diseases of immunity (1)
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Diseases of Immunity (1). Hypersensitivity Reactions. Normally, a balanced system optimizes the eradication of infecting organisms without serious injury to host tissues. - PowerPoint PPT PresentationTRANSCRIPT
Diseases of Diseases of ImmunityImmunity (1)
Hypersensitivity ReactionsHypersensitivity Reactions
Normally, a balanced system optimizes the eradication of infecting organisms without serious injury to host tissues.
However, immune responses may be inadequately controlled or inappropriately targeted to host tissues, and in these situations, the normally beneficial response will cause of disease.
Hypersensitivity ReactionsHypersensitivity Reactions
The term hypersensitivity is used to describe immune responses which are damaging rather than helpful to the host.
WHY? WHY? This term originated from the idea that individuals who
mount immune responses against an antigen are said to be "sensitizedsensitized" to that antigen, and therefore, pathologic or excessive reactions are manifestations of "hypersensitivityhypersensitivity."
CAUSES OF HYPERSENSITIVITY CAUSES OF HYPERSENSITIVITY REACTIONSREACTIONS
Autoimmunity. Reactions against microbes. Reactions against environmental antigens.
Hypersensitivity ReactionsHypersensitivity Reactions Classification:
Type I “Allergy & anaphylaxis”
Type II “Antibody dependant”
Type III “Immune complex - mediated”
Type IV “Cell-mediated (delayed type)”
N.B:N.B: First 3 types are antibody-mediated injury & the last type is cell-mediated injury
Type I Type I HypersensitivityHypersensitivity
ReactionReaction ALLERGIC REACTIONALLERGIC REACTION
ANAPHYLACTIC REACTIONANAPHYLACTIC REACTION
Type I Hypersensitivity
DefinitionDefinition : It is rapidly developing immunologic reaction
occurring within minutes after the interaction of an antigen (allergen) with IgE antibodies bound to surface of mast cells or basophils in individuals previously sensitized to the antigen
Antigen is usually exogenous , environmental and is called allergenallergen
Allergens may be introduced by inhalation, ingestion, touch, or by intravenous injection.
The reaction is mediated by IgE produced by previously sensitized B lymphocytes..
IgE binds to the main effector cells ; the mast cell (in tissues) or basophils (in blood).
The initiated reaction passes through 2 phases an early one and a late one.
Type I Hypersensitivity
Type I Hypersensitivity:Phases
As Seen in the localized reactions Initial response:Initial response:
Characterized by; Vasodilatation, Vascular leakage, and Smooth muscle spasm Increased glandular secretions These changes become evident within 5 to 30 minutes
after exposure to an allergen and subside in 60 minute. It is mainly mediated by histaminehistamine released by MAST
CELLS.
Type I Hypersensitivity:Phases
Late-phase reaction:Late-phase reaction: Develop in 2 to 8 hours later without additional
exposure to antigen and lasts for several days. Characterized by intense infiltration of tissues with
eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells, and tissue destruction.
Occurs under effect of esinophils and neutrophils chemotactic factors released by mast cells.
Type I Hypersensitivity:Clinical Manifestations
The resultant reaction can occur as a systemic disorder or as a local reaction depending on the route of entry of allergen
Type I Hypersensitivityclinical presentationclinical presentation
Local reactions:Local reactions: Antigen is confined to a particular site Skin contact Localized cutaneous swellings (urticaria,
hives) and eczema, Ingestion Allergic gastroenteritis (food allergy)
diarrhoea Inhalation bronchospasm allergic rhinitis, and
bronchial asthma .
Type I Hypersensitivity:
Clinical ManifestationsClinical Manifestations
Systemic Anaphylaxis:Systemic Anaphylaxis: This usually follows an intravenous injection of an antigen to which the host
has already became sensitized for. systemic vasodilatation “anaphylactic shock” is produced and even death
within minutes Example: IV administration of Penicillin, Bee venom.
NOTE: The immune response in the late-phase inflammatory reaction, plays an important protective role in parasitic infectionsparasitic infections.
Type II Type II HypersensitivitHypersensitivit
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reactionreaction
Type II Hypersensitivity
Antibody-mediated diseases;Antibody-mediated diseases; Target antigens are present on the surface of cells or other
tissue components
The antigens may be intrinsicintrinsic to the cell membrane, or they may take the form of an exogenousexogenous antigen, such as a drug metabolite, adsorbed on the cell surface
The antibodies unite with the antigens MAINLY in the bloodstream,
This union sets off the complement system, and destruction of the local tissue cells ensues.
