The immune system
Download
1 / 85

The Immune System - PowerPoint PPT Presentation


  • 178 Views
  • Updated On :

The Immune System . Chapter 21. Immune System. functional system rather than organ system Hematopoetic Vasculature Lymphatic. Fig 21.1. Innate vs. Adaptive Immune System – Introduction. Innate: structural defenses; responds to nonspecific foreign substances

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'The Immune System' - fritz


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Immune system l.jpg
Immune System

  • functional system rather than organ system

    • Hematopoetic

    • Vasculature

    • Lymphatic

Fig 21.1


Innate vs adaptive immune system introduction l.jpg
Innate vs. Adaptive Immune System – Introduction

  • Innate: structural defenses; responds to nonspecific foreign substances

    • First line: external surface epithelium & membranes

    • Second line: inflammatory processes – antimicrobial proteins, phagocytes, etc.

Fig 21.1


Innate vs adaptive immune system introduction4 l.jpg
Innate vs. Adaptive Immune System – Introduction

  • Adaptive: responds to specific foreign substances

  • Innate & adaptive mechanisms work together

Fig 21.1


Innate surface defenses l.jpg
Innate, Surface Defenses

  • Skin

    • physical barrier to microbes

    • Keratin resistant to most bacterial enzymes & toxins

    • secretions are acidic pH 3-5

  • Mucosa

    • physical barrier & produces a variety of protective chemicals

  • Gastric mucosa

    • very acidic & produces proteolytic enzymes

  • Saliva & lacrimal fluid contain lysozyme

  • Mucous

    • traps bacteria & moves them away from epithelial surface


Innate internal defenses l.jpg
Innate, Internal Defenses

  • Based on recognition of surface carbohydrates (glycocalyx)

    • Glycocalyx is recognized as “self” or “non-self”

Figure 3.3


Innate internal defenses7 l.jpg
Innate, Internal Defenses

  • Phagocytes

    • Macrophages: derived from monocytes

      • Free Macrophages: roam through tissues

      • Fixed Macrophages: Kupffer cells (liver) & microglia (brain)

      • Ingest cellular debris, foreign material, bacteria, fungi

    • Neutrophils: ingest pathogens

    • Eosinophils: weakly phagocytic of pathogens. Attack parasites (degranulation)

    • Mast Cells: phagocytic of various bacteria


Innate internal defenses8 l.jpg
Innate, Internal Defenses

  • Phagocytic mechanisms:

    • Adherence: cell binds to invader

      • Aided by opsonization (a chemical process that enhances binding via complement & antibodies)

    • Ingestion: formation of phagolysosomes

      • Respiratory Bursts: merge phagosome with lysosome & flood phagolysosome with free radicals (macrophage)

      • Defensins: proteins that crystallize out of solution & pierce pathogen membranes (neutrophils)



Innate internal defenses10 l.jpg
Innate, Internal Defenses

  • Natural Killer Cells:

    • Small population of large granular lymphocytes

    • Non specific for “non-self”

    • Not phagocytic: attack is by release of perforins that perforate the target cell plasma membrane.

      • Shortly after perforation the target nucleus disintegrates.

    • Release chemicals that enhance the inflammatory response


Innate internal defenses inflammation l.jpg
Innate, Internal Defenses: Inflammation

  • tissue response to injury

  • Triggered by injury – trauma, heat, chemical irritation, infection, etc.

  • Beneficial effects

    • Prevents spread of injury

    • Disposes of cellular debris & pathogens

    • Promotes repair


Innate internal defenses inflammation12 l.jpg
Innate, Internal Defenses: Inflammation

  • cardinal signs of inflammation

    • Redness

    • Heat

    • Swelling

    • Pain

    • (functional impairment Rigor)

    • Weapons of the Spanish Inquisition


Innate internal defenses inflammation13 l.jpg
Innate, Internal Defenses: Inflammation

  • Inflammatory response: signs are associated with vasodilation & increased vascular permeability

    • Dilation: redness, heat

    • Permeability: edema, (increased pressure) pain

    • Pain also associated with bacterial toxins & some mediators (kinins, PGs)


