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Immune system has two intrinsic systems

Innate (nonspecific) defense system
Adaptive (specific) defense system

Innate defense system has two lines of defense

First line of defense - skin and mucosa
Second line of defense - antimicrobial proteins, phagocytes, and other cells
inhibit spread of invaders

Inflammation is immunity's

most important mechanism

Adaptive defense system

Third line of defense attacks particular foreign substances

Surface barriers

skin, mucous membranes, and their secretions

Protective chemicals

inhibit or destroy microorganisms

Skin acidity

pH 3-5 inhibits bacterial growth

Lipids in

sebum and dermicidin in sweat are toxic to bacteria

HCl and protein-digesting

enzymes of stomach mucosae are protective chemicals

Lysozyme of

saliva and lacrimal fluid are protective barriers

Mucus traps

microorganisms in digestive and respiratory passageways

Respiratory system modifications

mucus-coated hairs in nose
cilia of upper respiratory tract

Internal defenses

phagocytes
NK cells
Inflammatory response
antimicrobial proteins (interferons and complement)
fever

Macrophages develop from

monocytes to become the chief phagocytic cells

Free macrophages

wander through tissue spaces in search of debris and invaders (alveolar macrophages)

Fixed macrophages

are permanent residents of some organs (Kupffer cells in liver and micrglia in brain)

Neutrophils (most abundant WBC)

become phagocytic on encountering infectious material on tissues

Adherence of phagocyte to pathogen

is facilitated by opsonization coating of pathogen by complement proteins or antibodies

Opsonization

"to make tasty"
so phagocytic receptors can bind

Destruction of pathogens

respiratory burst - release of cell killing free radicals

Natural Killer cells are

large granular lymphocytes

NK cells target

cells that lack "self" cell-surface receptors

NK cells induce

apoptosis in cancer cells and virus-infected cells

NK cells secrete

potent chemicals that enhance the inflammatory response

Inflammatory response is triggered

whenever body tissues are injured or infected

Inflammatory response prevents

the spread of damaging agents

Inflammatory response disposes of

cell debris and pathogens

Inflammatory response sets

the stage for repair

Cardinal signs of acute inflammation

redness
heat
swelling
pain
impairment of funciton

Inflammatory mediators

histamine
blood proteins
kinins, prostaglandins, leukotrienes, and complement

Inflammatory mediators released by

injured tissue, phagocytes, lymphocytes, basophils, and mast cells

Order of sequence of phagocytosis

C - A - I - D - K
Chemotaxis
Adherance
Ingestion
Digestion
Killing

Inflammatory chemicals cause dilation

of arterioles, resulting in hyperemia (redness and heat)

Inflammatory chemicals cause increased

permeability of local capillaries and edema (leakage of exudate)

Exudate contains

proteins, clotting factors, and antibodies, fluid that causes swelling

Surge of exudate moves

foreign material into lymphatic vessels

Surge of exudate delivers

clotting proteins to form a scaffold for repair and to isolate the area

Edema presses on

nerve endings causing pain

Leukocytes in phagocyte mobilization

release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells

Margination

neutrophils cling to the walls of capillaries in the inflamed area

Diapedisis

of neutrophils (flatten and squeeze through capillary walls)

Chemotaxis

inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils

Ultimate goal of inflammation

is to clear pathogens, dead tissue cells, and debris so tissue can be repaired

Interferons (IFNs) and complement proteins

attack microorganisms directly

Interferons (IFNs) and complement proteins hinder

microorganisms' ability to reproduce

Interferons

neighboring cells produce antiviral proteins that block viral reproduction by blocking protein synthesis and degrading viral RNA

Interferons also activate

macrophages and mobilize NK cells

Functions of interferons

anti-viral
reduce inflammation
activate macrophages
mobilize NK cells

Genetically engineered IFNs for

antiviral agents against hepatitus and genital warts
MS treatment

Complement

20 blood proteins that circulate in an inactive form

Complement is a major mechanism for

destroying foreign substances

Complement amplifies

all aspects of the inflammatory response

Complement kills

bacteria and certain other cell types by cell lysis

Complement enhances

both nonspecific (innate) and specific (adaptive) defenses

Activated complement

enhances inflammation
promotes phagocytosis
causes cell lysis

C3b initiates formation

of a membrane attack complex (MAC)

C3b also causes

opsonization

C3a causes

inflammation

Fever

systemic response to invading microorganisms

Leukocytes and macrophages exposed to

foreign substances secrete pyrogens

Pyrogens reset

the body's thermostat upward

High fevers are dangerous because

heat denatures enzymes

Benefits of moderate fever

liver and spleen sequester iron and zinc (needed by microorganisms)
Increases metabolic rate (speeds repair)

Adaptive immune system

specific defense system

Adaptive immune response

is specific
is systemic
has memory

Adaptive defenses have two separate overlapping arms

Humoral (antibody-mediated) immunity
Cellular (cell-mediated) immunity

Antigens are ultimate targets

of all adaptive immune responses

Antigens are substances that can

mobilize the adaptive defenses and provoke an immune response

Most antigens are

large, complex molecules not normally found in the body (nonself)

Complete antigens have

immunogenicity
reactivity

Immunogenicity

ability to stimulate proliferation of specific lymphocytes and antibodies

Reactivity

ability to react with products of activated lymphocytes and antibodies released
Examples: foreign protein, polysaccharides, lipids, and nucleic acids

Haptens

allergic reaction
poison ivy, animal dander, detergents, and cosmetics

MHC proteins

helpers to make things compatible

Two types of lymphocytes

B cells
T cells

B cells

humoral immunity (blood and lymph)

