Immunology Midterm 2

Cytokine definition

Small soluble proteins that regulate the immune system’s innate and adaptive responses to infection (communication molecules)

Cytokines are induced by

Bacterial lipopolysaccharides, flagellin, and other microbial receptors, signaling through B and T cells

Cytokine production begins when

Ligation of cell adhesions or recognition of foreign antigens/molecular patterns

Cytokine function

Regulation of growth, differentiation, and gene expression of different cell types

Autocrine definition

Self activation (affecting same cell if was secreted from)

Paracrine definition

Stimulating a nearby cell

Endocrine (systemic) definition

Stimulating a distant cell

Major cytokine families

Tumor necrosis factor (TNF), interferons (IFN), chemokines, transforming growth factors (TGF), and colony-stimulating factors (CSF)

Major colony stimulating factors

IL-3, erythropoietin, granulocyte, macrophage, granulocyte macrophage

Three criteria to classify interleukins

Must have had their genes cloned, inducible in leukocytes, biological activities in inflammatory processes must be cataloged

Pleiotropism definition

Cytokines doing different things to different cells (code switching)

Redundancy definition

Multiple cytokines perform the same function

Synergy definition

Cytokines working together to induce amplified effects

Antagonism definition

Cytokines counteracting the effects of other cytokines

IL-4 function

Take an activated CD4+ cell and tell it to produce B cells or TH2 differentiation (pleiotropism)

Interferons that directly interfere with viral replication and cell division

IFN-alpha and IFN-beta

IFN- alpha and IFN-beta are examples of

Type I interferons

Type I IFN functions

Activates NK cells, enhances the expression of MHC class I proteins, active against certain malignancies and inflammatory processes

Cytokines involved in the innate immunity function

sPhysical symptoms of inflammation like swelling, fever, pain, and cellular infiltrates into damaged tissue

Main function of innate immune response

Recruit effector cells to the area

Cytokines involved in triggering immune response

Tumor necrosis factor-alpha, interleukin-1, chemokines, and interferon alpha and beta

TNF-alpha is activated by

Monocytes and macrophages

TNF-alpha function

Activate T cells and causes vasodilation and increased vasopermeability

How does TNF-alpha activate T cells?

Induce expression of MHC class II, vascular adhesion molecules, and chemokines

Trigger for TNF-alpha production

Lipopolysaccharide

IL-1alpha and IL-1beta are produced by

Monos and macs

Proinflammatory cytokines

IL-1alpha and IL-1beta

IL-1beta function

Systemic activation including fever, activation of phagocytes, and production of acute-phase proteins

Interleukin involved in Chron’s Disease

TNF-alpha

Interleukins involved in rheumatoid arthritis (RA)

TNF-alpha and IL-1

Patients with sepsis have what inflammatory cytokine in their blood?

Pro-inflammatory (bacterial products cause inflammation)

Chemokine function

Direct immune cells to places of interest (enhance motility and promote migration of WBCs towards the source of chemokine)

Chemotaxis

Chemokines helping WBC go towards source of cytokine

IL-1 and TNF-alpha cause endothelial cells to

Express cellular adhesion molecules (CAM) and selectins

All chemokines have this

Two conserved cysteines

CC-

Two cysteines next to each other

CXC-

Some amino acid in middle

CX3C-

3 amino acids between them

IL-1 triggers secretion of

IL-6

IL-6 is produced by

Lymphoid and non-lymphoid cells

IL-6 stimulates

B cells to proliferate and differentiate into plasma cells and induces CD4+ T cells to produce greater quantities of both pro- and anti-inflammatory cytokines

IL-2 is known as

T-cell growth factor

IL-2 function

Drives growth and differentiation of both T and V cells and induces lytic activity in NK cells

IL-2 function ALONE

Activate proliferation of Th2 cells and helps to generate IgG1- and IgE-producing cell s

Th1 cells and function

IFN-gamma and TNF-beta; protect cells against intracellular pathogens

Th2 functions

Produce interleukins (IL-4, 5, 10, 13) and help B cells produce antibody against extracellular pathogens

IFN-gamma function

Affects RNA expression of 200 genes that regulate and activate CD4+ Th1 cells, CD8+, NK cells, bactericidal activities, IL-12R and IL-18R

Th2 cytokine function

Antibody-mediated immunity (B cell activation and antibody class switching)

Key cytokine involved in regulating Th2 immune activities

IL-4

What two interleukins are involved in deactivating macrophages?

