Overview of the Immune system Dr. Gamal Badr PhD in Immunology (Paris Sud University, France) Associate Professor of Immunology Assiut University, Egypt.

Overview of the Immune system

Dr. Gamal BadrPhD in Immunology (Paris Sud University, France)

Associate Professor of ImmunologyAssiut University, EgyptTel: +2 01110900710Fax: +2 0882344642

E-mails: [email protected] or [email protected] Websites:

http://www.aun.edu.eg/membercv.php?M_ID=393 https://www.researchgate.net/profil/Gamal_Badr/

http://scholar.google.com.eg/citations?hl=en&user=dz13dkQAAAAJ

Topics

Microbes: why they are formidable foes.

Gross anatomy of the immune system

Cells of the immune system

how the immune system protects

Immune recognition of pathogens: innate versus adaptive immunity

Cytokines and the inflammatory response

Pathogen: microbe that causes diseaseAntigen (Ag): material (from a pathogen) that induces an immune response

Immunogen: material that induces an immune response

Innate (natural) immunity: rapid, non specific immune response

Adaptive (acquired) immunity: slower, specific immune responseLeukocytes: WBCs

Lymphocytes: specialized blood cells that mediate adaptive immunity (e.g. T and B cells)

Immunity: Body defense against exogenous(microbes) and endogenous(tumor cells) agents.

Reaction of the body against any foreign Ag.

Immune response

Non specific

Specific

by B- cells

The cells of the immune system are developed in the primary lymphoid organs (bone marrow & Thymus), and they interact with antigens in secondary lymphoid organs (lymph nodes, spleen, addendix, Peyer’s patch etc.).

Lymph nodes: collect antigens from tissues

Spleen: collects antigens from blood stream

Lymphocytes arise in the stem cells in the bone marrow and then differentiate in the bone marrow (B cells) or thymus (T cells).

Organs of the immune system

T and B lymphocytes migrate via the peripheral blood to the peripheral/secondary lymphoid organs: lymph nodes, spleen, addendix, Peyer’s patch etc.

Naïve lymphocytes circulate between the blood and these organs until they encounter antigen. They become activated when they recognized an Ag in the secondary lymphoid organs.

The afferent lymphatic vessels carry APC cells from infected tissues to the lymph nodes where they activate T cells

Activated T cells (after they have undergone proliferation and differentiation) leave via the efferent lymphatic vessels

The cells of the immune system circulate through the body via lymph and blood. Pathogens and their antigens are transported from tissues via lymphatic vessels to the lymph nodes where they encounter immune cells.

QuickTime™ and aTIFF (LZW) decompressorare needed to see this picture.Most blood cells act to fight infection.

Adaptive immunityInnate

immunity

Dentritic cell(DC)

Cells of the immune system

Blood cells lineages

QuickTime™ and aTIFF (LZW) decompressorare needed to see this picture.Lymphocytes of the adaptive immune

systemT helper cells: regulate other immune cellsT cytotoxic (killer) cells: kill infected cells

B cells: produce antibodies (immunoglobulin)DC and macrophage (APC): directly kill microbes by phagocytosis and

other mechanisms. They also help to activate T cells (connection between innate and adaptive immunity)

NK cells are lymphocytes that have characteristics of innate and adaptive immunity.

Dentritic cell(DC)

Antigen presenting cells

(APC)

Antigen (Ag)

Cells of the Immune system (WBCs)

1- Granulocytes Neutrophils Eosinophils Basophils

2- Agranulocytes Lymphocytes

B cells T cells (many types) NK cells

Monocytes/Macrophages Dendritic cells

Divisions of leukocytes

Granulocytes Neutrophils

Band cells (immature neutrophils)

Eosinophils Basophils

AGranulocytes (Mononuclear cells)

Lymphocytes (many types)

Monocytes Dendritic cells

Neutrophils Granulocyte Phagocytes Short life span

(hours) Very important at

“clearing” bacterial infections

Cytoplasmic granules

Eosinophils A granulocyte A cell-killing cells

Orange granules contain toxic compounds

Important in parasitic infections

Basophils A granulocyte A cell-killing cells

Blue granules contain toxic and inflammatory compounds

Important in allergic reactions

Lymphocytes Many types;

important in both humoral and cell-mediated immunity

B-cells produce antibodies

T- cells Cytotoxic T cells Helper T cells

Memory cells NK cells

Benign WBCs Disorders

Leukopenia (Leukocytopenia) - Leukopenia: is a decrease in the number of WBCs Neutropenia is most common cause

