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Flashcards in Immunology III Deck (52)
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1

Cytokine

Small protein, secreted by cells to influence behavior of other cells where the effect is receptor-mediated- need receptors
Regulators & effectors
Work at low concentrations

Pyrogens: cytokine associated with fever; IL-1 in association with bacterial infection

Antiviral interferons: IFN-γ as T-cell-derived antiviral protein or activator of macrophage (macrophage-activating factor) - type of cytokine

2

Lymphokine

Cytokine made by lymphocytes- interleukins
Can have a monokine- cytokine produced by monocytes to influence the behavior of other cells

3

Chemokine

Chemotactic cytokine
Lymphocytes & phagocytes migration
Inflammatory responses

4

Cytokines of Innate Immunity

Produce cytokines by many cells: macrophages, NK, eosinophil, mast cell, basophil
Mediate immune and inflammatory reactions
Communication tool among leukocytes and between them and other cells

5

Cytokines Produced by Macrophages

Tumor necrosis factor (TNF)
Interleukins (IL): IL-1, 12, 10, 6, 15, 18, etc.
Type I interferons: IFN-α, IFN-β

6

IL-1 (alpha and beta)

produced by macrophages, T and B cells, monocytes, NK cells, and dendritic cells

functions: increase fever, acute phase protein synthesis, increase thymocyte and T cell activation, B cell growth, differentiation, and immunoglobin secretion

Influence the NK, B, macrophage, and PMNs, which then effect other cells
T helper cells produce IL-1, and IL-1 effects the T helper cell = autocrine

7

IL-2

produced by T cells

functions: increase growth and differentiation of T, B, and NK cells

8

IL-4

produced by T cells, mast cells, and basophils

functions: increase differentiation of B cells and TH2 cells, increase IgG and IgE synthesis, decrease proinflammatory TH1 cell and macrophage function

9

IL-6

produced by monocytes, macrophages, B and T cells, and vascular endothelial cells

functions: increase acute phase protein synthesis, increase thymocyte and T cell activation, B cell growth, differentiation, and Ig production

10

IL-10

produced by T cells, B cells, and macrophages

functions: decrease TH1, NK cell, and macrophage function including cytokine synthesis/release, increase B cell and mast cell proliferation

11

IL-12

produced by B cells and macrophages

functions: increase NK cells, CTL and TH1 generation, increase IFN-gamma production by NK cells and T cells, increase ADCC and NK activity, co-stimulates T cell production

12

IL-8/ CXCL8

Chemokine produced by: endothelial cells, fibroblasts, keratinocytes, macrophages, monocytes
IL-8 causes chemotaxis of neutrophils and naïve T-cells (attracts them)
Receptors: CXCR1 and CXCR2
Major functions: mobilization, activation & degranulation of neutrophil and building of blood vessels (angiogenesis)

13

RANTES/CCL5

Producer: Tc lymphocytes (secretes CCL5 as HIV suppressive), endothelium, and platelets
Cells attracted and major effects; chemokine chemotactic for monocytes, mast cells, basophils (degranulation), eosinophil, dendritic cells, NK & T cells (activate T cells)
Involved in chronic inflammation
Regulated on Activation, Normal T Expressed and Secreted
Regulated And Normal T cell Expressed and Secreted

14

TNF- gamma

produced by NK and T cells

functions: activation of macrophages

15

TNF

produced by macrophages and T cells

functions: activates endothelial and neutrophils; causes fever (pyrogenic) and apoptosis

16

Type I TNFs

IFN- alpha produced by macrophages
IFN- beta produced by fibroblasts

Functions- all cells: antiviral activity, increased MHC I expression
NK cells: activation

17

Lymphocyte Activation

Regulators of lymphocytes: IL-2, IL-4, TGF-β
TH produce cytokines involved in regulation of acquired, specific immune response

18

T helper/CD4+ Differentiation

Dependent on the IL and conditions
If infection comes along, TH0 will cause TH1 to activate to create cell mediated immunity
If the Ag comes in the form of a extracellular – humoral immunity comes along aka TH2
IL-12, IFN, and TGFb favor TH1
IL4 favors TH2
Viral infection- need cell mediated to Tm will go to TH1

19

IL-2 and IL-4 Receptors

IL-2 receptor has high-affinity
IL-2R is composed of 3 polypeptides: α & β bind to IL-2, and γ is involved in signaling to the cell in both receptors
IL-4R has only α chain with a binding site
Signaling: γ

20

Cytokine Action

Cytokine binds to its Receptor  Ligand-induced aggregation  Activation of intracellular signaling pathways (kinase cascade)  Activation of transcription factors  Into nucleus  Binding to promoter or enhancer  Gene transcription

21

Immune Mediated Inflammation

The immune system is involved in inflammatory reactions; cytokines play an important role in inflammation production
Main producer of cytokines: Ag-activated T cells
Heat from reactions leads to sweating and redness

