Chapter 21: Immune System
description
Transcript of Chapter 21: Immune System
![Page 1: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/1.jpg)
Chapter 21: Immune System
![Page 2: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/2.jpg)
Innate System• Nonspecific, rapid response
• Fast response
• First line of defense – skin and mucous membranes
• second line of defense– Phagocytes, NK Cells– Inflammation– Complement– Fever
![Page 3: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/3.jpg)
Adaptive System• Specific, slow response
• Third line of defense
– Humoral Immunity (B Cells)– Cellular Immunity (T Cells)
• Both systems work together
![Page 4: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/4.jpg)
Innate and Adaptive Defenses
Figure 21.1
![Page 5: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/5.jpg)
Innate Barriers Epithelial
– Chemical barrier (pH of 3 to 5) • Dermcidinin in sweat • Lipids in sebum• Vaginal secretions • HCl in stomach secretions• Lysozyme in saliva
– Mechanical Barrier • Mucus• Cillia
![Page 6: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/6.jpg)
Innate Barriers• Physiological
– Temperature– Low pH– Chemical mediators– Inflammation
• Non-specific cells– Natural Killer Cells (NK cells)– Macrophages– Neutrophils
![Page 7: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/7.jpg)
Macrophage
![Page 8: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/8.jpg)
Natural Killer (NK) Cells• Detect cancer and virus-infected cells
• Large granular lymphocytes
• Nonspecific
• Attack by releasing perforins and other cytolytic chemicals
• Enhance the inflammatory response
![Page 9: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/9.jpg)
Inflammation• Response to tissue insult or injury
– Prevents the spread of damaging agents to nearby tissues
– Disposes of cell debris and pathogens
– Sets the stage for repair processes
• Five cardinal signs inflammation
• Mast cells play a key role
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg
![Page 10: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/10.jpg)
5 Cardinal Signs of Inflammation
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg
![Page 11: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/11.jpg)
Inflammation Response• Release of inflammatory mediators
• Kinins, prostaglandins (PGs), complement, and cytokines
• Bind to Toll-like receptors (TLRs)
• Cause local small blood vessels to dilate, resulting in hyperemia
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg
![Page 12: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/12.jpg)
Toll-like Receptors (TLRs)• Macrophages, epithelial cells in GI tract
and respiratory system
• Detect specific classes of infecting microbes
• Cytokine release promotes inflammation and cellular responses
![Page 13: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/13.jpg)
Vascular Permeability Increased permeability of local capillaries
• Exudate—fluid containing proteins, clotting factors, and antibodies
– Exudate seeps into tissue spaces causing local edema (swelling), which contributes to the sensation of pain
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg
![Page 14: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/14.jpg)
Edema• The surge of protein-rich fluids into tissue
spaces – Dilute harmful substances
– Oxygen and nutrients needed for repair
– Clotting proteins prevent the spread of bacteria
![Page 15: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/15.jpg)
Phagocytic Mobilization• Four main phases:– Leukocytosis – neutrophils are released from
the bone marrow in response to leukocytosis-inducing factors released by injured cells
– Margination – neutrophils cling to the walls of capillaries in the injured area
– Diapedesis – neutrophils squeeze through capillary walls and begin phagocytosis
– Chemotaxis – inflammatory chemicals attract neutrophils to the injury site
Animation
![Page 16: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/16.jpg)
![Page 17: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/17.jpg)
Figure 21.3
![Page 18: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/18.jpg)
Antimicrobial Proteins• Enhance the innate defenses by attacking
microorganisms directly
• The most important:
– Interferon -chemotactic
– Complement proteins -destructive
![Page 19: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/19.jpg)
Interferon (IFN)• Activated T cells and NK secret interferon
• Interferon chemotactic, activating many other immune cells
– Response may be phagocytic or directly interrupt viral replication
• FDA-approved alpha IFN is used: – As an antiviral drug against hepatitis C virus
– To treat genital warts caused by the herpes virus
![Page 20: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/20.jpg)
Interferon (IFN)
Figure 21.5
![Page 21: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/21.jpg)
Complement• Circulating protein components which
interact causing:– Lysis of cells, bacteria, viruses
– Opsonization, promoting detection and phyagocytosis
– Opsonization triggers inflammation and secretion of immunoregulatory molecules
• Results in immune clearance
![Page 22: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/22.jpg)
Complement Pathways• Two pathways
–Classical pathway is part of cell mediated immunity
–Alternative pathway is part of innate immunity
![Page 23: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/23.jpg)
