Disorders of the immune system

What can go wrong with your immune system?

There are grossly FOUR bad situations.

i) An immune system that turns against its own self
aka autoimmunity
ii) Being born with a weak immune system (aka
primary immunodeficiency-PID).
iii) Suffering a disease/process/event that weakens the
immune system (aka. acquired immunodeficiency).
iv) Have an immune system that is over active (aka.
Hypersensitivity ...)
 1. Autoimmune disease
• An autoimmune disease (AD) is a condition arising
from an abnormal immune response to a normal body
part were the immune system attacks ones body
instead of protecting it

• It's unclear why autoimmune diseases occur but

there are at least 80 types of autoimmune diseases
which can involve any body part

• Symptoms of AD are nonspecific, diverse and the

symptoms are often recurrent i.e come and go.
• Autoimmune diseases can affect many types of
tissues and nearly any organ in your body

• They are associated with a variety of symptoms

including pain, tiredness (fatigue), rashes, nausea,
headaches, dizziness and more.

• Specific symptoms depend on the exact disease and

affected organ/tissue.
• “Experts don’t know why your immune system
turns on you. It is like it can no longer tell the
difference between self and what is not —
between what’s you and what’s an invader.
There are some theories about why this
happens, but experts aren’t quite sure why”
• Many ADs, eg. ulcerative colitis, are heritable
(genetic), quite common and can affect any
part/system of the body eg. skin, digestive,
reproductive, neural, joints and muscles, endocrine
systems.

• They affect at least 10% of the population,

predominantly women
• They are non communicable but can be fatal especially
in persons above 60 years

• Some ADs can affect conception and pregnancy and

one may require fertility treatments to conceive and
maintain pregnancy.

• For example, there is a higher risk for stillbirth or

preterm birth in females with an AD disease called
lupus erythomatosis.
 Factors that may predispose autoimmune
disease
These include:
• Genetical: Some diseases run in families
• Some medications.
• Certain Infections
• Exposure to toxins.
• Being female — 78% of people who have an
autoimmune disease are natural women.
• Foods/feeding (eg obesity) .
 Symptoms of autoimmune diseases
• Variable and depend on the disease and part of body
affected
Disease Symptoms
Organ/part affected
Diseases of the joints and muscles Muscle aches and pains.
Joint pain, stiffness and swelling.
Muscle weakness.

Diseases of the digestive tract: Bloating.

Constipation.
Acid reflux.
Nausea.
Food sensitivities.

Diseases of the skin Rashes, Itching, Dry eyes.

Hair loss, Dry skin

Diseases of the Dizziness. Headaches.

nervous system: Anxiety and depression.
 Diagnosis of autoimmune diseases

It is a lengthy procedure and requires:

i) A detailed list of any symptoms and duration - how
long you’ve had them.

ii) A record of your family’s health history. Eg family

member with an autoimmune disease record.
iii) Analysis of symptoms, some blood tests eg.
• Antinuclear antibody test (ANA).
• Complete blood count (CBC).
• Erythrocyte sedimentation rate (ESR)
 Examples of AD related/associated conditions
• Lupus
• Scleroderma
• Certain types of hemolytic anemia
• Vasculitis
• Type 1 diabetes (diabetes mellitus)
• Rheumatoid arthritis (aka Rheumatism)
• Multiple sclerosis)
• Some types of myopathy
• Alopecia
• TB, Leprosy, angina pectoris (myocarditis)
• Eg: 1)Rheumatoid arthritis (RA) is a long-term
autoimmune disorder that primarily affects
joints. It typically results in warm, swollen,
painful joints and deformity
• 2) Advanced stage leprosy
Rheumatoid arthritis
 Le

Leprosy autoimune reaction leading to deformity of limbs grade 2

deformity ( D2G)
 Treatment of autoimmune diseases
• There are no specific treatment regimes for
autoimmune diseases, therefore management is
done symptomatically

• Given that individuals’ immune system, genetics and

living environment are different, the treatment of
autoimmune diseases will also be unique.
• Most common treatments include:
• Painkillers, anti-inflammatories and
corticosteroids

• Alternative (traditional) medicines (herbs…

acupuncture have also been used
 2. Immunodeficiencies

• Immunodeficiency, also known as

immunocompromisation, is a state in which
the immune system's ability to fight infectious
diseases and cancer cells is impaired
• There are two types of immunodeficiency disorders:
those a person is born with (ie primary aka innate),
and those that are acquired (secondary).

