Biology of Immune Response

8/9/2019 Biology of Immune Response

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Presented by:

Christian Bernardes, Asher Dolina, Marycris Manuel, Genkei Parco


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Host reaction to a foreign

substance (antigen) in which this

reaction will provide protection to

the host, through recognitionand elimination of an antigen

Immune response could either be:

1. Humoral

2. Cellular


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adaptability to foreign invaders

specificity in responding to anyparticular invader

long term memory of first contactwith foreign material


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Ingested

Mode of Entry Site of Ag trapping

Peyers patchesIntestinal mucosa


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Inhaled


Alveolar lining


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Intracutaneous/

Subcutaneous

Regional lymph node


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Intravenous/

Intraperitoneal

Spleen


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Cell Group Surface components Function

B-lymphocytes Surfaceimmunoglobulin

(Ag recognition)

Immunoglobulin Fc

receptor

Class II MajorHistocompatability

Complex (MHC)

(Ag presentation)

Direct antigen

recognition

Differentiation into

antibody-producing

plasma cells

Antigenpresentation within

Class II MHC


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CD3molecule

T-cell receptor (TCR,Ag recognition)

Involved in both

humoral and cell-

mediatedresponses

T-lymphocytes


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CD4molecule Recognizes antigen

presented within

Class II MHC

Promotes

differentiation of B-

cells and cytotoxic

T-cells

Activates

macrophages

Helper T-cells (TH)


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CD8molecule shut down T cell-

mediated immunity

toward the end ofan immune reaction

suppress auto-

reactive T cells that

escaped the processof negative

selection in the

thymus.

Suppressor T-cells (TS)


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CD8molecule Recognizes antigen

presented within

Class I MHC

Kills cells expressing

appropriate antigen

Cytotoxic T-cells (CTL)


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CD4 & CD8 molecule providing the immune

system with

"m

em

ory" againstpast infections.

Memory T cells


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Variable Phagocytosis and cell

killing

Accessory cells


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Variable Phagocytosis and cell

killing

Accessory cells


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Immunoglobulin Fc

receptor

Complement

component C3b

receptor

Class II MHCmolecule

Bind Fc portion of

immunoglobulin (enhances

phagocytosis)

Bind complementcomponent C3b (enhances

phagocytosis)

Antigen presentation within

Class II MHC

Secrete IL-1 (macrokine)

promoting T-cell

differentiation and

proliferation

Can be "activated" by T-cell

lymphokines

Macrophages


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Immunoglobulin Fc

receptor

Complement

component C3b

receptor

ClassII

MHCmolecule

Bind Fc portion of

immunoglobulin (enhances

phagocytosis)

Bind complementcomponent C3b (enhances

phagocytosis)

Antigen presentation within

Class II MHC

Secrete IL-1 (macrokine)

promoting T-cell

differentiation and

proliferation

Can be "activated" by T-cell

lymphokines

Macrophages


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Class II MHC

molecule

Antigen presentation

within Class II MHC

Dendritic cells


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Immunoglobulin Fc

receptor

Complement

component C3b

receptor

Bind Fc portion of

immunoglobulin

(enhancesphagocytosis)

Bind complement

component C3b

(enhancesphagocytosis)

Polymorphonuclearcells (PMNs)


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Immunoglobulin Fc

receptor

Bind Fc portion of

immunoglobulin

Kills antibody-coated

target cells (antibody-

dependent cell-

mediated

cytotoxicity, ADCC

K cells


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High affinity IgE Fc

receptors

Bind IgE and initiate

allergic responses by

release of histamine

Mast cells


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Macrophages are in a restingstate until chemicals that arereleased during an immuneresponse activate them.

Upon activation, these cellstravel toward the site ofinjury and they engulfdisease-causing organisms

Once ingested, the pathogenbecomes trapped in aphagosome, which thenfuses with a lysosome.


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Non-encapsulated microorganisms are easily

phagocytosed and killed withinmacrophages


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Encapsulated microorganisms require the production of

antibody in order to be effectively phagocytosed. Onceengulfed, however, they are easily killed.


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Intracellular microorganisms elicit the production of antibody, which

allows effective phagocytosis. Once engulfed, however, they survivewithin the phagocyte and eventually kill it.


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I

ntracellularm

icroorganism

s can also activate specific T-cells (with or without theaid of antigen presenting cell), which then release lymphokines (e.g. IFN, TNF) thatcause macrophage activation. Activated ("killer") macrophages are then veryeffective at destroying the intracellular pathogens.

IFN

TNF


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Also known as the accessory cell

displays foreign antigen complex withmajor histocompatibility complex

(MHC) on its surface.

T-cells may recognize the MHC-antigen complex using their T-cellreceptor (TCR).

These cells process antigens andpresent them to T cells.


