1
Q
Overview of immunity
A
- System that protects individual against invasion by microorganisms and foreign substances
- Must recognize and destroy invaders – BUT do no damage to normal body tissue
- phagocytosis and/or membrane lysis
- destruction take place at point of infection - white blood cells, antibody and the complement system – variety of chemical mediators
2
Q
Antigen
A
- anything foreign that enters the body
- can bind to antibody and/or can bind to receptors on the T or B cells
3
Q
Antigen Examples
A
- Microorganisms (bacteria / viruses / parasites / fungi / yeasts)
- Allogeneic cells (transplant or transfusion)
- Malignant cells (cells turn cancerous)
- Infected cells (cells inhabited by viruses / certain bacteria / parasites)
4
Q
Target Cells
A
- antigenic cells that will be destroyed by immune system
5
Q
Immunogen
A
- any substance that can stimulate an immune response
- all are antigenic (can bind with antibody)
- not all antigens are immunogens (not all antigens will exhibit an immune response)
6
Q
Pathogen
A
- antigen with ability to cause disease
- usually microorganism or toxin
7
Q
Leukocytes: aka. White Blood Cells
A
- Avg adult has 75 billion circulating WBCs
- NORMAL COUNT: 5,000 to 10,000 per mL
- Neutrophils: 40 to 75% of total
- Lymphocytes (T Cells / B Cells): 20 to 45%
- Monocytes: Up to 8%
- Eosinophils and basophils very little
8
Q
Granulocytes
A
- Most numerous, named for granules in cytoplasm
- hang out in the lymph nodes
- Neutrophils
- Basophils
- Eosinophils
9
Q
Monocytes
A
- dont have granules
- circulating in the blood stream
- do not enter extravascular space
- Large white cells
- Become macrophages in body tissues
10
Q
what is a monocyte called when it goes into the tissue?
A
- macrophage
- becomes a lot larger
- job is to gobble stuff up
11
Q
Lymphocytes
A
- dont have granules
- Differentiate into B- and T-cells
- specific immune response
12
Q
Granulocytes: Neutrophils
A
- Made in hematopoietic marrow
- 50% circulate
- 50% adhere to blood vessel wall
- moves from vasculature to the tissues - phagoctotic
- Produce about 100 billion per day
- First to enter infected areas
13
Q
when the body has noticed a foreign substance, what happens first
A
- neutrophils go to that area
- Attracted via chemotaxis
- Phagocytize invading organism
- Die
- Phagocytized by macrophages
14
Q
Granulocytes: Eosinophils
A
- Develop and mature in hematopoietic marrow
- Appear where FOREIGN PROTIENS and PARASITES are
- Involved in allergic reactions (secrete histamine)
- Have binding sites for specific antibodies and complement proteins
- Designed to destroy cells coated with:
- IgG antibodies
- IgE antibodies
- Complement proteins
15
Q
Where are eosinophils and what are they effective against
A
- Reside in tissues (do not circulate)
- Skin, bronchi, bronchioles - Release antitoxin (Major Basic Protein) to destroy organisms (can also destroy normal tissues)
- Very effective against parasitic worms
16
Q
Granulocytes: Basophils
A
- Least common
- Have chemotaxis and phagocytic activity
- Main fxn: RELEASE OF HEPARIN in areas of foreign invasion to prevent blood clots from forming => allows WBC to get to that area to destroy foreign organism
- Also release histamine causing vessel dilation
- Circulate in blood
- Have receptors for IgE antibody
- Similar to mast cells
- Also contain histamine granules
- Also have surface receptors for IgE antibody
- Mast cells do not circulate – remain in tissues. Basophils are NOT in tissues
17
Q
Monocytes (Macrophages)
A
- Produced in bone marrow
- Circulate immature
- Leave the blood and travel to the tissues
- Monocytes in blood for 1-2 days
- Macrophages in tissues for months to years
18
Q
Lymphocytes
A
o Specific immune response when antigen invades
o Activated when they recognize foreign matter
o Circulate in blood
o Wait in lymph nodes for antigens to appear
o Play a role in rejection of organ transplants
19
Q
T-Lymphocytes (aka. T-Cells)
A
- Once T-Cells recognize – bind antigen
- Release cytokines (interleukins) - Different types of T-cells:
- Helper T-Cells (CD-4)
- Cytotoxic T Cells (CD-8)
- Regulatory / Suppressor T Cells
- Memory T Cells
20
Q
Antibody Molecules
A
- Protein molecules: (also called) =immunoglobulin
- 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) - Always present in small amounts
- blood & body tissues - Five classes IgG; IgM; IgD; IgA; IgE
