immunology lecture 1

7/29/2019 immunology lecture 1

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I. Nomenclature: General properties and components of the Immune systemA. Immunity: resistance to infectious disease

1. Immune system: physiological function is to prevent infections and to eradicate establishedinfections

a. Immune system recognizes and responds to tissue grafts and newly introduced proteinsb. Defends against tumors

II. Innate and adaptive immunityA. Innate Immunity mediates initial protection against infections

1. Mechanism of innate immunitya.

Block entry of microbes: epithelial barriers and specialized cells and natural antibioticspresent in epithelia

b. Eliminate microbes: agents specifically recognize and react against microbes if microbeenter tissues,

i. Attacked by phagocytesii. Specialized lymphocytes- natural killer cells (NK cells)iii. Complement system plasma proteins

2. Innate immune response enhances adaptive immune responses3. Microbes have evolved to resist innate immunity

B. Adaptive immunity (specific or required immunity) develops more slowly and mediate the later, moreeffective defense against infections

1. Stimulated by microbes that invade tissues adapts to presence of microbial invaders2. Consists of lymphocytes and their products, such as antibodies

a.

Lymphocytes express receptors that specifically recognize antigens produced by microbes aswell as noninfectious material

3. Adaptive immune response triggered only if microbes or antigens pass through epithelial barriersand are delivered to lymphoid organs

a. Responses are specialized to combat different types of infections4. Adaptive IR use cells of innate to eliminate microbes

a. Antibodies of adaptive bind to microbes and coated microbes bind o and active phagocytes(innate), which ingest and destroy the microbes

III. Types of Adaptive immunity mediated by different cells and moleculesA. Humoral immunity provide defense against extracellular microbes

1. Mediated by antibodies produced by B lymphocytes2. Antibodies secreted into circulation/mucosal fluids neutralize and eliminate microbes and toxins

present outside of t cells in the blood and lumens of mucosal organs

3. Function: block infections and eliminate extracellular microbesa. Stop microbes present at mucosal surfaces and in the blood from gaining access to and

colonizing host cells and connective tissues

b. Prevent infections from ever getting established4. Antibodies can recognize many types of molecules (proteins, carbs, lipids)

B. Cell mediated immunity provide defense against intracellular microbes1. Mediated by T lymphocytes

a. Helper T lymphocytes activate macrophages to destroy phagocytosed microbes that wereingested by phagocytes into intracellular vesicles

b. Cytotoxic T lymphocytes- kill any host cells that are infectedC. Immunity may be induced by infection or vaccination (ACTIVE immunity) or conferred on a person by

transfer of antibodies or lymphocytes from actively immunized person (PASSIVE immunity)

1. Passive immunity useful for rapidly conferring immunity before individual can mount activeresponse, but does not induce long term resistance to infection

a. Ex newborns acquiring antibodies from milkIV. Properties of adaptive immune responses

A. Specificity and diversity - Specificity for many different antigens shows that collection of lymphocytespecificities is diverse

1. Specificity- ensures that distinct antigens elicit specific responsea. Each nave lymphocyte expressed receptor molecules of one specific and he specific to each

lymphocyte I different

b. Specificity of receptors determined by genetic mechanism that occurs during lymphocytedevelopment in bone marrow and thymus to generate different variants of genes encoding

recepotr molecules

2. Diversity- enables immune system to respond to large variety of antigens


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3. Clonal selection: Lymphocytes express clonally distributed receptors for antigens, meaning that totalpopulation of lymphocytes consists of many different closes and each clone expresses an antigen

recepotr different from the recepotr of the other clones.Upon binding antigen, lymphocyte

activated to divide and produce many identical progeny all of whose receptors bind the same antigen

a. Lymphocyte clones with diverse receptors arise in generative lymphoid organsb. Clones of mature lymphocytes specific for many antigens enter lymphoid tissuec. Antigen specific clones are activated by antigensd. Antigen specific immune response occur (induce production of antibodies based on which

antigen_

B.

