking at the etiology and
response pathogenesis. When the antibodies are damaged,
5. State the role of lymphocytes activation in the we are going to end up with immunodeficiency. In
immunity of the host HIV, if the macrophages and CD4 cells are damaged
6. Classify hypersensitivity reaction based on a then there is no more immunity.
given case
7. Differentiate the autoimmune disorders Deficiency of Innate Immunity
Table 2 Deficiency of Innate Immunity
8. Classify the cause of immunodeficiency
9. Explain the role of the immune response in
HIV infection
10. Discuss the clinical importance of amyloids

Specific Learning Objectives:

• Given a clinical case involving an (1)
immunodeficiency disorder, (2) amyloidosis,
and (3) HIV/AIDS, differentiate each according
to types, causes, pathogenesis, morphology,
clinical manifestations, laboratory diagnosis,
and general management.
B. PRIMARY IMMUNODEFICIENCY
● Hereditary, development defect
● Infancy and childhood
Most of the time, primary immune deficiency is One of the things that we will see in Clinpath is
noted in pediatric patients showing recurrent Chediak-Higashi syndrome. In board exams, if the
infections within 6 months to 2 years of life. problem is in the complement the answer is
● Abnormal differentiation and development of Neisseria species. With Neisseria meningitidis, the
hemopoietic stem cells patients have complement system problems making
● Deficiency of innate immunity ★ them more susceptible to getting meningococcal
→ Leukocyte deficiency infection.
→ Phagocyte deficiency
→ Complement deficiency
● Deficiency of adaptive immunity
→ Humoral immunity deficiency
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Deficiency of Adaptive Immunity In T-cells, there is only one thing to remember:
• Congenital immunodeficiency disorders there is something wrong with thymic gland
→ B-cell disorders because of hypoplasia, called DiGeorge
▪ recurrent encapsulated bacterial syndrome, a congenital problem. Results in tetany
infections (Strep. pneumoniae) and recurrent infections, especially pulmonary.
▪ extracellular Table 5 Combine B- and T-cell Disorders
→ T-cell disorders
▪ recurrent infections caused by
intracellular pathogens (fungi,
viruses, protozoa)
▪ intracellular
→ Combined B- and T-cell disorder
Table 3 B-cell Disorders

In board exams, most likely Wiskott-Aldrich

syndrome is going to come out. Remember the
Triad: eczema, thrombocytopenia, recurrent
sinopulmonary infection.
Ataxia telangiectasia- abnormality of the blood
vessels; mutation in DNA repair
Board exam: Baby dies + parent has HIV, then that could be a
→ In Bruton’s agammaglobulinemia, the problem severe combined immunodeficiency.
is that pre-B-cells fail to become mature. Yielding
less antibodies.
→ IgA is for protection in mucosal surfaces. If this
is deficient, the pt. is going to have a lung
infection, giardiasis, and decreased IgA.
→ Failure of B-cell maturation to plasma cells
lead to sinopulmonary infection, upper or lower
respiratory tract infection, and less antibodies
Table 4 T-cell Disorders

In developed countries, the most common cause

of death in patients with HIV is pneumocystitis
jiroveci (carinii). In the Philippines (developing
countries), the most common cause is pulmonary
tuberculosis.

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Key Concepts
● Primary Immune Deficiency Diseases
→ Due to inherited mutation in genes-
lymphocytes/ innate immunity
→ Deficiency in innate immunity-
phagocyte, complement, immune
receptors
Figure 3 Amyloidosis w/ Congo red stain and in polarized light
→ Examples of the disorder of the adaptive
response
→ Presentation- susceptibility to infection in
early life
C. AMYLOIDOSIS
• Amyloid
→ Fibrillary protein that forms deposits in
interstitial tissue, resulting in organ
dysfunction.
• Characteristics
→ Linear, non-branching filaments in a beta-
pleated sheet
→ Apple green birefringence in polarized
light
→ Stains red with Congo red stain
→ Exhibits eosinophilic stain with H&E stain
• Types Alzheimer’s = beta-amyloid deposits
1. Systemic Parkinson’s = dopamine
→ Primary: associated with multiple Appearance of the brain with Alzheimer’s=
myeloma (30% cases) atrophy
→ Secondary (reactive): associated
with chronic inflammation, such as
rheumatoid arthritis or
tuberculosis
2. Localized
→ Confined to a single organ (i.e., brain)
3. Hereditary
→ Autosomal recessive disorder
involving familial Mediterranean
fever
• Diagnosis
→ Immunoelectrophoresis, tissue biopsy
(adipose, rectum)
Table 3 Classification of Amyloidosis