Complement: Classical Pathway
• Cell mediated immunity
• Antibodies bind to invading organisms
• Binding of complement proteins to the antigen-antibody complexes (complement fixation)
• Membrane Attack Complex (MAC)
• Lysis of cells
![Page 24: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/24.jpg)
Complement: Alternative Pathway
• Innate immunity
• Antibody independent • Components of pathogens are recognized
by complement proteins • Membrane Attack Complex (MAC)• Lysis of cells
![Page 25: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/25.jpg)
Complement Pathways• Each pathway is a cascade
• complement proteins are activated in a sequence
• Each step catalyzes the next
• Pathways converge and follow the same final cascade
• Membrane Attack Complex (MAC) forms channels in target cells plasma membrane– Result is lysis of cell
![Page 26: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/26.jpg)
Complement Pathways
Figure 21.6
![Page 27: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/27.jpg)
C-reactive Protein (CRP)• Produced by the liver in response to
inflammatory molecules
• Activates complement
• CRP is a clinical marker used to assess:
– The presence of an acute infection
– inflammatory condition and its response to treatment
![Page 28: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/28.jpg)
Fever• Increase in body temperature in response
to infection
• Pyrogen -cytokines secreted by leukocytes and macrophages
• Activate temperature control sites in hypothalamus
• Most pathogens thrive at temperatures lower than 37°C
• High fever is dangerous, proteins denature
![Page 29: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/29.jpg)
Innate Immunity Summery
• Surface Barriers– Epithelia: chemical, acidity, sebum, mucus, cillia
• Cellular Barriers– Mast cells, Neutrophils, NK cells, macrophages
• Physiological Barriers– Antimicrobial Proteins: TLR, CRP, Complement– Inflammation– Fever
![Page 30: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/30.jpg)
![Page 31: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/31.jpg)
Adaptive (Specific) Defenses• Recognizes specific foreign substances
• Immobilizes, neutralizes, or destroys foreign substances
• Amplifies inflammatory response
• Activates complement
• Antigen-specific, systemic, and has memory
• Two divisions
– Humoral, or antibody-mediated immunity (B cell)– Cellular, or cell-mediated immunity (T cell)
![Page 32: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/32.jpg)
Vocabulary
![Page 33: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/33.jpg)
Antigens• Any substance that binds specifically to an
antibody or a T-cell receptor
• Immunogenicity – ability of a substance to induce an immune response under a given set of circumstances
• Antigenicity (Reactivity) – ability to combine specifically with the final products of immunogenicity
• Examples: foreign protein, nucleic acid, some lipids, and large polysaccharides
![Page 34: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/34.jpg)
Haptens (Incomplete Antigens)• Small molecules,
• Not immunogenic but are antigenic
• Attached to protein carriers
• Adaptive immune system may recognize them as foreign and mount a harmful attack (allergy)
• Examples: poison ivy, dander, some detergents, and cosmetics
![Page 35: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/35.jpg)
Epitopes (Antigenic Determinants)
• Specific part of antigen that is immunogenic
• Epitopes are bound by antibodies and activated lymphocytes
• Some antigens have numerous epitopes– Mobilize several lymphocyte populations
– Varied antibodies formed
![Page 36: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/36.jpg)
Epitopes
Figure 21.7
Epitope
![Page 37: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/37.jpg)
MHC Proteins• Major Histocompatability Complex Proteins
• Antigen presenting glycoproteins
• Two classes of MHC proteins are:– Class I MHC proteins – present peptide
antigens from intracellular replicating pathogens
• Viruses and some bacteria– Class II MHC proteins – present peptide
antigens from extracellular pathogens
• Bacteria
![Page 38: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/38.jpg)
Cells
![Page 39: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/39.jpg)
Adaptive Immune System Cells
• Lymphocytes– B lymphocytes – oversee humoral (antibody)
immunity
– T lymphocytes – non-antibody-producing cells that constitute the cell-mediated arm of immunity
• Antigen-presenting cells (APCs):– Do not respond to specific antigens
– Present or display antigens
![Page 40: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/40.jpg)
Lymphocytes• Immature lymphocytes released from bone
marrow are essentially identical
• Type of lymphocyte determined by the tissue cells mature in
– B cells mature in the bone marrow– T cells mature in the thymus
![Page 41: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/41.jpg)
T Cells• T cells mature in the thymus under
negative and positive selection pressures– Negative selection – eliminates T cells that are
strongly anti-self
– Positive selection – selects T cells with a weak response to self-antigens
– Self tolerant and immunocompetent
![Page 42: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/42.jpg)
T Cell Selection in the Thymus
Figure 21.9
![Page 43: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/43.jpg)