Memory leads to enhanced (larger and more effective) response to repeated exposures to the same antigens1. Primary immune response response to the first exposure to antigena. Mediated by nave lymphocytes that seeing antigen for the first time

2. Secondary immune response more rapid and larger and better able to eliminate antigen thanprimary response

a. Due to activation of memory lymphocytes cells that were induced during the primaryimmune response

3. Memory allows immune system to combat persistent infections because each encounter withmicrobe generates more memory cells and activates previously generated memory cells

C. Other features of adaptive immunity1. Clonal expansion increases number of antigen specific lymphocytes to keep pace with microbes

a. When lymphocytes are activated by antigens, they undergo proliferation to generate clonalprogeny cells with same antigen specificity

2. Specialization generates response that are optimal for defense against different types of microbesa. Immune response are specialized - different response for different classes of microbes

3. Contraction and homeostasis allows immune system to respond to newly encountered antigensa. Immune responses are self limited and decline as infection is eliminated so the system can

return to a resting state

4. Nonreactivity to self prevents injury to host during responses to foreign antigensV. Cells of immune system

A. Lymphocytes only cells that produce specific receptors for antigens key mediators of adaptive immunity1. Different classes of lymphocytes recognize distinct antigens and differentiate into effector cells

whose function is to eliminate the antigens

a. B lymphocyte mediate humoral immunityi. Express membrane forms of antibodies that serve as receptors that recognize

antigens and initiate process of activation of the cells

ii. Soluble antigens and antigens on surface of microbes and other cells may bind to Blymph antigen receptors and elicit humoral response

b. T lymphocyte-cell mediated immunityi. Recognize peptide fragments of antigens bound to specialized peptide display

molecules called major histocompatibility molecules on the surface of specialized

antigen presenting cells (APCs)

ii. CD4+ T cells - Helper T cells help B lymphocytes produce antiiodes and helpphagocytes destroy ingested microbes

Regulatory T lymphocytes subset of CD4+ that prevent or limit immuneresponse

iii. CD8+ - Cytotoxic T lymphocyte (CTL) lyse cells harboring intracellular microbesc. Natural killer cells kill infected host cells

i. Recognize changes on surface of infected cellsii. Express receptors that bind to general classes of bacterial or viral antigensiii. Use this limited set of activating reports to detect stressed/infected cells or cells

with DNA damage and kill cells eliminated damaged cells or those that are

infected

iv. Components of innate immunity rapidly attacking infected cellsv. Do not express clonally distributed antigen receptors like B and T cells

2. Maturation of lymphocytes all arise from stems cells in bone marrowa. Generative lymphoid organs site where mature lymphocytes are produced

i. B lump mature in bone marrowii. T lymph mature in thymus

b. Mature lymphocytes enter the peripheral lymphoid organs (lymph nodes, spleen,mucosal/cutaneous lymphoid tissue)

i. Recirculate in blood and lymph


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ii. Encounter and respond to antigens3. When nave lymphocytes recognize microbial antigens and also receive signals induced by microbes,

the lymphocytes proliferate and differentiate into effector cells and memory cells

a. Nave lymphocytes recognize foreign antigens to initiate adaptive immune response but donot eliminate antigens

i. Circulate between peripheral lymphoid organs waiting to find and respond toantigen for weeks to months

ii. If not activated, nave lymph undergo apoptosis and replaced by new cells Homeostasis cycle of cell loss and replacement maintains stable Antigen

recognition initiates the differentiation of nave into effector cells andmemory cells

b. Antigen recognition initiates the differentiation of nave into effector cells and memory cellsi. Each nave lymphocyte expressed receptor molecules of one specific and the specific

to each lymphocyte is different

c. Effector cells differentiated progeny of nave cells that have the ability to producemolecules that eliminate antigens

