The three major players in immunity
white blood cells
antibody
complement system
Antigen
anything foreign that enters the body
–can bind to antibody and/or can bind to receptors on the T or B cells
Target cells
antigenic cells that will be destroyed by immune system
Immunogene
any substance that can stimulate an immune response
all are antigenic (can bind with antibody)
not all antigens are immunogens
Pathogen
antigen with ability to cause disease
usually microorganism or toxin
Are all antigens immunogens?
No
any substance that can stimulate an immune response
Immunogene
Microorganisms
bacteria / viruses / parasites / fungi / yeasts
cells from genetically dissimilar individual
Allogeneic cells
Infected cells
cells inhabited by viruses / certain bacteria /
parasites
Antigen examples
Infected cells, microorganisms, allogeneic cells, malignant
Leukocytes normal count? per mL
Avg adult has 75 billion circulating WBCs
NORMAL COUNT: 5,000 to 10,000 per mL
Neutrophiles: % of total
40 to 75% of total
Lymphocytes: % of total
20 to 45%
–
T Cells / B Cells
Monocytes: % of total
Up to 8%
Eosinophils: % of total
1 to 6%
Basophils: % of total
Up to 1%
Most numerous, named for granules in cytoplasm
Granulocytes
What are 3 Granulocytes
Neutrophils
Basophils
Eosinophils
large white cells, become macrophages in body tissues
monocytes
differentiate into B-and T-cells
Lymphocytes
Where are Neutrophils made?
hematopoietic marrow
Neutrophils where are they in body? Circulate ?
50% circulate
50% adhere to blood vessel wall
–Margination
–Ready to move into tissues
Neutrophils function ?
phagocytosis
Neutrophils life span
hours to days
Neutrophils size?
10-15micrometer diameter
What are the first to enter an infected area?
Neutrophils
Neutrophils are the first to enter an infected area - they are attracted via what?
and phagocytize/d what?
-Attracted via chemotaxis
–Phagocytize invading organism
–Die
–Phagocytized by macrophages
Where do Eosinophils develop and mature?
hematopoietic marrow
Eosinophils are appear in what areas?
where foreign protein and parasites are
Involved in allergic reactions
Eosinophils
Eosinophils destroy what?
Designed to destroy cells coated with IgG
antibodies, IgE antibodies and complement proteins
Eosinophils reside where?
tissues–Skin, bronchi, bronchioles
Eosinophils release what?
antitoxin (Major Basic Protein) to destroy organisms
Very effective against parasitic worms?
Eosinophils
Eosinophils life span
12-24 hrs
Least common Granulocyte
Basophils
What granulocyte chemotaxis and phagocytic activity
Basophils
Basophils main function to release what?
Release histamine (dilation)
release of heparin in areas of foreign invasion to prevent blood clots
from forming
–Blood clots–blood can’t circulate–WBC cannot get to foreign organism to destroy–tissue necrosis
Basophils have receptors for what?
Have receptors for IgE antibody
How are Basophils similar to mast cells?
Also contain histamine granules
Also have surface receptors for IgE antibody
Where do Basophils circulate
Blood
Where are monocytes/macrophages made?
bone marrow
Monocyte/macrophage circulate how/how long?
circulate immature - mono
Leave the blood and travel to the tissues (Mature into macrophages)
Actively phagocytic–Concentrated in liver sinusoids, spleen, lungs
Monocytes in blood for 1-2 days
Macrophages in tissues for months to years
Monocyte/macrophage size?
12-20 micrometers
Lymphocytes - activated? circulate? wait where
Specific immune response when antigen invades
Activated when they recognize foreign matter
Circulate in blood
Wait in lymph nodes for antigens to appear
Lymphocytes play a role in rejection of what?
Play a role in rejection of organ transplants
T cells - mature where and do what?
Mature in thymus
Learn to recognize self
Attack self tissues–destroyed
Membrane receptors on T-Cells bind to what?
protein antigens–Need to recognize certain fragments of protein antigens
Antigen presenting cells (ie. Macrophage)
digest and display a peptide fragment on cell surface that what recognizes?
that T-cells can recognize
Once T-Cells recognize–bind antigen what happens?
