Immunity (2)

Adaptive

acquired or specific immunity

A particular cell responds to one specific foreign substance

Takes several days to be effective

Anamnestic response (ability to “remember” pathogens)

Cell-mediated immunity

involving T-lymphocytes

Antibody-mediated immunity

involving B-lymphocytes, plasma cells, and antibodies

Humoral Immunity

B lymphocytes and antibodies

Humoral Immunity Function

Produces antibodies that circulate in body fluids (blood, lymph) to neutralize pathogens.

Humoral Immunity Mechanism

When B cells encounter antigens, they differentiate into plasma cells that secrete antibodies. These antibodies bind to antigens, marking them for destruction by other immune cells.

Humoral Immunity

Extracellular pathogens (bacteria, viruses in the bloodstream, toxins).

Immunocompetence

the ability to produce a healthy immune response.

Immunogenic

something that can produce an adaptive immune response

Reactive

can react with already active cells but will not cause a new response

Self-tolerance:

The ability of the immune system to not react to your own body antigens

Hapten

an incomplete antigen – must be paired with a carrier protein to produce an immune response. (Reactive, but not immunogenic)

Antigen

a substance/molecule capable of binding to a component of the adaptive immune system producing an immune response. (Immunogenic)

Antigenic Determinate (AD)

: the part of the antigen that the immune system responds to

Self-antigen:

antigens found on your own body cells that the immune system

Cytokines

small proteins that regulate immune activity

Produced by cells of innate and adaptive immune system

Chemical messengers released from one cell that bind to receptors

of target cells

Can act on cell that released it (autocrine); on local cells

(paracrine); or on distant cells after circulating through blood

(endocrine)

Cytokines Effect

Signaling cells (including non-immune cells, such as neurons)

Controlling development and behavior of immune cells

Regulating inflammatory response

Autoimmune disorders occur when

immune system initiates

immune response to a self-antigen

• Susceptibility of an individual depends upon genetic factors, hormone

levels, exposure

to infectious agents or chronic inflammation

Cross-reactivity

where a targeted foreign antigen is similar to selfantigen

Antigen presentation

cells display antigen on plasma membrane so T-cells can recognize it

Two categories of cells present antigens

1. All nucleated cells of the body

2. Antigen-presenting cells (APCs)

 Immune cells that present to both helper T-cells and cytotoxic T-cells

 Include: dendritic cells, macrophages, B-lymphocytes

Major Histocompatibility Complex Class I:

found on all body cells (think i = self), display protein from normal cells

Major Histocompatibility Complex Class II:

Display of MHC class II molecules on professional antigen-presenting cells

MHC class II molecules are also glycoproteins

Synthesized and modified by RER, sent to membrane

Exogenous antigens brought into cell through endocytosis

Phagosome merges with lysosome, forming phagolysosome, digest

substance into peptide fragments

Fragments “loaded” onto MHC class II molecules within vesicle

Vesicle merges with plasma membrane with antigen bound to MHC

molecule

 Provides means of communicating with helper T-lymphocytes

ORGAN TRANSPLANTS AND MHC MOLECULES

Transfer of organ from one individual to another

For example, kidney, liver, heart

Individuals tested prior to donation for MHC antigens and ABO group (blood type)

No two individuals with exactly same MHC molecules

Components of innate and adaptive immune system

Attempt to destroy transplanted tissue

Recipient’s immune system suppressed with drugs

Exception is transplant of cornea, which is an area of immune

privilege

B - Cells

Mature in bone marrow and migrate to

secondary lymphoid structures where they are housed

Humoral Immunity

T - Cells

– Mature in Thymus

Cell Mediated Immunity

Formation and selection of lymphocytes

Occurs in primary lymphoid structures (red marrow and thymus)

Become able to recognize one specific foreign antigen

Activation of lymphocytes

In secondary lymphoid structures they are exposed to antigen and

become activated

Replicate to form identical lymphocytes

Effector response:

: action of lymphocytes to eliminate antigen

T-lymphocytes migrate to site of infection

B-lymphocytes stay in secondary lymphoid structure (as plasma

cells)