Absolute neutrophil count (ANC) < 1.5 x 109 cells/L Many causes

Benign racial neutropenia common African Americans and Yemenite Jews may have ANC as low as 1.0

Viral infections Epstein-Barr, Hepatitis B, HIV

Drugs Careful review of medications ; be suspicious of any medication

recently started in patient with acute onset neutropenia Splenomegaly Autoimmune disorders

SLE (lupus), Rheumatoid Arthritis, etc. Bone marrow disorders

Leukocytosis Leukocytosis: is an increase in the number of WBCs WBC count > 11,000 Determine which type of WBC is leading to the

leukocytosis Neutrophilia = most common

Causes: Infection Connective tissue disorders Medications (especially steroids, growth factors) Cancer Myeloproliferative disorders Cigarette smoking Stress (physiologic)

Pain, trauma Idiopathic (unknown cause)

Leukocytosis Patients with acute bacterial infection often present

with neutrophilia and band formation Bands = young neutrophils

Viral infections are usually associated with low WBCs ; leukocytosis may suggest complications Ex: bacterial pneumonia with underlying

influenza infection

Leukocytosis Lymphocytosis: is an increase in the number or

proportion of lymphocytes in the blood Causes:

Viral infections: HBV, HCV, EBV, CMV Tuberculosis Pertussis Drug Reaction Stress (physiologic): Trauma, cardiac arrest,

etc Malignancy: ALL, CLL, lymphoma

Malignant WBCs Disorders

Types of Hematopoietic Malignancies

Leukemias • Acute leukemias • Acute myeloid leukemia • Acute lymphoblastic leukemia • Chronic leukemias • Chronic myeloproliferative disorders • Chronic lymphoproliferative disorders

Lymphomas • Non-Hodgkin's lymphoma • Hodgkin's disease

Plasma cell disorders • Myeloma

Myeloid vs. Lymphoid Myeloid malignancies

Acute myeloid leukemia Chronic myeloproliferative disorders

Lymphoid malignanciesB-cell malignancies• Acute lymphoblastic leukemia, B-cell type• Non-Hodgkin’s lymphoma, B-cell types• MyelomaT-cell malignancies• Acute lymphoblastic leukemia, T-cell type• Non-Hodgkin’s lymphoma, T-cell typesHodgkin’s disease

Leukemia Leukemia is a type of cancer of the blood or bone

marrow characterized by an abnormal increase of immature WBCs called “blasts".

Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader

group of diseases affecting the blood, bone marrow, and lymphoid system.

Chronic Leukemia Chronic myelogenous leukemia (CML)

Translocation between long arms of chromosomes

9 and 22 ; “Philadelphia Chromosome” ; bcr/abl

protein

Chronic lymphocytic leukemia (CLL) Clonal malignancy of B-lymphocytes Course is usually indolent ; affects older patients, average age at

diagnosis is 70 years

Acute Leukemia Acute Myelogenous Leukemia (AML)

Most common in adults Usually no apparent cause

Exposure to radiation, benzene, and certain chemotherapy drugs (alkylators) associated with leukemia

Underlying myelodysplastic syndrome (MDS) is risk factor Symptoms and signs

Related to replacement of marrow space by malignant WBCs Patients often very ill for period of just days or weeks Skeletal pain Bleeding Gingival hyperplasia Infection Pancytopenia with circulating blasts is hallmark ; bone marrow

biopsy required Auer rods on peripheral smear are pathognomonic

Lymphoma Hodgkin’s disease

Malignancy of B-lymphocytes Reed-Sternberg cells Various subtypes ; “nodular

sclerosing” is most common Non-Hodgkin’s Lymphoma (NHL)

Heterogeneous group of cancers affecting lymphocytes

Myeloma Malignancy of plasma cells

Abnormal paraproteins are created leading to systemic problems

IgG – 60% IgM – 20%

Primarily disease of elderly (median age 65 years)

Most common hematologic malignancy among African Americans ; #2 among Caucasians

Production of antibodies

TH1

MHC II

B cell

B cell

Pathogen (virus or bacteria)

