immnunity disorders · granulocytopenia, rh incompatibility and thrombocytopenia. type iii...
TRANSCRIPT
![Page 1: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/1.jpg)
IMMNUNITY DISORDERS
Dr Sameh Abou-Beih
Lecturer of Pathology
Fayoum University
![Page 2: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/2.jpg)
![Page 3: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/3.jpg)
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.
![Page 4: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/4.jpg)
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.
![Page 5: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/5.jpg)
Antibody
• A Glycoprotein
molecules that
are produced by
plasma cells in
response to an
immunogen.
![Page 6: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/6.jpg)
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
![Page 7: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/7.jpg)
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
![Page 8: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/8.jpg)
HYPERSENSITIVITY REACTIONS
![Page 9: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/9.jpg)
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.
![Page 10: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/10.jpg)
Type I
Hypersensitivity
![Page 11: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/11.jpg)
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).
![Page 12: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/12.jpg)
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).
![Page 13: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/13.jpg)
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.
![Page 14: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/14.jpg)
Type II Hypersensitivity
![Page 15: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/15.jpg)
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.
![Page 16: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/16.jpg)
Type III
Hypersensitivity
![Page 17: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/17.jpg)
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.
![Page 18: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/18.jpg)
• 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.
![Page 19: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/19.jpg)
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
![Page 20: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/20.jpg)
![Page 21: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/21.jpg)
CASEATING GRANULOMA
![Page 22: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/22.jpg)
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.
![Page 23: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/23.jpg)
Summary of hypersensitivity
reactions
![Page 24: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/24.jpg)
AUTOIMMUNE
DISEASES
![Page 25: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/25.jpg)
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
![Page 26: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/26.jpg)
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.
![Page 27: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/27.jpg)
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).
![Page 28: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/28.jpg)
Autoimmune diseases
• Rheumatoid arthritis
• SLE
• Scleroderma
• Sjögren syndrome
• Ankylosing spondylitis
![Page 29: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/29.jpg)
Graft Rejection
• Organs (GRAFTS) transplanted from
DONOR to RECIPIENT
• HLA match → excellent results (e.g
twins).
• Immunosupressive therapy to overcome
rejection
• GVHD
![Page 30: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/30.jpg)
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
![Page 31: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/31.jpg)
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
![Page 32: IMMNUNITY DISORDERS · granulocytopenia, Rh incompatibility and thrombocytopenia. Type III Hypersensitivity. Type III Hypersensitivity (Immune complex reaction) •The antigen may](https://reader031.vdocuments.us/reader031/viewer/2022011822/5ec080f14c806502fb5ddc19/html5/thumbnails/32.jpg)
THANK YOU