Immuno Final

“Fixed” defenses

“Fixed” defenses

skin, hair, and nails

what do fixed defenses do?

prevent most pathogens from gaining access to the cells and tissues of the body

Commensal microbes

Community of microbial species that inhabits a particular niche in the human body

how do commensal microbes enhance human nutrition

processing digested food and prevent colonization of disease-causing microorganisms-skin, mouth, gut, or vagina

innate immunity

a genetically programmed set of responses that can be mobilized immediately an infection occurs

purpose of complement?

help the effector cells by marking pathogens with molecular flags but also attack pathogens in their own right

cells of innate immune response

cytokines

what do cytokines do

interact with other cells to trigger the innate immune response

inflammation

heat, pain, redness, and swelling

adaptive immunity

organized around an ongoing infection and adapts to the nuances of the infecting pathogen

cells of adaptive immune response

lymphocytes

principle characteristics of innate immunity

• rapid response

• fixed

• limited specificities

• constant during response

principle characteristics of adaptive immunity

• love response

• variable

• numerous specificities

• improve during response

hematopoiesis

blood cell development and differentiations

neutralization

binding tightly to a site on a pathogen so as to inhibit pathogen growth, replication, or interaction with human cells

opsonization

antibodies coat the entire surface of a pathogen to be phagocytized

primary lymphoid tissues

bone marrow & thymus

secondary lymphoid tissues

lymph nodes, adenoid, tonsil, spleen, Peyer’s patch and appendix

B and T lymphocytes originate in

bone marrow and thymus (primary)

where mature lymphocytes become stimulated to respond to invading pathogens

lymph nodes, adenoid, tonsil, spleen, Peyer’s patch and appendix (secondary)

First line of cellular defense against invading pathogens

Innate immune system

complement system is used to…

coat the surface of bacteria and extracellular virus particles to be phagocytized

Complement component C3

• activated C3 is cleaved into C3a and C3b

• C3b attaches to surface of pathogen

• tags it for destruction by phagocytes

• C3a fragment acts as a chemoattractant to recruit effector cells from the blood to the infection

pathway that works at the start of infection

alternative pathway of complement activation

lectin pathway of complement activation is induced by

infection and requires some time before it gains strength

lectin pathway of complement activation is also a part of

innate immunity

classical pathway of complement activation is a part of

both innate and adaptive immunity

what does the classical pathway of complement activation require

the binding of either antibody or an innate immune-system protein called C-reactive protein to the pathogen’s surface

Importance of the nucleophilic attack on the thioester bond

thioester bonds of the vast majority of C3b molecules are attacked by water, and so most C3b remains in solutions in an inactive hydrolyzed form

Alternative Pathway

the first response of the innate immune system, especially to bacterial infection

C3 converses

Proteases that cleave and activate C3

iC3 binds to the inactive complement

factor B

When iC3 binds to factor B it is susceptible to cleavage by

factor D

Which proteins make up the pore complex?

C6, C7,C8,C9

what is the membrane attack complex

Assembles to generate a pore in the lipid bilayer membrane

what do soluble proteins S protein, clusterin, and factor J prevent?

soluble complex of C5b with C6 and C7 from associating with cell membranes

the human cell surface, the proteins homologous restriction factor (HRF) and CD59 (also called protec- tin) prevent

the recruitment of C9 by the complex of C5b, C6, C7, and C8

Classical pathway includes

• C3 -convertase; C4b and C2b

• C5 -convertase complex

• Membrane Attack Complex

Role of defensins

Penetrate microbial membranes and disrupt their integrity the mechanism by which they destroy bacteria, fungi, and enveloped viruses

Time frame for the induced innate immune response

4 hours to 4 days

Immediate Innate Immune Response

0-4hrs

Induced Innate Immune Response

4 hours-4 days

Adaptive Immune Response

4 days-until defeat pathogen

why are receptors crucial in the fight against infection?

on the surface of a macrophage to activate an immune response

Mannose receptor is a

cell-surface receptor and plasma protein that recognize carbohydrates

C-type lectin is a

carbohydrate-recognition domain in which a calcium ion coordinates the interaction of the carbohydrate ligand with the receptor

Scavenger receptors

• scavenge damaged molecules of low-density lipoprotein from blood

• recognize assortment of negatively charged microbial ligands

Toll-like receptors

recognize a variety of microbial ligands and are expressed by different types of innate immune cell

NOD-like receptors

recognize components of bacterial cell walls

Prominent cytokines

IL-1β, IL-6, CXCL8, IL-12, TNF-α

why are the prominent cytokines known to be inflammatory cytokines?

their combined effect is to create a state of inflammation in infected tissue

What is the CARD domain?

