IMMUNITY AND

IMMUNE SYSTEM

PREPARED BY: ASOGWA INNOCENT KINGSLEY

(АСОГВА ИННОСЕНТ КИНГСЛЕЙ)МЛ-508

SUBMITED TO:DR. НАДУЖДА АЛЕКСАНДРОВНА

ПОЛЕВИНЕКИНА

IMMUNITYIs the state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion.

It is the capability of the body to resist harmful microbes from entering it.

Immunity involves both specific and non-specific components

IMMUNE SYSTEM is a system of biological structures and processes

within an organism that protects against disease. To function properly, an immune system must

detect a wide variety of agents, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue.

The immune system recognizes foreign bodies and responds with the production of immune cells and proteins

Barriers help an organism to defend itself from the many dangerous pathogens it may encounter

BARRIER DEFENSESBarrier defenses include the skin and

mucous membranes of the respiratory, urinary, and reproductive tracts

Mucus traps and allows for the removal of microbes

Many body fluids including saliva, mucus, and tears are hostile to microbes

The low pH of skin and the digestive system prevents growth of microbes

CLASSIFICATION

INNATE IMMUNITY• Recognition of traits shared

by broad ranges of pathogens, using a small set of receptors

• Rapid response

ACQUIRED IMMUNITY• Recognition of traits

specific to particular pathogens, using a vast array of receptors

• Slower response

Humoral response:Antibodies defend againstinfection in body fluids.

Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.

Internal defenses:Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells

Barrier defenses:SkinMucous membranesSecretions

Pathogens(microorganisms and viruses)

INNATE IMMUNITYnonspecific immunity is the natural resistances with which a person is born. It provides resistances through several physical, chemical and

cellular approaches. Microbes first encounter the epithelial layers, physical barriers

that line skin and mucous membranes. Subsequent general defenses include secreted chemical signals

(cytokines), antimicrobial substances, fever, and phagocytic activity associated with the inflammatory responses.

The phagocytes express cell surface receptors that can bind and respond to common molecular patterns expressed on the surface of invading microbes.

Through these approaches, innate immunity can prevent the colonization, entry and spread of microbes.

A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe

There are different types of phagocytic cells:Neutrophils engulf and destroy microbesMacrophages are part of the lymphatic

system and are found throughout the bodyEosinophils discharge destructive enzymesDendritic cells stimulate development of

acquired immunity

ANTIMICROBIAL PEPTIDES AND PROTEINSPeptides and proteins function in innate

defense by attacking microbes directly or impeding their reproduction

Interferon proteins provide innate defense against viruses and help activate macrophages

About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation

Fig. 43-7

Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels Lymph

nodeMasses ofdefensive cells

Bloodcapillary

Lymphaticvessel

Tissuecells

Interstitial fluid

Inflammatory ResponsesFollowing an injury, mast cells release

histamine, which promotes changes in blood vessels; this is part of the inflammatory response

These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues

Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

Fig. 43-8-3

Pathogen Splinter

Macrophage

Mast cell

Chemicalsignals

Capillary

Phagocytic cellRed blood cells

Fluid

Phagocytosis

CLASSIFICATION

ACQUIRED IMMUNITYAdaptive immunity /Specificsub-divided into two major types depending on how the immunity

was introduced:Naturally acquired immunity occurs through contact with a

disease causing agent, when the contact was not deliberateArtificially acquired immunity develops only through

deliberate actions such as vaccination.

N/B:Memory cells are only produced in active immunity.Protection for active immunity is permanent whereas in passive immunity it is only temporary.Antigens are only encountered in active immunity.Active immunity takes several weeks to become active but passive is immediate.

NATURAL ACQUIRED IMMUNITYSubdivided into: Naturally acquired active immunity: occurs when a person is

exposed to a live pathogen, and develops a primary immune response, which leads to immunological memory. This type of immunity is “natural” because it is not induced by deliberate exposure. Many disorders of immune system function can affect the formation of active immunity such as immunodeficiency (both acquired and congenital forms) and immunosuppression.

Naturally acquired passive immunity: Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy through placenta. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.

ARTIFICIAL ACQUIRED IMMUNITYArtificially acquired active immunity: can be induced by a

vaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease.

Artificially acquired passive immunity: is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and in the form of monoclonal antibodies (MAb). Passive transfer is used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia. It is also used in the treatment of several types of acute infection, and to treat poisoning. Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma globulin of non-human origin.

