3. Immunopathology
(1) Hypersensitivity reactions, which give rise to
immunologic injury in a variety of diseases.
(2)Autoimmune diseases, which are caused by immune reactions
against self.
(3)Immunologic deficiency syndromes, which result from relatively
distinct, genetically determined or acquired defects in some
components of the normal immune response.
(4) Amyloidosis, a poorly understood disorder having immunologic
association.
4. Hypersensitivity reaction
• Defn. an exaggerated / inappropriate state of normal immune
response with onset of adverse effects on the body
• Immunologic reaction against antigens
• Classification based on the immunologic mechanism that mediates
the disease.
5.
6.
7.
8. Type- I Hypersensitivity Rxn
• Syn: anaphylactic reaction, IgE allergy, IgEmediated hypersensitivity
reaction.
• Defn. A state of rapidly developing or anaphylactic type of immune
response to an antigen to which the individual is previously
sensitized
• N.B the reaction appears 15-30 mts
9. Type I
• Etiology Humoral Ig E [Reagin]
Genetic
Environmental pollutants
Concomitant factors
• PATHOGENESIS B lymphocytes , plasma cells
mast cells , basophils
neutrophils and eosinophils.
21. Systemic anaphylaxis
i) Administration of antisera e.g. anti-tetanus serum (ATS).
ii) Administration of drugs e.g. penicillin.
iii) Sting by wasp or bee.
Cl. Features
itching, erythema, contraction of respiratory bronchioles,
diarrhea, pulmonary oedema, pulmonary haemorrhage,
shock and death.
22. Local anaphylaxis
• Hay fever (seasonal allergic rhinitis) due to pollen sensitisation of
conjunctiva and nasal passages.
• Bronchial asthma due to allergy to inhaled allergens like house dust.
• Food allergy to ingested allergens like fish, cow’s milk, eggs etc.
• Cutaneous anaphylaxis due to contact of antigen with skin
characterized by urticaria, wheal and flare.
• Angioedema, an autosomal dominant inherited
disorder characterized by laryngeal oedema, oedema of eyelids, lips,
tongue and trunk.
26. • Defn. reaction by humoral antibodies that attack cell surface antigens
on the specific cells and tissues and cause lysis of target cells.
• Tissue specific reaction
• 15-30 minutes /longer
• complement system, tissue macrophages, platelets, natural killer
cells, neutrophils and eosinophils
• main antibodies are IgG and IgM class.
27. etiopathogenesis
Three different antibody dependent mechanisms
I. Complement dependent reaction.
II. Antibody dependent cell - mediated cytotoxicity /ADCC/.
III. Antibody mediated cellular dysfunction.
28. A, Opsonization of cells by
antibodies and complement
components and ingestion
by phagocytes.
B, Inflammation induced by
antibody binding to Fc receptors
of leukocytes and by complement
breakdown products.
C, Antireceptor antibodies
disturb the normal function
of receptors. (Stimulation,
Inhibition).
29.
30. Opsoinization: By C3b, fragment of the complement to the cell
surface enhances phagocytosis.
• Examples include red blood cells, leukocytes and platelets disorders:
Transfusion reaction; haemolytic anemia; Agranuloytosis; Thrombocytopenia;
Certain drug reactions.
31. Direct lysis:
A) It is effected by complement activation, formation of
Membrane Attack Complex (C5 – 9) [MAC]. This membrane
attack complex then disrupts cell membrane integrity by
drilling a hole. In anucleated cells once and in nucleated
cells many attacks of the complex are needed for cell lysis,
because the latter ones have abilities to repair cell
membrane injuries rapidly.
I. Complement dependent Reaction
32. II.Antibody dependent cell - mediated
cytotoxicity /ADCC/
This type of antibody mediated Cell injury does not involve fixation of
complements. The target cells coated with IgG antibodies are killed by
a variety of nonsensitized cells that have Fc receptors.
The non-sensitized cells included in ADCC are monocytes/large
granular/ lympholytes / Natural killer cells, neutrophils and
eosinophils.
The cell lysis proceeds without phagocytosis. Example include graft
rejection.Hashimoto thyroiditis.
35. • The classic ABO incompatibility reaction is a type II, with IgM
antibodies causing complement lysis of erythrocytes.
• transfusion reactions cells from an incompatible donor react with and
are opsonized by preformed antibody in the host.
• Rhesus disease (or hemolytic disease of the newborn) is a special
example since the IgG antibodies which cause destruction of foetal
red blood cells by antibody dependent cellular cytotoxicity (ADCC) are
passively acquired by the host via the placenta.
