Immunity

Function of immune system

• defense against foreign substances

• maintaining health

• surveillance - go around check for foreign antigen to destroy

• when immune altered → inflammation, infection, tissue integrity

Types of immunity

• Innate:

  • present at birth

  • first-line defense against pathogens

  • quick response

• Acquired:

  • developed immunity

Types of acquired specific immunity

• Natural

  • Active:

    • natural contact with antigen thru actual infection (chickenpox, measles, mumps)

    • immunity takes time to develop but is long lasting

  • Passive:

    • transplacental and colostrum transfer from mother to child (maternal immunoglonbulins passed to baby)

    • immunity is immediate but short lived

Types of acquired specific immunity

Artificial:

• Active:

  • immunization with antigen (vaccines fie chicken pox, measles, mumps)

  • immunity take times to develop but long lasting

• Passive:

  • injection of serum with antibodies from one person (injection of hep B immune globulin) to another person who does not have antibodies

  • immunity is immediate but short lived

Antigens

Substances that elicits an immune response

• most are composed of protein

• other substances can act as antigens (polysaccharides, lipoproteins, nucleic acids)

• unique to each person

• enables the body to recognize itself

Antibodies

• Immune globulins produced by lymphocytes in response to antigens

Cental lymphoid organs

• Thymus gland:

  • differentiation and maturation of T lymphocytes

  • shrinks with age

• Bone marrow:

  • produces RBCs, WBCs, and platelets

  • lymphocytes migrate to the peripheral organs

Peripheral lymphoid organs

• lymph nodes - antigens carried thru blood or lymph channels here

  • filter foreign material

  • circulate lymphocytes

• Tonsils

• Spleen - primary site for filtering foreign antigens from blood

• lymphoid tissues associated with gut, genitals, bronchi, and skin

Lymphocytes

• made in bone marrow

• eventually migrate to peripheral organs

• differential into B and T lymphocytes (T-cytotoxic and T-helper)

Mononuclear phagocytes

• critical role in immune system

• include monocytes in blood and found thru body

• capture, process, and present antigens to lymphocytes to initiate immune response

• capture antigens by phagocytosis

Types of lymphocytes

• B cells (10-20%)

  • plasma make antibodies

• T cells (70-80%)

  • immunity to intracelluar viruses, tumor cells, fungi

  • account for long-term, immunity

• Natural killer (NK) cells: less than 10%

  • lymphocytes with many granules in their cytoplasm

  • virus-infected cells, tumor cells. transplanted grafts

T cytotoxic cells (CD8)

• sensitized by exposure to an antigen

• attack antigens on cell membrane of foreign pathogens

• release cytolytic substances that destroy the pathogen

T helper cells (CD4)

• involved in regulating cell-mediated immunity and the humoral antibody response

• differential into subsets of cell that make cytokines

Dendritic cells (macrophages)

• important in activating immune response

  • capture antigens at sites of contact with external environment

  • found in many places - skin, lining of nose, lungs, stomach, intestine

  • transport the antigen until it meets a T-cell with specific antigen

Cytokines

• Soluble, secreted by WBCs and a variety of other cells in body

• messengers between the cell types

• tell cells to change their proliferation, differentiation, secretion, or activity

• at least 100 different cytokines

• benefit role in hematopoiesis and immune fuction

• can have detrimental effects

  • chronic inflammation

  • autoimmune diseses

  • sepsis

a-Interferon (a-IFN) and β-interferon (β-INF)

• inhibit viral replication

• activate NK cells and macrophages

• anti-proliferation effects on tumor cells

γ-Interferon (γ-IFN)