B cell binds pathogen

Pathogen is internalized

and degraded

Peptides from the pathogen are presented (MHC II) to the T cell resulting in the

activation of the B cell

B cell proliferationB cells differentiate into

antibody-secreting plasma cells

Produce antibodies against pathogen

Plasma cells

Antigen recognition by T-cells

Cytotoxic T cells recognize antigen presented by MHC I and kills the cell

Kills

Cytotoxic T cell

MHC I

TH1 cells recognize antigen presented

by MHC II and activates

macrophages

TH2 cells recognize antigen presented

by MHC II and activates B cells

Activates

TH1

MHC II

Macrophage

Virus-infected

cell

Apoptotic cell

Dead intracellular

bacteria

Activates

TH2

MHC II

B cell

Anti-toxin antibodies

Th1 and Th2 response

To

Th1 Th2

NKMØ

B cell

TcPMN

IFN- IL-4

IL-10

IL-5

IL-6

IL-13

IL-2

TNF-IL-8

Monocytes/Macrophage Monocyte is a

young macrophage There are tissue-

specific macrophages

MØ process antigen, are phagocytes and produce cytokines (esp., IL1 & IL6)

Dendritic cells Found mainly in

lymphoid tissue Function as

antigen presenting cells (APC)

Most potent stimulator of T-cell response

Mechanism of the Immune response

• Physiological barriers at the portal of entry (The Skin & Mucous Membranes)

• Alternative pathway of complement

Mechanisms of Innate Immunity

A. Epithelial Surfaces1. Skin & mucous membrane - protect against

invasion by microbes. Healthy skin - high salt conc. in sweat - sebaceous secretions - long chain fatty acids & soaps Respiratory tract - nose architecture - cough reflex - mucosal secretions - phagocytes in alveoliIntestinal mucosa - mucus , peristalsis

A.Epithelial Surfaces

2. Saliva - inhibits many micro-organisms.3. Gastric acidity - destroys many microbes.4. Conjunctiva - flushing action of lachrymal

secretions. antibacterial substance - present in tissue fluid & all secretions except cerebrospinal fluid (CSF), urine & sweat - also present in phagocytes

A.Epithelial Surfaces

5. Flushing action of urine6. Acidic pH of adult vagina

7. Spermine & zinc in semen is antibacterial.

B. Antibacterial substances in blood & tissues1. Complement system - Alternative pathway of complement leads to opsonization of microbes2. Basic polypeptides – like leukins derived from leucocytes & platelets 3. Lactic acid in muscle & inflammatory zone 4. Lactoperoxidase in milk. 5. Interferons - antiviral

C. Microbial antagonism

- resident flora on skin & mucosa prevent colonization by pathogens.

- altered flora following oral antibiotics may lead to enterocolitis (inflammation of the digestive tract).

D. Cellular factors

1. Phagocytic cells are 2 types - polymorphonuclear (PMN) leukocytes - mononuclear phagocytes: in blood & tissues

monocytes macrophages

Imp. link between innate & acquired immunity

Chemotaxis - phagocytes are attracted to the site of infection by chemotactic factors.

Phagocytosis

This process involves - recognition & binding

- ingestion

- digestion

Requires opsonins - molecules on the surface of certain bacteria which bind to the receptor on phagocytes - Opsonization.

Killing by granulocytes through phagocytosis

Macrophages and neutrophils recognize pathogen by means of cell-surface receptors Example: mannose receptor, CD14 receptor, scavenger receptors,

glucan receptor etc. Binding of macrophage (MØ) or neutrophils with pathogen leads to

phagocytosis Bound pathogen is surrounded by phagocyte membrane Internalized (phagosome) Killing of pathogen (Phagolysosome)

Oxidative burst (synthesis of hydrogen peroxide (H2O2)or free oxygen radicals)

Acidification Antimicrobial peptides (e.g. defensins)

* Phagolysosome = lysosome +phagosome

Phagocytosis

The macrophage expresses receptors for

many bacterial

constituents

Mannose

receptor

LPS receptor (CD14)

Scavenger

receptor

Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of

inflammation

Lipid mediators

Cytokines

Lysosome

Phagolysosome

Phagosome

Macrophages engulf and digest bacteria to

which they bind

Bacteria

B cell: CD19+T helper cell: CD3+, CD4+ & CD8-T cytotoxic cell: CD3+, CD8+Macrophages/ monocyte: CD14+NK cell: CD3neg, CD16+ & CD56+