Antigen-Presenting Cells (APCs)• Engulf foreign particles
• Present antigen to T cells
• Major APCs are dendritic cells (DCs), macrophages, and activated B cells
• Dendritic cells are initiators of adaptive immunity
![Page 44: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/44.jpg)
Humoral Response
![Page 45: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/45.jpg)
Humoral Immune Response
Clonal selection of B cells Immunological Memory Active and Passive Immunity Antibodies
![Page 46: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/46.jpg)
B Cells• B cells become immunocompetent and
self-tolerant in bone marrow
– Exposed to initial antigen creating memory cell
– Subsequent antigen challenge results in plasma cell
• Specificity due to rearrangements of receptors
![Page 47: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/47.jpg)
![Page 48: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/48.jpg)
Immunological Memory• Primary immune response
• Cellular differentiation and proliferation
• First exposure to a specific antigen
• Lag period: 3 to 6 days after antigen challenge
• Peak levels of plasma antibody are achieved in 10 days
• Antibody levels then decline
![Page 49: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/49.jpg)
Immunological Memory• Secondary immune response
• Re-exposure to the same antigen
– Sensitized memory cells respond within hours
– Antibody levels peak in 2 to 3 days at much higher levels than in the primary response
– Antibodies bind with greater affinity
– Levels in the blood can remain high for weeks to months
![Page 50: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/50.jpg)
Humoral Responses
Figure 21.11
![Page 51: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/51.jpg)
Active Humoral Immunity• B cells encounter antigens and produce
antibodies against them– Naturally acquired – response to a bacterial or
viral infection
– Artificially acquired – response to a vaccine of dead or attenuated pathogens
• Vaccines – spare us the symptoms of disease, and their weakened antigens provide antigenic determinants that are immunogenic and reactive
![Page 52: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/52.jpg)
Passive Humoral Immunity• Differs from active immunity in the antibody
source and the degree of protection– B cells are not challenged by antigens
– Immunological memory does not occur
– Protection ends when antigens naturally degrade in the body
• Naturally acquired – from the mother to her fetus via the placenta
• Artificially acquired – from the injection of serum, such as gamma globulin
![Page 53: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/53.jpg)
Types of Acquired Immunity
Figure 21.12
![Page 54: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/54.jpg)
Antibodies• Also called immunoglobulins – Gamma globulin portion of blood proteins
– Secreted by activated B cells and plasma cells in response to an antigen
– Capable of binding specifically with that antigen
• There are five classes of antibodies: IgD, IgM, IgG, IgA, and IgE
![Page 55: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/55.jpg)
![Page 56: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/56.jpg)
Classes of Antibodies• IgD – monomer attached to the surface of B cells, B cell activation
• IgM – pentamer released by plasma cells during the primary immune response
• IgG – monomer that is the most abundant and diverse antibody in primary and secondary response; crosses the placenta and confers passive immunity
• IgA – dimer that helps prevent attachment of pathogens to epithelial cell surfaces
• IgE – monomer that binds to mast cells and basophils, causing histamine release when activated
![Page 57: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/57.jpg)
http://www.immunology.klimov.tom.ru/1-1.php
![Page 58: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/58.jpg)
Basic Antibody Structure
Figure 21.13a
![Page 59: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/59.jpg)
Antibody Targets• Antibodies themselves do not destroy
antigen; they inactivate and tag it for destruction
• All antibodies form an antigen-antibody (immune) complex
• Defensive mechanisms used by antibodies are neutralization, agglutination, precipitation, and complement fixation
![Page 60: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/60.jpg)
Mechanisms of Antibody Action
![Page 61: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/61.jpg)
Neutralization
• Antibodies bind
• Block specific sites on viruses or exotoxins
• Preventing antigens from binding to receptors on tissue cells
![Page 62: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/62.jpg)
Antibody Action
• Agglutination – antibodies bind the same epitope on more than one antigen – Makes antigen-antibody complexes that are
cross-linked into large lattices
– Cell-bound antigens are cross-linked, causing clumping (agglutination)
• Precipitation – soluble molecules are cross-linked into large insoluble complexes
![Page 63: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/63.jpg)
Complement Fixation and Activation• Main mechanism used against cellular antigens
• Antibodies expose complement binding sites
• Complement fixation and cell lysis
• Enhancment of the inflammatory response
• Promote phagocytosis
• Enlists more and more defensive elements
![Page 64: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/64.jpg)
Cell Mediated Immune Response
