Immunopathology

Dr Teketel.T
 Overview of Immunity

• Function is to protect from infectious pathogens

• Two broad categories
– Innate immunity (natural, native)
– Adaptive immunity (acquired, specific)

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 Innate Immunity
 Components

• Epithelial barriers
• Phagocytic cells (neutrophils, macrophages)
• Natural killer cells
• Plasma proteins – complement system, c- reactive proteins…

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 Adaptive Immunity

• Mediated by lymphocytes and their products

• Two types of adaptive immunity
Cell mediated – against intracellular pathogens
Humoral immunity – extracellular microbes and
their toxins

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 Cont…

• Essential features of the adaptive immune system

include
 Specificity
 Diversity
 Memory

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 Cytokines

• Interaction among cells of the immune system is

important for induction and regulation of immune
responses
– Cell to cell contact
– Short acting soluble mediators – cytokines

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 Cont…

• General properties of cytokines

– One cytokine produced by several different cell
types
– Pleotropic
– Autocrine, paracrine or endocrine effect
– High affinity receptors on target cells

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 Histocompatibility Molecules
• Bind peptide fragments of foreign proteins for presentation to Ag
specific T-cells
• In humans gene encoding for histocompatibility molecules are
clustered on chromosome 6
• MHC gene products are classified into

1. Class I MHC – cell surface glycoproteins for Ag presentation

2. Class II MHC – cell surface glycoproteins for Ag presentation
3. Class III – components of complement system
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 Class I MHC

• Expressed on all nucleated cells and platelets

• Bind and display peptides that are derived from
proteins such as viral Ags synthesized within the cell
• CD8 + T-cells recognize such Ags

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 Class II MHC

• Expressed on APC’s (macrophages, dendritic cells and

B-cells)
• Present exogenous Ag that have been internalized
and processed intracellularly
• CD4+ T-cells recognize such Ags

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Hypersensitivity Disease

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 Hypersensitivity

• The immune response is triggered and maintained

inappropriately
• Injurious immune reactions which could be induced
by
– Exogenous antigens
– Endogenous tissue antigens

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 Classification
• Depending on the mechanism
– Type I – immediate hypersensitivity
– Type II – antibody mediated
– Type III – immune complex
– Type IV – cell mediated

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 Type I (Immediate ) Hypersensitivity

• Rapidly developing immunologic reaction after

antigens bind antibodies on the surface of mast cells
• Can present as a systemic disorder or as a local
reaction
• Local reactions have two phases

– Initial response – 5 to 30 mins

– Late phase reaction – 2 to 24 hrs later

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 Atopy
• Susceptibility to immediate hypersensitivity is
genetically determined
• Refers to predisposition to develop localized
immediate hypersensitivity to variety of inhaled and
ingested antigens
• Atopic individuals have higher serum IgE and higher
number of IL-4 secreting TH2 cells
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 Systemic Anaphylaxis
• Characterized by vascular shock, widespread edema, difficulty in
breathing
• Manifestations

– Itching, hives and erythema

– Constriction of respiratory bronchioles and resp distress

– Laryngeal edema

– Vomiting and abdominal cramp, diarrhea

– shock
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 Cont…

• Local immediate hypersensitivity reactions

– Urticaria
– Angioedema
– Allergic rhinitis (hey fever)
– Atopic asthma

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 Type II hypersensitivity

• Mediated by antibodies directed towards antigens

present on cells surface or extracellular matrix
• Antigenic determinants may be intrinsic or
exogenous

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 Mechanisms of Ab Mediated Injury

1. Opsonization and complement & Fc receptor

mediated phagocytosis
– Transfusion reactions

– Erythroblastosis fetalis

– Autoimmune hemolytic anemia, thrombocytopenea

and agranulocytosis
– Certain drug reactions
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 Cont…

2. Complement and Fc receptor mediated

inflammation
– Antibody deposition in extracellular tissue
– Glomerulonephritis, vascular rejection in organ
transplants

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 Cont…

3. Antibody mediated cellular dysfunction

– Antibody directed against cell surface receptors
impair or deregulate function without causing cell
injury or inflammation
• Myasthenia gravis - Ach receptor
• Pemphigus vulgaris – desmosome
• Graves disease - TSH receptor
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 Type III Hypersensitivity
• Ag-Ab complexes produce tissue damage mainly by eliciting
inflammation at site of deposition
• Two general types of antigens

1. Exogenous – foreign protein, bacteria or virus

2. Antibodies against self components
• Generalized – immune complexes are formed in the
circulation and deposited in many organs
• Localized - glomerulonephritis, arthritis, vasculitis
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 Type IV Hypersensitivity

• Initiated by antigen activated T-lymphocytes

– Delayed type hypersensitivity reaction – CD4+ T-
cells
– Direct cell cytotoxicity – CD8+ T-cells

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 Cont…
• Principal pattern of immunologic response to a variety of
IC pathogens
– Mycobacterium tuberculosis

– Fungi, protozoa and parasitic infections

– Contact skin sensitivity

– Graft rejection

– autoimmunity
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 Autoimmunity

• Immune reaction against self antigens

• Three requirements must be fulfilled to classify a
disease as truly autoimmune
1. Presence of autoimmune reaction
2. Reaction not secondary to tissue damage
3. Absence of other well defined causes

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 Cont…

• Autoimmune disorders result from tissue injury

caused by T-cells or antibodies that react against self
antigens
– Organ specific – ex. Type 1 diabetes
– Limited to few organs – ex. Goodpasture
syndrome
– Systemic - SLE
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 Mechanisms of Autoimmune Diseases

• Development of autoimmunity is related to

inheritance of susceptibility genes and
environmental triggers

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Thank you

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