- Must bind with the outer surface of the antigen to be effective
- antigen binding site unique - Cannot cross cell membranes
21
Q
Antibody Molecules function
A
- opsonize (coat antigen with antibody) antigen (mark antigen for destruction)
- activate complement cascade
22
Q
Fab portion of the B cell
A
Variable
23
Q
Fc portion of the B cell
A
constant
24
Q
surface of B cells trigger
A
production of antibodies
25
B cell receptors and communication with the inside of the cell
- uses co-receptor to translate the signal down inside the cell
26
simple function of B cell function
- resting B cell encounters antigen (B cell has binding site for it) and bind the antigen to the B cell binding site
- stimulates the B cell and starts to produce antibodies
- once B cell becomes activated by the atigen, it becomes a plasma cell (actively secrete antibodies)
27
What cells actively secrete antibodies
- Plasma B cell
28
When specific B cells come in contact with their specific antigen
- Produce more B cells that have that specific receptor which produce more antibodies
- it's not just one B cell that produces all of the antibodies
29
Opsonization
- 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
30
Antigen Destruction Mediated by Antibody
- Opsonization
- 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
31
Antibody Classes
- Five classes
- IgG, IgM, IgD, IgA, and IgE
- Most antibodies are IgG or IgM
- Class determined by amino acid aarrangements in heavy and light chains
- same arrangement in specific area of change
32
IgM Antibody class
- First antibody produced against an antigen by the B cells / plasma cells
- First antibody produced by the fetus
- increased levels indicate infection in newborn
- Accounts for 10 to 15% of circulating antibody
- High levels of IgM in the blood means new infection
- Very large – remains in vascular system
- Main function to activate complement system
- Can cause antigen agglutination
- Anti-A and Anti-B antibodies are the IgM type
- Function: Activate Complement
33
IgD Antibody Class
- Second class of antigen to be released
- Not much is known about this class
- Found only in small amounts in serum and body fluids
- Has little immunologic effect on antigen
- May assist with the maturation of B cells into plasma cells
34
IgE Antibody Class
- Third class of antibodies released
- Found in very low concentrations in plasma
- Increases with allergic reactions and parasitic infections
- causative agent for asthma, hay fever and other allergic reactions
- Bind with basophils and mast cells stimulating them to release HISTAMINE
- Involved with anaphylactic reactions
35
IgG Antibody Class
- Fourth class released
- Most Important
- Most potent
- Comprises 80% of antibody in the immune system
- when it sees it for the second time, that is when there is best response
- Secreted by Memory B Cells
- only antibody that can cross the placenta
- provides immunologic protection for fetus
36
Rh antibody
- it is an IgG antibody
- mother is negative (has antibody to Rh factor) and wants to attack a Rh positive
- child that is Rh positive will get attacked by the Rh antibodies and cause cell lysis
37
IgG subgroups (4)
- IgG1 - protects body from (most) bacteria
- IgG2 – attacks and destroys organisms encased in a saccharide coat (rest of the bacteria)
- IgG3 – activates complement proteins (enhances phagocytosis of antigen)
- IgG4 – produces potent vasodilators (protects bronchioles)
38
IgA Antibody Class
- Major antibody in the body fluids and mucous secreted by the mucous membranes
- Binds with antigen to immobilize it – allows mucin (main ingredient of mucous) to remove antigen-antibody complex
- Cannot activate the complement system
- Can trigger cell-mediated immune reactions
39
Heaviest Immunoglobulin
IgM
40
Highest immunoglobulin serum levels in the blood
IgG1 and IgG2
41
Longest immunoglobulin half life
IgG1, IgG2, and IgG4
42
Immunoglobulin good for opsinization
IgG1
43
Immunoglobulin that stimulates our mast cells and involved in allergic rxns
IgE
44
Immunoglobulin best for activation of compliment system
IgM and IgG3
45
Immunoglobulin best for transport across epithelium
IgA
46
Immunoglobulin best for transport across placenta
IgG1
47
Immunoglobulin best for diffusion into extravascular sites
IgG
48
Immune System
- Protects individual against infectious pathogens
