Download Adaptive immune response

Introduction to Immunology
By
Dr. Nabil El Aila
Assistant Professor of Medical Microbiology
Medical Technology Department
Al -Aqsa University
Immunity
1.Immunity: : Meaning the state of protection from infectious disease.
In 430BC, a plaque in Athens, Those who recovered from the plaque
would not contact the disease a second time.
2. Agents: microorganisms (viruses, bacteria etc) and their products,
foods, chemicals, pollen, tumor cells, etc.
3.Immune system: immune tissues and organs, immune cells, immune
molecules
4.Immune response: collective and coordinated response to the
introduction of foreign substances.
5.Immunology: study the structure of immune system and its functions.
Immune Response
 Innate immune response
natural immune response
non-specific immune response
 Adaptive immune response
acquired immune response
specific immune response
The innate and adaptive immune response
Characteristics
Cells
Molecules
Innate immunity
Responds rapidly
No memory
No or low
specificity
Physical barriers
Phagocytes (PMNs
and macrophages)
Natural killer cells
Humoral factors
Complement
Acute phase
Proteins
Cytokines
T cells
B cells
Dendritic cells
Antibodies
Cytokines
Granzymes
Adaptive
immunity
Responds Slowly
Memory
Highly specific
Adaptive immune response
Innate vs. Adaptive Immune

Innate: structural defenses; responds to nonspecific
foreign substances
 First
line: external surface epithelium & membranes
 Second line: internal defenses: inflammatory processes –
antimicrobial proteins, phagocytes, etc.
Innate vs. Adaptive Immune

Adaptive: responds to specific foreign substances

Innate & adaptive mechanisms work together
Innate, Defenses
Innate, Surface Defenses





Skin
 physical barrier to microbes
 Keratin resistant to most bacterial enzymes & toxins
 secretions are acidic pH 3-5
Mucosa
 physical barrier & produces a variety of protective
chemicals
Gastric mucosa
 very acidic & produces proteolytic enzymes
Saliva & lacrimal fluid contain lysozyme
Mucous
 traps bacteria & moves them away from epithelial surface
LACRIMAL APPARATUS.
CILIARY ESCALATOR.
Innate, Defenses
Innate, Internal Defenses

Based on recognition of surface carbohydrates
(glycocalyx)
 Glycocalyx
is recognized as “self” or “non-self”
Innate, Internal Defenses

Phagocytes
 Macrophages: derived from monocytes
 Free Macrophages: roam through tissues
 Fixed Macrophages: Kupffer cells (liver) & microglia
cells (brain)
Ingest cellular debris, foreign material, bacteria, fungi
 Neutrophils: ingest pathogens
 Eosinophils: weakly phagocytic of pathogens. Attack
parasites (degranulation)
 Mast Cells: phagocytic of various bacteria
Innate, Internal Defenses

Phagocytic mechanisms:
 Adherence: cell binds to invader
 Aided by opsonization (a chemical process that
enhances binding via complement & antibodies)
 Ingestion: formation
of phagolysosomes
 Respiratory Bursts: merge phagosome with lysosome &
flood phagolysosome with free radicals (macrophage)
 Defensins: proteins that crystallize out of solution &
pierce pathogen membranes (neutrophils)
Mechanism of Phagocytosis
Figure 21.2
Innate, Defenses
Innate, Internal Defenses

Natural Killer Cells:
 Small population of large granular lymphocytes
 Non specific for “non-self”
 Not phagocytic: attack is by release of perforins that
perforate the target cell plasma membrane.
 Shortly after perforation the target nucleus disintegrates.
 Release chemicals that enhance the inflammatory response
Innate, Defenses
Innate, Internal Defenses: Inflammation



tissue response to injury
Triggered by injury – trauma, heat, chemical
irritation, infection, etc.
Beneficial effects
 Prevents
spread of injury
 Disposes of cellular debris & pathogens
 Promotes repair
Innate, Internal Defenses: Inflammation

cardinal signs of inflammation
 Redness
 Heat
 Swelling
 Pain
 (functional impairment Rigon)
Innate, Internal Defenses: Inflammation

