INDIAN INSTITUTE OF TECHNOLOGY ROORKEE
AUTOIMMUNITY
Autoimmune diseases
• Immune responses mounted against self components
that result in pathology.
• Prevalence: higher with age, in developed countries
(~3-5%); major cause of death for women under age
65.
• Are more common in women than in men
• May result when an individual begins to make
autoantibodies or cytotoxic T cells against normal body
components
• >80 autoimmune diseases
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Causes of Autoimmune Diseases
– Estrogen may stimulate destruction of tissue by cytotoxic T
cells
– Genetic factors include certain MHC genes
– T cells may encounter self-antigens that are normally
“hidden”
– Microorganisms may trigger autoimmunity because of
molecular mimicry (Coxsackie virus , HSV, Chlamydia
pneumoniae)
– Failure of the normal control/tolerance mechanisms of the
immune system
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Types
• Systemic autoimmune diseases
• Systemic lupus erythematosus
• Autoantibodies against DNA result in immune complex formation
• Autoantibodies against red blood cells, platelets, lymphocytes,
muscle cells
• Trigger unknown
• Immunosuppressive drugs reduce autoantibody formation
• Glucocorticoids reduce inflammation
• Single-organ autoimmune diseases
• Autoimmunity affecting blood cells
• Ex. Autoimmune hemolytic anemia
• Autoimmunity affecting endocrine organs
• Ex. Type I diabetes mellitus,
• Autoimmunity affecting nervous tissue
• Ex. Multiple sclerosis
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Therapeutics
1. Broad spectrum therapies
§ Immunosuppressive drugs: Corticosteroides, cyclophosphamide,
§ Plasmapheresis (SLE)
2. Targeting specific cell types
§ B cells: Anti-CD20 Antibody
§ T cells: Blocking CD3 (Type-1 Diabetes), CD4 ( Animal models-MS)
3. Inhibiting specific steps in inflammation
§ Anti-TNFα antibody for RA
4. Interfering with co-stimulation
§ Fusion protein containing extracellular domain of CTLA-4
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INDIAN INSTITUTE OF TECHNOLOGY ROORKEE
TRANSPLANTATION
IMMUNOLOGY
Transplantation
• Transfer of living cells, tissues and organs from one part of
the body to another or from one individual to another.
• Graft: transplanted cells, tissues, or organs.
• Donor: the individual who provides the graft.
• Recipient/host: the individual who receives the graft.
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Classification
• Degree and type of immune response to a transplant is
dependent on the source of the graft.
• Allograft is recognized as foreign as it is genetically dissimilar to the recipient
with unique antigens
• Most vigorous rejection seen in xenograft
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Immunology of transplant rejection
Transplantation antigens
ü MHC molecules (HLA complex in human and H-2 complex
in mice)
ü ABO Blood group antigens
ü Test For cross-matching is important before transplantation
Histocompatible: Tissues with antigenic similarity. Do not
induce immunologic rejection.
• CMI plays important role in allograft rejection
• Allograft rejection shows of memory and specificity
Faster secondary rejection to the same graft
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Stages of rejection
• Hyperacute rejection: Rejection in the presence of preexisting anti-MHC
antibodies)
• Acute rejection
• Chronic rejection
1. Sensitization Stage
- Shortly after transplantation
- Antigen presentation.
- Proliferation of alloantigen specific lymphocytes
2. Effector Stage
- Destruction of graft by recipient’s immune system.
- Influx of immune cells to the graft: CD4+ T cells (IL-2, IFN-γ, APCs,
macrophages, CD8+Tcells
- Delayed typer hypersensitivity responses (T-DTH), TH17
• Degree and type of immunologic response varies with the
type of transplant
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Effector mechanisms of graft rejection
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Immunological Modulation
1. Tissue typing
ü Blood group typing
ü HLA typing
2. Microchimerism
The presence of a small number of cells of donor, genetically distinct
from those of the host individual
• (Other Therapeutics discussed in autoimmunity)
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