immune system

define immune system

all tissues, cells, secreted molecules, and messengers are involved in sensing ‘self’ from ‘non-self’

describe the goals of the immune system

1. protection against infection from pathogens

2. isolate and eliminate pathogens

3. destroy cancer cells

define immunology

study of how the body defend itself against infection from different microorganisms

define leukocyte

white blood cells originating from the meatopoietic stem cell of the bone marrow

what are the primary lymphoid organs?

bone marrow and thymus

what do primary lymphoid organs generate?

all circulating leokocytes

what are the secondary lymphoid tissues?

lymph nodes, spleen, tonsil, GI tract, respiratory tract, urogenital tract

secondary lymphoid tissues are primary sites for what?

primary sites for generation of adaptive immune responses

what can develop at sites of strong immune responses?

ectopic, or tertiary, lymphoid tissues

why is the presence of Pathogen-Associated Molecular Patterns (PAMPs) important?

distinguishes foreign invaders from host cells

what do Pattern Recognition Receptors (PRRs) do?

recognize PAMPs

Toll-Like Receptors (TLR)

activated by many different pathogens like bacteria, viruses, fungi

NOD-Like Receptors (NLRs)

bind bacterial peptides

RIG-Like Receptors (RLRs)

recognize viruses

C-type Lectin Receptors (CLRs)

recognize fungi

what are the subtypes of C-type Lectin Receptors?

• macrophage mannose receptor (MR)

• dendritic cell-associated C-type lectin (dectin)

define antigen

any molecule that can stimulate an immune response

define immune surveillance

recognition of cancer cells and in some cases elimination of cancerous cells

define immune tolerance

the failure to respond to an antigen

define antibody (immunoglobulin Ig)

membrane-bound or secrete molecule with characteristic Ig folds, variable region, and constant region

define neutrophil (Nø)

among first cells in innate response

define eosinophil

defense against parasite

define basophil

key role in parasite response and allergy response

define mast cell

release histamine; involved in stimulation of innate immunity and inflammation

define dendritic cell (DC)

phagocytosis of pathogen for destruction and presentationto T-cells

define monocyte

circulate in blood and transform into macrophage when entering tissues

define macrophage (Mø)

role in phagocytosis, secretion of cytokines during innate response

define t-cell

mediate cellular arm of adaptive immunity

define b-cell

mediate humoral arm of adaptive immunity

define natural killer cell (NK)

mediate innate defense; killing cancer cells and virus-infected cells

define plasma cells

differentiate from B cells during immune responses; secretion of immunoglobulins

define Major Histocompatibility Complex (MHC)

a large group of genes on vertebrate DNA that code for cell surface proteins

what are MHC surface proteins essential for?

essential for function of the adaptive immune system

define Postive Selection

a process where developing B-cells and T-cells are presented with peptides residing on cells in the primary lymphoid tissue

what is required for positive selection?

that the developing B-cell or T-cell receptor binds with proteins

define thymocytes

developing T-cells

what must thymocytes do to survive?

must interact with MHC I or MHC II to receive a signal to survive, otherwise they die

what must be done to developing B-cells?

the pre B-receptor is tested for reactivity against its antigen

define negative selection

a process where developing B-cells and T-cels that strongly bind with self-antigens will die by apoptosis, which removes lymphocytes that may cause autoimmunity

what does naïve refer to?

to a mature lymphocyte that has not encountered an antigen

describe the development of t-cells in the thymus

• thymocytes from bone marrow migrate into the thymus for maturation

• T-cells undergo VDJ recombinationof the receptor gene for their TCR

• t-cells interact with MHC proteins on thymic epithelial cells, Møs, or DC to undergo negative and positive selection

• only about 4% pf thymocytes that enter the thymus are allowed to leave as “mature naïve” T-cells to circulate through lymphoid tissues

describe the development of B-cells in the bone marrow

• rearrange their BCR genes via VDKJ recombination

• immature b-cells leave the bone marrow

• circulate the blood and lymphoid tissue where they complete development to mature B-cells

what. happens to immature b-cells that are strongly reactive to self-antigens?

