COMPLEMENT SYSTEM

Classical Pathway

• Initiated by IgM and IgG. IgM is more effective

compared to IgG

• Considered to be a part of adaptive immune

response
Formation of Membrane Attacking complex/MAC
Alternative Pathway
 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

 Estrogen may stimulate destruction of tissue by cytotoxic

 Causes of Autoimmune Diseases

• Estrogen may stimulate destruction of tissue by cytotoxic T cells

• Some maternal cells may cross the placenta and trigger autoimmune disease
later in life •

• Environmental factors include viral infections •

• Genetic factors include certain MHC genes (HLAB27: Ankylosing spondylitis)

•

• 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 •

Cytokine pathways such as IFNgamma, IL-17 et
 Types of Autoimmune Diseases
• 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
- Others examples: : Multiple sclerosis, Rheumatoid arthritis

Single-organ autoimmune diseases

- Autoimmunity affecting blood cells
- Ex. Autoimmune hemolytic anemia
- Autoimmunity affecting endocrine organs
- Ex.Type I diabetes mellitus, Graves’ disease
 Immunomodulatory Therapeutics
• Broad spectrum therapies
• Immunosuppressive drugs: Corticosteroids,
Cyclophosphamide
• Plasmapheresis (SLE)

• Targeting specific cell types

• B cells: Anti-CD20 Antibody
• T cells: Blocking CD3 (Type-1 Diabetes), CD4 ( Animal
models-MS)

• Inhibiting specific steps in inflammation

• Anti-TNFα antibody for RA

• Interfering with co-stimulation

• Fusion protein containing extracellular domain of CTLA-4
 HYPERSENSITIVITY

• Inappropriate Immune response is called‘hypersensitivity’ or

‘allergy’

• Hypersensitive reactions develop during the course of either:

• Humeral response
• Cell-mediated response

• Those reactions initiated by Ab or Ag-Ab complexes are called

Immediate Hypersensitivities
• Develop within minutes to hours

• Those initiated by cell-mediated response are called Delayed-type

Hypersensitivities
• Develops after days of sensitization
Coombs and Gell’s Classification of Hypersensitivity
 Type I Hypersensitivity:
1.

6.
4.
3.

2. 5.

• Allergen induced humeral response

• Components: Reaginic antibody/IgE, Mast cells and basophils, IgE-binding FcR
• mediated by histamine, leukotrines, prostaglandins, cytokines
• Most allergic IgE responses occur on mucous membranes.
• Could have genetic etiology
• E.g. Allergic asthama, Allergic rhinitis, anaphylactic shock
 Antibody mediated cytotoxic (Type-II ) hypersensitivity

• Ab mediated destruction of cells

• Antibodies produced by the immune response bind to antigens on the patient's

own cell surfaces.

• IgG and IgM antibodies bind to these antigens to form complexes that activate
the classical pathway of complement activation, FcR mediated phagpcytosis and
ADCC via NK cells and eosinophils

• Many autoimmune diseases result from type II hypersensitivity generated

by autoantibodies

• E.g. Autoimmune hemolytic anemia, transfusion reaction (IgM

hemagglutinins), hemolytic disease of the newborns (IgG anti-Rh Ab) etc
 Immune Complex-Mediated (Type-III ) hypersensitivity

• Large amount of soluble immune complex lead to tissue damaging events (locally
or distant from the Ag entry)

• Deposition sites: Vessel wall (Vasculitis), synovial joints (arthritis), kidney

(glomerulonephritis)

• Complex deposition lead to neutrophil recruitment> granular release>damage

• Complement factor activation- Mast cell degranulation, neutrophil chemotaxis

• E.g. Arthus reaction, serum sickness,

• Autoimmune disease (RA, SLE), Drug reaction (Penicillin), Infectious diseases

(Meningitis, Hepatitis)
 TDTH mediated (Type-IV) hypersensitivity
• Type IV hypersensitivity is also known as cell mediated or delayed
type hypersensitivity.

• Host defense against intracellular bacteria and parasites.

• Cytotoxic T cells cause direct damage whereas helper T (Th1) cells

secrete cytokines which activate cytotoxic T cells, recruit and activate
monocytes and macrophages, which cause the bulk of the damage

• Reaction peaks 48 hours after the injection of antigen (PPD or old

tuberculin).

• E.g: Montoux reaction, Tuberculosis, Leprosy, Leishmaniasis, contact

dermatitis