IN ACQUIRED IMMUNITY, LYMPHOCYTE RECEPTORS PROVIDE PATHOGEN-SPECIFIC RECOGNITION

• White blood cells called lymphocytes recognize and respond to antigens, foreign molecules

• Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

• Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously

• Cytokines are secreted by macrophages and dendritic cells to recruit and activate lymphocytes

• The acquired immune system has three important properties:

• Receptor diversity

• A lack of reactivity against host cells

• Immunological memory

ACQUIRED IMMUNITY: AN OVERVIEWB cells and T cells have receptor proteins that can

bind to foreign moleculesEach individual lymphocyte is specialized to

recognize a specific type of moleculeAll antigen receptors on a single lymphocyte

recognize the same epitope, or antigenic determinant, on an antigen

B cells give rise to plasma cells, which secrete proteins called antibodies or immunoglobulins

Fig. 43-9

Antigen-bindingsite

Antigen-binding site

Antigen-bindingsite

Disulfidebridge

VariableregionsConstantregions

Transmembraneregion

Plasmamembrane

Lightchain

Heavy chains T cell

chain chainDisulfide bridge

Cytoplasm of T cell(b) T cell receptor

Cytoplasm of B cell

(a) B cell receptorB cell

VV

C C

VV

C C C C

VV

Fig. 43-10

Antigen-binding sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)

Antigen

Antibody B

Antibody CAntibody A

CC

CV

V

VV

C

THE ANTIGEN RECEPTORS OF B CELLS B cell receptors bind to specific, intact antigensThe B cell receptor consists of two identical heavy

chains and two identical light chainsThe tips of the chains form a constant (C) region,

and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another

Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane

THE ANTIGEN RECEPTORS OF T CELLSEach T cell receptor consists of two different polypeptide

chainsThe tips of the chain form a variable (V) region; the rest

is a constant (C) regionT cells can bind to an antigen that is free or on the

surface of a pathogenT cells bind to antigen fragments presented on a host cell These antigen fragments are bound to cell-surface

proteins called MHC moleculesMHC molecules are so named because they are encoded

by a family of genes called the major histocompatibility complex

THE ROLE OF THE MHCIn infected cells, MHC molecules bind and transport antigen

fragments to the cell surface, a process called antigen presentation

A nearby T cell can then detect the antigen fragment displayed on the cell’s surface

Depending on their source, peptide antigens are handled by different classes of MHC molecules:

Class I MHC molecules are found on almost all nucleated cells of the body

They display peptide antigens to cytotoxic T cellsClass II MHC molecules are located mainly on dendritic cells,

macrophages, and B cellsDendritic cells, macrophages, and B cells are antigen-presenting

cells that display antigens to cytotoxic T cells and helper T cells

Fig. 43-12

Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(a)

Antigenassociateswith MHCmolecule

T cellrecognizescombination

Cytotoxic T cell (b) Helper T cell

T cellreceptor

Class II MHCmolecule

Antigenfragment

Antigen-presentingcell

Microbe1

11

22 2

AMPLIFYING LYMPHOCYTES BY CLONAL SELECTION

In the body there are few lymphocytes with antigen receptors for any particular epitope

The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly

This proliferation of lymphocytes is called clonal selection

Two types of clones are produced: - short-lived activated effector cells and - long-lived memory cells

Fig. 43-14

B cells thatdiffer inantigen specificity

Antibodymolecules

Antigenreceptor

Antigen molecules

Clone of memory cells Clone of plasma cells

IMMUNE RESPONSEThe first exposure to a specific antigen

represents the primary immune response During this time, effector B cells called

plasma cells are generated, and T cells are activated to their effector forms

In the secondary immune response, memory cells facilitate a faster, more efficient response

Fig. 43-15

Antibodiesto A Antibodies

to B

Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.

Primary immune responseto antigen A producesantibodies to A.

Ant

ibod

y co

ncen

trat

ion

(arb

itrar

y un

its)

Exposureto antigen A

Exposure toantigens A and BTime (days)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

ACQUIRED IMMUNITY DEFENDS AGAINST INFECTION OF BODY CELLS AND FLUIDSAcquired immunity has two branches: -the humoral immune response and - the cell-mediated immune responseHumoral immune response involves

activation and clonal selection of B cells, resulting in production of secreted antibodies

Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

Helper T cells aid both responses

Fig. 43-16

Humoral (antibody-mediated) immune response

B cell

Plasma cells

Cell-mediated immune response

Key

StimulatesGives rise to

+

+

++

+

+

+Memory B cells

Antigen (1st exposure)

Engulfed by

Antigen-presenting cell

MemoryHelper T cells

Helper T cell Cytotoxic T cell

MemoryCytotoxic T cells

ActiveCytotoxic T cells

Antigen (2nd exposure)

Secretedantibodies

Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.

Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.