![Page 65: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/65.jpg)
Cell-Mediated Immune Response• Intracellular antigens
• T cells mediate cellular immunity:
– CD4 cells (T4 cells) → Helper T cells (TH)
– CD8 cells (T8 cells) → cytotoxic T cells (TC)
– Minor T cells
– Suppressor T cells (Ts)
– Memory T cells
– Regulatory (Treg)
![Page 66: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/66.jpg)
Major Types of T Cells
![Page 67: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/67.jpg)
Importance of Humoral Response• Soluble antibodies
– The simplest ammunition of the immune response
– Interact in extracellular environments such as body secretions, tissue fluid, blood, and lymph
![Page 68: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/68.jpg)
Importance of Cellular Response• T cells recognize and respond only to
processed fragments of antigen displayed on the surface of body cells
• T cells are best suited for cell-to-cell interactions, and target:– Cells infected with viruses, bacteria, or
intracellular parasites
– Abnormal or cancerous cells
– Cells of infused or transplanted foreign tissue
![Page 69: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/69.jpg)
Antigen Recognition and MHC Restriction• Immunocompetent T cells are activated
when the V regions of their surface receptors bind to a recognized antigen
• T cells must simultaneously recognize:– Nonself (the antigen)
– Self and MHC
![Page 70: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/70.jpg)
MHC Proteins• Both types of MHC proteins are important
to T cell activation
• Class I MHC proteins
• Recognized by CD8 T cells
• Display peptides from endogenous antigens
• Class II MHC proteins
• Recognized by CD4 T cells
• Display peptides from exogenous antigens
![Page 71: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/71.jpg)
![Page 72: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/72.jpg)
T Cell Activation:
• TC cells are activated by antigen fragments complexed with class I MHC proteins
• APCs produce co-stimulatory molecules that are required for TC activation
• TCR that acts to recognize the self-antiself complex is linked to multiple intracellular signaling pathways
• Other T cell surface proteins are involved in antigen binding (e.g., CD4 and CD8 help maintain coupling during antigen recognition)
![Page 73: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/73.jpg)
T Cell Activation
![Page 74: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/74.jpg)
Helper T Cells (TH)
• Regulatory cells that play a central role in the immune response
• Once primed by APC presentation of antigen, they:– Chemically or directly stimulate proliferation of
other T cells
– Stimulate B cells that have already become bound to antigen
• Without TH, there is no immune response
![Page 75: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/75.jpg)
Helper T Cells (TH)
Figure 21.18a
![Page 76: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/76.jpg)
Helper T Cell• TH cells interact directly with B cells that have
antigen fragments on their surfaces bound to MHC II receptors
• TH cells stimulate B cells to divide more rapidly and begin antibody formation
• B cells may be activated without TH cells by binding to T cell–independent antigens
• Most antigens, however, require TH co-stimulation to activate B cells
• Cytokines released by TH amplify nonspecific defenses
![Page 77: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/77.jpg)
Cytokines• Mediators involved in cellular immunity,
including hormonelike glycoproteins released by activated T cells and macrophages
• Some are co-stimulators of T cells and T cell proliferation
• cytokines amplify and regulate immune and nonspecific responses
![Page 78: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/78.jpg)
Cytokines• Examples include:
– Perforin and lymphotoxin – cell toxins
– Gamma interferon – enhances the killing power of macrophages
– Inflammatory factors
![Page 79: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/79.jpg)
Helper T Cells
Figure 21.18b
![Page 80: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/80.jpg)
Cytotoxic T Cell (Tc)• TC cells, or killer T cells, are the only T cells that can
directly attack and kill other cells
• They circulate throughout the body in search of body cells that display the antigen to which they have been sensitized
• Their targets include:
– Virus-infected cells
– Cells with intracellular bacteria or parasites
– Cancer cells
– Foreign cells from blood transfusions or transplants
![Page 81: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/81.jpg)
Cytotoxic T Cells• Bind to self-antiself complexes on all body cells
• Infected or abnormal cells can be destroyed as long as appropriate antigen and co-stimulatory stimuli (e.g., IL-2) are present
• Natural killer cells activate their killing machinery when they bind to MICA receptor
• MICA receptor – MHC-related cell surface protein in cancer cells, virus-infected cells, and cells of transplanted organs
![Page 82: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/82.jpg)
Mechanisms of Tc Action• In some cases, TC cells:– Bind to the target cell and release perforin into
its membrane• In the presence of Ca2+ perforin causes cell lysis by
creating transmembrane pores
• Other TC cells induce cell death by:– Secreting lymphotoxin, which fragments the
target cell’s DNA
