Chapter 16 – Adaptive Immunity
I. Adaptive Immunity – the 3rd line of defense
A. Overview
1. function
a. amplifies inflammatory response
b. responsible for bulk of complement activation
c. targets specific antigens
d. initial exposure “primes” body for next encounter
e. recognizes foreign molecules and acts to immobilize, neutralize, destroy
f. failure results in devastating diseases – AIDS, rheumatoid arthritis, cancer, etc.
2. important aspects of immune response
a. antigen specific
-recognizes and mobilizes against particular pathogens
b. systemic
-immunity response all over body
c. has memory
d. clonality
-cells fighting invaders clone generations of identical cells
e. does not react against normal cells
f. clonal deletion
-cells with receptors that respond to autoantigens (self antigens) are destroyed
3. antibodies – highly reactive proteins in serum – produced by lymphocytes
4. tissues and organs of lymphatic system
a. lymph vessels
b. lymph
–same as interstitial fluid
-flows from capillaries
-flows back into venous blood
c. primary lymph organs
-red bone marrow
-thymus gland
d. secondary lymph organs
-lymph nodes
-spleen
-tonsils
-adenoids
-MALT – mucosa associated lymphatic tissue
-moist tissue that lines body organs and cavities including your nose, mouth, lungs, and digestive system
B. 2 types of immunity
1. humoral – B cells in command
a. immunity provided by antibodies in body’s fluids (humors)
b. attach to bacteria, their toxins, and viruses marking them for destruction by
phagocytes or complement
c. responds against extracellular pathogens
2. cell mediated immunity – T cells in command
a. provided by antibody producing lymphocytes
-attacks/lyses foreign invaders
b. releases chemicals
-enhance inflammatory response
-help to activate lymphocytes or macrophages
c. responds to intracellular pathogens and abnormal body cells (cancer, virus,and intracellular bacteria and protozoa)
3. immunocompetence – ability of body’s cells to recognize specific antigens by binding to them
C. Cells of immune system -2 types of lymphocytes (wbc) and macrophages
1. types
a. T lymphocytes
-produced in red bone marrow
-develop immunocompetence (mature) in thymus gland
-our own cells have proteins on them (glycoproteins) – called self-antigens
-our immune system recognizes them as our own – “self”
-lymphocytes that bind to self-antigens destroyed (clonal deletion)
-how we develop tolerance for self-antigens
-provide cell mediated immunity
-does NOT produce antibodies
-are mobile
-does not bind directly to epitopes
-epitope - portion of a foreign protein, or antigen, that is capable of stimulating an immune response
-T cell specificity
-every T cell has membrane proteins called T cell receptors (TCRs)
-surface of each T cell has about 500,000 identical copies of its TCR
-each T cell has unique TCR
b. B lymphocytes
-produced in red bone marrow
-develop immunocompetence (mature) in bone marrow
-provide humoral immunity
-produces antibodies
-are mobile
-bind to epitopes directly.
-B cell specificity
-every B cell has membrane proteins called B cell receptors (BCRs)
-surface of each B cell has about 500,000 identical copies of its BCR
-each B cell has unique BCR
c. macrophages – antigen presenting cells (APCs)
-engulf foreign invaders
-present antigens to immunocompetent lymphocytes (T cells)
-only a portion of antigen presented on macrophage cell surface
-genes code forstructure of receptor proteins on immunocompetent cells
-this determines what specific invaders we can recognize/resist
-help activate T cells by secreting monokines (protein)
-activated T cells release chemicals converting macrophages into killer macrophages
-stationary – tend to remain fixed in lymphoid tissue
D. antigens
-intruders – foreign
-large complex molecules (macromolecules)
-most are proteins
-some are polysaccharides, lipids, phospholipids, nucleic acids, glycoproteins
- are nonself
-capable of mobilizing immune system
-capable of provoking immune response
1. complete antigens and haptens
a. complete antigens
– large molecules
-2 characteristics
-immunogenicity – stimulates reproduction of T/B lymphocytes and specific ABs
-reactivity – ability to react specifically with ABs produced
b. haptens
-incomplete antigens
-small molecules
-reactive only on own
-must combine with body protein before becoming immunogenic – allergies
-poison ivy, animal dander, peanuts, penicillin, etc.
