Specific Host Defenses

Adaptive Immunity ACQUIRED

or SPECIFIC IMMUNITY
Two major kinds of defense
-Innate immunity
-Acquired immunity
The Immune System is the Third Line of
Defense Against Infection

Immune Response: Third line of defense.

Involves production of antibodies and generation of specialized lymphocytes against

specific antigens.
• Innate or Natural or Non specific Immunity:
• Immunity an organism is born with.
• Genetically determined. Effective from birth.
• Present before exposure to pathogens
• Nonspecific responses to pathogens
• Acquired or Specific Immunity:
• Immunity that an organism develops during lifetime.
• Not genetically determined.
• Develops after exposure to antigens (microbes,
• toxins, or other foreign substances)
• Very specific response to pathogens
• May be acquired naturally or artificially.
Types of Acquired Immunity
Types of acquired immunity
(1). Natural Acquired Active immunity (2). Natural
Acquired Passively, (3) Artificially Acquired Active
Immunity, & (4) Artificially Acquired Passive Immunity
• Serum: Fluid that remains after blood has clotted and
• cells have been removed.
• Antiserum: Serum containing antibodies to a specific
• antigen(s). Obtained from injecting an animal (horse,
• rabbit, goat) with antigen (snake venom, botulism or
• diphtheria toxin).
• Serology: The study of reactions between antibodies
• and antigens.
• Gamma Globulins: Fraction of serum that contains
• most of the antibodies.
• Serum Sickness: Disease caused by multiple
• injections of antiserum. Immune response to foreign
• proteins. May cause fever, kidney problems, and joint
• pain. Rare today.
 • Types of Acquired Immunity
• 2. Naturally Acquired Immunity:
• - Obtained in the course of daily life.
• 1A. Naturally Acquired Active Immunity:
• Antigens or pathogens enter body naturally.
• Person contracts disease; generates specific immune response
• to the antigen.
• Immunity may be lifelong (chickenpox or mumps) or
• temporary (influenza or intestinal infections).
• 1B. Naturally Acquired Passive Immunity:
• Antibodies pass from mother to fetus via placenta or breast
• feeding (colostrum). No immune response to antigens.
• Develops immediately immunity & is usually short-lived
• (weeks to months).
• Affects all antigens to which the mother has immunity.
• Protection until child’s immune system develops.
 • 2. Artificially Acquired Immunity:
• Obtained by receiving a vaccine or immune serum.
• 2A. Artificially Acquired Active Immunity:
• Involves production of Antibody following exposure of
• specially prepared Antigen
• Antigens are introduced as vaccines (immunization).
• Body generates an immune response slowly and is specific
• to the antigen for which the immunization was given.
• Immunity can be lifelong (oral polio vaccine) or temporary
• (tetanus toxoid & Diphtheria toxoid).
• 2B. Artificially Acquired Passive Immunity:
• Transfer of immunity from the immunised person to a
nonimmunized
• person by trnsfering Abs or sensitised cells.
• Eg. Snake antivenom injection from horses or rabbits
• Used in the ttt. Of Tetanus, Diphtheria &Mumps
• Immunity is immediate, but short lived (half life 3 weeks).
• Affects all antigens to which the donor has the immunity.
• Host immune system does not respond to antigens.
 Lymphocytes
• Lymphocytes mount a
• dual defense
• Two kinds of ( B & T)
• lymphocytes carry out
• the immune responses
• 1. Humoral immunity
• (Antibody mediated)
• involves the production
• of antibody by the B
• cells which attack Ag.
• 2.Cell mediated
• immunity - is
• governed by Tlymphocytes.
• T cells
• attack cells infected
• with pathogens
 • Duality of Immune System

• I. Humoral (Antibody-Mediated) Immunity

• Involves production of antibodies by B cells against
• foreign antigens (bacteria, bacterial toxins, and
• viruses).
• B cells develop from stem cells in the bone marrow
• of adults (liver of fetuses).
• After maturation, B cells migrate to lymphoid
• organs (lymph node or Spleen).
• B cells are the main warriors of humoral immunity
Humoral Response to T Independent Antigens
• Cell growth
• division, and
• differentiation

