immune system and response
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Immune Response and Immunity
Envr 133
Mark D. Sobsey
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Antigens
Any foreign substance that eicits an immune response!hen introduced into the tissues of a susceptibeanima and capabe of combining !ith the specificantibodies formed.
"eneray high moecuar !eight#ypicay$ proteins or poysaccharides.
%oypeptides$ ipids$ nuceic acids and many othermaterias aso can aso function as antigens
Microbes are antigenic and they contain and producemany antigens
Antigens have specific sites that bind to antibodiescaed &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 partiallydegraded byproducts and
) ther foreign proteins and polysaccharides
(including nucleic acids)
( Host (human or animal) antigens not madeby the indi!idual are also antigens
) Result: in graft" transplant re#ection
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The Immune $ystem
• Human immune system begins to develop in the embryo.
• Starts with hematopoietic (from Greek, "blood-making" stem
cells.
• Stem cells differentiate into ma!or 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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omponents of Human #mmune System
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The Immune $ystem
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#mmunity and the #mmune $esponse System
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#mmunity and the #mmune $esponse System
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lonal Selection of % ells is &ue to 'ntigenic Stimulation
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*asses of Antibodies +Immunoghobuins,
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Humoral #mmune $esponse to 'ntigen
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Humoral #mmune $esponse to 'ntigen
• irst e)posure to antigen "'*+
– begin to make low levels of antibody in about a week
• Second e)posure to antigen "'*+
– produces a much faster response, and– several orders of magnitude higher levels of antibody.
– 'bility of antibody to bind antigen also increasesdramatically in the secondary response.
• #n!ecting a new antigen "%* with "'"– licits only a primary response
– Shows that a memory or prior e)posure is reuired forthe accelerated response.
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Humoral or B%Cell Mediated Immune Response
&roduces secreted antibodies (proteins)( Bind to antigens and identify the antigen comple'
for destruction( ntibodies act on antigens in the serum and
lymph
( B%cell produced antibodies may be ) attached to B%cell membranes or ) *ree in the serum and lymph
( +ach B lymphocyte ma,es a uni-ue antibodymolecule (immunoglobulin or Ig)
( !er a million different B lymphocytes areproduced in each indi!idual ) $o" each indi!idual can recogni.e more than a
million different antigens
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Immuoglobulin / (Ig/)
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Immunoglobulin and Reaction with ntigen
Ig/ antibody molecule ) Composed of 0 copies of 0 different proteins
) Two copies of a hea!y chain
( 1233 amino acids long ) Two copies of a light chain %
( 1033 amino acids long
( each Ig/ antibody molecule can bind 0antigens at one time ) single antibody molecule can bind to 0 antigens
(eg" !iruses" bacateria or other particle)" which
leads to clumping
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Effect of Antigen Size on Humoral Immunity
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*ate of ntigen%ntibody Comple'es
• 'g-'b comple)es engulfed into the %-cell and partially
digested
• 'ntigen is displayed on the %-cell surface by a special receptor
protein (H ## fo recognition by helper /-cells
• %-cell is activated by the helper /-cell to divide and produce
secreted antibodies
– 'bs circulate in the serum and lymph
• Some %-cells become memory cells to produce antibody at a
low rate for a long time (long term immunity
– /hey respond uickly when the antigen is encountered again
– the response is regulated by a class of /-cells called
suppressor /-cells
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Cell-Mediated Immunity and T Cells
( # ce receptors are ce surface receptors that bindnonsef substances on the surface of other ces
( Ma-or histocompatibiity compe +M/*, proteins
protrude from the surfaces of most ces inmammas ) #hey hep to distinguish sef from nonsef
) #hey coordinate interactions among ymphocytes andmacrophages