Innate internal defenses inflammatory response l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Mechanisms causing vasodilation & vascular permeability

    • Injured cells release inflammatory mediators

      • Histamines

      • Kinins

      • Prostaglandins

      • Complement

      • Cytokines (also activated by receptors on macrophages in response to microbial glycocalyx)


Innate internal defenses inflammatory response15 l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Edema

    • Dilutes harmful substances

    • Provides nutrients (& O2) for repair

    • Enhances entry of clotting protein

  • Epithelial breaches also stimulate b-defensin release from epithelial cells



Innate internal defenses inflammatory response17 l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Phagocyte mobilization: infiltration of damaged area by neutrophils & macrophages


Innate internal defenses inflammatory response18 l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Leukocytosis: leukocytosis inducing factors released by injured cells promote rapid release of WBCs from marrow

  • Margination: increased vascular permeability causes decreased fluid in vessels; blood flow slows & neutrophils are able to move to vessel margins. Here endothelial markers (CAMs) allow neutrophils to cling to vessel walls (pavementing).


Innate internal defenses inflammatory response19 l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Diapedesis: neutrophils migrate through capillary walls

  • Chemotaxis – inflammatory chemicals attract neutrophils to move up the chemical concentration gradient (neutrophils respond first)

  • As the process continues, monocytes diapedes into the area & become macrophages. With chronic inflammation, macrophages predominate


Inflammatory response phagocytic mobilization l.jpg
Inflammatory Response:Phagocytic Mobilization

Figure 21.4


Innate internal defenses inflammatory response21 l.jpg
Innate, Internal Defenses: Inflammatory Response

  • Macrophages clean up cellular debris & pathogens

  • If pathogens were associated with the injury, activation of the complement cascade occurs & elements of adaptive immunity join the process


Innate internal defenses22 l.jpg
Innate, Internal Defenses

  • Viral replication – (viruses lack metabolic processes) Viruses release nucleic acid (RNA or DNA) into cytoplasm. The information on the nucleic acid is incorporated into the cell’s DNA. Normal cellular mechanisms then produce viral structural components. Multiple new viral particles are produced & released from the cell (sometimes killing the cell)


Innate internal defenses23 l.jpg
Innate, Internal Defenses

  • Antiviral proteins: interferon & complement

  • Interferon: some cells produce & release interferons (IFNs) when invaded by virus

  • Released interferons stimulate nearby cells to produce proteins (PKR) that interfere with viral replication by disrupting protein synthesis & the ribosome

  • Not virus specific.


Interferon ifn l.jpg
Interferon (IFN)

Figure 21.5


Innate internal defenses25 l.jpg
Innate, Internal Defenses

  • Complement – a group of plasma proteins (20) that are activated in the presence of foreign substances

  • Complement activation enhances & amplifies inflammation

  • Bacteria & some other cell types are lysed by complement activation

  • Complement activation enhances both innate & adaptive defenses


Innate internal defenses26 l.jpg
Innate, Internal Defenses

  • Complement activation pathways

    • Classical pathway: requires antibodies

      • Antibodies bind to target (antigen)

      • Complement protein C1 binds to the antibody-antigen complex (complement fixation)

    • Alternative pathway: complement factors interact with microorganism glycocalyx

  • Both pathways lead to a cascade of protein activation, leading to activation of C3


Innate internal defenses27 l.jpg
Innate, Internal Defenses

  • C3 is the start of the; Final Common Pathway

    • C3 cleaves to form C3a & C3b

    • C3a (& C5a) enhance inflammation by increasing histamine release, increasing vascular permeability & stimulating chemotaxis

    • C3b coats bacterial membrane supplying adhesion points (opsonization)

    • C3b initiates the cascade forming the membrane attack complex (MAC)

    • The MAC forms a hole in the cell membrane & enhances Ca2+ influx  cell lysis



Innate internal defenses29 l.jpg
Innate, Internal Defenses

  • C-reactive proteins (CRP) produced by the liver in response to inflammatory molecules can activate the classical pathway by binding to membrane & activating C1. Also participates in opsonization.