Synthesize and release large quantities of antibodies

Clonal deletion

crucial process in the development of the immune system,

ensuring self-tolerance and preventing autoimmune diseases

 Elimination of self-reactive cells, prevention of autoimmunity,

distinguish between self and non-self

 Only about 2% of T cells pass all the testing and become naïve cells

 If you don’t pass the test – you get destroyed

T- and B-lymphocytes have unique receptor complexes

About 100,000 complexes per lymphocyte

Each complex binds one specific antigen

Structure of T-lymphocytes

Receptor complex includes both an antigen receptor and CD molecules

Antigen receptor is called the T-cell receptor (TCR)

CD molecules facilitate interaction with antigen-presenting cells

CD4 protein present on helper T-lymphocytes

CD8 protein present on cytotoxic T-lymphocytes

Helper T-lymphocytes

are also called CD4 cells because they contain

the CD4 protein

Assist (“help”) in cell-mediated, antibody-mediated, and innate

immunity

For example, activate NK cells and macrophages

Cytotoxic T-lymphocytes are also called

CD8 cells because they containthe CD8 protein

Release chemicals that destroy other cells

Other types include memory T-cells and regulatory T-cells

Structure of B-lymphocytes

• Receptor complex contains an antigen receptor called the B-cell

T-lymphocytes originate in red bone marrow

• Migrate to thymus as immature T-lymphocytes called thymocytes to

complete maturation

Thymic selection

eliminates 98% of original thymocytes

Positive selection

• Selects for the ability of T-cells to bind thymic epithelial cells with MHC molecules (those that can bind survive)

Negative selection

• Tests ability of T-lymphocyte to avoid binding self-antigens (selftolerance)

• Occurs in primary lymphoid structures, so called central tolerance

• Thymic dendritic cells present self-antigens and T-cells that bind to

them are destroyed

Differentiation of T-lymphocytes

• Helper T-lymphocytes lose CD8 protein, keep CD4 protein

Naive T-lymphocyte

not yet exposed to antigens they recognize

T-lymphocytes migrate from

thymus to secondary lymphoid structures

Regulatory T-lymphocytes (Tregs)

CD4+ cells formed from T-cells that bind self-antigens

Inhibit immune response

Function in tolerance outside of primary lymphoid structures; this is

called peripheral tolerance (a form of self-tolerance)

Some tumors foster Treg proliferation; some cancer treatments try to

inhibit tumor Tregs

Clonal selection

forming clones in response to an

antigen

All formed cells have same TCR or BCR that matches

specific antigen

Antigen challenge:

: first encounter between antigen and

lymphocyte

Usually occurs in secondary lymphoid structures

Antigen in blood taken to spleen

Antigen penetrating skin transported to lymph node

Antigen from respiratory, GI, urogenital tracts, in

tonsils or MALT

Lymphocyte recirculation

After a period of time, a lymphocyte exits secondary lymphoid

structure

Circulates through blood and lymph for several days

Different lymphocytes delivered to secondary lymphatic structures

Makes it more likely lymphocyte will encounter specific antigen

Effector response

mechanisms used by lymphocytes to help

eliminate antigen

Each lymphocyte type has its own response

Helper T-lymphocytes

Release IL-2 and other cytokines

Regulate cells of adaptive and innate immunity

Cytotoxic T-lymphocytes

Destroy unhealthy cells by apoptosis

Plasma cells

Produce antibodies

EFFECTOR RESPONSE OF B-LYMPHOCYTES

B-lymphocytes provide antibody-mediated immunity

• Most activated B-lymphocytes become plasma cells

Plasma cells synthesize and release antibodies

The cells remain in the lymph nodes

They produce hundreds of millions of antibodies

Antibodies circulate through lymph and blood until encountering

antigen

EFFECTOR RESPONSE OF T-LYMPHOCYTES

T-lymphocytes provide cell-mediated immunity

Effector response of helper T-lymphocytes

After exposure to antigen (in secondary lymphoid structures),

activated and memory helper T-lymphocytes migrate to infection site

Continually release cytokines to regulate other immune cells

Help activate B-lymphocytes

Activate cytotoxic T-lymphocytes with cytokines

Stimulate activity of innate immune system cells

Mature in Thymus

While in thymus, they must prove themselves

to be competent.