- Must recognize and destroy harmful invaders – but do no damage to normal body tissue
- Major players - white blood cells, antibody and the complement system – variety of chemical mediators
- innate and adaptive
49
Innate Immunity
- no control
- First line of defense – always present (skin)
- Able to respond quickly
- epithelial barriers / phagocytes / complement / natural killer cells
- Uses general recognition mechanisms to detect antigen
- Does NOT produce long term immunity to antigen
- INFLAMMATION
50
Innate macrophage activity process
1. bacterium binds to receptor on cell surface
2. Engulfment into phagosome
3. Degradation (phagolysosome)
4. Brought back to surface and spit it out
51
Adaptive Immunity
- Responds to specific antigen
- can be non microbial
- Develops after exposure to antigen
- Slow response
- Produces very powerful response
- Lymphocytes (T & B cells) are the major players
52
Characteristics of Adaptive Immunity
- 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: lymphocytes can shut down activity after antigen is destroyed
- Self-tolerance: lymphocytes can distinguish self-tissue from non self tissue
53
Recognition mechanisms of innate immunity
- rapid response (hours)
- invariant (doesn't depend on invader, it will be the same way every single time)
- limited number of specificities
- constant during response (acts the same way no matter what)
- destroys foreign invader
54
Recognition mechanisms of adaptive immunity
- slow response (days to weeks)
- variable (depends on invader)
- numerous highly selective specificities
- improve during response
- destroys foreign invader
55
phases of immune response
- cognitive phase (first phase)
- antigen interacts with the T lymphocytes
- activator phase (second phase)
- T cells respond by releasing cytokines
- cytokines stimulate proliferation of T & B cells
- effector phase (third phase)
- granulocytes / macrophages / complement activated
- antigen opsonized and engulfed
56
T Lymphocytes
- 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 response to antigen is called CELL-MEDIATED IMMUNITY
57
Role of T Cells
- Direct immune response
- Assist phagocytosis via release of cytokines that activate other phagocytic cells
- Destroy malignant cells, allogeneic cells and infected cells via lysis
- Aid B cells / plasma cells in antibody production
- Involved with delayed hypersensitivity immune reactions
- Cause some types of graft rejection in organ and tissue transplantation
- Responsible for certain types of autoimmune disorders
58
T Cell Production
- Produced in bone marrow
- Mature in thymus
- cells trained to distinguish self-tissue from non self tissue
- Leave thymus – travel to secondary lymphatic organs
- lymph nodes
- spleen
-tonsils
59
Types of T Cells
- Categorized by protein molecules on cell membrane (i.e. CD8+ / CD4+)
60
MHC class II
- Extracellular antigen
- endocytosis of the antigen and breaks it down by the phagolysosome
- MHC class II binds to broken down antigen and presents it at the cell surface
- comes in contact with receptors on the CD4 T Cell
61
MHC class I
- Intracellular antigen
- broken down by proteosome
- broken down antigen transported to ER and binds to MHC class I
- brought to surface of the cell
- comes in contact with the receptor on the CD8 cell
62
Process of B cells and T cells working together
- Digested protein bound into a groove on the MHC molecule on surface of dendritic cell
- Dendritic cells present antigen to CD4 cells (T Helper)
- Finds a CD4 T-cell (naïve – hasn’t interacted with other antigens)
- If T-Cell Receptor (TCR) of CD4 T-Cell sees a peptide it recognizes -> Becomes active -> divides and releases cytokines
- help induce a B-cell to make antibodies
- Meanwhile – antigen is also recognized by naïve B-cells with immunoglobulin molecule
- Antigen binds to immunoglobulin on B-Cell.
- ingested and digested by B-cells and react with activated T-cell to make antibodies
- CD4 cell recognized antigen peptide on dendritic cell will recognize peptide present on the B-cell.
- CD4 cell activated
- Activated CD4 cell with MHC-peptide on B-cells will
induce B-cells to become activated => releases antibodies
63
CD40 marker
- B-cells have CD40 marker on cell surface
- CD4 cells (activated helper) have a ligand CD40L
- CD40 : CD40L = costimulation
- NEED CO-STIMULATION TO MAKE ANTIBODIES
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