22

Cytotoxic T cells Kill Infected Cells

Prevent them from producing more pathogen
How? infected cells present viral peptides by their MHC I
Tc detect viral peptides by their specific TCR
The more virus specific Tc produced, the more successful the antiviral immune response
In an EBV infection of B cells
Tc make up the vast majority of WBCs

23

TH1 vs. TH2 Cells

TH1: Intracellular infection that requires cell mediated immunity, so TH1 will recognize the virus and will be activated and produce IL-gamma, which activates macrophages to become a killer machine; TH1 can also activate NK and Tc cells as well; ILN gamma will inhibit TH2
TH1 has no effector function, meaning that TH1 and 2 cannot kill by itself; it activates other cells to do the killing for them aka the Mafia Boss
TH2: Bacteria infection that is EXTRAcellular and this will present to the TH2 cell via APC, and TH2 is activated and produced IL-10 and releases IL-4 and 5; IL-10 inhibits the production of IFN gamma by TH1 so cell mediated immunity is not activated; these cytokines IL-4 and 5 will stimulate other cells that will be involved in humoral immunity; among these the B cells will be activated to plasma cells to form Ab including IgE and other types; IL-4 and 5 also activate mast cells and eosinophils

24

Roles of Macrophages

Many functions start before the specific immunity starts
1. Macrophages can use O2 radicals by fusing with microbes to kill them; also use acids/enzymes to hydrolyze bacteria and kill them; cationic proteins = defensins
2. Can also have tumor killing activity by using similar that involve O2, H2O2, C3a (anaphylactic reactions) to all kill the tumor cells; with these same products, it can also damage tissue
3. Macrophage is also involved in inflammation and fever by producing pyrogenic cytokines IL-6 and 1 alpha and beta; produce prostaglandins, complement, and clotting factors as well
4. Selection: IL-10 will stimulate TH2 to select the humoral pathway, but if produce IL-12 it will stimulate TH1 to activate the cell mediated immunity
5. Activation of Lymphocytes, especially T cells; virus or bacterial infected cells signal the macrophage to present the peptides with the MHC I or II to the Th or Tc cells
6. Tissue organization
Overall the macrophage is the tool for the T helper cell to have effector functions

25

Tolerance vs. Tolerogen

Tolerence: The acquisition of a specific nonresponsiveness to a molecule recognized by the immune system as nonself
Tolerogen: An otherwise immunogenic substance that, because of its chemical composition, dose, or route of introduction, induces immunologic tolerance rather than immunity; a foreign Ag that suppresses the immune response or produces immune tolerance

26

Anergy

An absence of cell-mediated immune reaction in supposedly sensitized animals or individuals
T or B cells are indifferent towards Ag
In advanced cases of TB, infections with Mycobacterium tuberculosis, the tuberculin test becomes negative

27

Tolerance Induction

Tolerance is unresponsiveness of the adaptive immune system to Ags as a result of inactivation or death of Ag-specific lymphocytes (T & B cells)
Induced by exposure to Ag (Tolerogen)
Conditions that influence tolerance induction:
The immunologic maturity of an animal & its immune cells
The dose of Ag
The physicochemical nature of the Ag
The immunogenicity of an Ag
The route of Ag administration
The kind of recipient

It is easiest to induct tolerance using a neonate with an undeveloped immune system

28

Mechanisms of Tolerance Induction

Physical elimination or clonal deletion
Functional inactivation, anergy
Regulated inhibition of Ag-reactive T and B cells
Induction of self-tolerance can occur at 3 levels:
1. The T-cell level
2. The B-cell level
3. The T-cell-B-cell cooperative level

29

Ag Induction: Clonal Abortion, Deletion, and Anergy

1. Clonal abortion: multivalent antigen can, when given in appropriate concentrations, cause immature B cells to abort by preventing their further differentiation because B cells are only supposed to react with one epitope, not many (multivalent); tolerizability of pre-B cells is high
2. Clonal deletion: very strong negative signals can cause deletion of mature B cells (B cells do not react to Ag when supposed to)
3. Clonal anergy: intermediate concentrations of multivalent antigen allows pre-B cells to develop into morphologically normal B cells, with normal numbers of immunoglobulin receptors, but renders them profoundly anergic; will not bind any epitopes, and will not produce Ab

30

IL-2 Synthesis

CTLA-4 is a CD28 homologue that is synthesized after the activation of T cell
When CTLA-4 ligates B7 on the APC blocking activation signals so no more IL-2 is synthesized leading to T cell death

TCR (t cell receptors) and MHC with peptide we need the CD4 that binds to it… these are the essential requirements
Sometimes need costimulatory signals on B cells, macrophages, or any of the APCs must have these costimulators; if this is done and the costimulators are bound, then we see that the T cell will produce IL-2 which will bind to IL-2 receptor and activate the T cell to proliferate and produce more cells
If we don’t have costimulators, like CTLA-4 binding to B7 = cannot transmit a signal to the T cell to make IL-2… this means no stimulation so the cell will most likely die via apoptosis