Type II Hypersensitivity MechanismMechanism
A, OpsonizationOpsonization
B, InflammationInflammation
C, Antireceptor antibodiesAntireceptor antibodies
Type II HypersensitivityMechanism
Clinical examples;Clinical examples; Incompatible transfusion reactions (mismatched blood
transfusion reaction) Erythroblastosis fetalis “Rhesus antigen
incompatibility” Autoimmune haemolytic anemia, or thrombocytopenia Certain drug reactions “penicillin hemolysis”
Type III Type III HypersensitivitHypersensitivit
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reactionreaction
Type III Hypersensitivity
Immune Complex - MediatedImmune Complex - Mediated Type III hypersensitivity is mediated by the deposition of
antigen-antibody complexesantigen-antibody complexes formed in blood vessels.formed in blood vessels. The antigens may be
Exogenous antigensExogenous antigens, such as bacteria, or viruses Endogenous antigensEndogenous antigens, such as DNA.
Immune complexes deposit in blood vessels in various tissue beds ,they have the ability to fix complement and trigger the subsequent injurious inflammatory reaction (either systemic or systemic or Localized )Localized )
Systemic Immune Complex DiseaseSystemic Immune Complex DiseaseMechanismMechanism
Favoured sitesFavoured sites of immune complex deposition are;
Renal glomeruli, Joints, Skin, Heart, Serosal surfaces, Small blood vessels
Type III Hypersensitivity Examples
Autoimmune diseases as:Autoimmune diseases as: Systemic lupus erythematosis Scleroderma Sjogren syndrome
Type IV Type IV HypersensitivitHypersensitivit
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reactionreaction
Type IV Hypersensitivity (Cell Mediated)(Cell Mediated)
Two types of T-cell reactions are capable of causing tissue injury and disease:
(1) delayed-type hypersensitivity (DTH), initiated by TH1-type CD4+ T cells
(2) direct cell cytotoxicity, mediated by cytotoxic CD8+ T cells that are responsible for tissue damage.
1-Delayed-Type Hypersensitivity
It is responsible for mediating immune reaction in case of; Defence against variety of intracellular persistent or persistent or
non-degradable antigensnon-degradable antigens, such as tubercle bacilli. pathogens, including mycobacteria, fungi, and certain
parasites, It may also be involved in transplant rejection. Tumour immunity
NOTE: In AIDS loss of CD4+ T lymphocytes increased
susceptibility for developing TB & fungal infection.
Delayed-Type HypersensitivitySequence of Cellular Events
On subsequent exposure of an individual previously sensitised, the memory TH1 cells interact with the antigen on the surface of APC .
APC become activated, they produce IL-12 that activate CD+4 cells. In turn CD+4 cells will secrete:
IFN-γ that activates macrophages to produce substances that cause tissue damage and promote fibrosis,
TNF promotes inflammation. When macrophages become activated they transform into epithelioid cells epithelioid cells
And they occasionally fuse multinucleated giant cells.giant cells.
Delayed-Type HypersensitivityMorphology
DTH is characterized histologically by the
formation of GranulomaGranuloma ( (a specific form
of chronic inflammation)
It refers to microscopic aggregate of
epithelioid cells, usually surrounded by a
collar of lymphocytes with or without the
formation of multinucleated giant cells.
Example for DTHExample for DTHTuberculin reactionTuberculin reaction
A classic example of DTH elicited by antigen challenge in an individual
already sensitized to the tubercle bacillus by a previous infection.
Between 8 and 12 hours after intracutaneous injection of tuberculin
(a protein extract of the tubercle bacillus), a local area of erythema and
induration appears, reaching a peak (typically 1-2 cm in diameter) in 24 to 72
hours (hence the adjective, delayed) and thereafter slowly subsiding.
2- Direct cell cytotoxicity In this variant of type IV hypersensitivity, sensitized CD8+
T cells kill antigen-bearing target cells
These effector cells are called cytotoxic T lymphocytes (CTLs)
They mediate their action through class I MHC molecule, where they directly lyse infected cells or stimulates their apoptosis.
It plays an important role in graft rejection, resistance to virus infections, and possibly tumor immunity