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Immunology

Organism encounters pathogens(anything cause diseases) +


foreign macromolecules(protein,pollen,venom) --- cellular
and molecular events
Focus on humans and mice.
Immune system
Cells and molecules responsible for immunity
Immune response
Response of host to introduction of foreign substances.
Innate and Adaptive responses
Early responses - innate ( natural immunity )
Biochemical and cellular defenses before infection and responds
rapidly(mins- hrs)
Biochemical + physical barriers
Later responses - adaptive(specific immunity)
Cellular and biochemical defenses stimulated by exposure to
pathogens - increases in magnitude with each successive
exposure.
Has capacity to remember encounters.
Immunoglobins + lymphocytes
Immunogenicity causing cell mediated immune response.
Antigens are recognized as foreign
Best antigen is protein chemical composition is imp.
Subs that can be easily degraded.
Large insoluble are better antigens.

Antigen cause of immune response.


Antigenic- capability to cause production of antibody
Antigenic determinant- site on antigen bound by antigenic

Continuous linear ; antibodies can recognize these areas.


- Epitope antibody binding to antigen
Break disulfide bond antigens cant be recognized anymore
change in epitope
Adjuvants boost immune response ; mix antigen with adjuvant
then stimulates immune system. They prolong the persistence of
antigen and increase inflammation.
Immunoglobulin molecules
Antibodies
Glycoproteins made in response to antigens
Animal blood albumin spike first , next globulins ( a , b, gamma )
After injection of adjuvant high spike of gamma globulins
Structure of antibody
2 light chains
2 heavy chains
variable(amino terminus) and constant(carboxy terminus) domain
Disease that helped understand antibody structure
- Cancer molecules as they produce large quantities for
sequencing
- B Cell tumors that secrete Ig (myeloma patients)
- Bence jones proteins : free excess light chains in urine
(myeloma patients)
- Heavy chain disease : abnormal heavy chains produced.
Chemical methods to help understand antibody structure
- Papin treatment
- Pepsin treatment
b-mercaptoethanol is a reducing agent to help separate heavy
and light chain
Bacteria
Fab site where antigen meets antibody

Fc crystalizable fragment helps antibody become part of


immune response
Fc receptor
Cell
Experiment
Inject antigen and inject into animal check which antibody is
produced
Isotype helps describe the differences in constant region of H or
L chain
Allotype determinants of one allele in Ig gene
Idiotype checks the Fab region of Ig molecule & changes In
hypervariable regions
Hypervariable regions CDRs these bind to the epitope
Framework regions are between the CDRs LESS variability gives
structure to cdr regions
Hinge region
Rich in proline and cysteine
Papin cleaves c-c , p-p , p-p
Pepsin cleaves c-c
Classes of Ig
IgM most reactive , found as a pentameric unit
J chain has extra disulfide bonds that help bind the pentameric
unit
No hinge region
Found on surface of B cells
High amount of carbs
B cell antigen receptor binds to e.coli which recognizes
epitope , B cells activated release Ab into tissue spaces
and bind to non-cell proteins
IgG very stable protein due to disulfide bonds
Complement system of blood born proteins that destroy invaders

They fix complement via classical pathway


Crosses placenta
Receptors on phagocytic cells and neutrophils (dont bind to Ig but
bind to immune complexes)
IgA predominant Ab present in external solutions ( tears , saliva
mucus etc.)
Secretory IgA held by J chain
Sturcture of secretory IgA
Release dimeric IgA binds to poly-ig receptor. It cleaves and
bought across cell layer to the secretory IgA
B lymphocytes in peyers patches produce IgA protects from oral
antigens
IgD plasmin proteolysis blood clot coagulation
Heat sensitive hence hard to isolate
Large hinge region
Membrane on b-cells at certain times
IgE immunoglobulin of allergic reactions
Binds to IgE Fc receptors on mast cells and basophils
Sensitive to heat
Cross linking of receptors , releases hypersensitivity mediators
from the cells
IgY Equiv to IgG found in reptiles , amphibians and birds
Similar biological roles
Has a higher MW and lacks hinge region
Therefore IgG may have evolved from IgY
Can cause allergic reactions

Antigen and Antibody Interactions


Affinity strength between antibody receptor site and ligand.
Affinity or association constant measure of affinity (attractive
and repulsive forces)
High affinity means less reversible reaction
Ka determination done by equilibrium analysis
Avidity overall strength of collective binding interactions that
occur during multivalent binding of antigen by a populations of
antibodies.
Low affinity doesnt mean it doesnt destroy the pathogen. It is
overcome by high avidity for Ag.
Avidity is more important than affinity because high avidity can
compensate for low affinity
Example ; IgM avidity makes up for its low affinity
Precipitation
- Small to large complexes
- Precipitation
Lattice of antibody and antigen builds up then visible ppt forms
Conditions
Valency of Ab and Ag
Ab needs to be bivalent molecular weight higher , more
binding multiple antibodies makes a ppt
- Fab fragment addition will only bind to epitope , no
cross linking
- Fab 2 WILL work because it can cross linking and form
lattice even though it doesnt have rest of Fc portion
its still bivalent

- Fc wont work because it doesnt bind to anything


Ppt reactions can be visualized
Fluid form 3 zones of Ab and Ag interactions taking place.
Gels radial and double immunodiffusion
Agglutination
- Reaction between Ab and particular Ag ; theres 2 types of
this
Techniques to see Ag interactions
- ELISA
- Western blotting
- Immunofluorescence
Defense systems
Mechanical barriers- cough sneeze
Surface barriers skin (physical), mucous
membranes(mechanical)
Gastric fluids acid in stomach
Lysozyme protein that kills bacteria by destroying cell wall
Cellular defenses phagocytosis , inflammation(complex series of
events that destroys pathogens)
Chemical defenses (COMPLEMENT) system of plasma proteins
that eliminate pathogens
Complement 3 biologic functions
Cytolysis is cell destruction
Opsonization is to coat an invader to make it easily recognized
WBC using their own complement receptor to engulf and destroy
invaders.
Activation of inflammation
Properties of complement molecules
PART of specific humoral immunity and natural immunity
Molecules cause proteolytic enzymes (zymogenes) become
activated to an active protease only after the complement
molecules are activated resulting in amplification(classical
pathway)

Complement Pathways
- Classical pathway initiated by Ag-Ab complexes or binding
of antibody to antigen on target cell ( specific to nonspecific)
- Lectin pathway plasma lectin binds to microbial
carbohydrates(mannose)
- Alternative pathway caused by various cell surface
constituents that are foreign to host
C1 activates C4
C1b associated with complex , C1a is floats away
C1
C1q needs to bind to 2 Fc sites for activated (IgM is
involved) IgM in circulation will be in planar form , when
bound to antigen it will have a spider/staple form.
C1r is activated by C1q configurational change
MBL
Binds to mannose residues and MASP-2 and 3 are exposed
, same activation events take place with MBL like C1q
Activation of classical pathway
Needs Ig to start
Starts on cell bound to Ab
Larger fragments are the ones that associate