T cells

cell-mediated immunity

Antigen presenting cells (APCs)

do not respond to specific antigens
play essential auxillary roles in immunity

Lymphocytes originate

in red bone marrow

B cells mature

in red bone marrow

T cells mature

in the thymus

Immunocompetence

mature lymphocytes are able to recongnize and bind to a specific antigen

Self-tolerance

mature lymphocytes are unresponsive to self antigens (does not attack body's own cells)

T cells mature in the thymus under

negative and positive selection pressures

Genes determine

which foreign substances the immune system will recognize and resist (it is not antigens)

Antigen presenting cells engulf

antigens

APCs present

fragments of antigens to be recognized by T cells

Major types of APCs

dendritic cells
macrophages
B cells

Macrophages and dendritic cells

present antigens and activate T cells

Activated T cells release chemicals that

prod macrophages to become insatiable phagocytes and to secrete bactericidal chemicals

Adaptive immunity uses

lymphocytes, APCs, and specific molecules to identify and destroy nonself substances

Adaptive immunity depends upon the ability of its cells to recognize (bind tightly)

antigens by binding to them

Adaptive immunity depends upon the ability of its cells to communicate

with one another so that the whole system mounts a specific response

Humoral immunity response

antigen challenge - first encounter between an antigen and a naive immunocompetent lymphocyte

If the lymphocyte is a B cell

the antigen provokes a humoral immune response
antibodies are produced

Clonal selection - B cell is activated when

antigens bind to its surface receptors and cross-link them

Stimulated B cell grows to form

a clone of identical cells bearing the same antigen-specific receptors

T cells are usually required to help

B cells achieve full activation

Most clone cellse become plasma cells and

secrete specific antibodies at the rate of 2,000 molecules per second for four to five days

Secreted antibodies circulate

in blood or lymph

Secreted antibodies bind

to free antigens

Secreted antigens mark

the antigens for destruction

Clone cells that do not become plasma cells becom memory cells

that provide immunological memory
mount an immediate response to future exposures of the same antigen

Primary immune response occurs

on the first exposure to a specific antigen

Primary immune response lag period

3 to 6 days

Primary immune response peak levels

of plasma antibody are reached in 10 days then decline

Secondary immune response occurs

on re-exposure to the same antigen

Secondary immune response causes sensitized

memory cells to respond within hours

Secondary immune response antibody levels

peak in 2-3 days at much higher levels

Secondary immune response antibodies bind

with greater affinity

Secondary immune response antibody level can remain

high for weeks to months

Active humoral immunity occurs when

B cells encounter antigens and produce specific antibodies against them

Two types of active humoral immunity

Naturally acquired - response to a bacterial or viral infection
Artificially acquired - response to a vaccine of dead or attenuated pathogens

Vaccines spare us

the symptoms of the primary response

Vaccines provide

antigenic determinants that are immunogenic and reactive

Vaccines target only one type of helper T cell,

so fail to fully establish cellular immunological memory

Passive humoral immunity B cells

are not challenged by antigens

Immunological memory does not occur in

passive humoral immunity

Two types of passive humoral immuntiy

Naturally acquired - antibodies delivered to a fetus via the placenta or to infant through milk
Artificially acquired - injection of serum, such as gamma globulin (protection immediate but ends when antibodies naturally degrade in body)

Artifically acquired passive humoral immunity examples

snakebites, hepatitis exposure, botulism, rabies, tetanus

Immunoglobulins are antibodies

gamma globulin portion of blood (IGSs)

Antibodies are proteins

secreted by plasma cells (effector B cells)

Antibodies are capable of binding

specifically with antigen detected by B cells

Antibodies are T or Y shaped

monomer of four looping polypeptide chains

Antibodies have two identical

heavy (H) chains and two identical light (L) chains

Antibodies have variable (V) regions

of each arm that combine to form two identical antigen-binding sites

Constant (C) region of stem determines

antibody class
cells and chemicals that antibody can bind to
how antibody class functions in antigen elimination

Classes of antibodies

IgM
IgA
IgD
IgG
IgE

IgM

pentamer
1st antibody released

IgA

secretory IgA
helps prevent entry of pathogens into body

IgD

functions as a B cell receptor

IgG

crosses the placental barrier

IgE

monomer active in some allergens and parasitic infections
causes mast cells and basophils to release histamine

Antibodies inactivate and tag antigens

form antigen-antibody (immune) complexes

Defensive mechanisms used by antibodies

neutralization and agglutination (most important)
precipitation and complement fixation

Neutralization

antibodies block specific sites on viruses or bacterial exotoxins

Neutralization prevents these antigens

from binding to receptors on tissue cells

In neutralization antigen-antibody complexes

undergo phagocytosis

In agglutination antibodies bind the same

determinant on more than one cell-bound antigen

Cross-linked

antigen-antibody complexes agglutinate (clumping of mismatched blood cells)

Complement fixation and activation is the main antibody defense

against cellular antigens

Several antibodies bind

close together on a cellular antigen

Their complement-binding sites trigger

complement fixation into the cell's surface

Complement triggers

cell lysis

T cells provide defense against

intracellular antigens

Two types of surface receptors of T cells

T cell antigen receptors
cell differentiation glycoproteins - CD4 or CD8
play a role in T cell interactions with other cells

Major types of T cells

CD4 - helper T cells when activated
CD8 - cytotoxic T cells that destroy cells harboring foreign antigens

Other types of T cells

Regulatory T cells
Memory T cells

Antibodies of the humoral response

the simplest ammunition of the immune response

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