It’s time for the special forces!

Specific Defenses

http://www.whfreeman.com/kuby/con_index.htm?99anm

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

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

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

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/immresp.html

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

Let’s Review!!! WooHoo!!!