Inflammatory response: signs are associated
with vasodilation & increased vascular
permeability
 Dilation:
redness, heat
 Permeability: edema, (increased pressure) pain
 Pain also associated with bacterial toxins & some
mediators (kinins, PGs)
Innate, Internal Defenses: Inflammatory
Response

Mechanisms causing vasodilation & vascular
permeability
 Injured





cells release inflammatory mediators
Histamines
Kinins
Prostaglandins
Complement
Cytokines (also activated by receptors on macrophages in
response to microbial glycocalyx)
Innate, Internal Defenses: Inflammatory
Response

Edema
 Dilutes harmful substances
 Provides nutrients (& O2) for repair
 Enhances entry of clotting protein

Epithelial breaches also stimulate b-defensin release
from epithelial cells
Events in
Inflammation
Figure 21.3
Innate, Internal Defenses: Inflammatory
Response

Phagocyte mobilization: infiltration of damaged area
by neutrophils & macrophages
Innate, Internal Defenses:
Inflammatory Response


Leukocytosis: leukocytosis inducing factors released
by injured cells promote rapid release of WBCs from
marrow
Margination: increased vascular permeability causes
decreased fluid in vessels; blood flow slows &
neutrophils are able to move to vessel margins. Here
endothelial markers (CAMs) allow neutrophils to
cling to vessel walls (pavementing).
Innate, Internal Defenses:
Inflammatory Response



Diapedesis: neutrophils migrate through capillary
walls
Chemotaxis – inflammatory chemicals attract
neutrophils to move up the chemical concentration
gradient (neutrophils respond first)
As the process continues, monocytes diapedes into
the area & become macrophages. With chronic
inflammation, macrophages predominate
Inflammatory Response:
Phagocytic Mobilization
Figure 21.4
Innate, Internal Defenses:
Inflammatory Response


Macrophages clean up cellular debris & pathogens
If pathogens were associated with the injury,
activation of the complement cascade occurs &
elements of adaptive immunity join the process
Innate, Internal Defenses

Viral replication – (viruses lack metabolic processes)
Viruses release nucleic acid (RNA or DNA) into
cytoplasm. The information on the nucleic acid is
incorporated into the cell’s DNA. Normal cellular
mechanisms then produce viral structural
components. Multiple new viral particles are
produced & released from the cell (sometimes killing
the cell)
Innate, Internal Defenses




Antiviral proteins: interferon & complement
Interferon: some cells produce & release interferons
(IFNs) when invaded by virus
Released interferons stimulate nearby cells to produce
proteins (PKR) that interfere with viral replication by
disrupting protein synthesis & the ribosome
Not virus specific.
Interferon (IFN)
Figure 21.5
Innate, Internal Defenses




Complement – a group of plasma proteins (20) that
are activated in the presence of foreign substances
Complement activation enhances & amplifies
inflammation
Bacteria & some other cell types are lysed by
complement activation
Complement activation enhances both innate &
adaptive defenses
Innate, Internal Defenses


Complement activation pathways
 Classical pathway: requires antibodies
 Antibodies bind to target (antigen)
 Complement protein C1 binds to the antibodyantigen complex (complement fixation)
 Alternative pathway: complement factors interact with
microorganism glycocalyx
Both pathways lead to a cascade of protein activation,
leading to activation of C3
Innate, Internal
Defenses;
Complement
Figure 21.6
Innate, Internal Defenses

C-reactive proteins (CRP) produced by the liver in
response to inflammatory molecules can activate the
classical pathway by binding to membrane &
activating C1. Also participates in opsonization.

Fever – a systemic response to infection. Leukocytes
& macrophages release pyrogens that raise the
hypothalamic “set point” for temperature
ADAPTIVE DEFENSES

ADAPTIVE DEFENSES
 Innate & adaptive mechanisms work together in a
cohesive fashion
Adaptive Defenses: Characteristics

Specificity: directed at specific targets

Systemic: not restricted to initial site of infection /
invasion

Memory: after initial exposure & activation, a more
rapid & more vigorous response is made to
subsequent exposures to pathogens

(secondary response)
Adaptive Defenses: Components


Humoral Immunity: (antibody mediated immunity)
provided by antibodies floating free in body fluids
Cell mediated immunity:
 lymphocytes directly attack specific invaders by
lysis or indirect attack by initiating inflammation
and/or activating other lymphocytes &
macrophages
Adaptive, Humoral Immunity