CD Structurally defined leukocyte surface molecule that is expressed on cells of a particular lineage (“differentiation”) and recognized by a group (“cluster”) of cell-specific antibodies is called a member of a cluster of differentiation (CD)

Cytokines Cytokines are soluble proteins that are produced in response to an

antigen and function as chemical messengers for regulating the innate and adaptive immunity

Innate immune system Macrophages and Dendritic cells produce:

Tumor necrosis factor-alpha (TNF-) Interleukin-1 (IL-1) Interleukin-12 (IL-12)

Adaptive immune system T-lymphocytes produce:

Interleukin-2 (IL-2) Interleukin-4 (IL-4)

02.10.07 Dr Ekta, Microbiology, GMCA

InvaginationInvagination

phagosome phagosome formationformation

fusion with lysosomefusion with lysosome

phagolysosomephagolysosome

release of lysosomal contentsrelease of lysosomal contents

Process of Phagocytosis

D. Cellular factors

2. Natural killer cells:

Class of lymphocytes important in non- specific defense against viral infections & tumor cells.

Activated by interferons & selectively kills viral infected cells & tumor cells.

Cell killing – NK cells NK cells do not require prior immunization

or activation They attach to ‘target’ cells Produce cytotoxic proteins (perforin &

Granzymes ) onto the surface of tumor or viral infected cells.

Effector proteins penetrate cell membrane and induce programmed cell death (Apoptosis)

Apoptosis: Cellular Suicide

•Nuclear fragmentation•Proteolysis•Blebbing•Death

Remnantsundergo

phagocytosis

Number increases during parasitic infections & allergic conditions.

Not efficient phagocytes but their granules contain molecules that are toxic to parasites.

E. Temperature - Many micro- organisms are temperature dependent e.g. tubercle bacilli,

pathogenic to mammals, do not infect cold-blooded animals.

- destroys infecting pathogen : e.g. fever induction used to destroy Treponema pallidum before penicillin became available for treatment.

D. Cellular factors

2. Eosinophils:

F. Inflammation

“Inflame” – to set fire. Inflammation is “A dynamic response of vascularised tissue to injury.” It is a protective response. It serves to bring defense & healing mechanisms to the site of injury. A type of non specific defense mechanism. Tissue injury or irritation caused by the entry of pathogens or other irritants lead

to inflammation. Events: that occur are – vasoconstriction followed by vasodilatation

- Increased vascular permeability, stasis, hyperemia, accumulation of

leukocytes, exudation of fluid, and deposition of fibrin.

Changes are brought about by chemical mediators like histamine. Signs : redness, heat, swelling, pain and lose of function.

Cardinal Signs of Inflammation

Redness : Hyperaemia (increase of blood

flow to different tissues).

Warm : Hyperaemia

Pain : Nerve, Chemical mediators. Swelling : Exudation (escape of fluid,

cells, and cellular debris from blood vessels and their deposition in tissues)

Loss of Function

Process of Inflammation

Innate vs. adaptive immunity

Innate immunity First line of defense (present in all individuals at all

times) Immediate (0 – 4 hours) Non-specific Does not generate lasting protective immunity

Adaptive immune response (late: > 96 hours) Is initiated if innate immune response is not adequate

(> 4 days) Antigen-specific immunity Generates lasting protective immunity (e.g.

Antibodies, memory T-cells)

Adaptive, Acquired, Specific immunity

Acquired Immunity

Passive Active

Cell mediated immunity Humoral Immunity

By T cell activation By B cell activation& production of Abs

Adaptive immune system Initiated by ingestion of pathogen by an

immature dentritic cell Antigen-presenting cell (APC)

Dendritic cells, macrophages, and B cells Migrate through lymph to the regional lymph nodes Interact with naive T lymphocytes (present antigen to

activate T cells) Proliferation Differentiation

Active and passive immunity

Active immunity: long-lasting protection (memory), multiple effector mechanisms activated, lag time

Passive immunity: rapid protection, short duration

Active Immunity Resistance developed by an individual as a

result of an antigenic stimulus.

Also called Adaptive immunity.

Involves active functioning of the host’s immune system leading to the synthesis of antibodies and / or the production of immunologically active cells.

Passive Immunity Resistance transmitted to a recipient in a

readymade form.

Preformed antibodies are administered.

