Disruptions in the Immune System - College of the Mainland

Disruptions in the Immune System
Immune Function
Benjamin “Jay” Ketcherside, II, MSN, RN
Assistant Professor, Department of Nursing

Normal Immune Response
• Immunity
• Body’s ability to resist disease
• Serves three functions
• Defense
• Homeostasis
• Surveillance
Copyright © 2017, Elsevier

Types of Immunity
• Innate
• Present at birth
• First-line defense against pathogens
• Acquired
• Developed immunity
• Active
• Passive

Types of Acquired Specific Immunity
• Active
• Natural contact with antigen
through actual infection (e.g.,
chickenpox, measles, mumps)
• Passive
• Transplacental and colostrum
transfer from mother to child
(e.g., maternal
immunoglobulins passed to
baby)
• Natural • Artificial
• Active
• Immunization with antigen
(e.g., vaccines for
chickenpox, measles,
mumps)
• Passive
• Injection of serum with
antibodies from one person
(e.g., injection of hepatitis
B immune globulin) to
another person who does
not have antibodies

Body System Disruption
• Innate Immune
Response
• Barriers (first
line)
• Physical and
Mechanical
• Biochemical

Body System Disruption
• Innate Immune Response (con’t)
• Inflammation (2nd line of defense)

Inflammatory Response
• Mechanism of inflammation basically the same
regardless of injuring agent
• Intensity of the response depends on
• Extent and severity of injury
• Reactive capacity of injured person
Copyright © 2017, Elsevier Inc. All Rights Reserved.

• Inflammatory response can be divided into
• Vascular response
• Cellular response
• Formation of exudate
• Healing

Vascular and Cellular
Response toTissue Injury

Vascular Response
• After cell injury, arterioles in area briefly undergo
transient vasoconstriction
• After release of histamine and other chemicals by
injured cells, vessels dilate, resulting in hyperemia
• Vasodilation chemical mediators
• Increased capillary permeability
• Movement of fluid from capillaries into tissue spaces

Vascular Response
• Fluid in tissue spaces
• Initially composed of serous fluid
• Later contains plasma proteins, primarily albumin
• Proteins exert oncotic pressure that further draws fluid from
blood vessels
• Tissue becomes edematous

Vascular Response
• As plasma protein fibrinogen leaves blood, it is
activated to fibrin by products of injured cells
• Fibrin strengthens blood clot formed by platelets
• In tissues, clot traps bacteria to prevent spread

Cellular Response
• Blood flow through capillaries in area of
inflammation slows as fluid is lost and
viscosity increases
• Neutrophils and monocytes move to inner
surface of capillaries and then migrate
through capillary wall to site of injury

Cellular Response
• Chemotaxis
• Directional migration of WBCs along concentration
gradient of chemotactic factors
• Mechanism for accumulating neutrophils and
monocytes at site of injury

Cellular Response
• Chemotactic factors
• Bacterial-derived
• Complement-derived (C5a, C3a)
• Lipid-derived
• Platelet-derived
• Coagulation-related
• Chemokines

Cellular Response
• Neutrophils
• First leukocytes to arrive at site of injury (6 - 12 hours)
• Phagocytize bacteria, other foreign material, and
damaged cells
• Short life span (24 - 48 hours)

Cellular Response
• Neutrophils
• Pus is composed of
• Dead neutrophils accumulated at site of injury
• Digested bacteria
• Other cell debris

Cellular Response
• Neutrophils
• Bone marrow releases more neutrophils in response to
infection, resulting in elevated WBC

Cellular Response
• Monocytes
• Second type of phagocytic cells to migrate to site of
injury from circulating blood
• Attracted to the site by chemotactic factors
• Arrive within 3 to 7 days after onset of inflammation

Cellular Response
• Monocytes
• On entering tissue spaces, monocytes transform into
macrophages
• Assist in phagocytosis of inflammatory debris
• Macrophages have a long life span and can multiply

Cellular Response
• Macrophages
• Important in cleaning area before healing can occur
• May stay in damaged tissues for weeks
• Cells may fuse to form multinucleated giant cell

