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General Info.• Involves B & T
cells(lymphocytes) which respond only to certain microbes & foreign molecules-not all of them
• Antigens-any foreign molecule eliciting a specific response– May be bacteria, fungi,
protozoa, worms, pollen, transplants, cancer cells, or PARTS OF any of these
– B & T cells have antigen (Ag) receptors in their membranes
• B receptors may be secreted as Abs
• T receptors always remain in the membrane
Clonal Selection
& T cells
Immediately active-Ab factories
Active T cells
B & T cells
Everyone has a “pool” of receptor shapes- ~ 1 trillion!!!
This is pre-determined to a large extent by your genes, and by the Ags you encounter as a young child
An Ag “selects” a receptor &, therefore, cell based on lock & key fit
The cells w/ this receptor then clone themselves
Self vs non-Self• Immune cells are self-
tolerant– Both B & T cells are
tested for self-reactivity during their maturation
– Self reactive cells undergo apoptosis
How do B & T cells recognize self?• Major Histocompatibility Complex (MHC)
– Group of 128 genes which code for 2 types of glycoproteins:• Class I MHC markers
– Found on all cells– Infected cells use these as billboards to display Ags to cytotoxic T
cells• Class II MHC markers
– Found only on immune cells– Macros & B cells use these as billboards to display Ags to T
helpers
T lymphocytes-Cell-Mediated Immunity• Not active against “free” Ag-Ag must be
bound to MHC markers (billboards)• All mature in thymus• 3 types
– T helpers (CD4+)-the generals• Key components of immunity because they
stimulate all other immune cells thru chemical signals
• Have receptors for combinations of Ag fragments & MHC II markers
• Do not kill any Ags or infected ells themselves– T cytotoxic cells (CD8)
• Have receptors for combos of Ag fragments & MHC I markers
• Respond to non-immune cells– Bind to virus infected cells displaying proper combo– Secrete perforin
• T helpers activate them– T suppressor cells
B lymphocytes-humoral Immunity• Kill Ags indirectly through Abs• Less effective against viruses , transplanted
tissues, & cancer• Abs (immunoglobulins)
– Found on B cell membrane– Secreted into blood– Quaternary globular protein, tetramer
Antibody Structure• Each polypeptide chain has 2 regions
– Variable region binds Ag (lock & key)-this makes up your individual “pool” of receptors (from genes)
• This region may vary from Ab to Ab, but is the same for a particular clone
– Constant region determines type (class) of Ab it is-all Abs of the same class have the same constant regions
Types of Abs• IgM-pentamer, 1st made,
activates complement, imp. Against viruses
• IgG-most abundant circulating Ab,crosses placenta, triggers complement,main Ab in secondary immunity
• IgA-found in mucus, saliva, tears, breast milk, can exit blood
• IgD-who knows?• IgE-allergies, parasites
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
Secondary Immune Response(Immunological Memory)
Secondary response-faster, more prolonged, greater magnitude Abs have greater affinity for Ag
Genetics of Immunity• MHC• Abs & T cell receptors
– 1 trillion receptors/Abs from 180 genes– DNA sequences are rearranged during development, PRIOR to Ag
exposure– Alternative RNA splicing also involved– Some evidence that Thelpers cause gene rearrangement which allows B
cells to produce various Ab classes
Diseases Related to Immune system• Cancer
– Tc & NKs patrol body-many cancer cells have mutated MHC markers
– Some cancers have normal markers or attack NKs
• Autoimmune disorders– Failure to distinguish self from non-self
• Arthritis-autoAbs form complexes around joints
• Diabetes-islet cells are attacked• MS-schwann cells are attacked• Lupus-attacks multiple systems in the
body which may include- the skin, joints, blood, lungs, kidneys, heart, brain & nervous system.
• Allergies-– During 1st exposure IgE binds to
mast cells– 2nd exposure causes massive
inflammation (histamine)-severe drop in blood pressure can lead to anaphylactic shock
Diseases cont…• Transplant rejections
– T cells attack due to foreign MHC markers– Immunosupressant drugs-usually against Th cells
(cyclosporin)
• AIDS– Immunosuppressive retrovirus– Destroys Th & macrophages– Opportunistic, secondary infections result when immunity is
sufficiently weakened
• Stress– Long term release of glucocorticosteroids from adrenal
depresses inflammation, decreases # of phagocytes (inc. APCs), decreases interleukins
• Aging– T cells less responsive to Ag