+

+ +

Fig. 43-16a

KeyStimulatesGives rise to

+

MemoryHelper T cells

Antigen-presenting cell

Helper T cell

Engulfed by

Antigen (1st exposure)

+

+

+

+ +

+

Defend against extracellular pathogens

MemoryB cells

Antigen (2nd exposure)Plasma cells

B cell

Secretedantibodies

Humoral (antibody-mediated) immune response

Fig. 43-16bCell-mediated immune response

Defend against intracellular pathogens

ActiveCytotoxic T cells

MemoryCytotoxic T cells

MemoryHelper T cells

Antigen-presenting cell

Antigen (2nd exposure)

Helper T cell

Engulfed by

Antigen (1st exposure)

Cytotoxic T cell

KeyStimulatesGives rise to

+

+

+

+

+ +

+

T HELPER CELLS: A RESPONSE TO NEARLY ALL ANTIGENS

A surface protein called CD4 binds the class II MHC molecule

This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs

Activated helper T cells secrete cytokines that stimulate other lymphocytes

Fig. 43-17

Antigen-presentingcell

Peptide antigen

Cell-mediatedimmunity (attack on

infected cells)

Class II MHC moleculeCD4TCR (T cell receptor)

Helper T cell

Humoralimmunity

(secretion ofantibodies byplasma cells) Cytotoxic T cell

Cytokines

B cell

Bacterium

+

+ +

+

CYTOTOXIC T CELLS: A RESPONSE TO INFECTED CELLS

Cytotoxic T cells are the effector cells in cell-mediated immune response

Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell

Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer

The activated cytotoxic T cell secretes proteins that destroy the infected target cell

Fig. 43-18-3

Cytotoxic T cell

PerforinGranzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cell

B CELLS: A RESPONSE TO EXTRACELLULAR PATHOGENS

The humoral response is characterized by secretion of antibodies by B cells

Activation of B cells is aided by cytokines and antigen binding to helper T cells

Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

Fig. 43-19

Antigen-presenting cell

Endoplasmicreticulum ofplasma cell

Secretedantibodymolecules

Bacterium

B cellPeptideantigen

Class II MHCmolecule

TCR CD4

Helper T cellActivatedhelper T cell

Cytokines

Clone of memoryB cells

Clone of plasma cells

2 µm

+

ANTIBODY CLASSESThe five major classes of antibodies, or

immunoglobulins, differ in distribution and function

Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen

Monoclonal antibodies are prepared from a single clone of B cells grown in culture

Fig. 43-20a

DistributionClass of Immuno-globulin (Antibody)

IgM(pentamer)

J chain

First Ig classproduced afterinitial exposure toantigen; then itsconcentration inthe blood declines

Promotes neutraliza-tion and cross-linking of antigens;very effective incomplement systemactivation

Function

Fig. 43-20b

Distribution FunctionClass of Immuno-globulin (Antibody)

IgG(monomer)

Most abundant Igclass in blood;also present intissue fluids

Promotes opsoniza-tion, neutralization,and cross-linking ofantigens; less effec-tive in activation ofcomplement systemthan IgM

Only Ig class thatcrosses placenta,thus conferringpassive immunityon fetus

Fig. 43-20c

Distribution FunctionClass of Immuno-globulin (Antibody)

IgA(dimer)

J chain

Secretorycomponent

Present insecretions suchas tears, saliva,mucus, andbreast milk

Provides localizeddefense of mucousmembranes bycross-linking andneutralization ofantigens

Presence in breastmilk conferspassive immunityon nursing infant

Fig. 43-20d

Distribution FunctionClass of Immuno-globulin (Antibody)

IgE(monomer)

Present in bloodat low concen-trations

Triggers release frommast cells andbasophils of hista-mine and otherchemicals that causeallergic reactions

Fig. 43-20e

Distribution FunctionClass of Immuno-globulin (Antibody)

IgD(monomer)

Trans-membraneregion

Present primarilyon surface ofB cells that havenot been exposedto antigens

Acts as antigenreceptor in theantigen-stimulatedproliferation anddifferentiation ofB cells (clonalselection)

THE ROLE OF ANTIBODIES IN IMMUNITYNeutralization occurs when a pathogen can no

longer infect a host because it is bound to an antibody

Opsonization occurs when antibodies bound to antigens increase phagocytosis

Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis

Fig. 43-21

Viral neutralization

Virus

Opsonization

Bacterium

Macrophage

Activation of complement system and pore formation

Complement proteins

Formation ofmembraneattack complex

Flow of waterand ions

Pore

Foreigncell

You should now be able to:1. Distinguish between innate and acquired immunity2. Name and describe four types of phagocytic cells3. Describe the inflammation response4. Distinguish between the following pairs of terms: antigens and

antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity

5. Explain how B lymphocytes and T lymphocytes recognize specific antigens

6. 6. Describe clonal selection and distinguish between effector cells and memory cells

7. Describe the cellular basis for immunological memory8. Explain how a single antigen can provoke a robust humoral

response9. Compare the processes of neutralization and opsonization