undergo one of the following: apoptosis, receptor editing, anergy, ignorance

where does VDJ recomb occur?

in the primary lymphoid organ

define VDJ recomb

the mechanism by which genetic recombination of gene segments results in a highly diverse repertoire of T-cell receptors and B-cell

describe the goal of VDJ recombination

produce novel antigen-binding regions in BCR (also Ig) and TCR

describe the 1st recombination event of a b-cell

• HEAVY CHAIN GENE

• there are several Variable, Diversity, and Joining segments, and a Constant region

1. the nucleotides between D and J segments are cleaved and D and J are ligated together

2. nucleotides between DJ segments and V segments are cleaved and DJ and V are ligated together

3. mRNA processing (splicing) joins the already combined VDJ segments and the constant region

describe the stages of maturation of a B-cell

stem cell —> progenitor B-cell —1st recomb event —>precursor B-cell —2nd recomb event —> immature B-cell —> naive B-cell —> mature B-cell

describe the 2nd recomb event

• LIGHT CHAIN GENE

• the pre-B cell matures into Immature B-cell

• the light chain gene goes through recomb (DOESNT HAVE D SEGMENT)

1. light chain region goes through recomb of V and J segments

2. mRNA splicing joins the VJ segment with the constant region

what is the result of the two recomb events in a B-cell

results in an immature B-cell that expresses only IgM that leaves the bone marrow and completes final development to mature B-cell in the periphery

what initiates Class Switch Recombination (CSR)?

by the Activation-Induced Deaminase enzyme

where is CSR initiated?

in naive B-cells upon activation by T-cells

define innate immunity

immediate available immune response

what is not done by innate immunity?

• does not recognize specific identity of pathogen

• does not lead to lasting immunity

define adaptive immunity

developed with exposure to pathogen; highly specific recognition of pathogen; often results in immunological memory

what type of Barriers are part of the adaptive, humoral immune response?

• skin and mucosa

• IgA in Mucosal membranes

what type of Cells are part of the adaptive, humoral immune response?

• B lymphocyte

• plasma cells secrete antibodies

what type of Circulating Molecules are part of the adaptive, humoral immune response?

• antibodies: Immunoglobulins IgG, IgM, IgE, IgA, IgD

what type of Soluble Mediators are part of the adaptive, humoral immune response?

cytokines from CD4+ cells

what type of Barriers are part of the adaptive, cell-mediated immune response?

skin and mucosa

what type of Cells are part of the adaptive, cell-mediated immune response?

CD8+ cells carry out cell mediated attack via secretion of lytic protein called perforin

what type of Soluble Mediators are part of the adaptive, cell-mediated immune response?

• cytokines from CD4+ cells

• perforin secretion from CD8+ cell in close contact with infected target cell

what type of Barriers are part of the innate immune response?

• skin and mucosal membranes

• secretion of antimicrobial chemicals

• mucus

• gastric acid

• presence of normal flora cough and sneeze reflexes

what type of Cells are part of the innate immune response?

• macrophages

• dendritic cells

• neutrophils

• eosinophils

• natural killer cells

what type of Circulating Molecules are part of the innate immune response?

complement protein

what type of Soluble Mediators are part of the innate immune response?

• cell-derived cytokines (TNF-alpha, IL-1, IL-6, INFs)

• secretion of eicosanoids, Membrane Attack Complex, opsonin, histamine, kinins

what four main task must be preformed by the immune system for the protection against pathogens

1. immunological recognition: detect pathogen; performed by cells of both innate and adaptive system

2. immune effector functions: activation of complement, secretion antibodies

3. Immune regulation: ability to self-regulate, failure leads to allergy or autoimmune disorders

4. Immunological memory: immediate and stronger immune response upon subsequent exposures

describe what occurs as a result of innate immunity

• mechanical and chemical defenses at body surface

• cytokine secretion: protein messengers that regulate innate and adaptive immune response