Antigen = any substance that can mobilize the
immune system & provoke an immune
response*
*Humoral and/or cell mediated
Adaptive, Humoral Immunity

Complete antigens (proteins, nucleic acids, lipids,
polysaccharides):
 Immunogenicity:
the ability to stimulate specific
lymphocytes & specific antibodies
 Reactivity: the ability to react with activated lymphocytes
& antibodies

Hapten (an incomplete antigen): a smaller molecule
that is not immunogenic until attached to proteins
Adaptive, Humoral Immunity

Antigenic determinants: sites on an antigenic molecule that are
immunogenic


Epitope
Major Histocompatibility Complex (MHC): cell surface
glycoproteins associated with self recognition
Adaptive Immune System: Cells


Lymphocytes
 T-cells
 B-cells
Antigen Presenting Cells (APCs)
Adaptive Immune System: Cells


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Lymphocytes: initially uncommitted
T-cells: are sorted in the Thymus
 Positive selection: recognize MHC survive
 Negative selection: react against to self-antigens on MHC
killed
 2% of initial T-cell precursors
 T-cells manage the immune response
B-cells: are sorted in the marrow by an incompletely
understood process
Adaptive Immune System: Cells

Immunocompetence: as T- or B-cells mature they
become immunocompetent, they display receptors on
their cell membrane for a specific antigen.

All of the receptors on one cell are identical;
immunity depends upon genetic coding for
appropriate receptors.
Adaptive Immune System: Cells


Antigen Presenting Cells (APCs)
APCs ingest foreign material, then present antigenic
fragments on their cell surface where they are
recognized by T-cells



T-cells: respond to antigen only if it is displayed on plasma membrane.
APCs: Macrophages & B lymphocytes
Interactions between APCs & lymphocytes &
lymphocyte-lymphocyte interactions are critical to
immune response
Adaptive, Humoral response




Humoral response (clonal selection)
B-cells: Antigen challenge to naïve
immunocompetent B-cell
Antigen binds to B-cell receptors & form cross-links
between receptors
Cross linked antigen-receptor complex undergoes
endocytosis; B-cell presents to T-cell
Humoral Immunity

Active humoral immunity:
 B-cells
encounter & respond to antigen to produce an
antibody

Passive humoral immunity:
 Introduced
“non-native” antibody
Active Humoral Immunity


Naturally acquired: natural exposure to antigen (i.e. infection)
Artificially acquired: vaccines; dead/attenuated or fragmented
pathogen injected to elicit an immune response
 Bestow immunity without disease; primary response
 Booster shots (secondary response); intensify response
 Shortcomings – adverse reactions & the immunity is less
durable (poor memory) & has less cell mediated
component
Passive Humoral Immunity


Natural: maternal antibody crosses the placental
barrier conferring temporary immunity to the baby
(degrades after a few months)
Artificial: antibodies harvested from an outside
source given by injection protect from immediate
threat but no memory is formed (antitoxins,
antivenins , gamma globulin, etc.)
Antibodies


A.K.A Immunoglobulins & gamma globulins
Structure
 variable
 hypervariable
 constant
Antibodies



Constant (C) region defines antibody class
determines chemical & cellular interactions
determines how class functions to eliminate antigens
Antibody Classes

Antibody Classes: IgM, IgG, IgA, IgD, IgE
(Ig = immunoglobulin)
Antibody Classes

IgG: the most abundant circulating Ig. The dominant
circulating Ig of the primary & the secondary
response. Crosses the placenta. Complement binding
(Monomer).

IgA: the Ig of secretions. Helps prevent antigen
penetration of membranes (Dimer).

IgD: the Ig of B-cell activation. Found on B-cell
surface (Monomer).
Antibody Classes

IgM: occurs as a monomer & a pentamer
 Occurs
 The
on the B-cell surface (Monomer).
Ig of early primary plasma cell response,
circulating antibody; a potent agglutinator.
Complement binding (Pentamer).
Antibody Classes

IgE: the Ig associated with allergies.
 Stem binds to mast cells & basophils.
 Receptor binding results in histamine release &
inflammation.
 Found mostly in mucosa of respiratory & GI tract
(Monomer).
Antibody Targets & Functions

Immune complex formation = antigen-antibody binding.