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very efficient at internalizing antigen,either by phagocytosis or by receptor-mediated endocytosis

Present the antigen to T cells via MHC II

There are three main types ofprofessional APCs:

Dendritic cellsM

acrophagesB cells


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does not constitutively express the Majorhistocompatibility complex, class II (MHC class II)

MHC II are expressed only upon stimulation of thenon-professional APC by certain cytokines such asI

FN-.

Non-professional APCs include:

Fibroblasts (skin)Thymic epithelial cells

Thyroid epithelial cellsGlial cells (brain)Pancreatic beta cellsVascular endothelial cells


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Involves proteins called immunoglobulinor antibodies that fight against diseaseand infection.

Secreted antibodies by the B cells bind to

antigens on the surfaces of invading

microbes (such as viruses or bacteria),

which flags them for destruction.

Humoral immunity is so named because it

involves substances found in the humours,

or body fluids.


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to bind specifically to the

molecules of the foreign agent

that triggered the immune

response.

to attract other cells and

molecules to destroy thepathogen after the antibody

molecule is bound to it.


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The B cells

are induced to proliferate and produce several identical cells

capable of producing the same antibody. Cytokines also signalthe B cells to mature into antibody producing cells or plasma cells

T cells then release certain chemicals known as cytokines (orlymphokines)

The helper cells recognize the pathogen bound to the C-II

proteinT cells become activated

The antigen-antibody pair is partially digested

bound to C-II that is displayed on the surface of the B cell

Engulfed by the antigen-presenting cells

B - cells

Foreign agent enters the body


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Neutralization - antibodies bind to the bacteria or toxinand prevent it from binding and gaining entry to a host

cell.

Opsonization - binding of the antigen to the phagocyteis greatly enhanced.

Phagocytosis antibodies attract cells likemacrophages to engulf the pathogens and destroythem


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biological process that prepares antigens for

presentation to special cells of the immune

system called T-lymphocytes.

involves two distinct pathways for processing of

antigens: Endogenous and Exogenous pathway


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1

Class Imolecules bind peptides that have been synthesizedwithin the cell-viral proteins

2

Peptides from degraded viral proteins are transported intothe endoplasmic reticulum

3

Partially folded MHC Imolecules bound by calnexinmeetsviral peptide in the endoplasmic reticulum

4

Peptide binding completes MHC 1 folding, releasing calnexin;

only folded molecules are exported to the Golgi Apparatus

5

Bound viral peptide is carried by MHC class I to the cellsurface


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1 Phagocytosis or endocytosis of antigen

2

Digestion of antigen into peptide fragments (APC)

3

Fusion of vesicles containing peptide fragments and MHC IImolecules

4 Peptide fragm

ents bind to MHCII

m

olecules

5

Vesicle undergoes exocytosis and Ag-MHC II complexes areinserted into the surface of the membrane


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Antigen presentation: a process inthe body's immune system by which

macrophages, dendritic cells andother cell types capture antigensand then enable their recognition

by T-cells.


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It is important for T cell to recognize whether theantigen is in the cytosol or in the vesicularsystems.

MHC class I route presents peptides derived fromcytoplasmic antigens.

MHC class II route presents peptides derived

from extracellular or intravesicular antigens.


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Cytoplasmic proteins are degraded bythe proteasome


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Proteosome-consist of 4 stacks of 7units

-in each of the 7 units, the2 middle stacks haveproteolytic enzyme activity


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MHCI is atransmembrane proteinmade in the ER

Cytoplasm-derivedpeptides must betransported into the

ER to bind MHCI


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The invariant chain (Ii)blocks the MHCIIpeptide-binding cleftwhile it is in the ER

Acid proteases cleave Iibut leave a fragment(CLIP) in the peptide-binding groove


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First time a helper T cellinteracts with its antigen, theresponse is slow (primary

immune response).

When re-exposure to pathogento which memory cells have

been generated, little lag occur.(secondary immune response)


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First time Ag is encountered/ first injection of Ag

Lag/ delayed response of several hours to several days(Latent/Induction period)

Dependent on (1) type of Ag introduced, (2) route ofadministration. (3) species of animal (4) serological test

Ab is detected (5th to 10th day)

Rises, reaches its peak, begins to drop

Stop the production ofIgM (switch to IgG)


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Lag phase delayedresponse

Log phase increase Ab

production

Plateau phaseAb titeris stabilized

Decline phase Ab iscleared


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Accelerated/Booster/Anamnestic response

Second injection of the same Ag

Ab drops first: still complexing with newly injected Ag

Rises, reaches its peak, persist for a long period of time

Long lived cells, more Ab production, more IgG than IgM (memorycells)

Faster response because the host is primed for the particular Ag


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Differences 1o response 2o response

1. Ab titer

1. Time course (Lag phase)

1. Ab class (IgG)

1. Ab affinity


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Biology of Immune Response