Physiology Chapter 18

Immunology

the study of the defenses of the body uses to recognize itself from foreign substances or cells; the immune system destroys or renders harmless foreign matter

Two categories of immune defenses

Innate: defend against foreign substances or cells without having to recognize their specific identities→non-specific

• faster

• defenses at body surfaces, inflammation, interferons

Adaptive: depend on specific recognition by lymphocytes of the substance or cell to be attacked→specific long-term immune response

• more sustained

Functions of immune defense mechanisms

-protection against infection by various types of pathogens (i.e. viruses and microbes)

-isolate and remove foreign substances that are not microbial

-destroy cancer cells that may arise (immune surveillance)

What is the single greatest contributor to decreased resistance to infection?

protein-calorie malnutrition

• leads to atrophy of lymphoid tissue → can’t carry out appropriate response

Graft Rejection

immune system recognizes the transplants (grafts) as foreign and launches an attack against them

• class I and II MHC proteins are recognized as foreign by T cells

• MHC proteins are destroyed by cytotoxic T cells with the aid of helper T cells

cyclosporine: drug that does not kill lymphocytes but blocks the production of IL-2 and other cytokines by helper T cells (IL-2 is in the cascade that starts normal immune response)

Transfusion Reactions

the illness cause when erythrocytes are destroyed during a blood transfusion; example of tissue rejection

• antibodies (Not T cells) are major factor in this rejection

• erythrocytes don’t have MHC proteins but do have membrane proteins and carbohydrates that act as antigens (ABO carbohydrate system and Rh proteins)

• blood types contain natural antibodies against RBC antigens that they don’t have

Type A blood can receive…

Type A and O

Type B blood can receive…

Type B and O

Type AB blood can receive…

Type A, B, and O (universal recipient)

Type O blood can receive…

Type O only (universal donor)

Hypersensitivity

diseases in which immune responses to environmental or sometimes endogenous antigens causes excessive inflammation and resultant damage to the body

• immunity gone wrong (inappropriate response to stimulus)

Types of Hypersensitivity

Immediate hypersensitivity: mediated by IgE antibodies, mast cells, and eosinophils

• most common

Cytotoxic Hypersensitivity: mediated by antibodies that lead to damage or destruction of cells (i.e. hemolytic disease of the newborn)

Immune-complex Hypersensitivity: mediated by antigen-antibody complexes deposited in tissue

Delayed Hypersensitivity: mediated by helper T cells and macrophages; independent of antibodies

Sequence of events for intermediate hypersensitivity

1. exposed to antigen

2. antibody synthesis

3. production of memory B cells that start active immunity

4. re-exposure

5. stronger antibody response with IgE antibodies along with helper T cells

6. release cytokines

7. more IgE producing cells

8. IgE cells come into contact with mast cells

9. secretion of histamines and then you really get the allergic reaction

What can increase hypersensitivity?

pregnancy

Anaphylaxis

when there are so many cytokines being released that the bronchioles constrict and can cause respiratory and circulatory failure

Autoimmune disease

inappropriate immune attack triggered by the body’s own proteins acting as antigens

• immune attack is mediated by autoantibodies and self-reactive T cells

• attack is specifically directed against the body’s own cells that contain these proteins

Ex: type I diabetes, rheumatoid arthritis, multiple sclerosis, myasthenia gravis

Neutrophils

produced in bone marrow

functions: phagocytosis and release chemicals involved in inflammation (vasodilators, chemotaxins, etc.)

Basophils

produced in bone marrow

functions: carry out functions similar to those of mast cells in tissues (release histamine and other chemicals for inflammation)

Eosinophils

produced in bone marrow

functions: destroy multicellular parasites and participate in immediate hypersensitivity reactions

Monocytes

produced in bone marrow

functions: carry out function in blood similar to those of macrophages and enter tissues to transform into macrophages

Lymphocytes

mature in bone marrow and thymus; activated in peripheral lymphoid organs

functions: serve as recognition cells in specific immune responses and are essential for adaptive immune responses

Steps:

1. encounter and recognition of antigen by lymphocytes

2. lymphocyte activation

3. attack launched by activated lymphocytes and their secretions

B cells

initiate antibody-mediated immune responses by binding specific antigens to the B cell’s plasma membrane receptors (receptors are immunoglobulins)

upon activation they are transformed into plasma cells which secrete antibodies

present antigen to helper T cells

Cytotoxic T cells

bind to antigens on plasma membrane of target cells (virus-infected cells, cancer cells, and tissue transplants) and directly destroy the cells