• Extrinsic factors can adversely (weakens) body’s

immune responses, producing states of secondary
immunodeficiency and consequent increased risk of
infections
• These immunodeficiencies can be encountered in
routine clinical practice and can arise from a
number of conditions eg.
i) Prolonged treatment with glucocorticoids and
immunomodulatory drugs
ii) Trauma and surgery
iii) Extremely stressful environmental conditions
iv) Chronic infections, such as those caused by
HIV.
 2.1 Primary Immunodefficiency

Clinical manifestations of PIDs are highly variable

should be suspected in patients with:
i) Frequent recurrent sinus or ear infections or
ii) Repeated pneumonias within a 1 year period
iii) Failure to thrive (stunting, wasting)
iv) Poor response to prolonged use of antibiotics
v) Persistent thrush or skin abscesses;
vi) a family history of PID
• The treatment of PIDs is complex and
generally requires both supportive and
definitive strategies
• Ig replacement therapy is the most effective
therapy for B-cell disorders, as well as for
patients with combined immunodeficiency ( B
& T cell deficiencies), aka CID
• For disorders involving the T-cell arm of the
adaptive immune system, such as severe
combined immunodeficiency (SCID),
immediate immune reconstitution is required
supported with antibiotics and antifungals
• In worse cases vaccinations and bone marrow
transplantation may be employed.
 2.2 Secondary immunodeficiencies (SID)

• Secondary immunodeficiency (SID) is said to occur

when the immune system is weakened by a
treatment or illness.
• Most common causes are:
- Disorders of blood due to bone marrow
malfunction (Leukemia),
- Drugs (medicines) for cancer treatment eg.
chemotherapy
- Immune-complex diseases, like viral
hepatitis and diabetes mellitus
- Severe burns
• Perhaps the most well known SID secondary
caused by HIV infection
• However, the most prevalent cause of
immunodeficiency worldwide is severe
malnutrition, which affects as many as 50% of
the population in many impoverished
communities.
• The immune defects observed in SID are usually
variable in their clinical presentation, and their
prognosis depends on the severity of the immune
defect.
• Management of the PIDs often results in
improvement of the immunodeficiency;
• However, this is sometimes not possible, and the risk
of infections must be reduced with prompt
antimicrobial treatment and prophylaxis
• The restoration of immunity in SIDs is
generally achieved with the management of
the primary condition eg good nutrition or
the removal or attenuation of the offending
agent eg. suppressing HIV by using ART.
 MALNUTRITION

• Worldwide, protein-calorie malnutrition is the

most common cause of immunodeficiency.
• Malnutrition can result from limited access to
food sources, eating habits and chronic
diseases that induce cachexia, such as
neoplastic (cancerous) diseases.
• Diarrhea caused by infections and respiratory
tract infections are common in such
communities.
• T-cell production and function decrease in
proportion to the severity of hypoproteinemia;
• Although , specific antibody titers and immune
responses to vaccines can be detected in a
malnourished subject for a prolonged period.
• Eventually, these immune responses decrease
too if malnutrition persists.
• The deficiency of micronutrients (eg, zinc and
ascorbic acid) contributes to increased
susceptibility to infections through the
weakening of skin and mucosa barriers, which
facilitates a pathogen invasiveness.
• Vitamin D appears to be necessary in the
macrophage activity against intracellular
pathogens, remarkably Mycobacterium
tuberculosis
• Correction of the nutritional deficiencies often
results in the resolution of these immunologic
defects.
 HIV

• HIV is transmitted sexually, for the most part,

but it is also transmitted parenterally among
intravenous drug users and vertically from
mothers to their infants
• Initially recognized during the early 1980s in a
handful of cases, it is currently estimated that
more than million persons are infected with
HIV worldwide.
• Two thirds of HIV subjects are living in the sub-
Saharan region of Africa, and approximately half of
them are women and childr

• Significant reduction of HIV related diseases has

been achieved in the past two decades thanks to
antiretroviral use

• However, there is an increasing number of reports of

viral multidrug resistance and clinical complications
caused by the chronic use of antiretroviral drugs.
 HIV infection process

The HIV uses CD4 cell receptors on the surface of the T-

helper (Th) lymphocyte gain entry into this important
immune regulator cell 
-The virus achieves this  through its viral
envelope protein known as gp120
- T helper cells (Th) are lymphocytes that are
an essential part of the human immune system.
- They are commonly  referred to as CD4+ cells, or T4
because of the specific type of peptide molecules
constituting it.
CD means Cluster of differentiation, and there are over 300
such clusters on different cells of animals and humans
• They are called helper cells because one of
their main roles is to send signals to other
types of immune cells, including CD8, aka
cytotoxic  killer cells, which specifically destroy
cells infected with intracellular pathogens.
 
• CD4+ is indeed a co-receptor on the 
T cell receptor (TCR) surface and
assists the latter in communicating with 
antigen-presenting cells in normal health
situations 
• The TCR-CD4 complex bind to distinct regions
of the antigen-presenting cells 
• HIV then inserts a fusion peptide into the Th cell that
allows the outer membrane of the virus to fuse with
the cell membrane

• Gradually it transduces the CD4+Tcell into producing

more of HIV particles and later cell dies while more
HIV particles are released to continue with the
cascade
• HIV infection leads to a progressive reduction in the
number of T cells expressing CD4+ in the lymphatic
system