• inhibit viral replication

• activate NK cells, macrophages and neutrophils

• promote B-cell differentiation

IL-1

• pro-inflammatory mediator

• promotes proliferation of B cells

• activates T cells, Nk cells, and macrophages

IL-2

• activate T cells, NK cells, and macrophages

• Stimulates release of other cytokines

  • α-IFN, TNF, IL-1, IL-6

IL-3

• hematopoietic growth factors for hematopoietic precursor cells

IL-4

• Anti-inflammatory mediator

• B-cell growth and differentiation

• induces differentiation into Th2 cells

• stimulates growth of mast cells

IL-5

• B-cell growth and differentiation

• Promotes growth and differentiation of eosinophils

IL-6

• T and B cells growth factor

• promotes differentiation of B cells into plasma cells

• stimulates antibodies secretion

• induce fever

• synergistic effects with IL-1 and TNF

Tumor necrosis factor (TNF)

• Activates macrophages and granulocytes

• promotes immune and inflammatory responses

• kill tumor cells

• responsible for weight loss - associated with chronic inflammation and cancer

Comparison of humoral and cell-mediated immunity

• cell involved

  • Humoral: B cells

  • Cellular: T cells, macrophages

• products:

  • humoral: antibiodies

  • cellular: t cells, cytokines

• Memory cells: both at present

• Protection:

  • humoral: bacteria, viruses (extracellular), respiratory pathogens, GI pathogens

  • cellular: fungus, viruses (intracellular), chronic infectious agents, tumor cells

Humoral immunity

• antibody-mediated immunity

• antibodies made by plasma cells (B cells)

• primary immune response is evident 4-8 days after the first exposure to antigen

• 5 classes immunoglobulins (IgG, IgA, IgM, IgD, IgE)

• When a person is exposed to the antigen for a second time, response is faster (1-3 days) and lasts lomger

  • memory cells account for more rapid production of antibodies

  • main product of secondary response IgG rather than IgM

Cell-mediated immmunity

• immune responses initiated thru specific antigen recognition by T cells

• several cell types and factors are involved in cell-mediated immunity (T cells, macrophages, NK cells)

• Roles:

  • immunity against pathogens that survive inside cells (viruses, some bacteria)

  • fungal infection

  • rejection of transplanted tissues

  • contact hypersensitivity reactions

  • tumor immunity

Effects of aging on immune system

Immunosenescence

• high incidences of cancer

• greater susceptibility to infection

• increase autoantibodies

• lowered cell-mediated immunity

• Thymus shrink with age, decreased number T cells (primary cause)

• Lower delayed hypersensitivity reaction

• reduced IL-1 and IL-2 synthesis

• reduced expression of IL-2 receptors

• reduced proliferation response of T and B cells

• reduced primary and secondary antibody response

Altered immune response

• Immunocompetence:

  • immune system identifies and inactivates or destroys foreign substances

• Incompetent or under responsive immune system

  • severe infections, cancers, immunodeficiency

• Overreactive immune system

  • hypersensitivity disorders

Hypersensitivity reaction

• immune response is overreactive against foreign antigens

• reacts against its own tissue

• results in tissue damage

• Autoimmune disease occurs when the body does not recognize self-proteins and reacts against self-antigens

• Classified by

  • source of antigen

  • time sequence (immediate or delayed)

  • immunologic mechanisms causing injury

• 4 types:

  • 1,2,3: immediate (ex: humoral immunity)

  • 4: delayed (ex: cell-mediated immunity)

Type 1 hypersensitivity reactions

• Anaphylactic reactions

  • occur in susceptible people who are highly sensitized to specific allergens

  • release mediators attack target tissue, causing clinical symptoms of an allergic response that are short acting and reversible

  • smooth muscle contraction

  • increased vascular permeability

  • vasodilation

  • hypotension

  • increased secretion of mucus

  • itching

• Genetic predisposition

  • develop allergic disease exist

  • sensitized to an allergen, rather than the specific allergic disorder

Manifestation of anaphylactic reaction

• Localized:

  • cutaneous wheal and flare reaction (ex: mosquito bite)

  • occurs in minutes or hours

  • usually not dangerous

• Systemic:

  • Anaphylaxis

    • occurs within 1 min

    • life threatening - bronchial constriction, subsequent airway obstruction, vascular collapse

    • Shock

    • bronchial edema and angioedema

    • drugs are the leading cause

  • Atopic - inherited tendency to become sensitive environmental allergens

Allergic rhinitis (hay fever)

• Most common type I hypersensitivity reaction

• Perennial allergic rhinitis - year-round

  • Dust, molds, and animal dander

• Seasonal allergic rhinitis - seasonal

  • pollens, dust, molds

• Nasal discharge, sneezing, tearing, mucosal swelling with airway obstruction, pruritus around eyes, nose, throat, mouth.

