Immunity and Immune Response

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Immunity, Immune System and Immune Response
Envr 421 Mark D. Sobsey
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Antigens

• Any foreign substance that elicits an immune
  response when introduced into the tissues of a
  susceptible animal and capable of combining with
  the specific antibodies formed.
• Generally high molecular weight
• Typically, proteins or polysaccharides.
• Polypeptides, lipids, nucleic acids and many
  other materials also can also function as
  antigens
• Microbes are antigenic and they contain and
  produce many antigens
• Antigens have specific sites that bind to
  antibodies called epitopes

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Immunity and Immune Response

• Made up of two cellular systems
• Humoral or circulating antibody system
• B cells
• Cell mediated immunity
• T cells

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Immunity and Immune Response

• Immune system identifies antigens (foreign
  proteins or polysaccharides)
• Components of microbes or their partially
  degraded byproducts and
• Other foreign proteins and polysaccharides
  (including nucleic acids)
• Host (human or animal) antigens not made by the
  individual are also antigens
• Result in graft, transplant rejection

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The Immune System Origin and Development

• Human immune system begins to develop in the
  embryo.
• Starts with hematopoietic (from Greek,
  "blood-making") stem cells.
• Stem cells differentiate into major cells in the
  immune system
• granulocytes, monocytes, and lymphocytes
• Stems cells also differentiate into cells in the
  blood that are not involved in immune function,
  such as erythrocytes (red blood cells) and
  megakaryocytes (for blood clotting).
• Stem cells continue to be produced and
  differentiate throughout ones lifetime.

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Biological Components of Human Immune System
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The Immune System
(Cell-mediated immunity)
(Antibody-mediated immunity)
(Red blood cell)
(Non-specific cells responding to antgens and
allergens)

• (AKA polymorphonuclear leucocytes)
• (neutrophils, eosinophils and basophils)

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Immunity and the Immune Response System
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Immunity and the Immune Response System
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Clonal Selection of B Cells is Due to Antigenic
Stimulation
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Classes of Antibodies (Immunoghlobulins)
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Humoral (Antibody-mediated) Immune Response to
Antigen

• First-time Antigen Exposure
• 1o Response
• Several day lag, then antibody becomes
  detectable.
• Antibody is IgM class
• After a short time, antibody level declines
• Later Re-exposure to Same Antigen 2o
  (anamnestic) response
• more rapid Ab appearance and in greater amount.
• IgG class of antibody
• Remains detectable for months, years or lifetime.

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Humoral Immune Response to Different Antigens

• First exposure to antigen "A
• Begin to make low levels of antibody after
  several days
• Second exposure to antigen "A
• produces a much faster response, and
• Several orders of magnitude higher levels of
  antibody.
• Ability of antibody to bind antigen also
  increases dramatically in the secondary response.
  
• Injecting a new antigen "B "A"
• Elicits only a primary response
• Shows that a memory or prior exposure is required
  for the accelerated response.

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Humoral or B-Cell Mediated Immune Response

• Produces secreted antibodies (proteins)
• Bind to antigens and identify the antigen complex
  for destruction.
• Antibodies act on antigens in the serum and lymph
  
• B-cell produced antibodies may be
• attached to B-cell membranes or
• Free in the serum and lymph.
• Each B lymphocyte makes a unique antibody
  molecule (immunoglobulin or Ig)
• Over a million different B lymphocytes are
  produced in each individual
• So, each individual can recognize more than a
  million different antigens

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Immunoglobulin G (IgG) and Reaction with Antigen

• IgG antibody molecule
• Composed of 2 copies of 2 different proteins
• Two copies of a heavy chain
• gt400 amino acids long
• Two copies of a light chain -
• gt200 amino acids long
• Each IgG antibody molecule can bind 2 antigens at
  one time
• A single antibody molecule can bind to 2 antigens
  (e.g., viruses, bacateria or other particle),
  which leads to clumping

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Effect of Antigen Size on Humoral Immunity
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Fate of Antigen-Antibody Complexes

• Ag-Ab complexes engulfed into the B-cell and
  partially digested
• Antigen is displayed on the B-cell surface by a
  special receptor protein (MHC II) fo recognition
  by helper T-cells
• B-cell is activated by the helper T-cell to
  divide and produce secreted antibodies
• Abs circulate in the serum and lymph
• Some B-cells become memory cells to produce
  antibody at a low rate for a long time (long term
  immunity)
• They respond quickly when the antigen is
  encountered again
• the response is regulated by a class of T-cells
  called suppressor T-cells

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Cell-Mediated Immunity and T Cells