2. antigenic determinants – epitopes
a. small portion of antigen that is presented and recognized as foreign
b. where ABs and T/B cells can bind
3. exogenous antigens
a. extracellular
b. can be toxins, secretions, parts of cell wall, membranes, flagella, pili
4. endogenous antigens
a. protozoa, bacteria, viruses that reproduce inside cell
b. must be part of cell’s membrane to be recognized and initiate immune response
5. autoantigens – self antigens
a. antigenic molecules that come from normal cellular process
b. clonal deletion
-if cell responds to autoantigens destroyed by apoptosis
c. where occurs
- T cells – thymus
-B cells – red bone marrow
d. failure of self-tolerance results in autoimmune disease
-lupus, Graves disease, MS, Myasthenia gravis, juvenile diabetes, Rheumatoid arthritis
Crohn’s disease, ulcerative colitis
E. 2 types of immune response
1. humoral immune response
2. cell mediated response
II. Humoral Immune Response
A. Activation
-occurs when B cell lymphocyte encounters a challenging antigen
-antibodies produced
1. clonal selection and differentiation of B cells
a. antigen binds to surface receptors on B cells (BCRs – B cell receptors)
b. sensitizes/activates lymphocyte
c. lymphocytes undergoes clonal selection
-that specific B cell “selected” b/c BCRs match challenging antigen’s epitopes
d. lymphocyte grows/multiplies
-forms cells just like itself
-all cells produced have same BCRs – so they are clones
e. most clone cells become plasma cells
– AB producing factories
2. immunological memory
a. some B clone cells become memory cell
b. memory cell capable of mounting quick response if same antigen encountered again
-called secondary response
B. active and passive immunity
1. active immunity
a. natural
-ABs acquired naturally during infections
-provides memory
b. artificial
-ABs acquired from vaccine
-provides memory
c. vaccine
-weakened (attenuated)/dead pathogen introduced into body
-confers immunological immunity
-no illness
2. passive immunity
a. natural
-ABs cross placenta
-ABs acquired during breast feeding
-no memory
-temporary protection
-good for only as long as ABs can survive (several weeks)
b. artificial
-ABs supplied by donor serum (human/animal)
-no memory
-temporary protection
-good for only as long as ABs can survive (several weeks)
C. Antibodies
-called immunoglobulins
-soluble proteins
-secreted by plasma cells
-descendants of B cells
-every antibody produced has same specificity as the BCR of the B cell that produced the plasma cell
1. basic structure
a. 4 amino acid chains linked together by disulfide bonds
-2 heavy chains (long)
-2 light chains (short)
b. antibody molecule has 2 identical halves
-each side composed of 1 long/1short chain
c. each of the 4 chains has a variable region (V) and a constant (C) region
-V region binds to antigen
-each antibody has 2 antigen binding sites
-antigen binding site on antibody is unique for its specific antigen (determined by genes)
-constant region
-determines type (class) of antibody formed – 5 classes
-determines how antibody carries out immune role
-determines cell types or chemicals with which antibody can bind
2. AB classes
a. IgM
-1st one to be produced
b. IgA
– in bodily secretions: semen, saliva, milk, tears
c. IgD
d. IgG
– most common
- longest lasting
– only one to cross placenta
-primary antibody to fight against bacteria
e. IgE
-triggers inflammatory response
-associated with allergies and parasites
3. antibody function
a. antibodies produced/bind to antigen forming antigen-antibody complex
b. what can happen
-complement fixation /inflammation
-causes antigen cell lysis
-main antibody ammunition against cellular antigens
-neutralization
-antibodies bond to bacterial exotoxins or viruses that can cause cell injury
-harmful effects blocked
-virus or exotoxins can’t bind to receptors on tissue cells and cause injury
-agglutination
-antibodies bind with more than 1 antigen at a time
-called cross linking
-causes clumping
-increases chance of phagocytosis
-precipitation
-when large numbers of antigen-antibody complexes become cross-linked
-they become insoluble and settle out of the solution
-increase chance of phagocytosis
-opsonization
-antibody acts as opsonins
-coat pathogen
-enhance chance of phagocytosis
-killing by oxidation
-some antibodies can catalyze production of H2O2, ozone, and other potent oxidants
-all kill bacteria
-antibody dependent cellular cytotoxicity (ADCC)
-similar to opsonization
-difference: target cell dies by apoptosis
4. monoclonal antibodies
a. ABs prepared commercially
b. come from single cell
c. exhibit specificity for only 1 antigen
d. uses
-clinical research, cancer treatment, diagnosis of pregnancy, hepatitis, rabies
III. Cell mediated immune response
-when lymphocytes themselves defend the body
A. clonal selection and differentiation of T cells
1. T cells activated to form clone by binding with “recognized” antigen
2. before binding, antigens must 1st be presented to T cells by macrophages (APCs)
a. antigen presentation by macrophage essential for activation and clonal selection
of T cells
b. macrophages also release a type of cytokine
-interleukin 1 – stimulates T cell proliferation/causes fever
c. T cell proliferation also enhanced by lymphokines
-secreted by activated T cells
3. double recognition by T cell must occur first
a. must recognize self and nonself
-self – what is self?
