Immuno Test 1

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protection, innocuous substance, inury, and immunologic tolerance come about because of....

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Recognition of foreign substances

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2 functions of immune system

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recognition of foreign substances and surveillance

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vaccination

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innoculated material is not virulent human pathogen

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Cellular Theory of Immunity

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Metchinoff; dependent on phagocytic cells

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Humoral THeory of Immunity

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Erhlich; dependent on substances in the cell-free portion of the blood

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4 charac of innate immunity

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constitutive, rapid, nonspecific, lack of memory

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innate: external defenses

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- prevent penetration
1. intact skin/mucous membranes; tears
2. respiratory tract
3. alimentaty tract
4. urogenital tract
5. normal intestinal flora

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innate: internal defenses

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- once a pathogen has entered
1. chemical barrier (incr in temp that drives malaise)
2. natural killer cells (dont need Ag exposure)
3. interferon (cytokines) (alpha and beta; dont let replication happen)
4. alternative complement pathway
5. detection of pathogens
6. phagocytes
7. inflammation

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PAMPS (pathogen-associated molecular pattern) / pattern recognition sequence

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biologic patterns unique to and needed for the survival of microorgs but arent found on mammalian cells
-encoded into DNA
-body can recognize anything that displays these patterns

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pattern-recognition receptors

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recognize PAMPS;
-scavenger, LPS, nucelotide-bind oligomerization domian (NOD), TLRs

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T cells need what to become activated:

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1. binding of foreign antigens
2. binding of costimulators (expressed on innate immune system cells with PAMPS)

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inflammation

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increases vasoldillation,
increases capillary permeability,
increases cytokine production,
increases influx of cells with more phagocytosis,
which leads to Acute Phase Response

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innate immunity binds what to what?

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peptidoglycan binds to TLR2

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adaptive immunity - basic

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-surveillance mech.
-recognizes foreign substances (Ag)
-selectively eliminates them
- leukocytes
-

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charac of adaptive

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1. inducible - needs to be turned on
2.specific - clonal selection
3. memory - effector and central memory cells
4. diversity
5. knows self from nonself
6. self-limiting

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effector memory cells

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secrete or migrate to inflamed peripheral tisses and display immediate effector function

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central memory cells

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stored in lymphnodes/spleen for memory

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humoral immunity

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mediated by serum proteins = antibodies
-protection against extracellular bacteria, exotoxins, and viruses
- derived from daughter B cells = plasma cells

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cell-mediated immunity (CMI)

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mediated by thymus-derived lymphs (Tcells)
-protection against viruses in intracellular phase, tumor cells
- imp in organ transplant rejection

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first 2 steps of response

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1. antigen recognition
-cognitive= touching, interacting with Ag
-activation
2. Ag elimination
- effector phase= lymphocyte proliferation and differentiation/synthesis of new proteins and memory cells

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selective theories of antibody formation

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cells that possess receptors for an antigen preexist before exposure to that Ag. it selects cells with the right receptors and causes their proliferation/differ.

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side-chain hypothesis

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a pop of cells existed with side-chains on the surface (antibodies). when Ag enters, it combines with side-chain. side-chain complex gets released, and the original side-chains are replaced

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instructive theories

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Ags act as a template around which antibodies are formed
WRONG

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watson and crick

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dna structure

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clonal selection theory

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Burnet- develop lots ot B-cell precursors in early development. each one is only for ONE Ag. stocks are taken of self-Ag, forbidden clones are destroyed. clonal expansion occurs

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NK Cells

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cytotoxic cell of innate immunity
-react to any target, tumor cell or viral cell

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Dendritic cells (DCs)

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controller cells of immune system
-myeloid derived, found in all tissues

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cells involved in inflammatory response

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monocytes
-neutrophils
-eosinphils
-basophils and mast cells

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why do stem cells proliferate?

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1. to renew itself
2. to give rise to new progeny that can differentiate into specialized cells

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what are the 2 ways that stem cells can differentiate?

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1. lymphoid pathway
2. myeloid

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5 cells involved in immune response

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1. T cells
2. B cells
3. phagocytic/Macrophages
4. NK cells
5. dendritic cells

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lymphocytes

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have receptors to bind Ag
-B-immunoglobulins = humoral
-T-TCRs=CMI

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B lymphocytes

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-only cells in body that can differentiate into plasma cells that produce antibodies
-responsible for humoral immun
-need help from Th to make antib's
-Ag specific
-glycoproteins
-immunoglobs (ab's)=receptors Ag
-Membrane Ig = Ag-speci receptor
-mature b cells = IgM, IgD
- express Fc and C receptors
-APC= Ag presenting cells
-MCH I and II

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T lymphocytes

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-from Tcell committed stem cells in bone marrow
- mature in thymus
-TCR specificity is set at double negative stage
-cant express cd3 and cd4 or cd8 at the same time
- most Th=cd4, Tc=cd8

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Th - helper T cells

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initiate and enhance an immune response

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Tc - Cytotoxic T cells

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cells that destroy foreign allografts, cancer cells, and virally infected cells

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T cell functions

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1. delayed-type hypersensitivity
2. graft-vs-host reaction
3. allograft rejection
4. immunity against tumors
5. immunity against viral infections
6. contact sensitivity
7. immunity against intracellular pathogenic parasites
8. control immune responses

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Macrophages

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1. mononuclear cells
2. possess peroxidase and esterase activity
3.have specific surface receptors for antibody
4. exhibit phagocytic pinocytic abilities
5. can be stimulated into a state of activation
6. possess a caried and prlific secretory ability

