IMMNUNITY DISORDERS

Dr Sameh Abou-Beih

Lecturer of Pathology

Fayoum University

Antigen (Immunogen)• Is a foreign substance

which can induce animmune response andreacts specifically with itsproducts. It may be aprotein, polysaccharide,nucleic acid or lipid.

• Epitope or AntigenicDeterminant– That portion of an antigen

that combines with theproducts of a specificimmune response. Theymay be recognized B or Tcells.

Hapten (Incomplete antigen)

• A substance that is non-immunogenic

but which can react with the products

of a specific immune response.

• Haptens are small molecules which

could induce an immune response

only when coupled to a carrier

molecule.

Antibody

• A Glycoprotein

molecules that

are produced by

plasma cells in

response to an

immunogen.

Immunoglobulin classes

1. IgG - Gamma heavy chains

2. IgM - Mu heavy chains

3. IgA - Alpha heavy chains

4. IgD - Delta heavy chains

5. IgE - Epsilon heavy chains

GENERAL FUNCTIONS OF

IMMUNOGLOBULINS (ANTIBODIES)

Each immunoglobulin actually binds to a specific antigenic determinant. Antibodies are effective against extracellular pathogens.

Classes 1. IgG

2. IgM

3. IgA

4. IgD

5. IgE

HYPERSENSITIVITY REACTIONS

HYPERSENSITIVITY REACTIONS

• Undesirable (damaging, and sometimes

fatal) reactions produced by the normal

immune system on re-exposure to the

antigen (pre-sensitized state).

• Hypersensitivity reactions can be divided into

four types: type I, type II, type III and type IV,

based on the mechanisms involved and time

taken for the reaction.

• A particular clinical condition (disease) may

involve more than one type of reaction.

Type I

Hypersensitivity

Type I Hypersensitivity (Immediate

hypersensitivity)• Immediate hypersensitivity is mediated by IgE.

• The primary cellular component in thishypersensitivity is the mast cell .

• The reaction usually takes 15 - 30 minutes fromthe time of re-exposure to the antigen.

• The reaction may involve skin (urticaria andeczema), eyes (conjunctivitis), nasopharynx(rhinorrhea, rhinitis), bronchopulmonary tissues(asthma) and gastrointestinal tract(gastroenteritis).

The mechanism of reaction

• Production of IgE, in response to certainantigen (allergens).

• IgE has very high affinity for its receptor onmast cells and basophiles.

• Re exposure to the same allergen cross linksthe cell-bound IgE and triggers the release ofvarious pharmacologically active substances(histamine, serotonin & kinins).

Examples of type I hypersensitivity• Anaphylactic shock: severe, may be fatal in

minutes. Manifested by generalized edema, severe bronchospasm, urticaria and peripheral circulatory failure.

• Atopic diseases: More localized. Has a hereditary base in most cases.

Examples: bronchial asthma, allergic rhinitis, hay fever.

Type II Hypersensitivity

Type II (antibody-mediated) reactions

• The antigens are normally endogenous,although exogenous chemicals (haptens) whichcan attach to cell membranes can also lead totype II hypersensitivity.

• Examples: Drug-induced hemolytic anemia,granulocytopenia, Rh incompatibility andthrombocytopenia.

Type III

Hypersensitivity

Type III Hypersensitivity (Immune complex

reaction)

• The antigen may be exogenous (chronic bacterial, viral or

parasitic infections), or endogenous (non-organ specific

autoimmunity: e.g., systemic lupus erythematosus, SLE).

• The antigen is soluble and not attached to the organ

involved.

• The damage is caused by platelets and neutrophils.

• The reaction may be general (e.g., serum

sickness) or may involve individual organs

including skin (e.g., systemic lupus

erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g., aspergillosis),

blood vessels (e.g., polyarteritis), joints (e.g., rheumatoid arthritis) or other organs.

Type IV Hypersensitivity (cell mediated or

delayed type hypersensitivity)

• T cell-mediated cytotoxicity

Cytotoxic T cells (Tc) kill the antigen-carrying cell

directly, examples include transplant rejection and

contact dermatitis.

• Granulomatous inflammationDelayed hypersensitivity reactions are characterized by the

formation of granulomas composed of helper T (TH) cells and

macrophages

CASEATING GRANULOMA

The Mechanism

• TH1 cells secrete cytokines esp IFN-γ & IL-12 →

macrophages attracted to the site of injury

• Macrophages due to continuous activation →

epitheloid cells (epaithelial like with eosinophilic

cytoplasm).

• Few others fuse together by the effect of lipoxins →

multinucleated giant cells.

• They also secrete substances PD-GF & TNF-β that

stimulate the fibrogenesis.

Summary of hypersensitivity

reactions

AUTOIMMUNE

DISEASES

Definition of autoimmunity

• Autoimmunity can be defined as

breakdown of mechanisms

responsible for self tolerance and

induction of an immune response

against components of the self

Autoimmunity

• Normally, individuals do not form potentially destructive Abs to their own cells, but only to foreign Ags.

• This is because the body has developed atolerance to the Ags normally presentwithin self.

• This state of the immune tolerance to selfAgs is maintained by a complex networkof T and B lymphocytes and theirregulatory products.

Pathogenesis of Autoimmune

Diseases

breakdown of mechanisms responsible for self tolerance and induction of an immune response against components of the self by one the following mechanisms:

– Loss of self tolerance (failure of clonal deletion,

failure of T-cell suppression).

– Antigen modification.

– Cross-reaction with infectious agent.

– Emergence of sequestered antigen.

– Genetic factors (mainly class II MHC).

Autoimmune diseases

• Rheumatoid arthritis

• SLE

• Scleroderma

• Sjögren syndrome

• Ankylosing spondylitis

Graft Rejection

• Organs (GRAFTS) transplanted from

DONOR to RECIPIENT

• HLA match → excellent results (e.g

twins).

• Immunosupressive therapy to overcome

rejection

• GVHD

Graft Rejection Cont

• HYPERACUTE (minutes-2d) AB

mediated in presensitized recipient

• ACUTE (days months): cellular

(INTERSTITIAL infiltrate → endothelial and parenchymal

damage) and humoral (VASCULITIS)

• CHRONIC (months): progressive vascular

fibrosis→ progressive ischemia, dysfunction and failure

IMMUNE RESPONSE AGAINST

CANCER

• TAA→ immune response against cancer.

• Mainly participated by NK cell and Tc cells.

Humoral response via opsonization

• Cancer higher in Immunodefiiciency states

• Value: immune surveilence- regression-

some cancers have favorable response with

lymphocyte infiltrate eg seminoma

THANK YOU