• Clone of many
• effector cells
• secreting
• antibodies
Humoral Response to T Dependent Antigens
 • Activation of B-Cells
• Activation of B cells involves various steps.
• Selection of B cells – 1 from many B-cell (Each lymphocyte
• bears a specific receptor to the antigen)
• Recognition of Antigens – by B cells or Macrophage
• Processing of Ag by Macrophages - immunogenic
• Antigen presentation by Macrophages to B cells. T dept Ag
• – needs the co operation of Th cells --(BSF) activate B cells
• Triggering of the B cell by the Ab or Th cells R-TCn-TLn
• Clonal proliferation–Cell division & prolfn- by BSF, BCGF
• Production of Plasma cells & Memory cells
• Secretion of Immunoglobulin into the serum.
 • Humoral Immunity (Continued)
• Apoptosis
• Programmed cell death (“Falling away”).
• Human body makes 100 million lymphocytes every
• day. If an equivalent number doesn’t die, will
• develop leukemia.
• B cells that do not encounter stimulating antigen
• will self-destruct and send signals to phagocytes to
• dispose of their remains.
• Many virus infected cells will undergo apoptosis, to
• prevent spread of the infection.
 • Clonal Selection
• Clonal deletion - Some self-reactive B cells are killed in
• the bone marrow (Not immunocompetent).
• Clonal selection- When antigen binds to antigen
• receptor, the “Selected” B cell undergoes proliferates into
• clones that will recognize one specific antigen.
• Clonal selection must be a defensive forces against a
• specific antigen.
• Stimulated B cell growth forms clones bearing the same
• antigen-specific receptors
• ■ A naive, immunocompetent B cell is activated when
• antigens bind to its surface receptors.
• ■ These, along with T cell interactions, trigger clonal
• selection
 • Fate of the Clones
• ■ Most clone cells become antibody-secreting
• plasma cells (effector cell - short-lived cells)
• ■ Plasma cells secrete specific antibody at a higher
• rate than B cells
• ■ Secreted antibodies:
• : Bind to free antigens
• BMark the antigens for destruction by specific or
• nonspecific mechanisms
• ■ Clones that do not become plasma cells become
• memory cells (long-lived) that can mount an
• immediate response to subsequent exposures of
• the same antigen
 • Immunological Memory

• Antibody Titer: The amount of antibody in the serum.

• Pattern of Antibody Levels During Infection
• Primary Response:
• After initial exposure to antigen, no antibodies are
• found in serum for several days.
• A gradual increase in titer, first of IgM and then of
• IgG is observed after 3 to 6 days.
• Most B cells become plasma cells, but some B cells
• become long living memory cells.
• Peak levels of plasma antibody are achieved in 10 days
• Gradual decline of antibodies follows.
 • Immunological Memory - Secondary Response:
• Subsequent exposure to the same antigen displays a faster and
• more intense antibody response with in an hour.
• It is due to the existence of memory cells, which rapidly produce
• plasma cells upon antigen stimulation.
• Antibody levels peak in 2 to 3 days
• Antibody levels in the blood can remain high for weeks to months
Antibody Response After Exposure to Antigen
 Monoclonal antibodies

• Monoclonal antibodies are

pure
• antibody preparations
• a Specific for a single
antigenic
• determinant
• dProduced from
descendents of
• a single cell
• a Hybridomas – cell hybrids
• made from a fusion of a
• tumor cell (easy-to-grow)
and
• a B cell (specific for a single
• antigenic determinant)
 • Uses - Monoclonal Antibodies

• ■ Monoclonal Abs are powerful tools in the lab

• MCommercially prepared antibodies are used:
• CIn research & clinical testing
• I To provide passive immunity
• These cells are useful in medical diagnosis
• T They are also useful in the treatment of certain
• cancers.
• ■ Have desirable properties of both parent cells –
• indefinite proliferation as well as the ability to
• produce a single type of antibody
Acquired Immunity: Ag-Specific Responses
T Lymphocytes: Cell Mediated Immunity
 • T Cells and Cell Mediated Immunity
• Cellular Components of Immunity:
• T cells develop from stem cells in bone marrow and
• mature in the thymus gland.
• After maturation they migrate to lymphoid organs
• T cells are key cellular component of immunity.
• T cells have an antigen receptor that recognizes and
• reacts to a specific intracellular antigen (T cell
• receptor).
• T cell receptor only recognize antigens combined
• with major histocompatability (MHC) proteins on
• the surface of cells.
• MHC Class I: Found on all nucleated cells &
• MHC Class II: Found on phagocytes.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
• II. Cell Mediated Immunity