Helper T cells

secrete cytokines that help to activate B cells, cytotoxic T cells, and macrophages

Regulatory T cells

act as inhibitors on other immune cells

NK cells

bind directly and non-specifically to virus-infected cells and cancer cells to kill them

Plasma cells

produced in peripheral lymphoid organs; differentiate from B cells during immune response

functions: secrete antibodies (adaptive immunity)

Macrophages

produced in bone marrow; reside in almost all tissues; differentiate from monocytes

functions: phagocytosis, extracellular killing via secretion of toxic chemicals, process/present antigens to helper T cells, secrete cytokines

Dendritic cells

produced in almost all tissues and organs; microglia in the CNS

functions: phagocytosis and antigen presentation

Mast cells

produced in bone marrow; reside in almost all tissues; differentiate from bone marrow cells

functions: release histamine and other inflammatory chemicals

Interleukin 1

source: antigen-presenting cells (i.e. macrophages)

target: helper T cells, certain brain cells

function: stimulate IL-2 receptor expression, induce fever, stimulate systemic responses to infection/inflammation

Interleukin 2

source: most immune cells

target: helper T cells, cytotoxic T cells, NK cells, and B cells

function: stimulate proliferation and promote conversion to plasma cells

Interferons type I

source: most cell types

target: most cell types

function: stimulate cells to produce antiviral proteins (innate response) I

Interferons type II

source: NK cells and activated helper T cells

target: NK cells and macrophages

function: stimulate proliferation and secretion of cytotoxic compounds

Chemokines

source: damaged cells

target: neutrophils and other leukocytes

function: facilitate accumulation of leukocytes at sites of injury/inflammation

Active Immunity

resistance built up as a result of the body’s contact with microorganisms and their toxins or other antigenic components (from an infection or vaccine)

Passive Immunity

the direct transfer of antibodies from one person to another with the recipient receiving preformed antibodies

• mother and baby

• gamma globulin injections

Defenses at Body Surfaces

not immune responses, but act as barriers

• intact skin and mucus membranes

• hairs at entrance of nose

• cough/sneeze reflex

• antimicrobial chemicals secreted by skin, saliva, and lacrimal glands

• antimicrobial chemicals in nose mucus

• acidity of stomach

Inflammation

a local response to infection or injury, which attempts to destroy or inactivate foreign invaders, wall off the site of infection to prevent spread, and promote tissue repair

• most important mediators are neutrophils, macrophages, and dendritic cells (phagocytic cells)

• occurs in innate and adaptive immunity

During inflammation, what is the role of chemical mediators?

induce vasodilation and cause increased permeability of capillaries and venules to proteins

• increased blood flow delivers proteins and leukocytes

• increased permeability to proteins allows plasma proteins that have a role in inflammation to gain access to inflamed area

• net filtration of plasma into interstitial space leads to edema

Chemotaxis

-Margination: loose attachment of neutrophils to endothelial cells by adhesion molecules, resulting in collection of neutrophils near infection site

-Diapedesis: squeezing of neutrophils between adjacent endothelial cells of the capillaries to enter infection site

-Chemotaxis: migration of neutrophils toward the infection site to the chemoattractants released by damaged cells

Phagocytosis

-engulfment/destruction of pathogens by phagocytes

-carbohydrates or lipids in the cell wall of the microbe interact with phagocyte receptors to initiate engulfment

-phagocytosis of bacteria with thick, gelatinous capsules requires opsonins to bind the phagocyte to the microbe

Eicosanoids

involved in vasodilation and trigger sensation of pain; induce fever

Complement system

at least 30 different proteins participate in cascade that eventually leads to the downstream development of a multiunit protein: membrane attack complex (MAC)

• MAC embeds in bacterial plasma membrane and forms pore-like channels in the membrane to make it leaky; water and small molecules enter the microbe, disrupting and killing the microbe

Primary vs secondary lymphoid organs

Primary: initial sites of lymphocyte development which supply the secondary lymphoid organs with mature by naive lymphocytes

• bone marrow and thymus

Secondary: organs in which naive lymphocytes are activated to participate in adaptive immune responses

• spleen, lymph nodes, tonsils, and various lymphocyte accumulations in the linings on the intestinal, respiratory, genital, and urinary tracts

Immunoglobulins

antibodies

produced by B cells in response to an antigen

Steps:

1. B cell is presented with antigen

2. divides and clones itself to make a population of B cells which can differentiate into plasma cells that can secrete antibodies