Immune System

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Ig alfa

Ig beta

Back 1

invariant molecules whose function is to deliver to the inside of the B-cell the activation signals that are triggered by membrane Ig

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BCR complex

Back 2

membrane IgD or IgM+Ig alfa or Ig beta on B cells

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TCR

Back 3

membrane-bound molecule found on T cells to recognize MHCs. Comparable to Ig on B cells. They transmit the signal inside the cell thanks to CD3 and ζ-chains.

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cross-linking

Back 4

activation of B cells by epitopes

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antibodies

Back 5

Igs: composed of 2 heavy chain and 2 light chains

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Fab region

Back 6

fragment antigen binding, to be found on antibodies

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Fc region

Back 7

tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system

(fragment crystallizable region)

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heavy isotype switching

Back 8

=switching in isotype of heavy chain in the antibodies.

It happens to T-dependent B cells after been activated by CD4+ lymphocytes together with the process of affinity maturation, B cells proliferation (clonal expansion) and production of Igs

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IgD

Back 9

naive B cell antigen receptor

Front 10

IgM

Back 10

pentamer

-naive B cell antigen receptor

-complement activation

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IgA

Back 11

<-cytokines produced in mucosa (a.o. TGF beta)

-mucosa immunity

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IgG

Back 12

<-IFN gamma

-neonatal immunity

-antibody feedback mechanism

-ADCC

-macrophages activation through Fc gamma

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IgE

Back 13

<-IL-4

-helmithic infections

-mast cells activation (fc epsilon)-hypersensitivity

-allergy

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CD3 and ζ-chains

Back 14

They transmit the signal from TCR into the T cells

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TCR complex

Back 15

TCR+ CD3 and ζ-chains

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somatic gene recombination

Back 16

V(D)J recombination is the mechanism of genetic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. The process results in the highly diverse repertoire of antibodies/immunoglobulins (Igs) and T cell receptors (TCRs) found on B cells and T cells, respectively

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CD4 and CD8

Back 17

co-receptors on T cells to recognize II MHC and I MHC, respectively

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what is needed for antigen recognition on T helper cells?

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-TCR

- CD3 and ζ-chains

-co-receptors CD4 or CD8

-adhesion molecules (integrins)

-costimulator (CD28+B7)

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CD28-B7 interaction

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B7=proteins expressed on APCs as costimulators of T cells

CD28= receptor present on all T cells to recognize B7

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CD40 Ligand

Back 20

-present on T cells, activates macrophages, B cells and B7 costimulators for T cells

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CD40

Back 21

-present on APCs, when it binds with CD40L on T cells it stimulates expression of B7 costimulators and cytokines

-present on macrophages->activation by T cells

-present on B cells->production of antibodies

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immunologic synapse

Back 22

region of contact between APC and T cell

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ITAMs

Back 23

=immunoreceptors tyrosine-based activation motifs

-present on CD3 and ζ-chains of T cells

-prensent on Ig alfa and beta of B cells

when phosphorylated it triggers effector pathways inside the lymphocyte->recruitment of adapter proteins-> activation of biochemical intermediates-> transcription factors (a.o. NF-kB)-> cytokines productions, cytokines receptors expression, effector molecules (CD40L)

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Functional responses of T cells

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1. Cytokines secretion

2. Clonal expansion

3. Differentiation into effector cells

4. Memory

5. Negative feedback

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Cytokines properties

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-produced in response to antigen

-autocrine or paracrine

-pleiotropism: multiple actions

-redundancy: several cytokines have the same action

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IL-2

Back 26

<-CD4+ and CD8+

-> T cells growth and differentiation factor

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IL-4

Back 27

<- CD4+ (Th2)

-> switching to IgE

->Th2

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IL-5

Back 28

<-CD4+ (Th2)

-> activation of eosinophils

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IFN-gamma

Back 29

<-CD4+, CD8+ and NK

-> activation of macrophages

->Th1

->IgG switching

much more

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IL-12

Back 30

<-macrophages

->NK activation

->Th1

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TGF-beta

Back 31

<- CD4+, macrophages, others

-/ inhibition T cells, B cells and macrophages

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Th1

Back 32

<- IFN gamma, IL-12

-> IFN gamma-> macrophages (CD40L)