  • Fever – a systemic response to infection. Leukocytes & macrophages release pyrogens that raise the hypothalamic “set point” for temperature


Adaptive defenses l.jpg
ADAPTIVE DEFENSES

  • ADAPTIVE DEFENSES

    • Innate & adaptive mechanisms work together in a cohesive fashion


Adaptive defenses characteristics l.jpg
Adaptive Defenses: Characteristics

  • Specificity: directed at specific targets

  • Systemic: not restricted to initial site of infection / invasion

  • Memory: after initial exposure & activation, a more rapid & more vigorous response is made to subsequent exposures to pathogens

    • (secondary response)


Adaptive defenses components l.jpg
Adaptive Defenses: Components

  • Humoral Immunity: (antibody mediated immunity) provided by antibodies floating free in body fluids

  • Cell mediated immunity:

    • lymphocytes directly attack specific invaders by lysis or indirect attack by initiating inflammation and/or activating other lymphocytes & macrophages


Adaptive humoral immunity l.jpg
Adaptive, Humoral Immunity

  • Antigen = any substance that can mobilize the immune system & provoke an immune response*

    *Humoral and/or cell mediated


Adaptive humoral immunity34 l.jpg
Adaptive, Humoral Immunity

  • Complete antigens (proteins, nucleic acids, lipids, polysaccharides):

    • Immunogenicity: the ability to stimulate specific lymphocytes & specific antibodies

    • Reactivity: the ability to react with activated lymphocytes & antibodies

  • Hapten (an incomplete antigen): a smaller molecule that is not immunogenic until attached to proteins


Adaptive humoral immunity35 l.jpg
Adaptive, Humoral Immunity

  • Antigenic determinants: sites on an antigenic molecule that are immunogenic

    • Epitope

  • Major Histocompatibility Complex (MHC): cell surface glycoproteins associated with self recognition

Figure 21.7


Adaptive immune system cells l.jpg
Adaptive Immune System: Cells

  • Lymphocytes

    • T-cells

    • B-cells

  • Antigen Presenting Cells (APCs)


Adaptive immune system cells37 l.jpg
Adaptive Immune System: Cells

  • Lymphocytes: initially uncommitted

  • T-cells: are sorted in the Thymus

    • Positive selection: recognize MHC survive

    • Negative selection: react against to self-antigens on MHC killed

    • 2% of initial T-cell precursors

    • T-cells manage the immune response

  • B-cells: are sorted in the marrow by an incompletely understood process

Figure 21.9


Adaptive immune system cells38 l.jpg
Adaptive Immune System: Cells

  • Immunocompetence: as T- or B-cells mature they become immunocompetent, they display receptors on their cell membrane for a specific antigen.

  • All of the receptors on one cell are identical; immunity depends upon genetic coding for appropriate receptors.


Adaptive immune system cells39 l.jpg
Adaptive Immune System: Cells

  • Antigen Presenting Cells (APCs)

  • APCs ingest foreign material, then present antigenic fragments on their cell surface where they are recognized by T-cells

    • T-cells: respond to antigen only if it is displayed on plasma membrane.

  • APCs: Macrophages & B lymphocytes

  • Interactions between APCs & lymphocytes & lymphocyte-lymphocyte interactions are critical to immune response


Adaptive humoral response l.jpg
Adaptive, Humoral response

  • Humoral response (clonal selection)

  • B-cells: Antigen challenge to naïve immunocompetent B-cell

  • Antigen binds to B-cell receptors & form cross-links between receptors

  • Cross linked antigen-receptor complex undergoes endocytosis; B-cell presents to T-cell


Humoral immunity l.jpg
Humoral Immunity

  • Active humoral immunity:

    • B-cells encounter & respond to antigen to produce an antibody

  • Passive humoral immunity:

    • Introduced “non-native” antibody


Active humoral immunity l.jpg
Active Humoral Immunity

  • Naturally acquired: natural exposure to antigen (i.e. infection)