IL-4 and IL-10

Main interleukins involved in Th1 reactions

IL-2, IFN-gamma, TNF-beta, GM-CSF, IL-3

Main interleukins involves in Th2 reactions

GM-CSF, IL-3, IL-4, IL-5, IL-10, and IL-13

Interleukins involved in suppressing immune responses

IL-10 and TGF-beta

Plasma complement proteins are synthesized in what organ

Liver

What complement protein is not made by the liver and where is it made

C1 is produced by intestinal epithelial cells

Where is Factor D made

Adipose tissue

Early complement components

C1, C2, C3, C4

Classical pathway activation

Antigen-antibody combination

Alternative (secondary) pathway activation

Antibody-independent, binding of complement proteins to microbial cell surface

Complement system role

Inflammatory response

Function of complement

Lysis, opsonization, activation of inflammatory response, clearance of immune complexes

Anaphylatoxin definition

Small peptide that causes increased vascular permeability, contraction of smooth muscle, and release histamine from basophils and mast cells

Complement split product categories

Anaphylatoxin, chemotaxins, opsonins

Examples of anaphylatoxins

C3a, C4a, C5a

C5a other function (anaphylatoxin)

Chemotaxin for phagocytic molecules

These facilitate phagocytosis and clearance of foreign substances

C4b, C3b, iC3b

What are the C5 convertases

C3bBb3b and C4b2a3b

C5a function

Anaphylatoxin, but more potent (more specific)

C5b function

Binds to cell surface (like C3b) and permits binding of C6, C7, and C8

C6, C7, C8 function

Anchor for C9 to form membrane attack complex

Classical pathway is initiated by

Binding of antibody

C1q function

Links antibody to IgG (two or more) or IgM (pentameric)

First step of Classical pathway

C1q binds antigen-bound antibody to surface of antigen. Two C1r activate C1s to form enzymatic ring

Second step of Classical pathway

C1s cleaves C2 and C4. C4b and C2a bind to form C3 convertase

What step is this? C1s cleaves C2 and C4. C4b and C2a bind to form C3 convertase

Second step of classical pathway

What step is this? C1q binds antigen-bound antibody to surface of antigen. Two C1r activate C1s to form enzymatic ring

First step of classical pathway

Third step of Classical pathway

C3 convertase hydrolyzes many C3 molecules. Some C3b bind to C3 convertase to form C5 convertase

What step is this? C3 convertase hydrolyzes many C3 molecules. Some C3b bind to C3 convertase to form C5 convertase

Third step of classical pathway

Fourth step of classical pathway

C3b component of C5 convertase binds C5, C4b2a then cleaves C5

What step is this? C3b component of C5 convertase binds C5, C4b2a then cleaves C5

Fourth step of classical pathway

Fifth step of classical pathway

C5b binds C6 which initiates the formation of the membrane attack complex

What step is this? C5b binds C6 which initiates the formation of the membrane attack complex

Fifth step of the classical pathway

Unique factors involved in alternative pathway

Factor B and Factor D

C3bBb complex name

Alternative pathway C3 convertase

First step of alternative pathway

C3 hydrolyzes spontaneously and C3b fragment binds to foreign surface

What step is this? C3 hydrolyzes spontaneously and C3b fragment binds to foreign surface

First step of alternative pathway

Second step of alternative pathway

Factor B binds C3a, exposes the site on C3a that is acted on by Factor D. Cleavage generates C3bBb, which is C3 convertase

What step is this? Factor B binds C3a, exposes the site on C3a that is acted on by Factor D. Cleavage generates C3bBb, which is C3 convertase

Second step of alternative pathway

Third step of alternative pathway

Properdin binds to C3 convertase to stabilize it

What step is this? Properdin binds to C3 convertase to stabilize it

Third step of alternative pathway

Fourth step of alternative pathway

Convertase generates C3b; some binds to C3 convertase which activates C5"‘ convertase. C5b binds to antigenic surface

What step is this? Convertase generates C3b; some binds to C3 convertase which activates C5"‘ convertase. C5b binds to antigenic surface

Fourth step of alternative pathway

Difference between classical and lectin pathway

C1q is substituted by mannose binding lectin (MBL) and C1r and C1s are substituted by MBL-associated serine proteases

MASP-2 role

Cleaving C4 and C2

Decay-accelerating factor (DAF or CD55) role

Accelerates dissociation of C4b2a and C3bBb

Type I Hypersensitivity Immune Reaction

IgE

Type II & III Hypersensitivity Immune Reactants

IgG/IgM

Type IV Hypersensitivity Immune Reactants

T-cells

Type I & III hypersensitivity antigen that causes reaction

Soluble molecule

Type II hypersensitivity antigen

Cell-associated molecule