->IL-2 -> T cells, NK cells, B cells proliferation

->TNF

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Th2

Back 33

<-IL-4

->IL-4-> IgE switching

->IL-5-> eosinophils

->IL-13

->alternative macrophages activation for tissue repair

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Th17

Back 34

<-IL-1, IL-6, TGF beta

->IL-17

->IL-22

=barrier function, neutrophils attraction, against bacteria and fungi

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IFN gamma

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<-NK, Th1, CD8+

-> macrophages activation

-> Th1 differentiation

much more

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I MHC

Back 36

diplayed by all nucleated cells

recognized by CD8+

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II MHC

Back 37

displayed by APCs

recognized by CD4+

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Granzymes

Back 38

granule proteins produced by CD8+, they cleave and thereby activate enzyme caspase to induce apoptosis in an infected cell

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Perforin

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granule proteins produced by CD8+, responsable for the delivery of granzymes inside the infected cell

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T dependent B cells charateristics (=follicular B cells)

Back 40

-heavy isotope switching

-affinity maturation

-long living plasma cells

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T indipendent B cells

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marginal zone B cells (in splenic white pulp for blood-borne polysaccharides)

B-1 cells (in mucosa for nonprotein antigens)

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Time of primary response

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5-10 days

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Time of secondary response

Back 43

1-3 days

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What is the second signal for B cells?

Back 44

C3d complement fragment (also microbial products on TLRs), that enhance the activation together with signal 1 (the antigen) attached to membrane Igs

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Consequences of B cell activation

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1. B cell proliferation

2. B cell differentiation

3. production of IgM (first humoral response)

4. migration out of follicle

5. B cell present II MHC to T cell

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What does the T cell express to activate the B cell?

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CD40L

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trigger of antibody feedback

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IgG

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Effects of antibodies (4)

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1. Neutralization of microbe and toxins

2. Opsonization and phagocytosis (IgG+phagocytes)

3. ADCC (IgG+NK)

4. Complement activation

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Effects of complement activation (3)

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1. Lysis of microbes

2. Phagocytosis of opsonized microbes

3. Inflammation

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Poly-Ig receptor

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receptor present on the basal side of the epithelium that binds to IgA and bring it to the lumen where it is cleaved off by a proteolitic enzyme

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cross-presentation

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the ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells

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PAMPs

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Pathogen associated molecular patterns, recognized by PRRs

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PRRS

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Patter recognition receptors

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NF-kB and IRF-3

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transcription factors activated by TLRs

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TNF

Back 55

Tumor necrotic factor, proinflammatory cytokine

produced by macrophages and Th1

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IL-1

Back 56

proinflammatory cytokine

produced by macrophages and endothelial cells

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IL-12

Back 57

cytokines produced by macrophages that activates NK

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E-selectin, P-selectin

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low affinity molecules expressed on epithelial cells to attach selectin ligands on leukocytes->rolling

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Integrins

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high affinity molecules present on leukocytes that attach for instance ICAM-1

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Metabolic effects of proinflammatory cytokines

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Endothelial cells: activation

Phagocytes: activation

Hypothalamus: fever

Liver: synthesis of acute phase proteins (a.o. CRP)

Muscle, fat: catabolism

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Follicular dendritic cells

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APCs for B cells

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NK-T cells

Back 62

they recognize lipids ipv peptides antigens (probably)

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GammadelyaT cell

Back 63

they recognize different types of antigens displayed, not only peptides

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DM

Back 64

proteinthat remove the CLIP from IIMHC from ER

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CLIP

Back 65

invariant chain attached to IIMHC in ER, removed by DM

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Immunodominant epitopes

Back 66

the only peptide of an antigen thatstimulate immune response (after been broken down)

Front 67

TAP

Back 67

protein, transportassociated with antigen processing from cytoplasamtic proteasome to ER withIMHC

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Functions of the complement

Back 68

1. MAC complex lysis of microbe

2. C3b coats microbe for phagocytosis

3. C3d activates humoral response

4. C5a,C4a, C3a proinflammatory

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3 pathways of complement actiavtion

Back 69

1. Alternative (directly bound to antigen)

2. Classical (IgM or IgG)

3. Lectin (mannone binding lectin)