lecture - adaptive

8/3/2019 Lecture - Adaptive

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WHAT HAS TO HAPPEN TO CLEAR A VIRAL

INFECTION??



INNATE COMPONENT

• Recognition of PAMP’s by PRR’s• Induction of the “anti-viral” state by Type1 IFN’s

• NK cell activation and cytolysis

• Complement



ADAPTIVE IMMUNITY



Goldsby, Immunology, 5th ed.

COMPARISON OF INNATE AND ADAPTIVE IMMUNITY



days

virus

Efficient response to an acute infection depends on

coordination of both innate and adaptive responses

7 2114

innate adaptive

INNATE AND ADAPTIVE IMMUNITY ARE BOTH

REQUIRED FOR VIRAL CLEARANCE



THE ADAPTIVE (ACQUIRED) IMMUNE RESPONSE

• humoral response:actions of serum and lymph proteins

• cellular response:actions of specific helper and effector cells



PLAYERS IN HUMORAL AND CELLULAR IMMUNITY

Humoral Cellular





INFECTION??

1. Recognize infection2. Activate adaptive immune response

a) T cells (Cellular)



REQUIREMENTS TO INITIATE A T CELL RESPONSE

Activation of T cells is a 3-step process…1. TCR/MHC/peptide recognition

2. Co-stimulatory signals

• T cell: CD28

• APC: B7 (CD80/86

3. Cytokine mediated differentiation



IMPORTANT RECEPTORS ON T CELLS

Th: Helper T cell Tc: Cytotoxic T cell

TCR: T cell receptor

CD4: co-receptor (MHCII)

CD8: co-receptor (MHCI)Goldsby, Immunology, 5th ed.



TCR’S RECOGNIZE PEPTIDE PRESENTED BY MHC



presents endogenous antigenproteins synthesized in an infected cell

- CD8 T cell restricted

MHC I

presents exogenous antigens proteins

or antigens endocytosed from outside

the cell


MHC II

ANTIGEN PRESENTATION



Cells presenting both

MHC I and MHC II:

Dendritic cells

macrophages

B-cells

Cells presenting MHC I:

all nucleated cells

ANTIGEN PRESENTING CELLS (APCs)



ANTIGEN PRESENTING CELLS

-

Dendritic cells, macrophages, B cells"

- Immature APCs patrol tissues and collect antigen"- Rapidly recognize danger through expression of PRRs"- Mature APCs migrate to lymphoid organs and activate

specific T cell response"- Bridge between innate and adaptive immunity "



presents endogenous antigenproteins synthesized in an infected cell


MHC I




cytosol

cytosol

cell

surface

MHC

class I

AG PRESENTATION BY MHC CLASS I

(infected cell)

TAP

transporter



AG CROSS-PRESENTATION BY MHC CLASS I (APC)

Immunology and Cell Biology (2008) 86, 353–362



presents exogenous antigens proteinsor antigens endocytosed from outside

the cell


MHC II




Ag

MHCII

AG PRESENTATION BY MHC CLASS II

(APC)



IMPORTANCE OF CO-STIMULATORY MOLECULES


2. Co-stimulatory signals• T cell: CD28

• APC: B7 (CD80/86)




Adapted from Nature Reviews Immunology 4, 24-35 (January 2004)

DENDRITIC CELL MATURATION:

REQUIREMENT FOR CO-STIMULATION

Immature DC

No B7 expression

Low MHCII expression

Mature DC

B7 expressed

High MHCII expression



Co-stimulation is essential for differentiation of

effector T cells



GRANZYMEB MEDIATED TARGET CELL KILLING USES

PERFORIN




Naïve CD4+ Th0

Effector Th1 OR Th2 (balance determines disease outcome)

Memory CD4 T cellsGoldsby, Immunology, 5th ed.

ROLE OF CD4 T CELLS



CD8

“help” for CTLs

via cytokines



IL-2 signals from nearby Th1 cells “help”

CTL differentiation and proliferation

TCR/CO-STIM ACTIVATION OF CD4 TH CELLS




CYTOKINE MEDIATED T CELL DIFFERENTIATION

• Activation of T cells is a 3-step process…1. TCR/MHC/peptide recognition

2. Co-stimulatory signals

• T cell: CD28

• APC: B7 (CD80/86)




BALANCE BETWEEN CELLULAR (TH1) AND

HUMORAL (TH2) RESPONSES

TH1 TH2



TH1 TH2





REQUIREMENTS FOR INITIATING A T CELL RESPONSE


• APC’s present multiple peptides

• T cells specifically recognize unique non-self peptide

2. Co-stimulatory signals• T cell: CD28

• APC: B7 (CD80/86)

• Co-stim signals NECESSARY for T cell priming,

proliferation and acquisition of effector function3. Cytokine mediated differentiation

• Determines T H 1 versus T H 2 response




INFECTION??

1. Recognize infection2. Activate adaptive immune response

a) T cells

b) B cells (Humoral)




HUMORAL IMMUNITY



ANTIBODIES



B CELL ACTIVATION



“help” for B-cells

via cytokines

IL-4



Janeway, Immunobiology, 6th ed.

1 - Ag/Ab cross-linking

2 - CD40/CD40L interactionwith Th cell

IL-4/CD40 IL-5/IL-6

B CELL ACTIVATION ALSO REQUIRES A SECOND SIGNAL



• Can be localized toinfection site and

inhibit infection• IgA in mucosal

secretions

• Inhibition of viralattachment

• Inhibiton of viral entry

• Opsonization

• Complement

mediated lysis

(enveloped)

ROLE OF B CELLS/HUMORAL IMMUNITY IN VIRAL INFECTION



CELLULAR AND HUMORAL IMMUNITY

- Putting it all together




INFECTION??



LYMPHOCYTE CLONAL EXPANSION AND MEMORY GENERATION




weeks

T cells

virusAb

Efficient response to an acute infection involves innate,

cellular and humoral responses

NK cells IgG

IgM

VIRAL CLEARANCE AND GENERATION OF MEMORY



Memory is specific and results in more robust

response with subsequent exposureGoldsby, Immunology, 5th ed.

ADAPTIVE RESPONSE RESULTS IN GENERATION OF MEMORY



WHY IS MEMORY “BETTER”?

• Higher frequency of Ag specific T and B cells

• Primed for quick response

• Memory T cells do not require co-stimulation for

activation

• Tissue localization



• Adaptive response: pliable, flexible

• Multiple antigens presented on a single APC

• Single lymphocyte = monospecific response



• Clonal selection and expansion of virus-specificB and T cells

• The host repertoire: genetic differences

• Recognition of antigen: specific, pluripotent

• Amplification of virus specific cells

• Somatic mutation in B cells: refinement

• Immune memory



• Specific recognition of Antigen

• Clearance of Antigen

• Memory of Antigens

P



PATTERNS OF INFECTION AND THEIR RELATIONSHIP

TO IMMUNE DEFENSES



weeks

CTLs

virus

Ab

Brief course; virus eliminated within days.

ACUTE INFECTION AND CLEARANCE OF VIRUS



weeks

CTLs

virus

Ab

No clearance of virus, lack of immune response

Ex: measles/SSPE, arenaviruses

PERSISTENT INFECTION



1) Acute infection

2) Immune reactivation and apparent clearance

3) Virus goes into hiding

• herpesvirus: latency in neurons

4) Virus is reactivated at later time.

LATENT INFECTION



Hallmarks: very slow replication

Low/no immune response

Ex: Scrapie, Kuru, Bovine Spongiform

Encephalopathy

“SLOW” INFECTION

lecture - adaptive

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