( *ytokines are soube signa proteins reeased by# ces ) #hey bind and ater the behavior of their target ces
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ell ediated #mmune System+ / lymphocytes
( T%cells mature in the thymus (thus the name T%cell)
( ct on antigens appearing on the surface of indi!idualcells
( !er a million different ,inds of T%cells ) +ach produces a different receptor in the cell membrane
) +ach receptor is composed of 4 molecule each of two
different proteins
) +ach receptor binds a specific antigen but has only one
binding site
) Receptor only recogni.es antigens which are 5presented5 to
it within another membrane protein of the MHC type (ma#or
histocompatibility comple')( Recogni.es specific antigens bound to the antigen%
presenting structures on the surface of the presenting cell
( Recogni.es antigens presented by B%cells" macrophages" or
any other cell type
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T Cells and their *unctions( Ha!e a specific receptor for a fragment of antigen
( Cytoto'ic T%cells: ) Contain a surface protein called C67
) 6estroy pathogen infected cells" cancer cells" and
foreign cells (transplanted organs)
( Helper T%cells: ) Contain a surface protein called C62 ) Regulate both cellular and humoral immune systems
) This regulation reduces autoimmunity
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utoimmune disease
( $elf immunity
( $ome e'amples:
– rheumatic fever
– rheumatoid arthritis
– ulcerative colitis
– myasthenia gravis
– 0yme disease (microbial etiology
– Guillan-%arre syndrome (microbial etiology
– $eiter1s syndrome or reactive arthritis (microbial etiology
– #nsulin dependent diabetes mellitus (#&& (microbial etiology2
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Interactions of the Components of The
Immune Response( T%cells" B%cells" and macrophages use MHC%II
receptors for presentation8
( ll other cells use MCH%I
) (responsible for most of tissue graft re#ection)( 9hen a T%cell is presented with an antigen:
) its receptor binds to the antigen and
) it is stimulated to di!ide and produce helper T%cells( acti!ate B%cells with bound antigen
( suppressor T%cells ) regulate the o!erall response
( Cytoto'ic 5,iller5 T%cells ) ,ill cells with antigen bound in MHC%I
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$ole of #mmunity in #nfections
0ocali3ed #nfections+
• #mmunity to infection is usually short-term and transient– ucosal (secretory or #g' immunity in the gut or
respiratory tract wanes over time• 4roof of concept+ live, oral rotavirus vaccine+
– immunity declines over time and reinfection with 5wild*
type rotaviruses occurs
• $epeated locali3ed (e.g., gastrointestinal re-infection is
possible. )amples+
– 6iruses+ rotaviruses, noroviruses, adenoviruses and someenteroviruses.
– Salmonella spp, Shigella spp., Campylobacter spp, and E. coli spp.
cause locali3ed infections– Giardia lamblia and Cryptosporidium parvum
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$ole of #mmunity in #nfections+
Generali3ed7Systemic7&isseminated #nfections
• #mmunity against generali3ed7systemic7disseminated infectionis usually lifelong, unless immune system is severely
compromised
• 0ocali3ed (e.g., gastrointestinal re-infection is possible
• Hepatitis ' and and many enteroviruses are viruses causingsystemic7generali3ed7disseminated infections
• Salmonella typhi is a bacterium causing systemic infection
• /ypically, immunity against severe illness is long-term and
probably lifelong– 4roof of concept+ live, oral poliovirus vaccine and poliomyelitis
eradication8 susceptibles are newborns and infants
• 'ntigenic changes in microbes may overcome long-term
immunity and increase risks of re-infection or illness
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Roe of Seection of 0e! Microbia Strains in
Susceptibiity to Infection and Iness• 'ntigenic changes in microbes overcome immunity, increasing
risks of re-infection or illness– 'ntigenically different strains of microbes appear and are selected
for over time and space– onstant selection of new strains (by antigenic shift and drift– 4artly driven by 5herd* immunity and genetic recombination,
reassortment , bacterial con!ugation, bacteriophage infection and
point mutations
• 'ntigenic Shift+– a!or change in virus genetic composition by gene substitution or
replacement (e.g., reassortment
• 'ntigenic &rift+– inor changes in virus genetic composition, often by mutation
involving specific codons in e)isting genes (point mutations
• ' single point mutation can greatly alter microbial virulence