Acquired (specific, adaptive) immunity 3
Third line of defense
Characterized by:
Discrimination - distinguish foreign from normal and two similar molecules
Diversity - recognize all foreign molecules
Memory- remember molecule exposed to it
Acquired immunity has Two components:
- Humoral immunity
- production of antibodies by B-cells (lymphocytes in bone marrow) response to antigens - Cell-mediated immunity
- Activation of T-cells (lymphocytes in thymus) for control of intracellular microbes (virus, bacteria, parasite)
Humoral Immunity (Antigen/Antibody/epitopes)
B CELLS
Antigen - substance that stimulates B cells to make antibodies (foreign or normal turned abnormal)
Antibody (immunoglobulins) - protein made by B-cells able to specifically recognize and bind to only that antigen
Note: If antigen too big only small portion (epitope) stimulate production of antibodies
(Single bacteria have many epitopes)
Structure of Antibodies (immunoglobulins)
Single antibody has four polypeptide chains and two ends:
- one constant end (same structure in all lg molecules)
- Variable end (differs in structure between lg molecules) = specifically recognize and bind to antigen
Therefore:
- antibody recognizes own antigen does not cross react with others (antibody specificity)
- Immune system make antibody for each different antigen (antibody diversity)
How does body make so many different antibodies?
2
Antibodies made by b-cells, each b cell make one type of antibody that recognizes one antigen
10^ 10 different b-cells
- B-cells move waiting to meet antigen to make antibody against
- B cells meet antigen, divide and differentiate
- Become antibody producing plasma cells (pump lg)
- become memory cells (produce more antibody if see same antigen again)
Events following first encounter of B-cell and an antigen
1,2.
3,4
5
1,2. Antigen recognized by specific B-cell
3,4. Binding antigen triggers B-cell to divide and differentiate (memory/plasma)
5. Plasma produce antibodies
memory cells circulate to rapid response future
Five Classes of Antibodies (lg)
- lgG -main antibody (80%)
- cross placenta (protect fetus) - LgA - 10-15%
- Found in secretions (milk, mucus, saliva)
- Blocks attachment of microbes to mucosal tissue surfaces - LgM 5-10%
- form large complex with antigen which are easily cleared - LgD <0.2%
- function unclear(regulate immune) - LgE <0.01
- development of allergies
TIming of Antibody production
First-time exposure leads to production of first LgM then LgG
Antibody level lower if no antigen (lg-producing plasma cells die off)
Second exposure to same antigen gives a stronger/faster lgG response
What does binding of antibody to antigen accomplish
4. MADGE
- Interacts with parts of innate immune system
- triggers complement production, helps inflamm. response - Opsonization (coating bacteria with antibody = better phagocytosis)
- Neutralization (blocks attachment of bacteria, virus, or toxin to host cell surface)
- Agglutination (clumping of antigen + Antibody cuz of lg has two binding sites)
- large clumps better phagocytosed / filtered out)
Cell Mediated immunity (CMI)
T CELLS
Eliminate human cells infected with a microbe (esp. virus)
-antibodies circulate freely and cant enter ab/normal cells
Eliminate abnormal cells that become threat to host (cancer) or foreign cells introduced from other human (transplant)
Regulate function of involved in innate immunity (macrophage) and humoral immunity (B-cells)
Mediated by T-cells
- grow in bone marrow
- mature in thymus
Types of T Cells
Grown in thymus
- Helper T cells
- Cytotoxic T cells
- enter circulatory system in an inactive state
- make contact with antigen via protein on surface(t-cell receptor)
-triggers divide and differentiate (functional/memory)
Activated Helper T-cells
Functional:
Secrete chemical signals (cytokines) that help other immune cells
-increase phagocytic activity of macrophage
-stimulate development of B cells (more T cells)
Memory:
-persist and allow faster response to future antigen
-No killing ability
Activated cytotoxic T cell(killer cell)
-search for cells carrying same antigen that activated it (infected, transplants, cancer)
- Attach to target cell, releasing toxin contain granules (create pores in membrane killing it)
- recycles T-cell unharmed
Overview of Acquired Immune System
4
-humoral and cell mediated work separately and together
- inducible(act when needed)
- discriminates
- remembers
- adaptive
How does immune system communicate
Cytokines- set of >100 molecules act as chemical messengers
-chemical produced by one immune system that has different biological effect on a different immune system cell
Effects of Cytokines
Regulating intensity and length of immune response
regulating development of immune system cells
Four families of cytokines
- Chemokines
- attract phagocytes to where they needed
- regulate inflammatory response - Hematopoietins (colony stimulating factors)
- Stimulate and regulate blood cell formation - Interleukins (IL-1 to IL-25)
- Regulate growth and differentiation of lymphocytes
- other biological effects (pyrogens) - Tumor Necrosis Factors (TNF)
- Promote inflammation and fever; stimulate immune system
- regulate production of cytokines and growth factors
Significance of cytokines in health and disease
- Disease potential
(if cytokine balance upset)
- Lymphoid tumors overproduce lymphocytes and over-produce of cytokines
- persistent or long-term bacterial infections (tuberculosis) stimulate prolonged, low-level production of cytokines(long term physiological effects = weight loss)
- bacterial toxins and viral infections trigger a sudden, massive over-production of cytokines (aka. “Cytokine Storm”) = fever, shock, clotting, tissue, organ dmg
Significance of cytokines in health and disease
- Therapeutic potential
A and B
a) Used as drugs
- Interleukin-2 (Proleukin)
- Stimulates production of T-cells
- Treatment of renal cell cancers, melanoma
b) Certain drugs block cytokine activity
- Humira
- Inhibits action of Tumor Necrosis Factor and therefore reduces inflammation caused by some “autoimmune diseases” (eg. Rheumatoid arthritis)
Targeting one cytokine can upset another
