The Immune Response & Lymphatic System

Lesson focus - Describe the immune system, compare innate and adaptive immunity, identify major immune cells, and explain how the body responds to infection.

Fundamentals

Immunology and Immunity

Immunology - study of the genetic, biological, chemical, and physical characteristics of the immune system.
Immunity - the body's ability to respond to the presence of any foreign substance.

Two Major Types of Immunity

Type	Description
Innate immunity	Nonspecific
Adaptive immunity	Specific

Antigens

An antigen is any agent capable of binding specifically to components of the immune system and triggering an immune response.

Major Histocompatibility Complex

The major histocompatibility complex, or MHC, recognizes and tolerates self-antigens and rejects foreign antigens.

MHC I

Encodes self-antigen characteristics.
Aids in recognition of self.
Allows NK cells and T cells to target infected cells.

MHC II

Receptors that recognize foreign antigens.
Located on macrophages and B cells.
Involved in presenting exogenous antigens to T cells during the immune response.

MHC at Work

In transplants, the body may reject transplanted tissue because it does not recognize the MHC as self.
Transplant patients may be placed on immunosuppressing medications.
Blood types are dictated by which antigens are present on RBCs.

Antibodies

Antibodies are also called immunoglobulins, or Ig.

Structure

Y-shaped
Made of a constant region and variable region
Contain an antigen-binding site and phagocyte-binding site

Function

Produced by B lymphocytes
Recognize and bind to foreign antigens
Neutralize antigen
Inhibit movement
Cause agglutination, or bacterial clumping, as antibodies bind to antigen
Facilitate clearing from the infection site
Mark antigen for destruction

Antibodies do not kill the antigen directly. They flag the antigen and signal phagocytes, resulting in phagocytosis.

Major Tissues and Organs of the Immune System

Lymphatic tissue
Lymphatic vessels
Lymphatic nodes
Lymphatic nodules
Tonsils
Spleen, the largest organ of the lymphatic system
Thymus gland
Red bone marrow

Cells of the Immune System

Leukocytes

Leukocytes are white blood cells.

Granulocytes

Neutrophils

Most abundant and motile phagocytes
Produced in bone marrow
Short lived
Migrate to the site of infection to engulf invading organisms
Usually first to respond to bacterial infection
Release digestive enzymes from lysosomes to dissolve cellular debris and antigens

Eosinophils

Increase during:

Allergic disorders
Asthma
Skin conditions
Fungal infections
Some cancers
Bone marrow disorders

Basophils

Least common leukocytes
Promote inflammation
Release histamine, heparin, and serotonin

Mast Cells

Found under the skin, near blood vessels and lymph vessels, in lungs, and in intestines
Produced in bone marrow
Long lived
Respond to antigens present in the body
Contain histamine, heparin, and cytokines
Have inflammatory properties

Agranulocytes

Monocytes and Macrophages

Monocytes are large circulating phagocytic cells.
Monocytes develop into macrophages when they leave blood vessels during inflammatory reaction.
A macrophage is a matured monocyte.

Macrophages:

Engulf and destroy bacteria and cellular debris
Present digested antigens to lymphocytes on the outer surface using MHC II
May be wandering or fixed

Examples of fixed macrophages:

Location	Cell type
Liver	Kupffer cells
Kidneys	Mesangial cells
Brain	Microglial cells

Dendritic Cells

Have long extensions on the surface
Break down foreign matter
Concentrated in areas where portals of entry are common

Examples:

Thymus cells that help mature T cells
Langerhans cells in the epidermis
Interstitial cells in the GI tract
Interdigitating cells in lymph nodes

Lymphocytes

B Cells

Produce antibodies
Antigen binds to antibody on the B cell
B cell rapidly divides and forms plasma cells and memory B cells
Responsible for antibody-mediated immunity

T Cells

Mature in the thymus gland
Responsible for cellular immunity

Natural Killer Cells

Kill infected cells and tumor/cancer cells by recognizing MHC I
Help activate macrophages to kill bacteria
Attack by recognizing dysfunction of the cell
Release cytotoxins that cause apoptosis
Act similarly to cytotoxic T cells

Host Defense

Host defense includes:

Defense present from birth
Nonspecific defenses
Mechanisms that impede replication and spread of infectious agents while adaptive immunity begins
Learned responses
Antigen-specific responses

First Line of Defense

Physical Barriers

Skin

Keratinocytes constantly slough off and are replaced.
Sweat mechanically flushes organisms from pores.
Skin colonizers contribute to defense.

Mucous Membranes

Pathogens are trapped in mucus.
Mucus is swept away by the ciliary escalator.
Tears, saliva, and urine flow help flush bacteria.
At the mucocellular level, cells are tightly packed, consistently slough off, and include cells that protect against foreign antigens.