Key Concepts
• Amyloidosis is a disorder characterized by
the extracellular deposits of misfolded
proteins that aggregate to form insoluble
fibrils.
• The deposition of these proteins may result
from: excessive production of proteins that
are prone to misfolding and aggregation;
mutations that produce proteins that cannot
fold properly and tend to aggregate; and
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 defective or incomplete proteolytic
degradation of extracellular proteins.
• Amyloidosis may be localized or systemic.
It is seen in association with a variety of
primary disorders, including monoclonal B-
cell proliferations (in which the amyloid
deposits consist of immunoglobulin light
chains); chronic inflammatory diseases such
as rheumatoid arthritis (deposits of amyloid
A protein, derived from an acute-phase
protein produced in inflammation);
Alzheimer disease (amyloid β protein);
familial conditions in which the amyloid
deposits consist of mutants of normal
proteins (e.g., transthyretin in familial “HIV is more of a social issue, especially now
amyloid polyneuropathies); and amyloidosis that we tend to stigmatize it” - Alera, 2021
associated with dialysis (deposits of β2-
microglobulin, whose clearance is Natural History of HIV Infection Summary
defective). ● HIV multiplies inside the CD4 cells, destroying
• Amyloid deposits cause tissue injury and them.
impair normal function by causing ● As CD4 cell count decreases and viral load
pressure on cells and tissues. They do not increases, the immune defenses are weakened.
evoke an inflammatory response. ● People infected with HIV become vulnerable to

D. SECONDARY IMMUNODEFICIENCy opportunistic infections.

● HIV is a chronic viral infection with no known
Table 4 Causes of Secondary (Acquired) Immunodeficiencies cure, but there is treatment.
● Without ARV, treatment, HIV progresses to
symptomatic disease and AIDS.
→ Antihypertensive and antidiabetic drugs
are expensive but ARV is free.
→ ARV should be taken for a lifetime
With decreased antibodies, there will be no
protection resulting to many opportunistic infections,
which are infections seen among healthy individuals.
Epidemiology
• Transmission
Most likely HIV 1. Blood
In the history taking, ask if the patient is under 2. Mother to child
some form of immunosuppression (most likely in 3. Sex
cancer treatment or if they have cancer) • Body fluids
Malnutrition can trigger immunodeficiency 1. Vaginal discharge
Splenomegaly= malaria or leukemia 2. Semen
3. Blood
4. Milk of mother
Remember the STIs
• Prevention
1. Advocacy for testing
2. Get tested
3. If positive, get treated
Test those who are at high risk:
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 ● People having multiple sex partners Clinical latency- TB, HIV, bacteria, and virus stay
● IV drug users in the macrophages. Once inside the macrophages,
● Babies with mothers infected with HIV they are not going to be attacked by the immune
response. As the immune system becomes weaker,
the latent infections become active.

AIDS is the terminal event of HIV, where there is

almost total depletion of CD4.

Table 5 AIDS-Defining Opportunistic Infections and Neoplasms found

in Patients with HIV Infection

What are HIV+ pinoys dying of?

Key Concepts
• Pathogenesis and Course of HIV Infection and
AIDS (5 steps)
1. Virus entry into cells: require CD4 and
co-receptors, which are receptors for
chemokines; involves binding of viral
gp120 and fusion with the cell mediated by
viral gp41 protein; main cellular targets are
CD4+ helper T cells, macrophages and,
DCs
2. Viral replication: provirus genome
integrates into host cell DNA; viral gene
expression is triggered by stimuli that
activate infected cells (i.e., infectious
microbes, cytokines produced during
normal immune responses)
3. Progression of infection: acute infection
of mucosal T cells and DCs; viremia with
dissemination of virus; latent infection of
cells in lymphoid tissues; continuing viral
Figure 4 Clinical Course of HIV Infection