Asthma

• often have a history of atopic disorders

• causes:

  • bronchial smooth muscle constriction

  • excess secretion of thick mucus

  • edema of the mucous membranes of the bronchi

  • decreased lung compliance

Atopic dermatitis

• chronic, inherited skin characterized by exacerbations and remissions

• caused by environmental allergens

Urticaria (hives)

• transient wheals (pink, raised, edematous, itchy area) vary in size and shape

• may occur all over the body

• develop rapidly after exposure and last minutes to hours

• Histamine caused localized vasodilation (erythema), transudation of fluid (wheal), and flaring

Angioedema

• localized cutaneous lesion involving deep layers of skin and submucosa

  • eyelids, lips, tongue, larynx, hands, feet, GI tract, genitalia

  • diffuse swelling occurs suddenly or over several hours

  • outer skin appears normal or has a reddish hue

  • usually lasts 24 hrs

Type 2 hypersensitivity reaction

• cytotoxic and cytolytic reaction

• target cells: erythrocytes, platelets, and leukocytes, some ABO blood groups

• Pathophysiologic disorders:

  • ABO compatibility transfusion reaction

  • Rh incompatibility transfusion reaction

  • autoimmune and drug-related hemolytic anemias

  • leukopenia

  • thrombocytopenia

  • erythroblastosis fetalis (hemolytic disease of the newborn)

  • Goodpasture syndrome

Hemolytic transfusion reactions

• recipient receives ABO-incompatible blood from a donor

• causing agglutination (clumping)

• cells lysis occurs → release hgb into urine and plasma → acute kidney injury can result from hemoglobinuria

Goodpasture syndrome

• disorders involving in lungs and kidneys

• results in pulmonary hemorrhage and glomerulonephritis

Type 3 Hypersensitivity reaction

• caused tissue damage in immune-complex reactions

  • result from antigen-antibody complexes → not effectively remove by phagocyte → deposit in tissue or small blood vessels → activation of complement system → release of chemotactic factors → inflammation and destruction involved tissues

  • local or systemic reactions

  • immediate or delayed reactions

  • associated with autoimmune disorders

    • systemic lupus erythematosus (SLE)

    • acute glomerulonephritis

    • rheumatoid arthritis

Type 4 hypersensitivity reaction

• delayed hypersensitivity reaction

  • cell-mediated immune response in 24-48 hrs

  • tissue damage:

    • sensitized T cells attack antigens or release cytokines

    • these cytokines attract macrophage → due to destruction of tissue

    • contact dermatitis

    • hypersensitivity reactions to bacterial, fungal, viral infections

    • transplant rejections

    • some drugs sensitivity reactions

Autoimmunity

• immune response against the self

• immune cells normally unresponsive are activated

• T cells and B cells have ability for tolerance to self-antigens, alteration can produce auto-antibodies and autosensitized T cells to cause pathophysiologic damage

Apheresis

a produce to separate components of the blood followed by the removal of 1 or more of the components

• Cytapheresis: cell separation and removal

• Plateletpheresis: removal of platelets (collecting platelets from normal person to infuse to pt with low platelet)

• Leukocytapheresis: removal of WBC (used in chronic myelogenous leukemia to remove high numbers of leukemic cells)

• Plasmapheresis: removal of plasma containing components causing or thought to cause disease

  • plasma replaced by substitute fluids - plasma exchange

  • used to treat autoimmune diseases: SLE, glomerulonephritis, Goodpasture syndrome, myasthenia gravis, rheumatoid arthritis, Guillain-Barre