Host defense mechanisms

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Host defense mechanisms

• Dr Rahul Dhodapkar

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Need for defense mechanisms

• Protection
• Daily our body is exposed to large number of
  pathogenic and non pathogenic organisms
• Immune surveillance
• Our own body cells might some times malfunction
  (malignancies)

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Types of host defenses

• Non specific
• Specific

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Types of host defenses

• Non specific defenses
• Mechanical defences
• Physio chemical barriers
• Anti bacterial substances
• Intestinal transit

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Types of host defenses

• Non specific defenses
• Cellular defenses

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Types of host defenses

• Specific defenses
• Natural
• Active
• Naturally acquired infection
• Passive
• Mother to fetus transfer of immunity
• Artificial
• Active
• Vaccination
• Passive
• Preformed antibodies administered to provide
  protection

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Humoral immune response

• Mainly against extra cellular pathogens
• Antibodies produced by activated B cells

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Humoral immune response

• Structure of antibody
• Heavy chain
• Light chain
• J chain

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Humoral immune response

• Functions of antibodies
• Neutralizing toxins
• Neutralizing organisms
• Opsonization
• Complement activation

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Cellular immune response

• CMI activation requires presentation of antigen
  with self MHC
• Depending upon the type of T cell activated
  different cells will get activated
• Th cells
• Tc cells

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Interaction b/n CMI and antibody mediated immunity
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Immune response

• Role of innate immune system in activation of
  adaptive immune response
• Bacterial components activate macrophages
• Cytokine secretion from macrophages makes way for
  T cells
• Antigen presenting cells take up bacterial
  antigens
• Present to T cells, activating them

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Immune response

• Maintainance of immune response
• Role of memory cells
• Memory B cells
• Number of memory cells is 10 100 fold that of
  naïve cells
• Antibodies of high affinity are produced
• Different isotypes of antibodies can be produced

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Control of immune response
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Immunity during infection
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Immunity against tumors

• Immunity surveillance against non infective/ non
  foreign abnormalities in cells is another facet
  of immune system
• Tumors produce following types of antigens
• Tumor specific antigens
• Tumor associated antigens

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Disorders of immune system

• Autoimmunity
• Hypersensitivity
• Immunodeficiency

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Autoimmunity

• Immune system is directed against self antigens
• Mechanisms
• Molecular mimicry rheumatic fever
• Release of sequestered antigens sympathetic
  ophthalmitis
• Presentation of altered self drug induced lupus
• Polyclonal activation of immune system Kawasaki
  syndrome
• Tissues become competent to present antigen

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Autoimmune endocrinopathies

• Thyroid
• Hashimoto disease
• Graves disease
• Thyroiditis
• Insulin dependent DM
• Addisons disease

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Immune related hematologic conditions

• Immune mediated thrombocytopenia
• Alloimmune hemolysis
• Drug induced hemolysis
• Autoimmune hemolytic anemia
• Immune mediated neutropenia

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• Immune related skin disorders
• pemphigus

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Hypersensitivity

• Hypersensitivity reactions occur when the immune
  system mounts an excessive response to a stimulus

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Immunodeficiency

• Defects of antibody mediated immunity
• Primary hypogammaglobulinemia
• Secondary hypogammaglobulinemia
• Increased susceptibility to infections with
  capsulated organisms
• Giardia infections are well described
• Respiratory illnesses are seen

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• Defects of T cell immunity
• Severe combined immunodeficiency
• Combined immunodeficiency disorders
• Ataxia telagiectasia
• Wiscott Aldrich syndrome
• T cell based defects
• Di george syndrome
• Chronic mucocutaneous candidiasis

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Immunodeficiency diseases

• Human immunodeficience virus
• Virus infection affects
• CD4 T cells
• ? Dendritic cells
• ? Monocytes/Macrophages
• ? Follicular dendritic cells
• ? CNS gut tissue.

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Immunodeficiency diseases

• HIV
• Depletion of CD4 cells
• Impaired T memory responses
• Defective cytotoxicity
• Defective antibody responses

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Diagnostic tests

• Serologic diagnosis of infectious diseases
• Antigen or antibody detection using specific
  antibodies
• Radial immunodiffusion
• ELISA
• Particle agglutination
• Nephelometry
• Radioimmunoassay
• Immunofluorescent staining
• Immunoblotting

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Diagnostic tests

• Detection of antigen
• Helps in real time diagnosis of infection
• Specific
• Lacks sensitivity
• Not possible for all infectious diseases
• Examples
• Malaria, filaria, viral antigens etc

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Diagnostic tests

• Detection of antibodies
• Requires upto 7 10 days for appearance of
  antibodies
• Paired serology
• Single titres not very significant
• Four fold rise in titres significant
• Retrospective diagnosis

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Serology of autoimmune diseases

• Rheumatoid disease
• Antibodies targeted against Fc portion of IgG
• RF antibodies can belong to all isotypes
• Interpretation of RF test
• Positive in 90 of patients with rheumatoid
  arthritis
• Non specific
• Also positive in other autoimmune diseases
• High titers are strongly indicative of disease
• Titers not reliable indicators for guiding
  treatment

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Serology of autoimmune diseases

• Serology of connective tissue disorders
• Anti nuclear antibodies
• Principle
• Indirect immunofluorescence on Hep 2 cells
• Pattern of staining is used to determine the type
  of antibody present

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Serology of autoimmune diseases

• Serology of connective tissue disorders
• Anti nuclear antibodies
• Interpretation
• ANA results should be correlated with clinical
  condition, age and sex of patient
• Positive ANA test can be followed with specific
  ANA test
• Negative predictive value of the test is high
• Anti nuclear antibodies have long half life,
  repeated tests to assess treatment response are
  not advised

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Coombs test

• Direct
• Used to detect antibodies or complement
  components attached to RBC membrane
• Done in case of babies born to mothers with Rh
  incompatibility

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Coombs test

• Indirect coombs test