Caspase-recruitment domain (CARD) is on the amino-terminal side of the NOD domain and is used to recruit proteases called caspases

Inflammasomes amplify the innate immune response by

increasing the production of IL-1β

how is NLRP3 activated?

activated by oligomerization

function of neutrophils

Short-lived dedicated killers that circulate in the blood, awaiting a call from a macrophage to enter infected tissue

function of adhesion molecules

Movement of leukocytes between blood and tissue are crucial to all aspects of the immune response

What is the purpose of the acute phase response?

Concentrations increase for some 30 plasma proteins involved in the response to infection.

* concentrations of some other plasma proteins go down, including albumin, the most abundant protein

What type of PRR is mannose binding lectin?

secreted

How are NK cells activated?

achieved by secretion of inflammatory cytokines that act mainly on resident macrophages and increase their capacity to secrete inflammatory cytokines and to phagocytize viral particles

Immunoglobulins

Antigen specific proteins produced by B lymphocyte

With what cells are immunoglobulins associated

activated B cells (IgM & IgD) and plasma cells

Recombination begins when

an endonuclease makes a double-strand break in a chromosome

What happens to gene segment (VDJ)

rearranged to form the coding sequence for the receptor variable region

function of immunoglobulins?

Essential in protecting against bacteria, viruses, and fungi

With what cells are antigens associated

Antigen specific proteins produced by plasma cells

antibody structure

glycoproteins composed of Polypeptide chains and carbohydrates

• Monomeric structure

• Polypeptide chains

• 2 identical heavy chains, 2 identical light chains

• Polypeptide chains joined by disulfide bonds and Carbohydrates

heavy chain

allow for antigen-specific binding and subsequent activation of B lymphocytes

light chain

ensure the expression and secretion of functional antibodies and contribute to antigen binding by increasing the variability of the antibodies

where does Proteolytic cleavage usually happen?

rough endoplasmic reticulum

enzymes involved in proteolytic cleavage

peptidases, proteases or proteolytic cleavage enzymes

What determines the antibody class type?

• Length of C region

• location of disulfide bonds

• hinge region & distribution of carbohydrates

(Classes have different effector functions)

What are CDRs (hypervariable regions)

domains on immunoglobin heavy and light chains variable regions that are in direct contact with antigen and are frequently mutated to allow diverse antigenic specifities to be recognized

An antigen-binding site is formed from

the hypervariable regions of a heavy-chain V domain and a light-chain V domain

Hypervariable regions also called

Complementarity-determining regions (CDR)

how many hypervariable regions in each V domain?

three

How are monoclonal antibodies produced?

Scientist expose a specific type of cell from the immune system to a particular viral protein

• produced using hybridoma cell lines (derived from single antibody producing cell fused with myeloma cell)

Germline mutations

changes to your DNA that you inherit from the egg and sperm cells during conception

Somatic mutations

changes to your DNA that happen after conception to cells other than the egg and sperm

Somatic Recombination is performed by

enzymes with cut and rejoin DNA

What are Recombination signal sequences?

Recognition sites for enzymes

Recombination occurs between

• 9/12/7

• 9/23/7

nF-kappa β activation pathway

is a family of highly conserved transcription factors that regulate many important cellular behaviors, in particular, inflammatory responses, cellular growth and apoptosis.

where are toll-like receptors located?

endosome

Where are NOD-like receptors located?

cytosol

NOD-like receptors ligands

NOD1 and NOD2

result of NOD-like receptors activation?

inflammasomes

how is NLRP3 inflammasome activated?

by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage

Where are RIG-I receptors (RLRs) located?

cytosol

RIG-I receptors (RLRs) ligands

type I interferon (IFN-I) and inflammatory cytokines

result of RIG-I receptors (RLRs) activation

triggers an immune response to RNA viruses

What is released from the liver during the acute phase response?

C- Reactive protein

what two responses for NK cells mediate

• inflammatory

• antiviral

enzymes involved in proteolytic cleavage

peptidases, proteases or proteolytic cleavage enzymes

Why is RAG important?

encode parts of a protein complex that plays important roles in the rearrangement and recombination of the genes encoding immunoglobulin and T cell receptor molecules

junctional diversity

different variable gene segments (those segments involved in antigen recognition) of TCRs and immunoglobulins are rearranged and unused segments removed

result of junctional diversity

diverse array of antibodies with unique idiotypes able to recognize foreign proteins

Somatic Hypermutation

Point mutations accumulate in the antibody V-regions of both the heavy and light chains

outcome of somatic hypermutation

cells that emerge will have a stronger and more specific response to the antigen

Affinity maturation

the process by which antibodies gain increased affinity, avidity, and anti-pathogen activity

class switching

Process by which B cell changes class of Ig produced while preserving antigenic

specificity