– Secreting gamma interferon, which stimulates phagocytosis by macrophages
![Page 83: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/83.jpg)
Mechanisms of Tc Action
Figure 21.19a
![Page 84: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/84.jpg)
Other T Cells• Suppressor T cells (TS) – regulatory cells
that release cytokines, which suppress the activity of both T cells and B cells
• Gamma delta T cells (Tgd) – 10% of all T cells found in the intestines that are triggered by binding to MICA receptors
![Page 85: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/85.jpg)
Figure 21.20
![Page 86: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/86.jpg)
Organ Transplants• The four major types of grafts are:
– Autografts – graft transplanted from one site on the body to another in the same person
– Isografts – grafts between identical twins
– Allografts – transplants between individuals that are not identical twins, but belong to same species
– Xenografts – grafts taken from another animal species
![Page 87: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/87.jpg)
Prevention of Rejection• Prevention of tissue rejection is
accomplished by using immunosuppressive drugs
• However, these drugs depress patient’s immune system so it cannot fight off foreign agents
![Page 88: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/88.jpg)
Immunodeficiencies• Conditions in which the function or production of immune
cells, phagocytes, or complement is abnormal
– SCID – severe combined immunodeficiency (SCID) syndromes; genetic defects that produce:
• A marked deficit in B and T cells
• Abnormalities in interleukin(cytokine) receptors
• Defective adenosine deaminase (ADA) enzyme
– Metabolites lethal to T cells accumulate
– SCID is fatal if untreated; treatment is with bone marrow transplants
![Page 89: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/89.jpg)
Acquired Immunodeficiencies• Hodgkin’s disease – cancer of the lymph
nodes leads to immunodeficiency by depressing lymph node cells
• Acquired immune deficiency syndrome (AIDS) – cripples the immune system by interfering with the activity of helper T (CD4) cells
![Page 90: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/90.jpg)
AIDS• Caused by human immunodeficiency virus (HIV)
transmitted via body fluids – blood, semen, and vaginal secretions
• HIV enters the body via:
– Blood transfusions
– Contaminated needles
– Intimate sexual contact, including oral sex
– Destroys TH cells
– Depresses cell-mediated immunity
![Page 91: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/91.jpg)
Autoimmune Diseases• Loss of the immune system’s ability to
distinguish self from nonself
• The body produces autoantibodies and sensitized TC cells that destroy its own tissues
• Examples include multiple sclerosis, myasthenia gravis, Graves’ disease, Type I (juvenile) diabetes mellitus, systemic lupus erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis
![Page 92: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/92.jpg)
Hypersensitivity• Immune responses that cause tissue damage
• Different types of hypersensitivity reactions are distinguished by:
– Their time course
– Whether antibodies or T cells are the principle immune elements involved
• Antibody-mediated allergies are immediate and subacute hypersensitivities
• The most important cell-mediated allergic condition is delayed hypersensitivity
![Page 93: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/93.jpg)
Immediate Hypersensitivity• Acute (type I) hypersensitivities begin in
seconds after contact with allergen
• Anaphylaxis – initial allergen contact is asymptomatic but sensitizes the person– Subsequent exposures to allergen cause:
• Release of histamine and inflammatory chemicals
• Systemic or local responses
![Page 94: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/94.jpg)
Subacute Hypersensitivities• Caused by IgM and IgG, and transferred via
blood plasma or serum– Onset is slow (1–3 hours) after antigen exposure
– Duration is long lasting (10–15 hours)
• Cytotoxic (type II) reactions– Antibodies bind to antigens on specific body cells, stimulating
phagocytosis and complement-mediated lysis of the cellular antigens
– Example: mismatched blood transfusion reaction
![Page 95: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/95.jpg)
Subacute Hypersensitivities• Immune complex (type III) hypersensitivity– Antigens are widely distributed through the
body or blood
– Insoluble antigen-antibody complexes form
– Complexes cannot be cleared from a particular area of the body
– Intense inflammation, local cell lysis, and death may result
– Example: systemic lupus erythematosus (SLE)
![Page 96: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/96.jpg)
Delayed Hypersensitivities (Type IV)
• Onset is slow (1–3 days)
• Mediated by mechanisms involving delayed hypersensitivity T cells and cytotoxic T cells
• Cytokines from activated TC are the mediators of the inflammatory response
• Antihistamines are ineffective and corticosteroid drugs are used to provide relief
![Page 97: Chapter 21: Immune System](https://reader035.fdocuments.net/reader035/viewer/2022081503/568163c5550346895dd4f100/html5/thumbnails/97.jpg)
Delayed Hypersensitivities (Type IV)
• Example: allergic contact dermatitis (e.g., poison ivy)
• Involved in protective reactions against viruses, bacteria, fungi, protozoa, cancer, and rejection of foreign grafts or transplants