Pathophysiology Chapter 4: Altered Immunity

immunity

the process by which the body recognizes foreign substances and neutralizes them to prevent damage

innate immunity

-Present from birth

-Capable of attacking any non-self substance

-Rapid and broad (shotgun)

parts of innate immunity

-neutrophils

-natural killer cells

-dendritic cells

-monocytes

adaptive immunity

-Intercepts non-self, learns, programs, produces specific response (rifle)

-"immune response"

immunology

The study of the structure and the function of the immune system, including

1. immunity

2. induced sensitivity

3. allergies

specificity

the immune cells seek out and destroy targeted foreign invaders

memory

immune cells produce substances that remember and more easily destroy return offenders

antigen

substance that induces a state of sensitivity or an immune response

recognized by the body as foreign and "non-self"

pathogen

A disease causing entity or foreign antigen that causes disease

the adaptive immune response is initiated by 2 main components

1. type of antigen presented to the cells

2. type of cells to which the antigen is presented

the pluripotent hematopoietic stem cells (adaptive immunity) produce two precursor types

1. lymphoid progenitor (natural killer cells, T lymphocytes, and B lymphocytes)

2. myeloid progenitor (monocytes, dendritic cells, granulocytes, and mast cells

leukocytes

-Functional units of the immune system

-Lymphocytes account for ~ 20 - 25% of leukocytes circulating in the blood

-99% of lymphocytes reside in the lymph fluid

3 major types of leukocytes are derived from lymphoid progenitor cells

1. T lymphocytes

2. B lymphocytes

3. natural killer cells

T lymphocytes

-Mature and fully differentiate in the thymus

-Require contact with an antigen that signals the T-lymphocytes to proliferate and differentiate into one of 3 types

T lymphocyte types

1. cytotoxic lymphocytes

2. helper T lymphocytes

3. suppressor T lymphocytes

cytotoxic T lymphocytes

direct destruction of antigen carrying cells

attack tumor cells and cells infected with viruses

helper T lymphocytes

enhance humoral and cell mediated response of the immune system

activates other cells needed for an appropriate immune response

suppressor T lymphocytes

inhibit humoral and cell mediated responses

provide a balance, limiting immune responses

T-cell receptor (TCR)

unique receptor able to bind to antigens promoting a specific immune response

B lymphocytes

-Develop in bone marrow; become activated when in contact with an antigen after migrating to lymphoid tissues

-Binding with antigen stimulates differentiation into plasma cells which secrete antibodies

B-cell receptor (BCR)

- bound to cell membranes of B-lymphocytes

- help B lymphocytes recognize certain antigens

- uniqueness of antigen-BCR binding contributes to specificity of the adaptive immune response

- after binding, the B-lymphocytes differentiate into plasma cells which proliferate and begin to produce and secrete large quantities of antibodies that target the specific antigen bound to the BCR

-plasma cell membranes release antibodies (Ig's)

immunoglobulin (Ig)

antibodies released from plasma cell membranes that target antigens bound to BCR

immunoglobulin classes

IgA (15%) - body secretions

IgG (75%) - most common circulating antibody

IgM (10%) - first Ig to proliferate in immune system

IgD (0.2%) - bound to activate B cells

IgE (0.004%) - stimulates mast cells in skin and mucous membranes

IgA

body secretions ; protection of mucous membrane

IgD

Bound to and activates B cells

IgE

Stimulates mast cells in skin and mucous membranes

IgG

1' and 2' immune response; activates complement; passive immunity in NB via placental transfer; antibody activity against toxins, viruses, and bacteria

IgM

-FIRST Ig to proliferate in immune system

-Bound to B-lymphocytes; activates complement

natural killer cells

large granular lymphocytes; circulate until they come in contact with threatening cells, then excrete cytotoxic effect through attack and killing targeted cells

myeloid progenitor cells

produce granulocytes and monocytes (both leukocytes essential to immune function)

granulocytes

-neutrophils aka PMNs

-eosinophils (parasites)

-basophils (Complement mast cells; important in allergic reactions)

monocytes

differentiate into macrophages

macrophage cell types

1. histiocytes (loose connective tissue)

2. microglial cells (brain)