Cellular Response
• Lymphocytes
• Arrive later at the site of injury
• Primary roles of lymphocytes involve
• Cell-mediated immunity
• Humoral immunity

Cellular Response
• Chemical mediators
• Histamine
• Serotonin
• Kinins (e.g., bradykinin)

Cellular Response
• Chemical mediators
• Complement system (C3a, C4a, C5a)
• Prostaglandins and leukotrienes
• Cytokines

Cellular Response
• Complement system
• Major mediator of inflammatory response
• Enzyme cascade (C1-C9) consisting of pathways to
mediate inflammation and destroy invading pathogens

Cellular Response
• Major functions of complement system
• Enhanced phagocytosis
• Increased vascular permeability
• Chemotaxis
• Cellular lysis

Cellular Response
• Complement system
• Final components of complement system create holes in
cell membrane, causing targeted cell death by
membrane rupture

Cellular Response
• Prostaglandins
• Following injury, arachidonic acid is converted into
prostaglandins, thromboxane, and leukotrienes
• Considered proinflammatory
• Potent vasodilators

Pathway of Generation
Pathway of generation of prostaglandins, thromboxane, and
leukotrienes. Corticosteroids, nonsteroidal antiinflammatory drugs
(NSAIDs), and acetylsalicylic acid (ASA) act to inhibit various steps in this
pathway.

Cellular Response
• Thromboxane
• Powerful vasoconstrictor
• Platelet-aggregating agent
• Promotes clot formation

Cellular Response
• Leukotrienes
• Slow reacting substance of anaphylaxis (SRS-A)
• Constricts smooth muscle of bronchi

Cellular Response
• Exudate
• Consists of fluid and leukocytes that move from
circulation to site of injury
• Nature and quantity depend on type and severity of
injury and tissues involved

Clinical Manifestations
• Local response to inflammation
• Redness
• Heat
• Pain
• Swelling
• Loss of function

• Local Response
Inflammation secondary to postoperative deep wound infection
following wrist surgery
(From Hayden RJ, Jebson PJL: Wrist arthrodesis, Hand Clinics 21[4]:631, 2005)

• Systemic response to inflammation
• Increased WBC count with a shift to the left
• Malaise
• Nausea and anorexia
• Increased pulse and respiratory rate
• Fever

• Causes of the systemic response are poorly understood,
but it is probably due to complement activation and
release of cytokines
• Some of the cytokines are interleukins (ILs) and tumor
necrosis factor

• Fever
• Onset is triggered by release of cytokines
• Cytokines cause fever by initiating metabolic changes in
temperature-regulating center in hypothalamus
• Epinephrine released from adrenal medulla increases
metabolic rate

Production of Fever
When monocytes/macrophages are activated, they secrete cytokines such as interleukin-1 (IL-1),
interleukin-6 (IL-6), and tumor necrosis factor (TNF), which reach the hypothalamic
temperatureregulating center. These cytokines promote the synthesis and secretion of prostaglandin
E2 (PGE2) in the anterior hypothalamus. PGE2 increases the thermostatic set point, and the autonomic
nervous system is stimulated, resulting in shivering, muscle contraction, and peripheral
vasoconstriction.

• Fever
• Patient then experiences chills and shivering
• Body is hot, yet person seeks warmth until circulating
temperature reaches core body temperature

• Beneficial aspects of fever include:
• Increased killing of microorganisms
• Increased phagocytosis
• Increased proliferation of T cells

Types of Inflammation
• Acute
• Healing occurs in 2 to 3 weeks, usually leaving no
residual damage
• Neutrophils are predominant cell type at site of
inflammation

• Subacute
• Has same features as acute inflammation but persists
longer

• Chronic
• May last for years
• Injurious agent persists or repeats injury to site
• Predominant cell types involved are lymphocytes and
macrophages
• May result from changes in immune system (e.g.,
autoimmune disease)

Nursing and Interprofessional
Management
• Nursing Implementation
• Health Promotion
• Prevention of injury
• Adequate nutrition
• Early recognition of inflammation
• Immediate treatment