-not clonally restricted or ag-specific

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Dendritic Cells

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-possess and present Ag to Th
-can induce primary immuno response
-immatures= highly phagocytic
-mature=no phago and no Ag interaction
-migrate to lymph or bloodand become mature, where they present the Ag to Th
-come from hematopoietic cells
- control 3 Rs - repetoire, recognition, response

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circulating dendritic cells

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in blood and lymph

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interdigitating dendritic cells

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in T-cell areas of 2ary lymphoid tissue then medulla

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interstitial dendritic cells

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more organs

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langerhans; cells

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in epidermis and mucous membrane
-interstitial

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follicular dendritic cell

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in B-cell rich follicles of lymph nodes
-dont act as APCs
-low levels of membrane receptors

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NK cells

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-mediators of innate immunity
-discriminate between self and nonself
-large granular lymphocytes
-Fc receptor bearing cytotoxic cells
-NOT MHC restricted
-can secrete cytokines
-dont express antibody receptors or TCRs

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primary lymphoid organs

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1. bone marrow
2. thymus

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bone marrow

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- source of all immune cells
- site of B-cell development in adults
- reticular tissue and blood vessels

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thymus

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-development of T cells
-important organ in immunogenesis
-bilobed, encapsulated
- cells move from cortex to medulla

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secondary lymphoid organs

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1. lymph nodes
2. spleen

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lymph nodes

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2 functions: filtration and recirculation of ag-stimulated lymphocytes
3 regions:
- outer cortex: B-cell nodules called follicles
- paracortex: T-cell area
- medulla: B cells, plasma cells, reticular cells, dendritic, and macrophages

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spleen

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-collects dead or dying cells
- removes worn-out red blood cells
-filters antigen from blood
-generation of mainly humoral immunity to foreign Ags

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where do lymphoid cells come from?

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common ancestor called the pluripotent hematopoietic stem cell

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what does the stem cell differentiate into?

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actively metabolizing progenitor cell

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Hematopoietic Pathways

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-origin of immune cells
-Ag-independent activity

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common myeloid progenitor cell

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leads to non-specific cells (interstitial cells, monocytes, macrophages, etc)

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common lymphoid progenitor

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can lead to specific or non-specific

leads to T cells and B cells

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can T cells bind directly to their TCR?

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no, they must first be cut into peptides and processed and bound to (presented on) MHC molecules

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who do macrophages and dendritic cells present antigen to?

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T-cells, NOT b-cells

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germinal center

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where final steps of maturation occur in lymph node

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primary follicle

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cells that react with Ag undergo proliferation and differentiation here

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antigens def

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substances that when introduced into verts induce the formation of antibodies that react specifically with them.

most common = proteins

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immunogenicity

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ability of a substance to induce or elicit humoral or cell mediated immunity.

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antigenicity

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the ability of a substance to react or bind with the specific antibodies it induces

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*** is an immunogen an antigen and/or an antigen an immunogen?

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an immunogen is an Ag, but not the other way around

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antigens - charact

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1. large molecular size
2. chemical complexity
3. degradability
4. foreignness

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antigenic determinants/epitopes

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immunologically active portions of the antigen molecule
- reactive sites of an antigen
-come in direct contact with combining sites of Abs

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haptens

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-not immunogenic in themselves
-can react with preformed antibodies of the proper specificity
-gain adaptive immunity by coupling haptens with a carrier molecule
-chemicals that are functionally equivalent to anitgenic determinants

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how are haptens recognized?

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their chemical structure
- the Ab reacts with homologous hapten
- nature of chemical group
- electrical charge
-shape (position, size, stereoisomers)

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where are the Ag determinants of a macromolecule?

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at its surface.
- they induce adaptive immunityand the Abs react with them

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epitopes of myoglobin

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sequential/continuous: linear, size, surface, and unique
-minority of epitopes recognized by antibody but the MAJOR epitopes recognized by T cells

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epitopes of hen egg white lysozyme

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discontinuous/nonsequential: conformational or assembled topographic
- bcells

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where are epitopes located?

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in flexible regions of immunogen

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antibody - definition

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glycoproteins found in the serum and other body fluids of verts that react specifically with the Ag that induced their formation
-family of immunoglobulins

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family of antibody?

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Ig superfamily

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pathogenic Igs (myeloma proteins)

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characteristic structure of Abs but come from a disease state instead of a challenge with an immunogen

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Ig structure

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1. versatility in Ag binding
2. Ab specificity
3. Ab effector functions

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What type of globulins are Abs?

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Gamme-globulins

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Gamma-globulins

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any molecule that migrates in the gamma-glob peak on electrophoresis. includes most antibodies.

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immunoglobulins

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family of molecules with similar structures and physical properties. have homologous aa's and similar domain structures and quaternary structures

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antibody

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molecule in the Ig family.
-has binding specificity for a particular Ag.
-All Abs are Igs, not all Abs are gammas

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Fab fragments

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fragments bind antigenic dexterminants = antigenic binding (ab)
- dont show precip or agglutination and will not fix complement

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Fc fragments

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fragments dont combine with Ag and crystallize upon cold storage

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F(ab')2

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large fragment that contains both ag-binding sites of IgG and can also be treated with reducing agents to yield 2 Fab-like fragments

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V region

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composed of hypervariable (complementarity-determining regions CDRs) separated by less variable regions called framework regions
-CDRs contain aa's that line the Ag-binding cleft of the Ab molecule

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CL

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disulfide bond, Bstrands

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VL

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CDR, NH2