No antigenic stimulus.

Host’s immune system is not actively involved.

Comparison of Active & Passive Immunity

Active immunity Produced actively by host’s

immune system Induced by infection or by

immunogen Durable effective protection Immunity effective only after

long period Immunological memory present

Booster effective Not applicable in the

immunodeficient

Passive immunity Received passively, no active

host participation Readymade antibody transferred

Transient, less effective Immediate immunity

No memory

Not effective Applicable in the immunodeficient

Active immunity Natural active immunity – results from an

infection by a parasite e.g. an attack of measles give lifelong immunity.

Artificial active immunity – resistance induced by vaccines.

Vaccines are preparations of live or killed micro- organisms or their products.

Passive immunity

Natural passive immunity – resistance passively transferred from mother to baby

Artificial passive immunity – resistance passively transferred by the administration of readymade antibodies. e.g. tetanus immunoglobulin

Lymphocytes (effector cells of the adaptive immune system)

Antigen receptors with single specificity (T and B cells) Gene re-arrangement

T and B cells have 2 distinct recognition systems for detecting pathogens

T cells - recognize intracellular pathogens (T cell receptors, TCR)

B cells – recognize extracellular pathogens (immunoglobins, BCR)

Clonal selection Interaction of antigen and lymphocyte receptor Activation of lymphocyte Differentiation (progeny with identical specificity)

Cell mediated immunity: Antigen recognition by T-cells

T cells detect presence of intracellular pathogens T cells receptors Peptide fragments Major histocompatibility complex (MHC)

MHC I (cytotoxic T cells /CD8) MHC II (T helper (1 and 2)/ CD4)

Cell death

Cell mediated immunity: Antigen recognition by T-cells

Cytotoxic T cells recognize antigen presented by MHC I and kills the cell

Kills

Cytotoxic T cell

MHC I

TH1 cells recognize antigen presented

by MHC II and activates

macrophages

TH2 cells recognize antigen presented

by MHC II and activates B cells

Activates

TH1

MHC II

Macrophage

Virus-infected

cell

Apoptotic cell

Dead intracellular

bacteria

Activates

TH2

MHC II

B cell

Anti-toxin antibodies

Antigen presenting cells (APC)

Dendritic cell

Macrophages

B cell

Antigen-presenting cells are distributed differentially in the lymph node

An antigen-presenting cell (APC) or accessory cell is a cell that displays foreign Ag complexe with major histocompatibility complexes (MHC) on their surfaces. T cells may recognize these complexes using their T cell receptor (TCR). These APC engulf and process antigens and present them on their surface to T-cells.

Lymph node Lymph node Lymph node

MMM

MMM

Listeria

Listeria

Where does antigen processing take place?

M

M

Incubate with CHLOROQUINE

TAdd Listeriaspecific T cells

T CELLS BIND

NO T CELLS BINDChloroquine inhibits lysosomal function (a lysosomotrophic drug)

Antigen processing involves the lysosomal system

Ag presentation to T cells

The T cell antigen receptor (TCR)

Carbohydrates

Hinge

Monovalent

Resembles an Ig Fab fragment

Fab

Fc

No alternative constant regions

Transmembrane region

Never secreted

Domain structure: Ig gene superfamily

Heterodimeric, chains are disuphide-bonded

Cytoplasmic tail

Very short intracytoplasmic tail++

+Positively charged amino acids in

the TM region

Antigencombining site

Antigen combining site made of juxtaposed V and V regions

T cell co-receptor (TCR) molecules

CD8

MHC Class I MHC Class II

CD4

CD4 and CD8 can increase the sensitivity of T cells to peptide antigen MHCcomplexes by ~100 fold

Ag

Th1 and Th2 response

To

Th1 Th2

NKMØ

B cell

TcPMN

IFN- IL-4

IL-10

IL-5

IL-6

IL-13

IL-2

TNF-IL-8

TCR and BCR (B cell Receptor)

Humoral Immunity

It is the production of proteins called “immunoglobulin's” or “antibodies”.

.

Memory (long-lived cells).

Humoral ImmunityHumoral ImmunityB Cell Receptors for AntigensB Cell Receptors for Antigens

B cell receptors Bind to specific, intact antigens Are often called membrane antibodies or membrane

immunoglobulin's (Ig)Antigen-binding

site

Antigen-binding site

Disulfidebridge

Lightchain

Heavy chains

Cytoplasm of B cell

VA B cell receptor consists of two identical heavy chains and two identical light chains linked by

several disulfide bridges.