All the following events are initiated by antigen-antibody
binding.
Complement fixation:
Neutralization:
Agglutination:
Precipitation:
Inflammation & phagocytosis prompted by debris

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Antibody Targets & Functions
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Complement fixation: cells & bacteria.
 Immune complex formation exposes a complement binding
site on the C region of the Ig.
 Complement fixation results in cell lysis.
Neutralization: immune complex formation blocks specific
sites on virus or toxin & prohibit binding to tissues
Agglutination: cells are crosslinked by immune complexes &
clump together
Precipitation: soluble molecules (such as toxins) are
crosslinked, become insoluble, & precipitate out of the
solution
Inflammation & phagocytosis prompted by debris
Antibody Targets & Functions

Monoclonal antibodies: antibodies produced by
descendants of a single cell
 Pure
antibody preparations that are specific for a single
antigenic determinant
 Research / diagnostic / therapeutic use
Cell Mediated Immune Response

T-cell activation: involves recognition of PM surface
antigens only
 Antigen
is combined with MHC & displayed on PM
 T-cell receptors: bind to the MHC & are stimulated by the
associated antigen
 The addition of a co-stimulator (cytokines, interleukins,
etc) prompts the T-cell to form a clone
 In the absence of a co-stimulator the T-cell becomes
tolerant to antigen (anergy)
Cell Mediated: MHC

MHC occurs as two classes
 MHC
I on virtually all tissue cells
 MHC II only on PM some immune system cells
Cell Mediated:
MHC display properties

MHC I on virtually all tissue cells
 Display only proteins produced inside the cell
 Endogenous antigens = foreign proteins produced by
the cell (viral / cancer)
 Stimulate the CD8* cell population
 form cytotoxic T-cells (Killer T, TC)
 *formerly T8 cells
Cell Mediated:
MHC display properties

MHC II found only on PM of B-cells, some T-cells &
APCs
 Display proteins derived from a phagocytized target
 Exogenous antigen: foreign protein from outside the
cell – presented to PM surface
 Stimulates the CD4* cell population
 form Helper T-cells (TH)
 *formerly T4 cells
Cell Mediated: T-cell roles

Helper T-cells (TH)
stimulate B-cells
& other T-cells to
proliferate
Cell Mediated: T-cell roles

Activated TH cells interact
with B-cells displaying
antigen & produce
cytokines that prompt the
B-cell to mature & form
antibody
Cell Mediated: T-cell roles



TH cells also produce
cytokines that promote TC
cells
TH cells recruit other WBCs
& amplify innate defenses
(inflammatory)
Subpopulations of TH cells
specialize in specific sets of
activations
Cell Mediated: T-cell roles


Cytotoxic T-cells (TC, Killer T): directly attack &
kill cells with specific antigen
Activated TC cells are co-stimulated by TH cells
Cell Mediated:
T-cell roles

TC mechanism (Cytotoxic
T-cells, Killer T)





TC binds to cell & releases
perforin & granzymes
In the presence of Ca2+
perforin forms pores in
target cell PM
Granzymes enter through
pores & degrade cellular
contents
TC then detaches & moves
on
Macrophages clean up
Cells, tissues and organs of
the immune system

Immune cells are bone marrow-derived, & distributed through out the
body

Primary lymphoid organs:
– Thymus: T cell maturation
– Bone marrow (bursa of Fabricius in birds): B cell maturation

Secondary lymphoid organs:
– Lymph nodes
– Spleen
– Mucosal lymphoid tissues (lung, gut)
Cells of the Immune system: FORMED
ELEMENTS IN BLOOD
Many cells of the
immune system
derived from the
bone marrow
 Hematopoetic stem
cell differentiation

COMPONENTS OF THE
LYMPHATIC SYSTEM.
The bursa of Fabricius in birds
Types of Acquired Immunity
Figure 21.11
Major Types of T Cells
Figure 21.14
T Cell Activation: Step One – Antigen Binding
Figure 21.16
Helper T Cells (TH)
Figure 21.17a
Helper T Cells
Figure 21.17b
Summary of the Primary Immune Response
Figure 21.19