36. III.Antibody-Mediated Cellular Dysfunction
• In some cases, antibodies directed against cell-surface receptors
impair or dysregulate function without causing cell injury or
inflammation.
• Examples:- myasthenia gravis.
pemphigus vulgaris, Ab against desmosomes disrupt
intercellular junctions in epidermis, leading to the formation of skin
vesicles.
• Antibody-mediated stimulation of cell function is noted in Graves
disease. In this disorder, antibodies against the thyroid-stimulating
hormone receptor on thyroid epithelial cells stimulate the cells,
resulting in hyperthyroidism.
37.
38. TYPE-III: IMMUNE-COMPLEX MEDIATED.
Mediated by immune-complexes[Ag-Ab], formed by soluble
antibody and soluble antigen.
Complex Formation……… Circulation.
Extravascular space.
Two types
Systemic Local
39. Etiology
• Serum SICKNESS: Horse or bovine serum can
be injected into human's as an antidote to bee
venom or snake bites. The foreign serum will then
induce formation of immune-complexes, which elicit
symptoms 6 to 8 days later.
• SYMPTOMS: Fever, arthralgia, vasculitis, acute
glomerulonephritis.
Systemic
• ARTHUS REACTION: Experimental vasculitis, in
which a localized injury is produced by immune
complexes. Immune-complexes accumulate on vessel
walls which activated complement ------> vascular
enodthelial lesions.
• Fibrin will accumulate in vessel-walls which will result
in a fibrinoid necrosis in the area. Fibrinoid Necrosis of
vascular walls is common in all Type-III diseases.
Local
46. Cell-Mediated (Type IV) Hypersensitivity
• The cell-mediated type of hypersensitivity is initiated by antigen-
activated (sensitized) T lymphocytes. It includes the delayed type
hypersensitivity reactions mediated by CD4+ T cells, and direct cell
cytotoxicity mediated by CD8+ T cells .
• Microbial Agents:-Mycobacterium tuberculosis.
viruses, fungi, protozoa,
parasites.
• So-called contact skin sensitivity to chemical agents and graft
rejection are other instances of cell mediated reactions.
48. Examples of T Cell-Mediated (Type IV)
Hypersensitivity
Disease Specificity of Pathogenic
T Cells
Clinicopathologic
Manifestations
Type 1 diabetes mellitus Antigens of pancreatic islet b cells
(insulin, glutamic acid
decarboxylase, others
Insulitis (chronic inflammation
in islets), destruction of b
cells; diabetes
Multiple sclerosis Protein antigens in central
nervous system myelin (myelin
basic protein, proteolipid protein)
Demyelination in CNS with
perivascular inflammation;
paralysis, ocular lesions
Rheumatoid arthritis Unknown antigen in joint
synovium (type II collagen?); role
of antibodies?
Chronic arthritis with
inflammation, destruction of
articular cartilage and bone
Peripheral neuropathy;
Guillain- Barré syndrome?
Protein antigens of peripheral
nerve myelin
Neuritis, paralysis
49. Perivascular infiltration
by T cells and
mononuclear
phagocytes. Immunoperoxidase staining
marks positively with anti-CD4 antibodies
Schematic illustration of the three major mechanisms of antibody-mediated injury.. In these examples, antibodies against the thyroid stimulating hormone (TSH) receptor activate thyroid cells in Graves disease, and acetylcholine (ACh) receptor antibodies impair neuromuscular transmission in myasthenia gravis.
Diagrammatic representation of the sequence of events triggered by the deposition of soluble
immune complexes that eventually results in inflammation and tissue damage
Mechanisms of T cell-mediated (type IV) hypersensitivity reactions. A, In delayed type hypersensitivity reactions, CD4+ T cells (and sometimes CD8+ cells) respond to tissue antigens by secreting cytokines that stimulate inflammation and activate phagocytes, leading to tissue injury. B, In some diseases, CD8+ cytolytic T lymphocytes (CTLs) directly kill tissue cells. APC, antigen presenting cell.
Delayed hypersensitivity in the skin. A, B, reveals a predominantly perivascular cellular infiltrate that.
A section of a lymph node shows several granulomas, each made up of an aggregate of epithelioid cells and surrounded by lymphocytes. The granuloma in the center shows several multinucleate giant cells.
Schematic illustration of the events that give rise to the formation of granulomas in cell-mediated (type IV) hypersensitivity reactions. Note the role played by T cell-derived cytokines.
