MIC-401 (GENETICS)

Immunodeficiencies
Dr Rubab Rizvi

27th MARCH 2024

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Immunodeficiency

Deficiency of immune response against pathogens or immunogens.

Primary Immunodeficiencies Secondary Immunodeficiencies

• Congenital • Acquired
i. Severe combined i. Hypogammaglobulinemia
immunodeficiency (SCID) ii. Acquired
ii. Immunoglobulin class immunodeficiency
deficiency syndrome (AIDS)
iii. Thymus defects

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Primary Immunodeficiencies

• Congenital and hereditary • Consequences include:

• Caused by genetic disorders • Susceptibility to infections
• Mild to severe → can be fatal
• Affects innate and adaptive immunity
• Defects in:
• Hematopoietic stem cells
• Myeloid or Lymphoid progenitor cells
• Lymphocytes maturation

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Primary Immunodeficiencies: Lymphoid deficiencies
a) B- cell (Humoral) defects:
• Maturation or differentiation
• Antibody production
• Immunoglobulin class switching
• Susceptible to bacterial infections
• Unaffected Cell-mediated immunity
• Normal response with viruses, fungi
and protozoa
b) T- cell (Cell-mediated) defects:
• Maturation or differentiation
• Affects Humoral immunity
• Susceptible to viral and fungal
infections
• Severe consequences; death at an
early age

Combined B- and T- cells defects are the most serious!

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Primary Immunodeficiencies:
i. Severe combined immunodeficiency
(SCID)
• Combined defects in B- cell/T- cell/both
• Low lymphocyte counts
• Activation or proliferation defects
• Thymus not developed
• Myeloid (innate) unaffected
• Severe recurrent infections
• Death in early years
• Immune system too compromised
• Infection from live attenuated
whole organism vaccines
• Precautionary measure: confining
patients to sterile environments
to extend life span → challenging
• Treatment by:
• Cells transfusion
• Thymus transplantation
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Primary Immunodeficiencies:

ii. Immunoglobulin class deficiency: iii. DiGeorge syndrome

• Normal Antibody-secreting plasma • Congenital thymic aplasia
cells • Undeveloped thymus
• But deficiency of Immunoglobulin • Immature thymocytes
classes • Treatment by thymus
• IgA deficiency is the most common transplantation
• Treatment by administration of IgA

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Secondary Immunodeficiencies:

i. Acquired
hypogammaglobulinemia:
• Not by birth • Low level of Antibodies in blood
• Acquired during life • Unknown cause
• Caused by infectious agents • Non-hereditary
• Babies born to affected mothers
are deficient in maternal
Antibodies

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Secondary Immunodeficiencies:
ii. Acquired immunodeficiency syndrome
(AIDS)
• Marked decrease of T helper CD4⁺ cells
• Caused by Human Immunodeficiency
Virus (HIV-1)
• Transmission via:
• Body fluids (e.g., infected blood or
blood products)
• Sexual activity (homosexual males or
many intimate partners are at risk)
• Drug abusers
• Untreated mother to baby
• Mostly fatal, but treatable using anti-
viral drugs
• Infection:
• HIV-1 binds to CD4⁺ on TH cells →
enter cells → replicates → cell lysis
• Chronic asymptomatic phase up to
several years
• Switching to end stage AIDS
• Patients die from malignancies
(pneumonia, diarrhoea, tuberculosis,
etc.) caused by opportunistic
organisms
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 MIC-401 (GENETICS)

Autoimmunity
Dr Rubab Rizvi

27th MARCH 2024

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Autoimmunity

• Host immune system mounts a response against self antigens

• Humoral or Cell-mediated response
• Paul Ehrlich termed it as a “horror autotoxicus” condition
• A common form is Type II Hypersensitive reaction against surface antigen of host
cell → tissue injury
• Auto Antibodies recognize and bind to self antigen
• Complement-dependent or ADCC
• Consequences:
• Cells or organ damage → loss of function
• Can be fatal

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Autoimmunity

Immune response against self antigens.

Organ-specific Autoimmunity Systemic Autoimmunity

• Against specific cells or organ • Against several cells and organs

i. Autoimmune haemolytic i. Rheumatoid arthritis
anaemia ii. Systemic lupus
ii. Good pasture’s syndrome erythematosus
iii. Type I Diabetes mellitus iii. Multiple sclerosis

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Autoimmunity: Organ-specific
i. Autoimmune haemolytic anaemia:
• Auto Antibodies attack surface
antigens of RBC → Haemolysis
• Type II Hypersensitive reaction (IgE-
dependent)
ii. Good pasture’s syndrome:
• Auto Antibodies against lungs and
kidneys
• Bleeding → Kidney failure
iii. Insulin-dependent Diabetes
mellitus (Type I):
• TDTH cells or Auto Antibodies
• Attack on beta cells in islets of
Langerhans of pancreas
• Decreased insulin production
• Affects regulation of blood glucose
→ hyperglycaemia
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Autoimmunity: Systemic
i. Rheumatoid arthritis:
• Inflammation of joints
• Affects women (40-60 years old)
• Auto Antibodies or rheumatoid factors (IgM) against joints
• Auto IgM binds to circulatory IgG → IgM-IgG complex → deposited in joints
→ activate complements cascade → chronic inflammation
• Generalised Type III Hypersensitive reaction (immune complex-mediated).

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Autoimmunity: Systemic
ii. Systemic lupus erythematosus:
• Auto Antibodies against skin, brain,
blood vessels, tissues, DNA, etc.
• Mostly in females (20-40 years old)
• Fever, rash, arthritis, kidney
dysfunction, etc.
iii. Multiple sclerosis:
• Auto T-cells form lesions in myelin
sheaths of nerve fibres
• Cerebrospinal fluid contains
activated T-cells
• Brain and spinal cord inflammation
→ neurological dysfunction
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