Humoral Immune Response

Antibody-mediated Immunity

-Globulin proteins -Blood contains 3 types: alpha, beta, gamma (antibodies) -Classes: IgG, IgM, IgA, IgD, IgE

Alternative Pathway

Activated by presence of bacterial cell wall structures, fungi structures, viral envelopes

Lectin Pathway

Mannan-binding lectin or mannose binding protein binds to micobes bearing mannan (polymer composed of mannose) Useful in early infection

Humoral

non-cellular reponse

IFN's help protect

non-infected cells from viruses

Interleukin 6

(IL-6) is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine -secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other tissue damage leading to inflammation. IL-6 also plays a role in fighting infection,

Interleukin-10 (IL-10),

- also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine -IL-10 is a cytokine with pleiotropic effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production.

Function of Antibody-mediated Immunity

- neutralize pathogens -opsonize microbes -activate complement -prevent microbial attachment

Classic Pathway

-Activated by antigen-antibody complexes -Antibodies involved: IgM, IgG

Complement System

-Approximately 20 proteins (C1, C2, etc.) -Found in serum as zymogens -Produced mainly by the liver (also monocytes, macrophages, etc.) -Function: to "complement" the effects of other components of the immune response

How are antibodies produced?

-B-lymphocytes, via clonal selection -The antigen "selects" B-cell that has capacity to make antibodies for this antigen -B-cell becomes plasma cell, synthesizes the immunoglobulin

Significant Complement Proteins

-C3a-most potent anaphylatoxin -C3b-enahncement of antibody production potent opsonin -C5a-adhesion of neutrophils

Interferons

-Cytokine family -Derived from a natural antiviral factor -Composed of glycoproteins that exhibit species-specific antiviral activity -Human interferons are classified as alpha, beta, gamma -DRUG MOA: mediators of immune response Synthase -interferons are very specific to us -use Ecoli to produce interferons Usually gamma interferon that's use a lot in treapetuic ways

Structure of Antibodies

-Glycoproteins -Light and heavy chain -H and L chains -Variable region-antigen binding -Constant region-other biological functions

Molecular Structure of Antibodies

-Hypervariable regions on heavy and light chain form antigen binding site AKA fragment antigen binding domain Fab -Fragment crystallizable AKA Fc composed of two constant domains -Varaible regions: at the y bridging point -Know the constant and heavy and light

effects of complement system

-Lysis of pathogens -Generation of mediators (C3a, C5a) for chemotaxis -Opsonization

IgG

-Major immunoglobulin (75% in serum) -Monomer -4 subclasses -Responsible for SECONDARY response (against bacteria and viruses) -FUNCTION: Crosses PLACENTA (most abundant in newborns) Activates complement system Opsonization of pathogens Neutralization of pathogens proinflammatory, antinflammatory

Humoral Immune Response

-Mediated by soluble pattern recognition molecules -Examples: antibodies, interferon, complement system, cytokines, other antimicrobial peptides -Secreted by liver, B-lymphocytes, etc. -Elements of INNATE and ADAPTIVE immune response

IgE

-Mediates immediate (anaphylactic) hypersensitivity reactions -Management of parasitic infections -Causes release of allergic reaction mediators from basophils and mast cells

Complement Activation

-Parallel but independent pathways of activation -Highly regulated process -Generates a cascade of production of proteolytic enzymes -B-lymphocytes, neutrophils, macrophages, etc. all express complement receptors (CR) which recognize opsonizing components of complement

IgA

-Present in secretions (prevents microbial attachment) -Usually dimer structure -FUNCTION: prevents attachment of pathogens to mucous membranes -Tears, saliva, Find in nose, breathing passages

IgD

-Present on the surface of many B lymphocytes -Small amount found in serum -Unknown function...

Antibody Response

-Primary and Secondary response

IgM

-Produced as PRIMARY response to antigen Pentamer -Antigen receptor on surface of B-cells (antigen binding receptor) -Complement activation

Cytokine Functions

-Proinflammatory effect: (chemokines) 1) IL-1 2) IL-6 3) TNF alpha -T-cell growth factor : IL-2 -Antinflammatory effect: 1) IL-10 2) Transforming growth factor beta 3) Stimulation of immune response: interferons

TNF-alpha

-a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. It is produced chiefly by activated macrophages (M1), although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells and neurons. - primary role of TNF is in the regulation of immune cells. TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 production. D

Primary Response

-first time exposure -longer lag period -IgM, IgG

Interferons have

-funky side effects -flu like symptoms

Secondary Response

-rapid antibody response -higher levels -IgG

The lectin binding complement activation pathway depends on the presence of IgM t/f

False. -IgM is used in the Classical pathway

This is the "first responder" (primary response) antibody to appear. Its presence indicates active infection. It can activate complement.

IgM

Interleukin 1

a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

Transforming growth factor beta

a protein that controls proliferation, cellular differentiation, and other functions in most cells. I

IFN's are produced

by virus infected cells

Interleukin 2:

interleukin, a type of cytokine signaling molecule in the immune system. It is a protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. -play stimulating CD 8