  • Artificially acquired: vaccines; dead/attenuated or fragmented pathogen injected to elicit an immune response

    • Bestow immunity without disease; primary response

    • Booster shots (secondary response); intensify response

    • Shortcomings – adverse reactions & the immunity is less durable (poor memory) & has less cell mediated component


Passive humoral immunity l.jpg
Passive Humoral Immunity

  • Natural: maternal antibody crosses the placental barrier conferring temporary immunity to the baby (degrades after a few months)

  • Artificial: antibodies harvested from an outside source given by injection protect from immediate threat but no memory is formed (antitoxins, antivenins , gamma globulin, etc.)


Antibodies l.jpg
Antibodies

  • A.K.A Immunoglobulins & gamma globulins

  • Structure

    • variable

    • hypervariable

    • constant

Figure 21.13a


Antibodies47 l.jpg
Antibodies

  • Constant (C) region defines antibody class

  • determines chemical & cellular interactions

  • determines how class functions to eliminate antigens


Antibody classes l.jpg
Antibody Classes

  • Antibody Classes: IgM, IgG, IgA, IgD, IgE (Ig = immunoglobulin)


Antibody classes49 l.jpg
Antibody Classes

  • IgG: the most abundant circulating Ig. The dominant circulating Ig of the primary & the secondary response. Crosses the placenta. Complement binding (Monomer).

  • IgA: the Ig of secretions. Helps prevent antigen penetration of membranes (Dimer).

  • IgD: the Ig of B-cell activation. Found on B-cell surface (Monomer).


Antibody classes50 l.jpg
Antibody Classes

  • IgM: occurs as a monomer & a pentamer

    • Occurs on the B-cell surface (Monomer).

    • The Ig of early primary plasma cell response, circulating antibody; a potent agglutinator. Complement binding (Pentamer).


Antibody classes51 l.jpg
Antibody Classes

  • IgE: the Ig associated with allergies.

    • Stem binds to mast cells & basophils.

    • Receptor binding results in histamine release & inflammation.

    • Found mostly in mucosa of respiratory & GI tract (Monomer).


Antibody targets functions l.jpg
Antibody Targets & Functions

  • Immune complex formation = antigen-antibody binding.

  • All the following events are initiated by antigen-antibody binding.

  • Complement fixation:

  • Neutralization:

  • Agglutination:

  • Precipitation:

  • Inflammation & phagocytosis prompted by debris


Antibody targets functions53 l.jpg
Antibody Targets & Functions

  • Complement fixation: cells & bacteria.

    • Immune complex formation exposes a complement binding site on the C region of the Ig.

    • Complement fixation results in cell lysis.

  • Neutralization: immune complex formation blocks specific sites on virus or toxin & prohibit binding to tissues

  • Agglutination: cells are crosslinked by immune complexes & clump together

  • Precipitation: soluble molecules (such as toxins) are crosslinked, become insoluble, & precipitate out of the solution

  • Inflammation & phagocytosis prompted by debris

Figure 21.14


Antibody targets functions54 l.jpg
Antibody Targets & Functions

  • Monoclonal antibodies: antibodies produced by descendants of a single cell

    • Pure antibody preparations that are specific for a single antigenic determinant

    • Research / diagnostic / therapeutic use


Cell mediated immune response l.jpg
Cell Mediated Immune Response

  • T-cell activation: involves recognition of PM surface antigens only

    • Antigen is combined with MHC & displayed on PM

    • T-cell receptors: bind to the MHC & are stimulated by the associated antigen

    • The addition of a co-stimulator (cytokines, interleukins, etc) prompts the T-cell to form a clone

    • In the absence of a co-stimulator the T-cell becomes tolerant to antigen (anergy)


Cell mediated mhc l.jpg
Cell Mediated: MHC

  • MHC occurs as two classes

    • MHC I on virtually all tissue cells

    • MHC II only on PM some immune system cells


Cell mediated mhc display properties l.jpg
Cell Mediated: MHC display properties

  • MHC I on virtually all tissue cells

    • Display only proteins produced inside the cell

    • Endogenous antigens = foreign proteins produced by the cell (viral / cancer)