3. kupffer cells (liver)

dendritic cells

processing and display of antigens to T lymphocytes

Langerhans cells

immature dendritic cells

two components of lymphatic system

1. peripheral organs

2. central organs

peripheral organs

spleen, lymph nodes, and lymphoid tissue

central organs

sites for lymphocyte maintenance

bone marrow and thymus

lymph fluid

-Filtered from tissues and returned to vascular system

-Circulates lymphocytes through body

-Maintains signals to naïve lymphocytes

*Those that have not yet encountered an antigen

*Absence of a signal results in apoptosis

active immunity

-Development of antibodies to an antigen

-Achieved by having a specific disease or vaccine

passive immunity

-Immunity transfer from host to recipient

-Achieved via mother-infant transfer (placenta or breast milk) or injection of antibody

key properties of active immunity

-Specificity: Targeted response to a distinct antigen

-Diversity: Recognition of a wide variety of antigens

-Memory: Rapid and robust response to previously recognized antigens

-Self and Non-self recognition: Ability to distinguish between antigens on body cells and foreign antigens

humoral immunity

-Refers to adaptive immunity involving antibodies

-Primary adaptive immune response (Activation with first recognition of a specific antigen)

-Secondary adaptive immune response (Reactivation with later recognition of the same antigen)

-mediated by B lymphocytes

antibodies protect cells from pathogens in 3 major ways

-Neutralization: binding of antigen to antibody prevents the antigen from infecting cells

-Opsonization: promotes phagocytosis of bound antigen

-Activation of complement system: enhances actions of the antibodies

cell-mediated immunity components

-Cytotoxic T lymphocytes: CD8 (primary cell involved)

-Helper T lymphocytes (TH1, TH2): CD4

-MHC (class 1 and 2)

process of altering immune function

-Host defense failure

-Hypersensitivity

-Autoimmunity

-Alloimmunity

host defense failure

-Antigenic variation

-Viral latency: period of inactivity; remains undetected

-Immunodeficiency

antigenic variation

-Method used by antigens to evade immune response

-Many pathogens have multiple variations of antigens making recognition difficult

viral latency

Period of viral inactivity used to evade immune response

immunodeficiency

-Most significant form of immunosuppression

-Frequently presents with recurrent, frequent infections

types of immunodeficiencies

1. primary - Often caused by a genetic mutation impairing immune responsiveness

2. secondary - Immunodeficiency that is a result of another disease

secondary immunodeficiencies include

-Defective humoral function

-Deficient phagocyte numbers and functional ability

-Altered T-lymphocyte signaling

-Altered cytokine production and function

hypersensitivity type 1

-immediate hypersensitivity reaction

-IgE mediated

-Allergic reactions; local (atopic) inflammation; system (anaphylactive) life-threatening reactions

hypersensitivity type 2

-antibody-mediated hypersensitivity reaction

-IgG or IgM mediated

-reaction against normal "self" antigens; opsonization and lysis of cells

hypersensitivity type 3

-immune complex-mediated reaction

-IgG or IgM mediated

-Deposition of insoluble antigen-antibody complex

hypersensitivity type 4

-cytotoxic T lymphocyte-mediated hypersensitivity reaction

-Inflammatory response leading to cell lysis

-T-CELL MEDIATED

-Direct cell-mediated toxicity

-Delayed hypersensitivity reaction

autoimmunity

-Failure to distinguish self from non-self

-Causes damage to specific organs or to the entire system

major causes of autoimmunity

1. Specific recognition of "self" antigens

2. Overzealous responses to chronic infection

autoimmunity triggers

-Inadequate elimination of self-reactive lymphocytes in the central lymphoid tissues

-Altered lymphocyte ignorance (converting lymphocytes from non-responsive to self-reactive)

-Stimuli (exp: infection) overriding the non-responsive nature of naïve T-lymphocytes

-Failure to recognize antigen due to MHC-antigen complex interaction

-Molecular mimicry: close resemblance between foreign and self antigens

-Release of antigens sequestered during development

-Action of super-antigens

alloimmunity

-Occurs when an immune response is stimulated in response to the presence of cells from another individual of the same species

Examples:

Following grafts

rH factor disease

alloantigen

Proteins that vary between individuals

grafts

Unattached tissues or organs used for implantation commonly used in treatment of disease

autograft

Grafts from different sites on the same person

syngenic grafts

Grafts from genetically identical monozygous twins

allografts

Grafts between unrelated individuals

graft vs. host disease

-Medical condition following transplant from genetically different individual

-Commonly associated with stem cell (BM) transplant

-Immune cells from the donated tissue (graft) recognize the recipient (the host) as foreign (non-self)

-Transplanted immune cells then attack the host cell's body cell

type I immune reactions (hypersensitivity)

immediate hypersensitivity (allergic reactions)

ex)

-Hay fever (seasonal allergies)

-Asthma

-Anaphylaxis

AIDS (pathophysiology)

-Altered host defense resulting from secondary immunodeficiency

*Infection of CD4 helper T lymphocytes with human immunodeficiency virus (HIV)

-Results in loss of cell-mediated and humoral immunity due to loss of CD4 TH1 lymphocytes

AIDS (clinical manifestations)

-Immunosuppression

-Opportunistic infections

*Fungal infection

*Pneumocystis jiroveci pneumonia

-Kaposi sarcoma

AIDS (treatment)

-antiretroviral therapy (ART)

*Suppress viral load

*Restore or preserve immune function

*Reduce morbidity and mortality

-drugs in combination to reduce the development of drug resistance

Anaphylactic reaction (pathophysiology)

-Exaggerated systemic immune response due to a type 1 hypersensitivity reaction

-Antigen exposure stimulates an IgE-mediated response in a previously sensitized individual

-Degranulation of mast cells and basophils causes local and systemic responses

*Dilation of vascular smooth muscle

*Constriction of bronchial smooth muscle

*Increase in vascular permeability

Anaphylactic reaction (clinical manifestations)

Phase 1:

-Difficulty breathing

-Skin flushing and itching

-Angioedema

Phase 2:

-Difficulty breathing

-Severe hypotension

-Severe edema

Anaphylactic reaction (treatment)

-symptomatic: limit inflammation

*Drugs to relax bronchial smooth muscle

*Drugs to constrict vascular smooth muscle

-preventative: desensitization to allergen

Systemic Lupus Erythematosus (SLE)

-Type III hypersensitivity reaction

-Autoimmune response

-Involves responses by the innate and adaptive immune systems

-Chronic disease due to persistent antigen

*Activation of B cells, producing antibodies

*Activation of T cells, promoting inflammation

-Systemic condition

*Autoantibodies targeted against the cell membrane, cytoplasm and nucleus

SLE (clinical manifestations)

Local (Skin, musculoskeletal, pulmonary, and kidney)

Systemic (Neurologic, pulmonary, hematologic, and cardiac disease)

Rh Isoimmunization (Pathophysiology)

-Mechanism that causes Hemolytic Disease of the Newborn (HTN)

-Type II cytotoxic antibody-mediated reaction

-Direct antigen-antibody hypersensitivity reaction involving the Rho(D) antigen on red blood cells

-Antibodies against the Rh antigen (anti-D) attack red blood cells causing hemolysis

-Often occurs in Rh-negative mothers exposed to fetal Rh-positive antigen

Rh Isoimmunization (clinical manifestations)

Fetal effects - anemia, hydrops (edema), death

Infants - kernicterus (bilirubin deposits in brain), lethargy, hearing loss, cerebral palsy, learning problems

type II immune reactions (antibody mediated)

-Tissue-specific reactions

-Cytotoxic hypersensitivity

-Includes:

*Blood transfusion reaction

*Goodpasture's disease

Goodpasture's disease

-Rare autoimmune disease in which antibodies attack the basement membranes in the lungs and kidneys

-leads to bleeding from the lungs and renal failure

type III immune reactions (complex mediated)

-Reactions to autoimmune diseases

-arthrus reaction

arthrus reaction

-Local vasculitis associated with deposition of immune complexes and activation of complement

-Rarely reported after vaccination

-Can occur after DPT vaccines

Type IV Cell-mediated tissue reactions

-Cellular hypersensitivity

-TB

-Tuberculin Skin Test (PPD)

-Contact dermatitis

-Transplant rejection

purified protein derivatives (PPD)

The TB antigens used in a tuberculin skin test