Management
• Acute Intervention
• Observation
• Vital signs
• Fever management

Management
• Drug therapy
• Aspirin
• Acetaminophen
• NSAIDs
• Corticosteroids

Management
• RICE
• Rest
• Ice
• Compression and immobilization
• Elevation

Inflammation
Healing Process
• The final phase of the inflammation process is
healing
• Healing includes two major components:
• Regeneration
• Repair

• Antigens
• Substances the body recognizes as foreign that elicit an
immune response
• Most are composed of protein
• Antibodies
• Immune globulins produced by lymphocytes in
response to antigens

Organs of Immune System

Lymphoid Organs
• Central (primary) lymphoid organs
• Thymus gland
• Thymus gland shrinks with age
• Involved in the differentiation and maturation of T
lymphocytes
• Bone marrow
• Produces RBCs,WBCs, and platelets

Lymphoid Organs
• Peripheral lymphoid organs
• Lymph nodes
• Tonsils
• Spleen
• Lymphoid tissues associated with gut, genitals, bronchi,
and skin

Macrophages and Lymphocytes in
Immune Response
Copyright © 2017, Elsevier 53

Normal Immune System
Cells of Immune Response
• Mononuclear phagocytes
• Include monocytes in blood and macrophages found
throughout body
• Capture, process, and present antigens to lymphocytes
to initiate an immune response
• Capture antigens by phagocytosis

Normal Immune System
Cells of Immune Response
• Lymphocytes
• Produced in bone marrow
• Eventually migrate to peripheral organs
• Differentiate into B andT lymphocytes
• T Cytotoxic cells
• T Helper cells

Types of Lymphocytes
T cells 70%–80%
B cells 10%–20%
Natural killer (NK) cells <10%

• Dendritic Cells
• Important in activating immune response
• Capture antigens at sites of contact with external
environment
• Transport an antigen until it encounters aT cell with specificity
for antigen

• Cytokines
• Soluble factors secreted byWBCs and a variety of other
cells in body
• Act as messengers among cell types
• Instruct cells to alter their proliferation, differentiation,
secretion, or activity

• Cytokines
• Currently at least 100 different cytokines
• Have a beneficial role in hematopoiesis and immune
function
• Can have detrimental effects
• Chronic inflammation
• Autoimmune diseases
• Sepsis

• Cytokine types
• Interleukins
• Interferons
• Tumor necrosis factor
• Colony-stimulating factors
• Erythropoietin

Cytokines
• IL-1
• Augments immune response
• Inflammatory mediator
• Promotes proliferation of B cells
• Enhances activity of natural killer cells
• ActivatesT cells, NK cells, and macrophages

Cytokines
• IL-2
• ActivatesT cells, NK cells, and macrophages
• Stimulates release of other cytokines
• α-IFN,TNF, IL-1, IL-6

Cytokines
• IL-3
• Hematopoietic growth factor for hematopoietic
precursor cells

Cytokines
• IL-4
• Antiinflammatory mediator
• B-cell growth and differentiation
• Induces differentiation into TH2 cells
• Stimulates growth of mast cells

Cytokines
• IL-5
• B-cell growth and differentiation
• Promotes growth and differentiation of eosinophils

Cytokines
• IL-6
• T- and B-cell growth factor
• Enhances inflammatory response
• Stimulates antibody secretion
• Promotes differentiation of B cells into plasma cells

Cytokines
• IL-6
• Induces fever
• Synergistic effects with IL-1 andTNF

Cytokines
• -Interferon (-IFN) and β-interferon (β-INF)
• Inhibit viral replication
• Activate NK cells and macrophages
• Antiproliferative effects on tumor cells

Cytokines
• γ-Interferon (γ-IFN)
• Activates macrophages, neutrophils, and NK cells
• Promotes B-cell differentiation
• Inhibits viral replication

Mechanism of Action of Interferon

Cytokines
• Tumor necrosis factor (TNF)
• Activates macrophages and granulocytes
• Promotes immune and inflammatory responses
• Kills tumor cells
• Responsible for extensive weight loss
• Associated with chronic inflammation and cancer