• Clonal selection increases number of effector T cells

• and destroy the invader.
• T cells regulate proliferation and activity of other
• cells of the immune system: B cells, macrophages,
• neutrophils, etc.
• Defense against:
• Bacteria ,Viruses, Fungi, protozoa, and helminths
• Cancer cells & Transplanted tissue
• Unlike humoral immunity, cell mediated immunity
• is not transferred to the fetus (no passive immunity).
• Types of T cells

• Helper T (CD4+ T H) Cells - have central role in

• immune response, these activate macrophages and
• help form cytotoxic T cells
• Cytotoxic T (CD8+ CTLs) destroy target cells on
• contact by producing perforin that lysis an infected
• cells
• Delayed hypersensitivity T (T D) Cells: Mostly T
• helper and a few cytotoxic T cells that are involved
• in some allergic reactions (poison ivy) and rejection
• of transplanted tissue.
• Suppressor T (Ts) Cells -inhibit the production of
• CTL cells to shut down immune response once
• they are unneeded, least they cause more damage
• than necessary. (Now called regulatory T cells).
• T Cells and Cell Mediated Immunity

• 1. T Helper (TH) Cells: Central role in immune response.

• Most are CD4+ (clusters of differentiation)
• The helper T cell’s receptors recognize antigen on the
• surface of antigen presenting cells (e.g.: macrophage).
• The interaction activates the macrophages & TH cells
• The helper T cell releases IL2 & other cytokines
• to activate itself, Cytotoxic T cells & the B cell
• Activated CTL directly attack the infected cells by Cell
• mediated immune response
• B cells produce plasma cells which secrete antibodies –
• Humoral immune response.
• T cells mount the cell-mediated defense and aid
• humoral immunity
Central Role of Helper T Cells
 • Cytokines

• Mediators involved in cellular immunity, including

• hormone like glycoproteins released by activated T cells
• and macrophages
• ■ Interleukin 1 (IL-1) released by macrophages co-stimulates
• bound T cells to release IL 2.
• IL-2 is a key growth factor, which activates T cells to divide
• ■ Other cytokines amplify and regulate immune and
• nonspecific responses. Examples includes:
• n Perforin and lymphotoxin – Cell toxins
• PGamma interferon – enhances the killing power of
• macrophages
• mInflammatory factors
 • Cytotoxic T cells
• T cells that express CD8 molecule on their surface
• Class I MHC molecules (nucleated body cells) expose foreign proteins
• Recognize antigens on the surface of all cells:
• Kill host cells that are infected with viruses or bacteria.
• Recognize & kill - Foreign cells from blood transfusions or transplants.
• Recognize and destroy cancer cells & transplanted tissue.
• TC cell release protein called perforin and granzymes which forms a
pore in
• target cell membrane, causing lysis of infected cells and/or Apoptosis
• Interrelationship between cell mediated and humoral immunity

• production depends on macrophages and T cells (T

• dependent antigen)
• 1. Antigen is ingested and presented by the APC
• 2. The helper T cells reacts with this MHC-antigen complex
• 3. This activates the T cell and it begins to proliferate and
• produce cytokines.
• 4. The cytokines activate macrophages, CD8 cells, and natural
• killer cells
• 5. IL-2 influences a B cell to differentiate into a plasma cell that
• produces antibody
• Sometimes antigen can stimulate B cells directly without the
• help of T cells. This is called T independent antigen.
• In this case the antigen reacts directly with the B cell receptors.
• This is usually weaker
• Summary
• Evolutionary need for adaptive immunity:
• Self/non-self discrimination, specificity, amplification, regulation, duration
• and memory
• T and B cells are mediators of adaptive immunity
• T cells: cell-mediated immunity
• B cells: humoral immunity
• Cells of innate immunity also participate (DCs, Macrophages)
• Activation of T and B cells are different:
• T cells: specific recognition of peptide/MHC complex (signal 1) and
• costimulatory signals by APC (Signal 2)
• B cells: recognize native proteins (signal 1). May/may not require signal 2
• from CD4+ Th cells (TD and TI antigens)
• Immunological memory: an important hallmark
• Faster and rapid response on a second antigen encounter
• Innate immune response shapes the adaptive immunity