IMMUNOLOGY Dr. Nadeem Ikram MBBS, DCP (Clinical pathology), FCPS (Immunology)
Jan 02, 2016
IMMUNOLOGY
Dr. Nadeem IkramMBBS, DCP (Clinical pathology), FCPS (Immunology)
IMMUNOLOGY
Divided into two major categories Normal individual has two levels of defense against
foreign agents Innate, Natural or non specific Immunity Acquired, Specific or adaptive Immunity
Non specific or Innate Immunity
First line of defense Response is antigen independent No memory of an encounter with a foreign organism
Elements of non specific or innate immunity
Anatomic barrier Physiologic barrier Secretory molecules Cellular components
ANATOMIC BARRIER
Skin Mucous membrane Intestinal movement Oscillation of bronchopulmonary cilia Hairs in ears and nose
PHYSIOLOGIC FACTORS
pH temperature oxygen tension acid environment of stomach commensal flora cough reflex
SECRETARY MOLECULES
Acids in skin secretions Bile acids in GIT Lysozyme Complement Acute phase proteins Interferon
Cellular component of the non specific Immune system
Cellular components (non specific)
Circulatory cells Neutrophils (Polymorphonuclear leukocytes) 40-
60% Eosinophils 1-4% Basophils <1% Monocytes 2-8%Others Dendritic cells Natural Killer cells Mast cells
Neutrophils
Most important cellular components in bacterial destruction
Relatively large Most abundant WBC Lobed nucleus
Eosinophils
Bilobed nuclei Majority reside in connective tissues Immune response against parasites and helminths Increase in allergic reaction
Monocytes
• Circulate in the blood for 1 day. Enters the tissues to become macrophages (scavengers)
• Largest blood cell in the circulation• Tissue macrophages: life span 2-4 months
Natural killer cells
Nonphagocytic Directed against viral infection and malignancies Resemble lymphocytes in morphology but larger
Phagocyte response to infection
Chemotaxis Attachment Phagocytosis Intracellular killing
Properties of Specific or adaptive or acquired immunity
• Specificity• Memory• Diversity• Tolerance
Types
1. Humoral immunity Formation of antibodies in response to an antigen
& is mediated by B lymphocytes2. Cell mediated immunity Mediated by T lymphocytes
Specific Immune Cells
Lymphocytes 20-40%• T cells• B cells
B cells
• 10-15% of circulating lymphocytes• Synthesize immunoglobulins
Antibodies Immunoglobulins are glycoproteins, produced by
B lymphocytes plasma cellsStructure• 2 identical light polypeptide chains• 2 identical heavy polypeptide chains
Functions of Antibodies
IgG• Cross placentaIgM• Predominant antibody in primary immune responseIgA• Present in SecretionsIgD• Function remains unclearIgE• It binds to basophils & tissue mast cells• Involved in allergic reactions• Immunity against parasites and helminthes
Antibody ResponsePrimary response: Following primary antigenic challenge1. Lag phase2. Log phase3. Plateau phase4. Decline phase
Secondary response: Secondary antigenic challenge1. Short lag phase2. Persist for longer period of time.3. Attains a higher titer4. Consist predominantly of IgG antibodies
Effector functions of Antibodies
• Neutralisation• Opsonization• Antibody dependent cell mediated
cytotoxicity• Complement activation
T cells
• 70 -80 %of circulating lymphocytes• Mature in thymus and called T lymphocytes
T cell subsets
T helper cell (CD4)
T cytotoxic cell (CD8)
Antigen presenting cells
Antigen presenting cells located in the epithelium and tissues, capture antigens, transport them to peripheral lymphoid tissues, and displays them to lymphocytes
• Langerhan’s cells • Interdigitating dendritic cells Macrophages• B cells
Activation of T cells
Activation of T cells occurs by antigen presenting cells
MHC class I and II receptors
MHC Class I and II : Activation and proliferation of T and B cells
Function of MHC Class I
• Present antigen to CD8 T cells
Function of MHC Class II
• Present antigen to CD4 helper T cells
Activation of T cellsFirst signal: Formation of MHC:TCR:(CD4/CD8) complexSecond signal: Costimulatory molecules
B cell activation
Activation by T dependent antigens• B cell presents antigen to T cell, and receives
signal from T cells for division and differentiation
• Antigen is protein in nature
Hypersensitivity
Exaggerated or inappropriate immunological reactions leading to host tissue damage
OrImmune responses capable of causing tissue
injury and disease
TYPES OF HYPERSENSITIVITY REACTIONS
Based on immunological mechanism that mediates disease
• Type I or Immediate / anaphylactic / atopy• Type II or Cytotoxic / antibody mediated• Type III or immune complex disease• Type IV or cell mediated/ delayed
Hypersensitivity Type I
Rapidly developing immunological reaction occuring with in minutes after combination of an antigen with antibody bound to mast cells
or basophils in individuals previously sensitized to the antigen
Mechanism
• Antigen (allergen) binds to IgE on the surface of mast cells/basophils with the consequent release of mediators
• Reaction time is 5-30 minutes from the time of exposure to the antigen
Type I hypersensitivity
Localized reactions• Skin • Eyes • Nasopharynx• Bronchopulmonary tissue• GIT
Systemic reactions (anaphylaxis)
Hypersensitivity Type II
Antibodies (IgM, and IgG) that react with antigens present on cell surface or in the extracellular matrix
Antigen• Endogenous : intrinsic to the cell membrane or
matrix• Exogenous: drug metabolite
Examples of Type II Hypersensitivity
Reaction against blood cells & platelets Transfusion reactions Hemolytic disease of new born Autoimmune hemolytic anemia Antibodies against neutrophils Antibodies against plateletsReaction against tissue antigens Good pasture's syndrome Pemphigus vulgaris Myasthenia gravis Graves disease Acute Rheumatic fever Pernicious anemia Hyperacute graft rejection
IMMUNE COMPLEX MEDIATED INJURY (TYPE III)
Inflammatory reaction triggered by a soluble antigen forming large insoluable immune complexes with IgG or IgM antibodies in the circulation
ETIOLOGYExogenous
Infectious agents• Bacteria : streptococci • Viruses : Hepatitis B, CMV• Parasites : plasmodium sp.• Fungi: ActinomycetesDrugs or chemicals• Foreign serum• Quinidine• Heroin
Endogenous• Nuclear antigens• Immunoglobulins• Tumor antigens
MECHANISM
• Formation of antigen antibody complexes in the circulation
• Deposition of immune complexes in the blood vessels
• Tissue injury by Inflammatory reaction
Free Ag + Ab Larger immune complex
Deposit in tissue or blood vessel wall
Inflammation
MECHANISM OF DAMAGE
EXAMPLES
Localized Type• Arthus reaction
Systemic Type• Serum sickness• Systemic Lupus Erythematosus (SLE)• Poststreptococcal glomerulonephritis• Reactive arthritis• Polyarteritis nodosa• Hypersensitivity pneumonitis
HYPERSENSITIVITY TYPE IV
Delayed type HypersensitivityCell mediated Hypersensitivity
• Immunopathological damage that occurs at about 24-72 hours after exposure of a sensitized individual to an antigen
• The cell mediated hypersensitivity is initiated by specifically sensitized T lymphocytes
HYPERSENSITIVITY TYPE IV
Examples of diseases• Type I diabetes mellitus• Multiple sclerosis• Contact dermatitis• Peripheral neuropathy• Chronic graft rejection• Tuberculosis• Environmental antigens (contact sensitivity)