Download Immunology -- Natural Defenses

Overview of the Immune system
Dr. Gamal Badr
PhD in Immunology (Paris Sud University, France)
Associate Professor of Immunology
Assiut University, Egypt
Tel: +2 01110900710
Fax: +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
Immunity: Body defense against exogenous(microbes)
and endogenous(tumor cells) agents.
Pathogen: microbe that causes disease
Antigen (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 response
Leukocytes: WBCs
Lymphocytes: specialized blood cells that mediate adaptive immunity
(e.g. T and B cells)
Immune response
Reaction of the body against any foreign Ag.
Non specific
Specific
by B- cells
Organs of the immune system
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).
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.
Cells of the immune system
Blood cells lineages
Most blood cells act
to fight infection.
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Dentritic cell
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Innate
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Adaptive
immunity
Dentritic cell
(DC)
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Antigen presenting
cells
(APC)
Lymphocytes of the adaptive immune system
T helper cells: regulate other immune cells
T 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.
Cells of the Immune system (WBCs)

1- Granulocytes





2- Agranulocytes
Lymphocytes





Neutrophils
Eosinophils
Basophils
B cells
T cells (many types)
NK cells
Monocytes/Macrophages
Dendritic cells
Divisions of leukocytes
AGranulocytes
Granulocytes

Neutrophils



Band cells
Eosinophils
Basophils
(Mononuclear cells)
(immature neutrophils)



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 malignancies
B-cell malignancies
•
Acute lymphoblastic leukemia, B-cell type
•
Non-Hodgkin’s lymphoma, B-cell types
•
Myeloma
T-cell malignancies
•
Acute lymphoblastic leukemia, T-cell type
•
Non-Hodgkin’s lymphoma, T-cell types
Hodgkin’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
Pathogen
(virus or
bacteria)
Pathogen is
internalized and
degraded
B cell
Plasma
cells
B cell binds pathogen
TH1
MHC
II
B cell
Peptides from the pathogen are
presented (MHC II) to the T cell
resulting in the activation of the
B cell
B cell proliferation
B cells differentiate into
antibody-secreting plasma
cells
Produce antibodies against
pathogen
Antigen recognition by T-cells
Cytotoxic T cells
recognize antigen
presented by MHC I
and kills the cell
TH1 cells recognize
antigen presented by
MHC II and activates
macrophages
Kills
TH2 cells recognize
antigen presented by
MHC II and activates
B cells
Activates
Activates
MHC I
Cytotoxic
T cell
Virusinfected cell
TH1
MHC
II
TH2
MHC
II
B cell
Macrophage
Dead intracellular
bacteria
Apoptotic cell
Anti-toxin antibodies
Th1 and Th2 response
To
Th1
Th2
IFN-
IL-4
IL-10
IL-5
IL-2
NK
MØ
TNF-
IL-8
Tc
IL-6
IL-13
B cell
PMN
Monocytes/Macrophage



Monocyte is a young
macrophage
There are tissuespecific
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
• Alternative pathway of complement
•
Physiological barriers at the portal of entry (The Skin & Mucous Membranes)
Mechanisms of Innate Immunity
A. Epithelial Surfaces
1. 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 alveoli
Intestinal 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 urine
6. Acidic pH of adult vagina
7. Spermine & zinc in semen is antibacterial.
B. Antibacterial substances in blood & tissues
1. Complement system - Alternative pathway of
complement leads to opsonization of microbes
2. 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
Bacteria
Lipid
mediators
Mannose
receptor
Lysosome
Phagosome
Scavenger
receptor
LPS receptor
(CD14)
The macrophage
expresses receptors for
many bacterial
constituents
Cytokines
Bacteria binding to
macrophage receptors
initiate the release of
cytokines and small lipid
mediators of inflammation
CD Structurally defined leukocyte surface molecule
Phagolysosome
Macrophages engulf and
digest bacteria to which
they bind
B cell: CD19+
T helper cell: CD3+, CD4+ & CD8that is expressed on cells of a particular lineage
(“differentiation”) and recognized by a group (“cluster”) T cytotoxic cell: CD3+, CD8+
Macrophages/ monocyte: CD14+
of cell-specific antibodies is called a member of a
NK cell: CD3neg, CD16+ & CD56+
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)

release of lysosomal contents
phagolysosome
Invagination
fusion with lysosome
phagosome
formation
02.10.07
Dr Ekta, Microbiology, GMCA
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
Remnants
undergo
phagocytosis
D. Cellular factors
2. Eosinophils:

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.
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
Cell mediated immunity
By T cell activation
Active
Humoral Immunity
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
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


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
TH1 cells recognize
antigen presented by
MHC II and activates
macrophages
Kills
TH2 cells recognize
antigen presented by
MHC II and activates
B cells
Activates
Activates
MHC I
Cytotoxic
T cell
Virusinfected cell
TH1
MHC
II
TH2
MHC
II
B cell
Macrophage
Dead intracellular
bacteria
Apoptotic cell
Anti-toxin antibodies
Antigen presenting cells (APC)
B cell
Dendritic cell
Lymph node
Macrophages
Lymph node
Lymph node
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.
Where does antigen processing take place?
Add Listeria
T
specific T cells
Listeria
M
M
M
M
T CELLS BIND
Listeria
Incubate with CHLOROQUINE
M
M
M
M
NO T CELLS BIND
Chloroquine inhibits lysosomal function (a lysosomotrophic drug)
Antigen processing involves the lysosomal system
Ag presentation to T cells
The T cell antigen receptor (TCR)
Antigen
combining site
Resembles an Ig Fab fragment
Fab
Fc
Domain structure: Ig gene superfamily
Monovalent
Carbohydrates
No alternative constant regions
Hinge
+
+
Cytoplasmic tail
+
Transmembrane region
Never secreted
Heterodimeric, chains are disuphidebonded
Very short intracytoplasmic tail
Positively charged amino acids in the
TM region
Antigen combining site made of
juxtaposed V and Vb regions
T cell co-receptor (TCR) molecules
TCR
TCR
Ag
CD8
CD4
b 
MHC Class I
MHC Class II
CD4 and CD8 can increase the sensitivity of T cells to peptide antigen MHC
complexes by ~100 fold
Th1 and Th2 response
To
Th1
Th2
IFN-
IL-4
IL-10
IL-5
IL-2
NK
MØ
TNF-
IL-8
Tc
IL-6
IL-13
B cell
PMN
TCR and BCR (B cell Receptor)
Humoral Immunity

It is the production of proteins
called “immunoglobulin's” or
“antibodies”.
.
Memory (long-lived cells)
.
Humoral Immunity
B Cell Receptors for Antigens

B cell receptors

Bind to specific, intact antigens

Are often called membrane antibodies or membrane immunoglobulin's (Ig)
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
Variable
regions
Light
chain
C
C
Constant
regions
Transmembrane
region
Plasma
membrane
Heavy chains
B cell
Cytoplasm of B cell
(a)
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
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
Chains:
Light (L)
Heavy (H)
Domains:
Variable (V)
Single V domain in H and L chains
Constant (C)
Single C domain in L chains
Three to four (C) domains in H
chains
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 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 Classes
IgM
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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 Classes
IgA
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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 Classes
IgD
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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 Classes
IgE
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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 cells act as APC
B
1. Capture by antigen
specific Ig maximises
uptake of a single antigen
2. Binding and internalisation via
Ig induces expression
of CD40
3. Antigen enters exogenous antigen
processing pathway
4. Peptide fragments of antigen are loaded
onto MHC molecules intracellularly.
MHC/peptide complexes are
expressed at the cell surface
B
T cell help to B cells
Signal 2 - T cell help
B
Y
Signal 1
antigen & antigen receptor
MHC class II
Th
Th
1. T cell antigen receptor
2. Co-receptor (CD4)
3.CD40 Ligand
Clonal Selection
Only one type of
antibody—and one
type of B cell—
responds to the
antigenic determinant
That cell type
then produces a
large number of
clones
Dr.T.V.Rao MD
93
Benefits of Immunological Memory
Primary
Latent period
Gradual rise in Ab
production taking
days to weeks
Secondary
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