• T cell receptors are cell surface receptors that
  bind non-self substances on the surface of other
  cells
•  Major histocompatibility complex (MHC) proteins
  protrude from the surfaces of most cells in
  mammals
• They help to distinguish self from nonself
• They coordinate interactions among lymphocytes
  and macrophages
•  Cytokines are soluble signal proteins released
  by T cells
• They bind and alter the behavior of their target
  cells

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Cell Mediated Immune System T lymphocytes

• T-cells mature in the thymus (thus the name
  T-cell)
• Act on antigens appearing on the surface of
  individual cells.
• Over a million different kinds of T-cells
• Each produces a different receptor in the cell
  membrane
• Each receptor is composed of 1 molecule each of
  two different proteins
• Each receptor binds a specific antigen but has
  only one binding site
• Receptor only recognizes antigens which are
  "presented" to it within another membrane protein
  of the MHC type (major histocompatibility
  complex)
• Recognizes specific antigens bound to the
  antigen- presenting structures on the surface of
  the presenting cell.
• Recognizes antigens presented by B-cells,
  macrophages, or any other cell type

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T Cells and their Functions

• Have a specific receptor for a fragment of
  antigen
• Cytotoxic T-cells
• Contain a surface protein called CD8
• Destroy pathogen infected cells, cancer cells,
  and foreign cells (transplanted organs)
• Helper T-cells
• Contain a surface protein called CD4
• Regulate both cellular and humoral immune systems
• This regulation reduces autoimmunity.

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Autoimmune disease

• Self immunity
• Some examples
• rheumatic fever
• rheumatoid arthritis
• ulcerative colitis
• myasthenia gravis
• Lyme disease (microbial etiology)
• Guillan-Barre syndrome (microbial etiology)
• Reiters syndrome or reactive arthritis
  (microbial etiology)
• Insulin dependent diabetes mellitus (IDDM)
  (microbial etiology?)

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Interactions of the Components of The Immune
Response

• T-cells, B-cells, and macrophages use MHC-II
  receptors for presentation
• All other cells use MCH-I
• (responsible for most of tissue graft rejection)
• When a T-cell is presented with an antigen
• its receptor binds to the antigen and
• it is stimulated to divide and produce helper
  T-cells
• activate B-cells with bound antigen
• suppressor T-cells
• regulate the overall response
• Cytotoxic "killer" T-cells
• kill cells with antigen bound in MHC-I

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Role of Immunity in InfectionsLocalized
Infections

• Immunity to infection is usually short-term and
  transient
• Mucosal (secretory or IgA) immunity in the gut or
  respiratory tract wanes over time
• Proof of concept live, oral rotavirus vaccine
• immunity declines over time and reinfection with
  wild type rotaviruses occurs
• Repeated localized (e.g., gastrointestinal)
  re-infection is possible. Examples
• Viruses rotaviruses, noroviruses, adenoviruses
  and some enteroviruses.
• Salmonella spp, Shigella spp., Campylobacter spp,
  and E. coli spp. cause localized infections
• Giardia lamblia and Cryptosporidium parvum

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Role of Immunity in InfectionsGeneralized/System
ic/Disseminated Infections

• Immunity against generalized/systemic/disseminated
  infection is usually lifelong, unless immune
  system is severely compromised
• Localized (e.g., gastrointestinal) re-infection
  is possible
• Hepatitis A and E and many enteroviruses are
  viruses causing systemic/generalized/disseminated
  infections
• Salmonella typhi is a bacterium causing systemic
  infection
• Typically, immunity against severe illness is
  long-term and probably lifelong
• Proof of concept live, oral poliovirus vaccine
  and poliomyelitis eradication susceptibles are
  newborns and infants
• Antigenic changes in microbes may overcome
  long-term immunity and increase risks of
  re-infection or illness

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Role of Selection of New Microbial Strains in
Susceptibility to Infection and Illness
Antigenic Shift and Drift

• Antigenic changes in microbes overcome immunity,
  increasing risk of re-infection or illness
• Antigenically different strains of microbes
  appear and are selected for over time and space
• Constant selection of new strains (by antigenic
  shift and drift)
• Partly driven by herd immunity and genetic
  recombination, reassortment , bacterial
  conjugation, bacteriophage infection and point
  mutations

• Antigenic Shift
• Major change in virus genetic composition by gene
  substitution or replacement (e.g., reassortment)
• Antigenic Drift
• Minor changes in virus genetic composition, often
  by mutation involving specific codons in existing
  genes (point mutations)
• But, a single point mutation can greatly alter
  microbial virulence!

Driftminor change
Shiftmajor change