PathologyDr. KHALID W. ABDULATTAH
pathology department/Mousel Medical college
Diseases of Immunity (Immunopathology) Lecture 1
IntroductionImmunity is the protection from infectious pathogens.
There are two mechanisms for this protection:
Innate (natural or native) immunity.
Adaptive immunity (also called acquired, or specific immunity)
Innate Immunity:refers to the mechanisms that are ready to react to infections even before they occur.
Innate immunity is the first line of defense and induce rapid protective host reactions.
2-phagocytic cells (neutrophils, macrophages)
3-natural killer cells and dendritic cells.
4-plasma proteins including proteins of the compliment system ,C-reactive protein and Lung surfactant providing protection against inhaled microbes.
MacrophagesAre part of mononuclear phagocytic system derived from blood monocytes.
Natural killer cells
Make up to 15% of peripheral blood lymphocytes but are larger than lymphocyte and do not contain receptors on their surfaces. They are part of innate immunity ( do not require previous sensitization for its activation). They help to kill tumor cells, virally infected cells.
Dendritic cellsAre cells with cytoplasmic processes distributed in epithelial surfaces (interdigitating dendritic cells) and in the epidermis ( langerhan’s cells) and in the germinal center of lymphoid follicles of lymph nodes ( follicular dendritic cells). These cells are the most important antigen presenting cells for initiating primary immune response, they have many receptors on their surface that help to capture microbes from their site of entry at epithelial surfaces.
Adaptive immunity:Which includes two major typesCell mediated immunity responsible for defense against intracellular microbes e.g. mycobacterium, viruses, tumor cells, parasites. It is mediated by T (thymus-derived) lymphocytes.Humoral immunity protects against extracellular bacteria and their toxins. It is mediated by B (bone marrow–derived) lymphocytes and their secreted antibodies ( immunoglobulin).
Adaptive immunity develops later, after exposure to microbes and other foreign substances, and is even more powerful than innate immunity in combating infections.
T lymphocytesAre derived from the thymus.they constitute 60% to 70% of lymphocytes in peripheral blood. Depending on the presence of a specific membrane glycoprotein receptors on T cell surface, T cells are subdivided into:CD4+ T cells ( T helper cells) constitute 60% of T cells, they express CD4+ molecule on cell surface. This CD4 molecule binds to class II MHC molecule on the surface of antigen presenting cell. CD4+ T cells are “helper” T cells because they secrete soluble molecules (cytokines) that help B cells to produce antibodies, and also help NK cells and macrophages to destroy phagocytized microbes.
2. CD8+ T cells ( Cytotoxic T cells) : constitute 40% of T cells, they express CD8 molecule on their surface and bind to class I MHC molecule. CD8+ T cells can also secrete cytokines, but they play a more important role in directly killing virus-infected or tumor cells.
T cell activationB- Lymphocytes:
Are derived from bone marrow and constitute 10% to 20% of circulating peripheral lymphocytes.
The activation of B cells requires the help of CD4+ T helper cells which first recognize the antigen ( presented by antigen presenting cells in association with specific MHC molecule). Once T cells are activated they start to secrete cytokines and tumor necrosis factor (TNF) which activate B cells that differentiate into plasma cells, these are antibody secreting cells, they secrete immunoglobulin which mediate humoral immunity
Fab regionFc portion
These immunoglobulin are of five typesIgG is the most abundant type present in the plasma, tissue fluids and can cross the placenta
IgA is the next most common type present in plasma and in saliva and intestinal secretion and has a protective mechanism in the mucosa of GIT.
IgM is the largest Ig ,found only in plasma and the first immunoglobulin which appear after antigenic stimulation of B cells
IgE present in serum and on the surface of mast cells and basophils. It is involved in protection against parasites and mediate allergic reaction.
IgD present in serum and surface of B cells
Disorders of the Immune SystemHypersensitivity reactions
Autoimmune diseases (immune reaction against self)
Immunodeficiency syndromes ( genetically determined or acquired defects in some component of normal immune system).
Amyloidosis: a poorly understood disorder having immunologic association.
