IMMUNITY

IMMUNITY II

Clinical immunology
Important cells are: 1- Ag presenting cells 2- Neutrophils polymorphs 3- Macrophages 4- Natural killer cells 5- Eosinophils 6- Mast cells 7- T-Lymphocytes 8- B-Lymphocytes

Autoimmunity: Autoimmune diseases arise when immune responses , either antibodies or T - cells directed against self - antigens, cause tissue damage. The etiology of these diseases is multifactorial involving both environmental and genetic influences. Susceptibility to many auto immune diseases is linked to specific HLA genotypes as: * Mysthenia gravis * Grave's disease * SLE * Rheumatoid arthritis *Ankylosing spondylitis

Both humoral & cell – mediated immunity may contribute to the tissue damage that occurs in autoimmune diseases but in varying degree.

Rheumatoid Arthritis

Is characterized by: 1) local inflammation 2) destruction of the joint 3) the synovial membrane is infiltrated by CD4 & T-cells , activated B-cell polymorphnuclear leucocytes & macrophages. Cytokines including IL - 1 , IL - 15 ,TNF alpha, IFN sigma can be detected in synovial fluid. In clinical trials, treatment with Anti TNF alpha antibody has been reported to have transient therapeutic effects.

In addition to T - cells activity antibodies, predominantly IgM and IgG autoantibodies, are generated and form immune complexes which lead to complement activation and further tissue damage.

SLE: (Systemic Lupus Erythematous)

Is a systemic immune disease, in which immune complexes are formed between: 1) antinuclear (IgG) antibodies 2) their target antigens (DNA ,ribonucleoprotein, histones & ribosomes). These may become trapped in arteriolar walls & induce inflammatory responses such as glomerulonephritis, arthritis ,vasculitis affecting small arteries throughout the body.

Revised American Rheumatism Association criteria for systemic lupus erythematosus

Features Characteristics Malar rash Fixed erythema, flat or raised, sparing the nasolabial folds Discoid rash Erythematous raised patches with adherent keratotic scarring and follicular plugging


Photosensitivity Rash due to unusual reaction to sunlight

Oral ulcers Oral or nasopharyngeal ulceration which may be painless

Arthritis Non-erosive, involving two or more peripheral joints

Serositis Pleuritis (history of pleuritic pain or rub, or pleural effusion) or or pericarditis (rub, ECG evidence or effusion) Renal disorder Persistent proteinuria > 0.5 g/day or cellular casts (red cell, granular or tubular)


Immunological disorder Anti-DNA antibodies in abnormal titre or presence of antibody to Sm antigen or positive antiphospholipid antibodies ANA disorder Abnormal titre of ANA by immunofluorescence A person has SLE if *Any 4 out of these 11 features are present serially or simultaneously On two separate occasions


Insulin Dependant DM: (Type I , IDDM ) Is an organ specific autoimmune disease appears to be caused by auto- reactive T cells both CD4 + CD8 + T cells , which together with macrophages infiltrate & destroyed the B cells of the islets of Langerhan's.

Autoimmune hemolytic anemia: Is caused by antibodies reactive with Rh or I antigen on the surface of RBCs,the auto antibodies adhere to the RBCs which are then lysed by complement or destroyed through FC receptors and complement mediated phagocytosis.

Mechanism of auto immunity: Tolerance to self - antigens occurs by deletion of self reactive B & T - cells during their maturation in the bone marrow & thymic environments , recognition of peptide / MHC complexes by peripheral T - cells in the absence of co-stimulatory signals elecits energy & therefore, may prevent the activation of potentially self reactive T - cells in the periphery, similarly ,clonal expansion of auto reactive cells may be inhibited by suppressor T - cells , which produce immune suppressive cytokines as TGF- beta , IL-10 , IL-4 .

Ankylosing spondylitis

Chronic inflammatory arthritis predominantly affecting the: 1) Sacroiliac joints 2) Spine, which can progress to bony fusion of the spine. More than 90% of those affected are HLA B27-positive. is thought to arise from an as yet ill-defined interaction between: 1) environmental pathogens 2) the host immune system in genetically susceptible individuals.


Increased faecal carriage of Klebsiella aerogenes occurs in patients with established AS and may relate to exacerbation of both joint and eye disease. Wider alterations in the human gut microbial environment are increasingly implicated, which could lead to increased levels of circulating cytokines such as IL-23 that can activate enthesial or synovial T cells.

Its antigen-presenting function (it is a class I MHC molecule) or because of its propensity to form homodimers that activate leucocytes. HLA-B27 molecules may also misfold, causing increased endoplasmic reticulum stress. This could lead to inflammatory cytokine release by macrophages and dendritic cells, thus triggering inflammatory disease.