Special Forces, Day II

B lymphocytes-humoral ImmunityB lymphocytes-humoral Immunity Kill Ags indirectly through AbsKill Ags indirectly through Abs Less effective against viruses , transplanted Less effective against viruses , transplanted

tissues, & cancertissues, & cancer Abs (immunoglobulins)Abs (immunoglobulins)

Found on B cell membraneFound on B cell membrane Secreted into bloodSecreted into blood Quaternary globular protein, tetramerQuaternary globular protein, tetramer

Antibody StructureAntibody Structure Each polypeptide chain has 2 regionsEach polypeptide chain has 2 regions

Variable region binds Ag (lock & key)-this makes up your Variable region binds Ag (lock & key)-this makes up your individual “pool” of receptors (from genes)individual “pool” of receptors (from genes)

• This region may vary from Ab to Ab, but is the same for a particular This region may vary from Ab to Ab, but is the same for a particular cloneclone

Constant region determines type (class) of Ab it is-all Abs of the Constant region determines type (class) of Ab it is-all Abs of the same class have the same constant regionssame class have the same constant regions

Types of AbsTypes of Abs IgM-pentamer, 1IgM-pentamer, 1stst made, made,

activates complement, imp. activates complement, imp. Against virusesAgainst viruses

IgG-most abundant IgG-most abundant circulating Ab,crosses circulating Ab,crosses placenta, triggers placenta, triggers complement,main Ab in complement,main Ab in secondary immunitysecondary immunity

IgA-found in mucus, saliva, IgA-found in mucus, saliva, tears, breast milk, can exit tears, breast milk, can exit bloodblood

IgD-who knows?IgD-who knows? IgE-allergies, parasitesIgE-allergies, parasites

How Do Abs Kill Ags?

Classical Complement PathwayRequires activation by Ab-Ag complex

Alternative complement pathway•Non-specific•May be triggered by membrane markers of bacteria, viruses, or protozoa•No Ab-Ag complex necessary

http://www.cancerresearch.org/immhttp://www.cancerresearch.org/immresp.htmlresp.html

Secondary Immune Response(Immunological Memory)

Secondary response-faster, more prolonged, greater magnitude Abs have greater affinity for Ag

Genetics of ImmunityGenetics of Immunity MHCMHC Abs & T cell receptorsAbs & T cell receptors

1 trillion receptors/Abs from 180 genes1 trillion receptors/Abs from 180 genes DNA sequences are rearranged during development, PRIOR to Ag DNA sequences are rearranged during development, PRIOR to Ag

exposureexposure Alternative RNA splicing also involvedAlternative RNA splicing also involved Some evidence that Thelpers cause gene rearrangement which allows B Some evidence that Thelpers cause gene rearrangement which allows B

cells to produce various Ab classescells to produce various Ab classes

Diseases Related to Immune systemDiseases Related to Immune system CancerCancer

Tc & NKs patrol body-many cancer cells Tc & NKs patrol body-many cancer cells have mutated MHC markershave mutated MHC markers

Some cancers have normal markers or Some cancers have normal markers or attack NKsattack NKs

Autoimmune disordersAutoimmune disorders Failure to distinguish self from non-selfFailure to distinguish self from non-self

• Arthritis-autoAbs form complexes Arthritis-autoAbs form complexes around jointsaround joints

• Diabetes-islet cells are attackedDiabetes-islet cells are attacked• MS-schwann cells are attackedMS-schwann cells are attacked• Lupus-attacks multiple systems in the Lupus-attacks multiple systems in the

body which may include- the skin, body which may include- the skin, joints, blood, lungs, kidneys, heart, joints, blood, lungs, kidneys, heart, brain & nervous system.brain & nervous system.

• Allergies-Allergies- During 1During 1stst exposure IgE binds to exposure IgE binds to

mast cellsmast cells 22ndnd exposure causes massive exposure causes massive

inflammation (histamine)-severe inflammation (histamine)-severe drop in blood pressure can lead drop in blood pressure can lead to anaphylactic shockto anaphylactic shock

Diseases cont…Diseases cont… Transplant rejectionsTransplant rejections

T cells attack due to foreign MHC markersT cells attack due to foreign MHC markers Immunosupressant drugs-usually against Th cells Immunosupressant drugs-usually against Th cells

(cyclosporin)(cyclosporin) AIDSAIDS

Immunosuppressive retrovirusImmunosuppressive retrovirus Destroys Th & macrophagesDestroys Th & macrophages Opportunistic, secondary infections result when immunity is Opportunistic, secondary infections result when immunity is

sufficiently weakenedsufficiently weakened StressStress

Long term release of glucocorticosteroids from adrenal Long term release of glucocorticosteroids from adrenal depresses inflammation, decreases # of phagocytes (inc. depresses inflammation, decreases # of phagocytes (inc. APCs), decreases interleukinsAPCs), decreases interleukins

AgingAging T cells less responsive to AgT cells less responsive to Ag

Let’s Review!!! WooHoo!!!Let’s Review!!! WooHoo!!!