Release cytokines (interleukins)
Different types of T Cells
-Helper T-Cells
–Cytotoxic T Cells
–Suppressor T Cells
–Memory T Cells
Antibody molecules: protein molecules:
immunoglobulin
Antibody molecules produced by what>
Produced by B lymphocyte cells (plasma cells) in response to a specific antigen–after initial exposure, takes 14 days to reach full power (lag time)
Five classes of Antibody Molecules
IgG; IgM; IgD; IgA; IgE
Antibody molecules must do what to be effective ?
Must bind with the outer surface of the antigen
Can antibody molecules cross the cell membrane ?
NO
Antibody molecules functions (2)
opsonize antigen (mark antigen for destruction) activate complement cascade
Opsonization does what?
Coating of antigen with antibody and complement
Provides targeting mechanism for the phagocytic neutrophils and macrophages allowing them to bind, engulf, and destroy the antigen
Provides points where the phagocytes can attach to the antigen
Phagocytic cells have two specific receptors on their membrane surface
–Fc receptor: binds with antibody
–C3 receptor: binds with complement
Antigen Destruction Mediated by Antibody types(4)
Opsonization
Lysis
Antibody dependent cell-mediated cytotoxicity
Neutralization
Lysis
complement activation leads to production of the membrane attack complex (MAC)
–the MAC will lyse the antigens membrane
Antibody dependent cell-mediated cytotoxicity
cell destruction carried out by natural killer cells, macrophages, neutrophils and eosinophils of target cells opsonized by antibody
Neutralization
antibody renders the antigen toxins harmless
Most antibodies fall into what two classes?
IgG or IgM class
What is the antibody class determined by?
Class determined by the amino acid arrangements in heavy and light chains
–same arrangement in specific area of chain
IgM antibody class First antibody produced against an antigen by what cells?
B cells/ plasma cells
–increased levels indicate new infection
IgM antibody class First antibody produced by what age?
fetus–increased levels indicate infection in
newborn
IgM antibody class is what % if circulating antibodies
Accounts for 10 to 15% of circulating antibody
Largest antibody class?
IgM
remains in vascular system
Anti-A and Anti-B antibodies are part of what class of antibodies?
IgM
IgM function?
Activate Complement system
IgM can cause antigens to do what?
Can cause antigen agglutination
Second class of antigen to be released
IgD
IgD fxn?
Has little immunologic effect on antigen
May assist with the maturation of B cells into plasma cells
Third class of antibodies released
IgE
IgE concentrations?
Found in very low concentrations in plasma
Increases with allergic reactions/anaphylactic reactions and parasitic infections
–causative agent for asthma, hay fever and other allergic reactions
IgE bind with what two types of cells?
Bind with basophils and mast cells stimulating
them to release histamine
Fourth antibody class released
Most Important
Most potent
IgG
IgG % of antibody in system?
Comprises 80% of antibody in the immune system
–produced in greatest amounts on second exposure to antigen
Only antibody that can cross the placenta?
IgG
provides immunologic protection for fetus
Rh antibody is an IgG antibody
Hemolytic disease of the newborn
IgG is very effective at binding and destroying what?
Very effective at binding and destroying antigen
4 subgroups of IgG
IgG1-4
–IgG4
produces potent vasodilators
Protects bronchioles
-IgG3
activates complement proteins
Enhances phagocytosis of antigen
–IgG2
attacks and destroys organisms encased in a saccharide coat. i.e. - Rest of bacteria
IgG1
protects body from (most) bacteria
IgA major antibody where?
Major antibody in the body fluids and mucous
secreted by the mucous membranes
–tears / breast milk / bronchiole secretions /saliva
IgA does what to the antigen ?
Binds with antigen to immobilize it– allows mucin (main ingredient of mucous) to remove antigen-antibody complex
What does IgA do to the complement system
Cannot activate the complement system
IgA triggers what?
trigger cell-mediated immune reactions
Immune system does what?
Protects individual against infectious pathogens
Must recognize and destroy harmful invaders–but do no damage to normal body tissue
Immune system major players
Major players-white blood cells, antibody and the complement system–variety of chemical mediators
Immune types? (2)
innate, adaptive
Innate Immunity how does it work?