• Ultimately the entire cell mediated arm of immune

defense becomes impaired

• Consequently, the body becomes weakened and more

vulnerable to pathogens, including high rise of
opportunistic infections
• HIV infection can be suppressed by use of
antiretroviral (ARV) drugs
• To monitor infection status medical
professionals refer to the CD4+ cell count to
appreciate the level of severity of disease for
inception of ARV use during HIV infection,
• Recent WHO guidelines require
 treatment at all HIV victims, regardless the
CD4+ count soonest if HIV is diagnosed
• A CD4+ count merely  indicate  the number of
T cells expressing CD4+ but are not a direct 
HIV test—e.g. they do not check the presence
of viral DNA load.
 3 Hypersensitivity

• Hypersensitivity reaction or intolerance) refers

to undesirable reactions by the normal immune
system
• It is the third major disorder of the immune
system, also referred to as an overreaction of
the immume mechanism
• Hypersensitivity may cause a severe discomfort
to an individual and in some cases serious
impairment and even death
 Types of Hypersensitivity
There a four types (i-iv) of   hypersensitivity
Type I hypersensitivity
• Type I hypersensitivity occurs as a result of
exposure of an antigen to the immune
system after which two stages of events occur,
namely sensitization and the effect stages.
• In the "sensitization" stage, the
host experiences an asymptomatic reaction to
the antigen.
• In a subsequent re-encounter with the antigen , ie in
the "effect"  period, the sensitized host over reacts
to the antigen

• This over-reaction is also referred to as type 1

anaphylactic, atopic or allergic immune response.
Triggers of Hypersensitivity Type I include: 
• Foods products: nuts, eggs,
soy, wheat, shellfish…,
• Animal/insect sources: bee, wasp,  hairs of
cats, rats, 
• Environmental factors: dust mites, latex,
pollen, molds, etc.
Immune responses include:
• Allergic asthma, allergic rhinitis, conjunctivitis,
dermatitis, etc.
• Medication-associated allergic reactions vs
 antibiotics, sulphonamides
Type II hypersensitivity
Type II hypersensitivity reaction is also referred to as
antibody-mediated immune reaction

• In this type, antibodies (IgG or IgM) are directed

against “self” cellular or extracellular antigens with
the resultant “self”cellular destruction, functional
loss, or damage to tissues.
• Damage can be accomplished via three
different mechanisms:
i) Antibody binding to cell surface receptors and
altering cellular activity
ii) Activation of the complement pathway ending
with MAC.
ii) Antibody-dependent cellular cytotoxicity.
 
Type III hypersensitivity
• In type III hypersensitivity reaction, an abnormal
immune response is mediated by the formation
of Ag-Ab aggregates (aka "immune
complexes)".
• These complexes then precipitate in various
tissues such as skin, joints, vessels, or glomeruli,
and trigger the classical complement pathway.
• Complement activation leads to the recruitment of
inflammatory cells (monocytes and neutrophils) that
release lysosomal enzymes and free radicals eg (O-)at
the site of immune complexes, causing tissue damage.

• The most common diseases involving a type III

hypersensitivity reaction include: serum sickness,
post-streptococcal glomerulonephritis, post
streptococcal pericarditis (angina pectoris),’
hypersensitivity pneumonitis, and rheumatoid
arthritis.
• The principal feature that distingishes type III
reactions from other hypersensitivity reactions is that
in type III reaction, the antigen-antibody complexes
are pre-formed in the circulation before their
deposition in tissues.
 Type IV hypersensitivity
• Type IV hypersensitivity reactions are, to some
extent, “normal” physiological events that help
fight infections, and dysfunction in this system can
predispose to multiple opportunistic infections.
• Adverse events can also occur due to these
reactions when an undesirable interaction between
the immune system and an allergen happens.
See summary Figure 2 (nxt slide)  
Rheumatoid arthritis
Management of Immediate hypersensitivity reactions

• The treatment of reactions may include:

(i) Treatment of anaphylaxis with intramuscular
epinephrine and antihistamine
(iii)Sustaining blood pressure with fluids,
(iv)Avoiding latex materials (eg gloves) if
handling who are allergic to rubber
(v) Surgical procedures such as tracheotomy in
case of severe laryngeal edema.
 
Allergic bronchial asthma can be treated with any of
the following:
• Inhalation of short- and long-acting bronchodilators
(anticholinergics and corticosteroids)
• Maintaining allergen (dust, hairs, polen..) free
environmental control to avoid contact with allergens
as much as possible.
• Use of anti-IgE antibody where available .
Treatment of delayed hypersensitivity (iv)reactions
• It involves the treatment of the eliciting cause
eg: The most common drugs to treat tuberculosis
include isoniazid, rifampin, ethambutol.

For drug-resistant TB, a combination of antibiotics such

as amikacin and kanamycin, should be used.
• The most common drugs to treat
multibacillary leprosy include rifampicin and
clofazimine in combination with dapsone for
leprosy.
• A single dose of antimicrobial combination to
cure single lesion paucibacillary leprosy
comprises ofloxacin, rifampicin, and
minocycline.
• Praziquantel can be useful for treating
infections caused by all Schistosoma spp
• Hydroxychloroquine and chloroquine can be
use in the therapy of sarcoidosis involving the
skin, lungs, and the nervous system.