i. B lymphocyte lineage produces antibody secreting cells (plasma cells)ii. Effector Helper T cells produce cytokines that activate B cells and macrophagesiii. Effector cytotoxic T cells have machinery to kill infected cellsiv. Most effectors are short lived and die as antigen is eliminated. Undergo apoptosis

and consumed by phagocytes

Plasma cells may migrate to bone marrow and produce antibody long afterinfection is gone

d. Memory cells are also generated from progeny of antigen stimulated lymphocytes survivefor long periods of time in absence of antigen

i. Frequency of memory cells increases with ageii. Functionally inactive dont perform effector functions unless stimulated by antigeniii. When stimulated by the same antigen that induced their development, the cells

respond to give rise to secondary immune response

B. Antigen presenting cells specialized cells located in epithelium that capture antigens and transport them toperipheral lymphoid tissues and display them to lymphocytes

1. Dendritic cells initiation of T cell responsesa. Capture antigens of microbes that enter through epithelia and transport antigens to lymph

nodes, where they display the antigen for recognition by T lymphocytes

b. Professional APCs display antigens to T cells and provide additional activating signalsi. Respond to microbes by producing surface and secreted proteins that are required

to activate nave T cells to proliferate and differentiate into effector cells

2. Macrophages: initiation and effector phase of cell mediated immunitya. Microbes also phagocytosed by macrophages in tissueb. Macrophages can present antigens to T cells

3. Follicular dendritic cell (FDC) displays antigens that stimulate differentiation of B cells in humoralimmune response

a. Reside in germinal centers of lymphoid follicles in PLOb. B -lymphocytes may directly recognize antigens of microbes or macrophages lining

lymphatic channels capture antigens and display them to B cells

c. Dont present to T cellsC. Effector cells cells that eliminate microbes; consist of lymphocytes and other leukocytes

1. B lymphocytes recognize soluble or cell surface antigens and differentiate into antibody secretingplasma cells

a. Leads to neutralization of microbe, phagocytosis, complement activation2. Effector CD4+ T cells (helper T cells) recognize antigens on surfaces of APCs and produce cytokines

that activate B cells and macrophage,

a. Stimulates mechanism of immunity and inflammation3. Effector CD8+ T cells recognize antigens on infected cells and have machinery to kill infected host

cells

4. Elimination of microbes can requires non-lymphoid leukocytes such as granulocytes andmacrophages

a. Macrophages and monocytes: cells of mononuclear-phagocyte systemb. Granulocytes: eosinosides, neutrophilsc. Innate immunity macrophages and granulocytes directly recognize microbe and eliminate

them


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d. Adaptive products of b and T lymphocytes call in other leukocytes and activate them to killmicrobes

VI. Tissues of immune systemsA. Lymphoid system: lymphatic circulatory system

1. Lymphatics drain ECF (lymph) via capillary network from tissue to a lymph node to the thoracic ductthen to let subcliavn vein

B. Peripheral lymphoid organs1. Organized to optimize interactions of antigens, APCs and lymphocytes that promotes development of

adaptive immune response site of lymphocyte activation by antigen

a.

Lymphocytes recirculate between blood and these organs until they encounter specificantigen

2. Lymph nodes nodular aggregates of lymphoid tissue, with cortex and inner medullaa. Organization of lymph node

i. Outermost cortex: mostly B cells organized in follicles During immune response, intense B cell proliferation in germical centers

ii. Pararcortex: T cells and dendritic cellsiii. Medulla- macrophages and plasma cellsiv.

b. APCs in the nodes sample the antigens of microbes that enter through epithelia into tissuesc. Dendritic cells pick up antigens and transport them to nodesd. Afferent lymphatics:e. Lymphatics drain ECF from peripheral tissues, through the lymph nodes and into thoracic

ducts which empties into left subclavin vein lymph

f. Net result is that aintigesn of microbes that enter through epithelia or colonize becomeconcentrated in draining lymph nodes