Inborn / natural First line of defense–always present Able to respond quickly Uses general recognition mechanisms to detect antigen–recognizes microorganisms–limited number of recognition proteins available Inflammation
Innate Immunity major players
epithelial barriers / phagocytes / complement / natural killer cells
Innate Immunity long term?
Does NOT produce long term immunity to antigen
Inflammation is what type of Immunity ?
Innate Immunity
Adaptive Immunity is what?
Responds to specific antigen–can be non microbial–millions of recognition proteins
Develops after exposure to antigen
Slow response
Produces very powerful response
Adaptive Immunity major players
Lymphocytes (T & B cells) are the major players
Characteristics of Adaptive Immunity (5)
Specificity
–immune reaction specific for offending antigen
Diversity
–lymphocytes can respond to millions of antigens
Memory
–lymphocytes can remember any antigen previously encountered
Self-regulation
Self-tolerance
–lymphocytes can distinguish self-tissue from non self
Self Regulation of Adaptive Immunity
lymphocytes can shut down activity after antigen is destroyed
Diversity (adaptive immunity)
lymphocytes can respond to millions of antigens
When is the immune response stimulated?
Immune response initiated when antigen stimulates activation of T and B cells
Immune response phases?
cognitive phase
activator phase
effector phase
Cognitive phase of immune response?
First phase
antigen interacts with the T lymphocytes
Activator Phase of immune response?
Second phase
T cells respond by releasing cytokines
cytokines stimulate proliferation of T & B cells
Effector Phase of immune response?
(third phase)
granulocytes / macrophages / complement activated antigen opsonized and engulfed
T Lymphocytes do what?
Direct immune response against protein antigen
Responsible for the type of white cells that respond and how they respond
T cells must recognize the antigen
T cell antigen response is called
CELL-MEDIATED IMMUNITY
T cells destroy what?
Destroy malignant cells, allogeneic cells and infected cells via lysis
T cells assist phagocytosis how?
Assist phagocytosis via release of cytokines that activate other phagocytic cells
Involved with delayed hypersensitivity immune reactions
T cells
Responsible for certain types of autoimmune disorders
T cells
Cause some types of graft rejection in organ and tissue transplantation
T cells
T cells aid what?
Aid B cells / plasma cells in antibody production
T cells produced and mature where?
Produced in bone marrow
Mature in thymus
–cells trained to distinguish self-tissue from non self-tissue
T cells travel where once mature?
Leave thymus–travel to secondary lymphatic organs
–lymph nodes
–spleen
–tonsils
How are T cells categorized
by protein molecules on cell membrane (i.e. CD8+ / CD4+)
Types of T cells (2)
cytotoxic cells CD8+
–helper cells CD4
–suppressor cells
Cytotoxic T cell once activated destroy what?
Destroy virally infected cells, allogenic cells (organ transplant), malignant cells
Once activate, release lytic molecules that rupture target cell
Helper T cells (CD4) do what?
Assist or activate other white cells–release cytokines to call other cells
Do not destroy antigen directly
what is MHC
MHC is major histocompatibility complex
found on most body cells
divided into Class I or Class II
binds with antigen fragments
Helper T cells - CD4 - two subsets
-TH1: inflammatory helper; releases cytokines that convert inactive T cells into cytotoxic T cells
–TH2: release cytokines needed for B cell activation and antibody secretion; MUST be present
Suppressor T cells
Activated to stop immune response once antigen has been destroyed
B Lymphocytes -Produce antibody in response to antigen
–called HUMORAL IMMUNITY
B Lymphocytes Must be activated by what type of cells before producing antibody against protein antigen
TH2 helper cells
Once B Lymphocytes are activated what happens?
proliferate and differentiate into plasma cells
–plasma cells produce the antibodies for the specific antigen
–antibody will be produced until antigen has been destroyed
Protein antigen is present
Ingested by _____1____
Dendritic cell moves to the lymph node
Digested protein bound into a groove on the __2___ on surface of dendritic cell
- dendritic cells (in skin)–Antigen is digested to small peptides
- MHC molecule