• complement pathway: extracellular elimination of pathogens

• phagocytosis: destroy pathogen and present it to immune cells

• inflammation: local response to destroy or inactivate pathogens

describe the body’s mechanical/chemical defense of innate immunity

• epithelial cells

• acid pH in stomach

• antimicrobial substances

  • lysozyme (tears) and phospholipase (saliva)

  • alpha-defensins: cells in the small intestines

  • beta-defensins: epithelial cells and cells in urogenital tract

  • Reactive Oxygen Species (ROS): Mø and Nø

describe the different cytokines that act during innate immunity

• IL-2: secreted from most cells of the immune system

  • stimulates proliferation of CD4 & 8, NK cells, and B-cells

• TNF-alpha, IL-1, IL-6: secreted from antigen presenting cells

  • stimulates expression of IL-2 receptor, induces fever, stimulate systemic responses to inflammation, infection, and injury

• IFN-type I: secreted from most cells

  • promote apoptosis of virally infected cells, induce genes that restrict viral replication, and stimulates function T-cells, B-cells, NK cells, DC, Mø

• IFN-type II: secreted primarily from NK cells during innate immune response

  • promotes antiviral immunity through its regulation of innate immune responses, activates the adaptive immune response

define antigen

any molecule that can bind an antibody

Antigen-presenting Cell (APC)

any cell (MΦ, DC, B-cell) that can uptake an antigen, process it, and present it on its MHC molecule to T-cells

Apoptosis

programmed self-death that does not trigger an immune inflammatory response

B-Cell Receptor (BCR)

the receptor that is membrane-bound to B-cells that recognize antigens and can trigger signaling into the cell (like TCRs)

Chemokine

chemical messengers that instruct leukocytes directed migration to a certain area

Class Switch Recombination (CSR)

a somatic recombination event whereby isotype switching between antibodies occur

Clonal expansion

rapid proliferation and replication of a T-cell that generates many T-cells that are clones of each other

Combinatorial diversity

diversity of different Vs and Ds and Js in VDJ re-arrangement

Common Lymphoid Progenitor (CLP)

give rise to lymphoid-derived leukocytes Common Myeloid Progenitor (CMP)

Co-stimulation

molecular interaction between leukocytes that synergizes with MHC and TCR interaction to provide positive signals

Cytokine

chemical messengers that help exert immune response

Degranulation

release of stored cell granules by effector cell (mast, basophil)

Diapedesis

movement of leukocyte across endothelium, from the blood into the tissue

Epitope

the portion of an antigen that an antibody, BCR, or TCR recognizes

Fc Receptor (FcR)

a membrane-bound receptor that recognizes the Fc portion of an antibody

Hematopoietic Stem Cell (HSC)

a self-renewing and pluripotent stem cell that gives rise to all leukocytes

Isotype

the class of Ig with main differences in the constant region

Junctional diversity

random nucleotide inserted between Vs, Ds, and Js during VDJ re-arrangement to generate diversity

Lymphocyte

B and T-cells

Major Histocompatibility Complex (MHC)

Classic MHC molecules are involved in presenting peptide antigens to T-cells

MHC restriction

context by which a TCR will only recognize a specific peptide and MHC at the same time

Opsonization

a molecule that can bind and coat a pathogen surface for an immune response

Pathogen-associated Molecular Patterns

conserved pathogen motifs that can trigger innate immune response

Pattern Recognition Receptor (PRR)

conserved germ-line encoded receptors that recognize conserved pathogen motifs

Perforin

a molecule that inserts itself on the surface of targets to induce efflux of cytosolic contents and induce lysis of the target cell (creates a hole in infected cell and allows the entrance of granzymes)

Phagocytosis

ingestion of an organism (pathogen) or particle by MΦ, NΦ, and monocyte Plasma cell

Polygeny

related MHC expressed in 1 individual

Polymorphism

different alleles of a MHC between humans

Reactive Oxygen Species (ROS)

highly reactive anti-microbial oxygen radicals

Receptor Editing

rearrangement of the BCR during development to prevent self-reactive B-cells to leave the BM