3. Segregation of b and T lymphocytes within PLOsa. In lymph nodes B cells concentrated in follicles located around the periphery of each node

i. T y lymphocytes are concentrated outside the follicle in the paracortex4. Spleen red pulp (site of RBC destruction) instpersid with lymphoid white pup

a. Antigen enters spleen from the blood rather than the lymphb. Blood veneering spleen flows though sinusoids (network of channels)c. Blood borne antigens trapped and concentrated by dendritic cells and macrophages in

spleen

d. Spleen has abundant phagocytes which ingest and destroy microbes in blood5. Mucosal associated lymphoid tissues (MALT) protect mucosal surfaces from pathogens

C. Lymphocyte recirculation and migration into tissues1. Nave lymphocytes recirculate between blood and PLOs2. T lymphocytes igrate from blood through high endotheial venules (HEVs) in to T cell zones of lymph

notesk where the cells are activated by antigens

a. In lymph node , nave T cells move around raidly scnning surfaces of dneric cells searchingfor antiens

3. Activated T cells eit nodes and enter the blood stream and migrate to peripheral tissues at sides ofinfection an inflammation

VII. Overview of immune responsesA. Early innate immune response to microbes most infectious agents induce inflam. Response by activating

innate immunity that mediates initial protection

1. Principal barriers between the host are epithelia of the skin and epithelia of GI and respiratory tractsa. Tight junctions between cells provide barrierb. Anti microbial chemicals secreted by epithelia inhibit microbe growth

2. If they enter the tissue and circulation, microbes are met by innate immunity3. Phagocytes including neutrophils and macrophages ingest microbes into vesicles and chemically

destroy them

4. Macrophages and dendritic cells secrete cytokines, which stimulate inflammation and lymphocyteresponse

a. Cause capillary dilation leading to increased blood flow and leakiness which allows fluid andprotein to pass into tissue

b. Also produce chemokines which direct migration of neutrophils to site of infectionc. Accumulation of fluid and cells causes redness, swelling and pain

5. NK cells kill virus infected cells and produce macrophage activating cytokine interferon gamma (IFNgamma)

6. Complement is a system of plasma proteins that bind to and are activated by pathogens


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a. activated in a cascadeb. Three effects of complement system:

i. 1. Enhances inflammatory response, e.g.: attracts phagocytes C 3 and C5 induce changes that contribute to local vascular permeability

and attract phagocytes

ii. Increases phagocytosis through opsonization or immune adherence Formation of membrane attack complex which creates ores in cell

membranes disrupting integrity o cell lysis of foreign cells

iii. Opsonization - C3b binds to microbe function as an opsonin

Opsonins (complement proteins or antibodies) coat bacteria and promoteattachment to phagocyte

7. Complement system is composed of several proteins that circulate in blood stream.a. Complement proteins ecprots on the surface activate a cascade of proteolytic reactions of

microbial surface

b. Opsionize microbes by coating surfaces with fragments that are recognized and boundphagocytic receptors on macrophages

c. Coating microbes surface with molecule to increase digestiond. cause phagocytosis by interacting with complement protein receptors on the surface of

macrophages

e. Terminal component of complement cascade can form lytic complexes that are lethal to cellsB. Adaptive immune response

1. Capture and display of microbial antigens2. Secreted antibodies bind to EC microbes, block their ability to infect host cells and promote their

ingestion and destruction by phagocytes

3. If they enter the tissue and circulation, microbes are met by innate immunity4. Phagocytes including neurtorihils and macrophages ingest microbes into vesicles and chemically

destroy them

C. Decline of immune response and immunological memory1. Majority of effectors induced by infectious pathogen die by apoptosis after the microbe is eliminated

a. Returning to basal resting state homeostasisb. Microbes provide essential stimuli for lymphocyte survival and activation, so as stimuli is

eliminated the activated lymphocytes no longer kept alive

2. Initial activation of lymphocytes generates long lived memory cellsa. Activation specific lymphocytes that are more numerous than nave cells and respond faster

against the antigen

immunology lecture 1

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