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)