Chemical Barriers

Acidity of skin
Oil from hair follicles
Lysozymes in tears, saliva, nasal secretions, and sweat break down organism cell walls
Acidity of the stomach
Digestive enzymes and proteolytic enzymes such as pepsin
Alkalinity of intestines and bile salts

Mechanical Defenses

Crying and tear production
Blowing the nose
Movement of intestinal contents

Second Line of Defense

Skin-Associated and Mucous-Associated Lymphoid Tissue

SALT is skin-associated lymphoid tissue found within the dermal layer of the skin.
MALT is mucous-associated lymphoid tissue deep to skin and mucous membranes.
MALT mediates specific and nonspecific responses.
The complement system includes proteins activated by the immune system or by the presence of foreign organisms.

Phagocytosis and Phagocytes

Phagocytes engulf foreign material by extending pseudopods around the organism or debris.
The encircled organism forms a sac called a phagosome.
The phagosome protects the cell from toxic material.
The phagosome fuses with a lysosome.
The lysosome releases bactericidal chemicals that break down the organism.
The phagocyte presents antigen protein on the cell surface for lymphocyte recognition through MHC.

Inflammatory Response

Injury to capillaries and tissue cells releases bradykinin from injured cells.
Bradykinin activates sensory nerves and initiates pain.
Pain stimulates mast cells and basophils.
Histamine and leukotrienes are released.
Bradykinin and histamine cause capillary dilation.
The coagulation system helps isolate antigen to one area and wall off infection from deeper tissues.
Neutrophils and monocytes migrate to the injury site and phagocytize microbes.

Signs of Inflammation

Sign	Cause
Redness	Capillary dilation and increased blood flow
Swelling	Capillary dilation allows increased blood in the area
Heat	Increased blood flow; raises metabolic rate and healing rate
Pain	Caused by prostaglandins

Prostaglandins are lipids secreted by damaged cells that intensify the effects of histamines and kinins.

Fever

Systemic response to extensive inflammation or microbial invasion
Helps slow bacterial growth and infection spread
Regulated by the hypothalamus in response to pyrogens released from WBCs

Interferons

Glycoproteins produced by virus-infected cells
Interfere with viral replication
Impede spread of the pathogen

Cytokines

Small proteins that act as chemical mediators
Secreted by cells for communication
Also called signaling proteins

Complement System

The complement system is a series of proteins that function together to help rid the body of infection or colonization by the microbe to which it was exposed.

Third Line of Defense

Cell-Mediated Immunity

Cell-mediated immunity requires activated T cells.

Cytotoxic T Cells

Cannot respond to free-floating antigens.
Respond only to antigen-presenting cells.
Recognize MHC I.
Release perforin into infected cells.

Helper T Cells

Respond to MHC II-presenting cells.
Release cytokines that stimulate growth and division of cytotoxic T cells and B cells.
Attract more macrophages to the area.

Suppressor / Regulatory T Cells

Release chemicals to suppress further development of helper T cells.
Suppress antibody production by plasma B cells.

Memory T Cells

Persist after suppression of the immune response.
Recognize and respond to a pathogen that previously invaded the body.
Secrete cytokines to stimulate macrophages and B cells during repeat invasion.

Antibody-Mediated Immunity

Also called humoral immunity.

Action of B cells
Specific antibodies are produced in response to a specific antigen
Stimulates production of specific B cells and memory B cells through clonal selection
Plasma B cells are generally short lived
Memory B cells are long lived and stimulate reproduction of more specific B cells if exposed to the same antigen again

Active Immunity

Antigen enters the body and the body learns how to respond.
Specific B cells and memory cells are formed.
Examples include vaccines and natural exposure.
Repeat exposure produces faster response because memory cells are already formed.
This is the idea behind booster shots.

Passive Immunity

Antibodies are exogenous, meaning they come from an outside source.
Immunity lasts only as long as antibody is present in the bloodstream.
Passive immunity can help hold off severe infection while the body makes its own antibodies.

Emerging and Reemerging Diseases

Infection Prevention Program Components

Investigation
Prevention
Control
Reporting
Surveillance

Surveillance

State and federal efforts collect and analyze data on infectious disease cases reported by healthcare providers.
Information is reported to the CDC.
Surveillance helps determine whether clinical symptoms associated with an incident warrant intensive public attention.
Epidemics are often detected through routine surveillance or unusual clusters of cases recognized by a healthcare provider.

Example: rising cases of West Nile in an area.

Investigation

Quick and precise identification of the pathogen, transmission route, and appropriate response may prevent additional cases.
Current response may be evaluated.
New response plans may be developed if needed.

Response

Responses may include:

Immunization programs
Vector control
Retraining and education
Food recall
Isolation or quarantine

Review

Host-microbe relationship
Stages of infection
Epidemiology
Healthcare-associated infections
Immune response and lymphatic system