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 replication and progressive loss of CD4+ T Burkitt lymphoma, Epstein-Barr Virus (EBV),
cells Kaposi’s sarcoma herpesvirus (KSHV)
4. Mechanism of immune deficiency:
→ Loss of CD4+ T cells: T cell death
during viral replication and budding
(similar to other cytopathic
infections); apoptosis as a result of
chronic stimulation; decreased
thymic output; functional defects
→ Defective macrophage and DC
functions Figure 5 Pathogenesis of B-cell lymphomas in HIV infection
→ Destruction of architecture of
lymphoid tissues (late)
5. Clinical manifestations of AIDS include
opportunistic infections, tumors such as B-
cell lymphomas, and CNS abnormalities.
You can never tell who has the infection
D. HIV DISCUSSIONS To stop the spread of HIV, never tell people not to
have sex, because this is a physiologic need.
Instead, we should raise awareness and promote
safe sex.

Figure 6 Comparison of HIV Cases

Figure 6 Life Cycle of HIV

This is a retrovirus, which has to make a DNA

copy of its genome. If there is DNA, there is
integration of the provirus, consequently replicating
into many viruses, leading to cell death (in most
cases).

Figure 9 Losing the Fight Against HIV in the Ph

Figure 7 Pathogenesis of B-cell Lymphomas in HIV Infection
In 1984, there were 2 cases of HIV infection in the
Abnormality of the immune response causes
Ph
cancer
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What’s causing the alarming increase of HIV in
our country?
Answers of 2nd year Med students that are wrong:
→ Call center agents
The aforementioned are good examples of
▪ This is not true. It is not the office. It
ignorance. A group of people who think they know
is the behavior.
and can place ideas in the mind of everyone
→ Gays surrounding them. But that's not going to happen,
▪ The virus does not know who is especially if you tell a person with any types of illness
straight and who is gay. The virus will that they’re going to die tomorrow; that's not being a
not choose. There is no border, race, good doctor, because a good doctor is someone
gender, and preference. Everyone is who saves lives.
going to be affected. “The kindest thing you can do for someone else is
→ Men having sex with men is “not listen without forming an opinion.” - Lori Deschene
appropriate.” If you're listening to someone who's HIV positive,
▪ The phrase “not appropriate” will don't tell that person, “I know about your case..” or
cause us problems. “How many boyfriends have you had?“. This person
▪ “What is normal?” It should be is going to walk out on you because that is none of
between a male and a female, maybe your business. You did not ask the correct question.
because of religious beliefs. This is the way that a physician would ask
However, putting people in boxes is questions sensitive questions, especially sexual
unfair. exposure:
Tell the patient or the donor, “I'm going to ask you
→ “Young adult people and gay people
questions that's sensitive but this is important for me
because they are active in sex and more
to make a diagnosis.” So that the person will not be
tempted to sexual life”.
shocked.
▪ Everyone is active in sex. It is a
→ We need to start always with the transmission:
choice to have sex or remain virgin.
▪ “HIV is transmitted most of the time in our
No one can contest your opinion and
country more than 95% through sex.”
beliefs because they are yours.
▪ Tempted to sexual life – don’t worry → Followed by prevention:
about temptation because our brain is ▪ “This can be prevented by the proper and
wired to have sex. We cannot tell consistent use of condoms.”
people not to have sex. We need to → Then you can now ask the questions:
multiply as people; if not, that’s going ▪ Did you have any unprotected sexual
to be the end of the human race. encounters with males or females?
▪ Doctors, think about this, we are not ▪ Other than telling the person, “You got your
pastors or priests. Let the people in infection from your boyfriend.” What if this
the church talk about temptation, person got HIV from prick injury from
that’s not going to be our problem. transfusion of blood?
→ Horny gay person Be very careful with the things that we tell our
▪ If there's a person who is not horny, patient. Never form an opinion not unless the patient
tells you so. This is the reason why we really need
then there is something wrong with
to ask questions. If these are STIs, it's really
their brain and they need to see a
important to talk about transmission.
psychiatrist, because sex is a normal
part of our life. We need to long for
sex because we're human, and if not,
then we are most likely a robot or
someone from space.”

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 This was a study done in Manila and Baguio. The
subjects were more than 500 men having sex w/
men (MSM; now termed men loving men). One of
those 500 and > 600 partners in a year.