If they fail the test – apoptosis

Only about 2% of T cells pass all the testing

and become naïve cells

Two major types of mature cells in thymus

Effector T cells & Memory T Cells

Cytotoxic T cells

directly attack abnormal/not-self cells

Helper T cells

assist with B cell activation, stimulates phagocytes and other WBC’s

Suppressor T cells

allow for a modulated immune response, inhibit plasma cells and other T cells

Plasma cells

antibody factories

Memory B Cells

store information for a later exposure

Once a B cell has been activated two different cell lines are produced

plasma cells and memory B cells

Immunoglobulins (Ig)

proteins produced against a particular antigen

The antigen binding site is

specific to the antibody (Lock and Key) Different classes of antibodies are like different shaped blanks at the locksmith

Immunoglobulin A (IgA)

: found in mucus linings of the respiratory tract and digestive system, as well as in saliva (spit), tears, and breast milk

IgG

This is the most common antibody in blood and other body fluids; protects against bacterial and viral infections. (make up 75 to 85% of antibodies in blood)

IgM:

in blood and lymph fluid, this is the first antibody the body makes when it fights a new infection. Also responsible for rejection of mismatched transfusions.

IgE

Normally found in small amounts in the blood, but increases in response to allergens or fighting an infection from a parasite

Neutralization

deactivates antigen

Agglutination

binds antigens together (clumping)

Precipitation

brings solute out of solution

Forms antigen-antibody complex that becomes insoluble + precipitates out of

body fluids

Precipitated complexes engulfed and eliminated by phagocytes

Opsonization

a tasty coating for phagocytes – acts as marker

Antibody titer:

concentration of antibody

Initial exposure and the primary response (can be active infection or

vaccine)

Primary response:

antibody production to first exposure

Lag or latent phase:

initial period of no detectable antibody (3 to 6

days)

 Includes antigen detection, activation, proliferation, differentiation

Production of antibody

plasma cells produce IgM and then IgG

(within 1 to 2 weeks)

 Antibody levels peak, then decline over time

Subsequent exposures and the secondary response (after variable length

of time):

Measurable response to subsequent exposure is the secondary

Natural vs. Artificial

Natural = exposure in the course of life

Artificial = vaccination

Active vs. Passive

Active = body mounts an immune response

Memory cells against specific antigen are formed

Passive = transfer of antibodies

Can occur naturally via transfer of antibodies from mother to fetus (through

placenta or milk)

Can occur artificially when serum transferred from one person to another (for

example, antibodies to snake venom)

Neither form of passive immunity produces memory cells

Vaccines

• Contain weakened or dead microorganism or component

• Stimulate immune system to develop memory B-lymphocytes

• If later exposed, secondary response triggered

• May provide lifelong immunity or require booster shot

Herd immunity:

• Resistance of members within a population to a disease

• Sufficiently high proportion (83 to 94%) of individuals are immune to

the disease, so the number of infectible people are low and disease

unable to proliferate

Hypersensitivity

: abnormal and exaggerated response of immune system to antigen

Acute hypersensitivities

occurring with seconds and Subacute

hypersensitivities occurring within 1-3 H

• Both involve humoral immunity

Acute hypersensitivity (allergy)

• Exaggerated response of immune system to a noninfectious substance,

or allergen (such as pollen, peanuts)

• Sensitization, activation, and effector phases

• May cause multiple symptoms:

• Runny nose and watery eyes, labored breathing and coughing (allergic

asthma), red welts and itchy skin (hives), vomiting and diarrhea

• ALSO systemic vasodilation and inflammation which may result in

anaphylactic shock

AIDS (acquired immunodeficiency syndrome)

Result of human immunodeficiency virus (HIV):

Infects and destroys helper T-lymphocytes

Resides in body fluids of infected individuals

Can be transmitted by intercourse, needle sharing, breastfeeding

Diagnosis is AIDS when helper T-lymphocyte count drops below 200 cells

per cubic milliliter

Death is usually from opportunistic infections or cancer

Prevention through safe sex and more recently medications