    • Stimulate the CD8* cell population

      • form cytotoxic T-cells (Killer T, TC)

      • *formerly T8 cells

Figure 21.16a


Cell mediated mhc display properties58 l.jpg
Cell Mediated: MHC display properties

  • MHC II found only on PM of B-cells, some T-cells & APCs

    • Display proteins derived from a phagocytized target

    • Exogenous antigen: foreign protein from outside the cell – presented to PM surface

    • Stimulates the CD4* cell population

      • form Helper T-cells (TH)

      • *formerly T4 cells

Figure 21.16b


Cell mediated t cell roles l.jpg
Cell Mediated: T-cell roles

  • Helper T-cells (TH) stimulate B-cells & other T-cells to proliferate

Figure 21.18


Cell mediated t cell roles60 l.jpg
Cell Mediated: T-cell roles

  • Activated TH cells interact with B-cells displaying antigen & produce cytokines that prompt the B-cell to mature & form antibody

Figure 21.18


Cell mediated t cell roles61 l.jpg
Cell Mediated: T-cell roles

  • TH cells also produce cytokines that promote TC cells

  • TH cells recruit other WBCs & amplify innate defenses (inflammatory)

  • Subpopulations of TH cells specialize in specific sets of activations

Figure 21.18


Cell mediated t cell roles62 l.jpg
Cell Mediated: T-cell roles

  • Cytotoxic T-cells (TC, Killer T): directly attack & kill cells with specific antigen

  • Activated TC cells are co-stimulated by TH cells


Cell mediated t cell roles63 l.jpg
Cell Mediated: T-cell roles

Figure 21.19a

  • TC mechanism (Cytotoxic T-cells, Killer T)

    • TC binds to cell & releases perforin & granzymes

    • In the presence of Ca2+ perforin forms pores in target cell PM

    • Granzymes enter through pores & degrade cellular contents

    • TC then detaches & moves on

    • Macrophages clean up


Cell mediated t cell roles64 l.jpg
Cell Mediated: T-cell roles

  • Other T-cells

    • *Regulatory T-cells (TReg): release inhibitory cytokines that suppress B-cell & T-cell activity

      • Help to prevent autoimmune events

      • *formerly Suppressor T (TS)

    • Gamma Delta T-cells (Tgd): live in the intestine. Function in surveillance & are triggered much like NK cells


Organ transplants rejections l.jpg
Organ Transplants/Rejections

  • Types of Organ Transplants

    • Autograft: tissue graft from one body site to another (same person)

    • Isograft: graft received from a genetically identical donor (identical twin)

    • Allograft: graft received from genetically non-identical donor (same species)

    • Xenograft: graft received from another species of animal


Organ transplants rejections66 l.jpg
Organ Transplants/Rejections

  • Transplant rejection: mediated by the immune system (especially TC, NK, antibodies)

    • Auto/Isograft: MHC compatible

    • Xenograft: most MHC incompatible

    • Allograft: attempt to obtain the best MHC match


Organ transplants rejections67 l.jpg
Organ Transplants/Rejections

  • Immunosuppressive therapy: used to delay/prevent rejection

    • Corticosteroids: suppress inflammation

    • Antiproliferative: prevent/kill rapidly dividing cells

    • Immunosuppressant: prevent/kill rapidly dividing cells

    • Side effects tend to be harsh

    • Increased risk of infection


Immunologic dysfunction l.jpg
Immunologic Dysfunction

  • Immunodeficiency

    • Congenital/Genetic: varied inborn errors

    • Acquired:

      • Drugs: immunosuppressive / cancer drugsRadiation therapy – marrow

      • Cancer: can be viewed as a failure of immune surveillance

      • Hodgkin’s disease: lymph node cancer

      • AIDS/HIV: kills TH cells


Immunologic dysfunction69 l.jpg
Immunologic Dysfunction

  • Autoimmune disease: production of antibody & TH against self tissues

    • Examples & tissue effected

      • Multiple sclerosis: white matter of nervous system

      • Graves disease: thyroid

      • Type I diabetes mellitus: beta cells of pancreas

      • Systemic Lupus Erythrematosis: (anti DNA) kidneys, heart, lungs & skin

      • Rheumatoid Arthritis: destroys joints (cartilage)