Hypersensitivity reactionsImmune responses that normally are protective are also capable of causing tissue injury. Injurious (excessive) immune reactions are grouped under hypersensitivity, and the resulting diseases are called hypersensitivity diseases.
On the basis of immunologic mechanism which mediates the disease, hypersensitivity reactions are classified into 4 types:
Type I (immediate) hypersensitivity.
Type II hypersensitivity ( antibody-mediated disorder)
Type III hypersensitivity ( immune complex mediated disorders)
Type IV hypersensitivity ( cell-mediated or delayed type).
PathogenesisThe main inflammatory cells which mediate type I reaction are mast cells and basophiles. Mast cells are derived from bone marrow and contain cytoplasmic granules filled with vasoactive amines. Type I reaction is mediated by IgE antibodies secreted from differentiated B cells. The surface of mast cells posses Fc receptor for the binding of Fc portion of IgE.
The sequence of events begins with the initial exposure to certain antigen or allergen (such as pollen, drugs, food) . These allergens stimulate induction of CD4+ lymphocytes of TH2 type. Once CD4+ lymphocytes recognize the antigen presented to it with antigen presenting cells, they start to secrete cytokines (IL4, IL5) which stimulate the production of IgE antibodies from B cells. IgE binds to Fc receptors on surface of mast cells and basophiles.
Re-exposure to the same antigen results in cross-linking of IgE on the surface of mast cells resulting in degranulation of mast cells and release of inflammatory mediators from granules in the cytoplasm of mast cells
Because inflammation is a major component of late-phase reaction in type I hypersensitivity, its control usually requires anti-inflammatory drugs such as corticosteroid.
chronic inflammation due to type I hypersensitivity reaction: Nasal mass with edematous stroma with chronic inflammatory cell infiltrate ( mainly eosinophils) covered by ciliated columnar epitheliumallergic nasal polyp
Bronchial asthma is an example of type I hypersensitivity reaction & is characterized by eosinophilic infiltrate, mucus collection & congestion.
Type II hypersensitivity ( Antibody-dependent type)Is mediated by antibodies directed against target antigens that are fixed on the surface of cells or other tissue components. The antigen may be endogenous as normal molecules in the cell membrane or may be exogenous like drugs, blood transfusion. The antibodies mediating this type of reaction are of IgG or IgM.
Clinical examples for this type of reactionTransfusion reaction: incompatible blood transfusion for either ABO or Rh incompatibility when RBCs from incompatible donor enter the recipient circulation, they become coated with antibodies directed against RBC antigen of the donor and are lysed.
Gravis disease: antibodies against thyroid-stimulating hormone receptor stimulate thyroid epithelial cells and result in hyperthyroidism.
Type III hypersensitivity ( Immune complex-mediated)Is mediated by deposition of antigen-antibody (immune) complexes followed by complement activation and accumulation of polymorph nuclear leukocytes.
It is either
Systemic Immune Complex Disease.
Local Immune Complex Disease.
Antigens may be exogenous e.g. bacteria and viruses or endogenous e.g. DNA and these immune complexes either form in the circulation (systemic) and then subsequently deposited in tissues or form and implanted locally at specific extra vascular sites e.g. kidney, joint, skin (localized) but the mechanism of tissue injury is the same.
Systemic Immune Complex DiseasePathogenesis
Formation of antigen-antibody complexes,
Deposition of immune complexes in various tissues.
Initiating an inflammatory reaction in various tissues and complement activation
PathologyWhen immune complexes are deposited in blood vessels the pathologic lesion is called vasculitis while their deposition in the glomeruli is called glomerulonephritis and in the joint is called arthritis
The deposition of immune complexes in an artery is called vasculitis with circumferential bright pink area of fibrinoid necrosis with protein infiltration & inflammation
Type IV Hypersensitivity ( Cell-Mediated ):Is mediated by specifically sensitized T lymphocytes ( without antibodies)
It is subdivided into two types:
Delayed Type Hypersensitivity: mediated by CD4+ T lymphocytes
Direct Cell Cytotoxicity: mediated by CD8+ T lymphocytes
The granuloma is composed of localized collection of epithelioid cells surrounded by lymphocytes with langhans type giant cell.