(a)

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

B cell

V

V

C

C C

C

V

WHAT ARE ANTIBODIES?

Antigen specific proteins produced by plasma cells Belong to immunoglobulin (Ig) superfamily Located in blood and extravascular tissues, secretions and

excretions Bind pathogenic microorganism and their toxins in extracellular

compartments

Structural configuration of Antibody

Domains:Variable (V)

Single V domain in H and L chains

Constant (C)Single C domain in L chainsThree to four (C) domains in H chains

Chains:Light (L)Heavy (H)

CLASSES (ISOTYPES) OF IMMUNOGLOBULINS

Classes based on constant region of heavy chains Immunoglobulin A (IgA) alpha  heavy chains

Immunoglobulin D (IgD) Delta  heavy chains

Immunoglobulin E (IgE) Epsilon  heavy chains

Immunoglobulin G (IgG) Gamma  heavy chains

Immunoglobulin M (IgM) Mu heavy chains

Differentiation of heavy chains Length of C region, location of disulfide bonds, hinge region, distribution of

carbohydrate Classes have different effector functions

Different classes of Antibodies

Immunoglobulin ClassesImmunoglobulin Classes

IgG

Structure: Monomer Percentage serum antibodies: 80% Location: Blood, lymph, intestine Half-life in serum: 23 days Complement Fixation: Yes Placental Transfer: Yes (the only Ig) Known Functions: Enhances phagocytosis, neutralizes

toxins and viruses, protects fetus and newborn.

Immunoglobulin ClassesImmunoglobulin Classes

IgM

Structure: Pentamer Percentage serum antibodies: 5-10% Location: Blood, lymph, B cell surface (monomer) Half-life in serum: 5 days Complement Fixation: Yes Placental Transfer: No Known Functions: First antibodies produced during an

infection. Effective against microbes and agglutinating antigens.

Immunoglobulin ClassesImmunoglobulin Classes

IgAIgA

Structure: Dimer Percentage serum antibodies: 10-15% Location: Secretions (tears, saliva, intestine, milk), blood

and lymph. Half-life in serum: 6 days Complement Fixation: No Placental Transfer: No Known Functions: Localized protection of mucosal

surfaces. Provides immunity to infant digestive tract.

Immunoglobulin ClassesImmunoglobulin Classes

IgD

Structure: Monomer Percentage serum antibodies: 0.2% Location: B-cell surface, blood, and lymph Half-life in serum: 3 days Complement Fixation: No Placental Transfer: No Known Functions: In serum function is unknown.

On B cell surface, initiate immune response, discriminate between naïve (IgD+), memory (IgD neg) and plasma cells (IgD neg)

Immunoglobulin ClassesImmunoglobulin ClassesIgE

Structure: Monomer Percentage serum antibodies: 0.002% Location: Bound to mast cells and basophils throughout

body. Blood. Half-life in serum: 2 days Complement Fixation: No Placental Transfer: No Known Functions: Allergic reactions. Possibly lysis of

worms.

B

B

2. Binding and internalisation via Ig induces expression

of CD40

3. Antigen enters exogenous antigenprocessing pathway

4. Peptide fragments of antigen are loadedonto MHC molecules intracellularly.

MHC/peptide complexes areexpressed at the cell surface

B cells act as APC

1. Capture by antigenspecific Ig maximises

uptake of a single antigen

YYY

T cell help to B cells

B

Signal 1antigen & antigen

receptor

Th

1. T cell antigen receptor

2. Co-receptor (CD4)

3.CD40 Ligand

Th

Signal 2 - T cell help

MHC class II

Clonal SelectionClonal Selection

Only one type of Only one type of antibody—and one antibody—and one

type of B cell—type of B cell—responds to the responds to the

antigenic determinantantigenic determinant

That cell type That cell type then produces a then produces a large number of large number of

clonesclonesDr.T.V.Rao MD 93

Primary

Secondary

Benefits of Immunological MemoryBenefits of Immunological Memory

Latent periodGradual rise in Ab production taking days to weeks

Second exposure to same Ag.Memory cells are a beautiful thing.Recognition of Ag is immediate.Results in immediate production of protective antibody, mainly IgG but may see some IgM