The holiest person in the world is not going to

judge HIV positive individuals. Do not tell the people
they’re going to hell because they are a very bad
person with so many sex partners. It’s none of your
Figure 10 Factors that Inc. HIV Infection among MSMs and
business as a doctor, because our business now is Transgender Females
treating that infection. You can talk about
prevention, but we should not judge.
Versatile anal sex- versatile meaning left and right;
top or bottom.
When you have a patient with HIV, check for other
STIs because they don’t usually come sickly.
Alcohol and drugs are the best way to get the
infection because there will be no more inhibition.

This is the reason Filipinos are not fond of using

condoms. They tend to get judged by people around
them when buying one.
Where people use the condoms for is none of our
business.

For prevention, test and treat

→ Main reasons why people don’t get tested for
HIV: fear, lack of time, and feels no need to
get tested

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Clinical Findings of HIV syndrome 3-6 weeks after infection, and this
● Acute phase resolves spontaneously in 2-4 weeks
→ Mononucleosis-like syndrome 3-6 • Acute illness with non-specific symptoms:
weeks after infection. → Sore throat, myalgias, fever, rash, weight
● Latent (chronic) phase loss, and fatigue
→ Others: coccidioidomycosis (CM),
→ Asymptomatic period 2-10 years after
cervical adenopathy, diarrhea, and
infection vomiting.
→ CD4 T-cells >500 cells/uL
→ Viral replication in follicular dendritic cells
● Early symptomatic phase
→ CD4 T-cells 200-500 cells/uL
→ Generalized lymphadenopathy, hairy
leukoplakia, EBV- caused glossitis
→ Fever, weight loss, diarrhea
● AIDS
→ HIV + with CD4 T cell count ≤200 cell/ul or
with an AIDS-defining condition

HIV Tests
• CD4 count monitoring immune status
Figure 8 Laboratory Parameter
• HIV viral load
→ Detection of actively dividing virus • Two times in the life of the patient that the viral
→ Most sensitive test for diagnosis of acute load is high
HIV before seroconversion 1. Initial infection
→ Test to find out progression to AIDS 2. AIDS stage
Clinically, any patient with good appetite, are • If the patient is asymptomatic, the viral load is
physically active, and afebrile are signs that the low.
patient is getting well. Table 6 Major Abnormalities of Immune Function in AIDS

Figure 7 Western Blot Reactivity

In other countries, the way to test HIV is two (2)

different positive ELISA tests. The Ph is still using
the Western Blot (only in two areas of the PH)
• It is estimated that 40-90% of individuals who
acquire a primary infection develop the viral Know the different abnormalities that’s causing
immunodepression
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Table 7 AIDS-Defining Opportunistic Infections and Neoplasms Found
in Patients With HIV Infection

→ Not all PLHIV will look like this

→ Patients with pneumocystis, candidiasis,

cytomegalovirus are going to be blind

→ Answer: Don’t judge!!!

Everyone has the right to be happy

Figure 9 Kaposi Sarcoma

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 Sad thing is, we always laugh about the
misfortunes of others. We tend to discriminate. We
can never tell what’s going to happen to your
classmate so the important thing to remember is, we
should not judge.

We have what is known as care counselling.

These people would try to make their life as healthy
as possible. But the most important thing is if we talk
to these individuals, and they would finally accept
themselves, most likely HIV transmission is going to
stop.

When should the patient be treated?

Answer: As soon as the patient tests positive

If we don’t address the issue, most likely we will

lose this patient to follow up and this patient is going
to be the source of infection. So, we need to respect
the rights of these people (right to have sex and the
right to have a happy life).

Figure 10 Advocate for consistent and correct use of condoms

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 Ask the patient:
How many times are you injecting?
Are you sharing needles?

→ Research shows that on the average, the earliest

time that Filipinos have sex is at 16 yo and the
earliest time that Filipinos use drug is at 19 yo.
How do you prevent the transmission of HIV
infection among our drug users?
Answer: Harm reduction

The best prevention is treatment. When the

patients are taking the ARV, only 4% of them are
likely to transmit the infection and this is especially
good for serodiscordant couples. one is positive and
one is negative.

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 Treatment is all about viral suppression. After 6
months of taking the meds daily, the suppression
goes down immediately to 90% (92% at 12 mos).

The worst barrier really are the doctors

themselves, such as when that doctor tells people
not to get immunized.

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