      • Glomerulonephritis: impaired renal function (may be secondary to other autoimmune disease)


Immunologic dysfunction70 l.jpg
Immunologic Dysfunction

  • Mechanisms of immunologic dysfunction

    • Failure of lymphocyte programming

    • New self antigens

      • Gene mutation

      • Structural change – haptens, infection

    • Foreign antigens that closely resemble self antigen resulting in cross reactivity.


Immunologic dysfunction71 l.jpg
Immunologic Dysfunction

  • Hypersensitivities (Allergies): the immune system responds to a harmless substance as if it were a threat.

    • Allergen = antigens of an allergic response

Figure 21.21


Hypersensitivities types l.jpg
Hypersensitivities: Types

  • Immediate hypersensitivity (Type I): symptoms within seconds of exposure to an allergen

    • (requires sensitization = previous exposure)

Figure 21.21


Hypersensitivities type i l.jpg
Hypersensitivities: Type I

  • Anaphylaxis (IgE mediated; mast / basophils)

    • Local: histamine induced vasodilation & increased permeability. Watery eyes, runny nose, itching & redness. Respiratory  allergy induced asthma

    • Systemic: anaphylactic shock: associated with allergens that have systemic distribution. Widespread vasodilation, airway swelling

  • Atopy: the tendency to display Type I symptoms to certain environmental antigens without prior sensitization


Hypersensitivities types ii iii l.jpg
Hypersensitivities: Types II & III

  • Subacute hypersensitivity (IgG & IgM mediated)

    • Cytotoxic reactions (Type II): antibodies bind to cellular antigens promoting complement fixation / inflammation / phagocytosis (transfusion reaction)

    • Immune complex h. (Type III): widely distributed antigen reacts with antibody.

      • Antigen-antibody complexes cannot be cleared; persistent inflammation / tissue damage (farmer’s lung; associated with autoimmune disorders)


Hypersensitivities type iv l.jpg
Hypersensitivities: Type IV

  • Delayed hypersensitivity (cell mediated) takes one to three days to react.

    • Involves TC, TH1 & macrophages.

    • Allergic contact dermatitis (poison ivy, heavy metals, TB tine tests).

    • Agents act as haptens & elicit response after binding to tissue


Developmental aspects of the immune system l.jpg
Developmental Aspects of the Immune System

  • Stem cells arise from embryologic liver & spleen

  • Self tolerance develops in Thymus (T-cells) & bone marrow (B-cells)

  • Immunocompetence: the “library” of receptors is genetically determined

  • Immune system degrades with aging


Immunocompetent b or t cells l.jpg
Immunocompetent B or T cells

Key:

= Site of lymphocyte origin

Red bone marrow

= Site of development of immunocompetence as B or T cells; primary lymphoid organs

= Site of antigen challenge & final differentiation to activated B & T cells

Immature lymphocytes

Circulation in blood

1

Lymphocytes destined to become T cells migrate to the thymus & develop immunocompetence there. B cells develop immunocompetence in red bone marrow.

1

1

Thymus

Bonemarrow

2

After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the lymph nodes, spleen, & other lymphoid tissues where the antigen challenge occurs.

2

Immunocompetent, but still naive, lymphocyte migrates via blood

2

Lymph nodes, spleen, & other lymphoid tissues

Mature (antigen-activated) immunocompetent lymphocytes circulate continuously in the bloodstream & lymph & throughout the lymphoid organs of the body.

3

3

3

Activated immunocompetent B & T cells recirculate in blood & lymph

Figure 21.8






Helper t cells t h l.jpg
Helper T Cells (TH)

Figure 21.17a


Helper t cells l.jpg
Helper T Cells

Figure 21.17b



ad