-glycoproteins on cell surface of every body cell
-coded for by genes of MHC – major histocompatibility complex
-nonself – what is nonself?
-antigens
b. binding occurs between antigen and macrophage
c. clonal selection now occurs
d. clone members differentiate into either effector T cells or regulatory T cells
-effector T cells – cytotoxic and delayed hypersensitivity T cells
-regulatory T cells – helper and suppressor T cells
B. different classes of T cell clones
1. cytotoxic T cells (killer T cells) – CD8 cells – CD8 is a glycoprotein on cell surface
a. effector cells
b. only T cells that can directly attack/lyse cells
c. specialize in killing virus infected cells, cancer cells, or foreign graft cells
d. binds to them and inserts toxic chemical
- perforin – creates holes in cell membrane
– cell ruptures - apoptosis
e. source of many lymphokines
2. delayed hypersensitivity cells
a. effector cells
b. play major role in cell mediated allergies (contact dermatitis) and long term/chronic
inflammations
c. when activated, release deluge of lymphokines that promote an intense inflammatory
response
3. helper T cells – CD4 or T4 cells – CD4 is a glycoprotein on cell surface
a. regulatory T cells
-regulate B cells and cytotoxic Tcells
b. no immune response without these
c. director of immune system
d. activated, then circulate getting other cells to fight invaders
e. release lymphokines
-stimulate killer T cells and B cells to grow and divide
-attract other wbc to area
-enhance ability of macrophages to engulf/destroy microorganisms
f. HIV virus targets these cells
-results in profound deficit of ABs
-suppressor T cells enhanced
-abnormal antibodies produced
4. suppressor T cells/regulatory T cells
a. regulatory T cells
b. slows stops activity of T cells and B cells
c. needed to stop immune response after antigen inactivated
d. may function in preventing autoimmune reactions
5. memory cells
a. most T cells dead within few days
b. few member of each T cell clone are long lived memory cells
c. remain behind to provide memory of each antigen encountered
d. enables body to response quickly with subsequent encounters with same antigen –
secondary response
IV. Preparation for an Adaptive Immune Response
A. Preparation
1. make Major Histocompatibility Complex (MHC) proteins
2. process antigens so can be recognized by T cells
B. Role of MHC
1. MHC
a. group of genes on chromosome 6
b. codes for major histocompatibility antigens
2. major histocompatibility antigens
a. glycoproteins
b. in membranes of most cells of vertebrate animals
c. used for compatibility of tissue for transplants/grafting
d. hold and position epitopes for presentation to T cells
-antigens bind in the antigen binding groove of MHC molecules
3. 2 classes of MHC
a. class I MHC
- our self-antigens (autoantigens)
-found in all cells except red blood cells
b. class II MHC
-found only on APCs
-B cells, monocytes, macrophages, dendritic cells
C. antigen processing by APC
1. antigen processed so MHC proteins can display epitopes
2. process different for exogenous and endogenous antigens