Cytokines
• Colony-stimulating factors (CSFs)
• Granulocyte colony-stimulating factor
(G-CSF)
• Granulocyte-macrophage colony-stimulating factor
(GM-CSF)
• Macrophage colony-stimulating factor
(M-CSF)

Comparison of
Humoral and Cell-Mediated Immunity
Humoral Cellular
Cells involved B cells •T cells
• Macrophages
Products Antibodies • SensitizedT cells
• Cytokines
Memory cells Present Present

Comparison of
Humoral and Cell-Mediated Immunity
Humoral Cellular
Protection • Bacteria
• Viruses
(extracellular)
• Respiratory
pathogens
• GI pathogens
• Fungus
• Viruses
(intracellular)
• Chronic infectious
agents
• Tumor cells

Humoral Immunity
• Antibody-mediated immunity
• Antibodies produced by plasma cells
(differentiated B cells)
• Primary immune response is evident
4 to 8 days after initial exposure to antigen

Humoral Immunity
• Five classes of immune globulins
• Each has specific characteristics
• IgG
• lgA
• lgM
• lgD
• lgE

Humoral Immunity
• When an individual is exposed to an antigen for a
second time, response is faster (1 to 3 days) and
lasts longer
• Main product of secondary response is IgG rather than
IgM
• Memory cells account for more rapid production of IgG

Primary and Secondary Immune
Response

Cell-Mediated Immunity
• Immune responses initiated through specific
antigen recognition byT cells
• Several cell types involved in cell-mediated
immunity
• T cells
• Macrophages
• NK cells

Cell-Mediated Immunity
• Important roles
• Immunity against pathogens that survive inside cells
(viruses, some bacteria)
• Fungal infections
• Rejection of transplanted tissues
• Contact hypersensitivity reactions
• Tumor immunity

Immune Response toVirus
The immune response to a virus. A, A virus invades the
body through a break in the skin or another portal of
entry. The virus must make its way inside a cell to replicate
itself. B, A macrophage recognizes the antigens on the
surface of the virus. The macrophage digests the virus and
displays pieces of the virus (antigens) on its surface. C, T
helper cell recognizes the antigen displayed and binds to
the macrophage. This binding stimulates the production of
cytokines (interleukin-1 [IL-1] and tumor necrosis factor
[TNF]) by the macrophage and interleukin-2 (IL-2) and γ-
interferon (γ-IFN) by the T cell. These cytokines are
intracellular messengers that provide communication
among the cells. D, IL-2 instructs other T helper cells and T
cytotoxic cells to proliferate (multiply). T helper cells
release cytokines, causing B cells to multiply and produce
antibodies. E, T cytotoxic cells and natural killer cells
destroy infected body cells. F, The antibodies bind to the
virus and mark it for macrophage destruction. G, Memory
B and T cells remain behind to respond quickly if the same
virus attacks again.

Effects of Aging on
Immune System
• Immunosenescence
• ↑ Incidences of tumors
• Greater susceptibility to infection
• ↑ Autoantibodies
• ↓ Cell-mediated immunity
• Thymic involution

Effects of Aging on
Immune System
• Immunosenescence
• ↓ Delayed hypersensitivity reaction
• ↓ IL-1 and IL-2 synthesis
• ↓ Expression of IL-2 receptors
• ↓ Proliferation response ofT and B cells
• ↓ Primary and secondary antibody responses

References
• Hoffman, J., and Sullivan, N. Medical-Surgical Nursing:
Making connections to practice. F.A. Davis Company,
Philadelphia.
• Lewis, S., Bucher, L., Heitkemper, M., Harding, M.,
Kwong, J., and Roberts, D. (2017). Medical- Surgical
Nursing, 10th Edition. Elsevier, St. Louis.
• Lilley, L., Collins, S., and Snyder, J. Pharmacology and the
Nursing Process. Elsevier, St. Louis.
• Smith, B. T. (2016). Pharmacology for Nurses. Jones &
Bartlett Learning, Burlington.
• All other material is the copyrighted material of Benjamin
Ketcherside, II, MSN, RN.
Copyright © 2018-19. Benjamin Ketcherside. All Rights Reserved.

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