immune iii Flashcards
Antibodies
- immunoglobulins = gamma globulin portion of blood
- proteins secreted by plasma cells
- capable of binding specifically with antigen detected by B cells
- grouped into 5 Ig classes
Antibody structure
- T or Y shaped antibody monomer of 4 looping polypeptide chains linked by disulfide bonds
- 2 heavy chains with hinge region at “middles”
- two identical light chains
- variable regions at one end of each arm combine to form two identical antigen-binding sites
- Constant regions of stem determine antibody class and serve common funcs in all antibodies
IgM
- Pentamer (biggest)
- 1st antibody released
- potent agglutinating agent
- readily fixes and acticates complement
IgA
- secratory IgA
- monomer or dimer
- in mucus, breast milk, and other secretions
- helps prevent entry of pathogens
IgD
- Monomer attached to surface of B cells
- Functions as B cell receptor
IgG
- monomer
- 75-85% of antibodies in plasma
- from secondary and late primary responses
- crosses placental barrier
IgE
- monomer active in some allergies and parasitic infections
- causes mast cells and basophils to release histamine
B cell specieal antibody skill
- B cells can switch antibody classes, but retain antigen specificity
- IgM at first, then IgG
- almost all secondary responses are IgG
Antibody targets and functions
- antibodies inactivate and tag antigens; do not destroy them –> form antigen-antibody complexes
- defensive mechanisms used by antibodies: neutralization, agglutination, precipitation, and complement fixation
Neutralization
- simplest defensive mechanism
- antibodies block specific sites on viruses or bacterial exotoxins
- prevent these antigens from binding to receptors on tissue cells
- antigen-antibody comlexes undergo phagocytosis
agglutination
- antibodies bind same determinant on more than one cell-bound antigen
- cross-linked antigen-antibody complexes agglutinate (e.g. clumping of mismatched blood cells)
Precipitation
- soluble molecules are cross-linked
- complexes precipitate and are subject to phagocytosis
Complement fixation and activation
- main antibody defense against cellular antigens (bacteria or mismatched RBCs)
- several antibodies bind close together on a cellular antigen –> complement-binding sites on stem regions of antibodies align –> triggers complement fixation to cells surface –> cell lysis
activated complement functions
- amplifies inflammatory response
- promotes phagocytosis via opsonization –>positive feedback cycle that enlists more and more defensive elements
- activated complement forma MAC
Example of adaptive immune response enhancing innate response
Cell mediated immunity: activation of T cells
first signal in activation:
- T cell receptors recognize and bind to a specific foreign antigen fragment that’s presented in antigen-MHC complexes
- CD4 and CD8 proteins are coreceptors
second signal required for activation
- costiulation: 20 known substances (cytokines, plasma membrane molecules)
- may prevent immune response from occuring accidentally
- anergy = recognition without costimulation (in both B and T cells) –> leads to prolonged state of inactivity
Activation and clonal selection of helper T cells
- most that display CD4 develop into helper T cells –> some become regulatory T cells which moderate immunne response
- recognize exogenous antigen fragments associated with MHC-II molecules on the surface of an APC
- after activation, undergoes clonal selection
- Makes active helper T cells and memory helper T cells
- Active hleper T cells secrete cytokines (interleukin 2 needed for all immue resposes)
- Memory helper t cells aren’t active –> can quickly proliferate and differentiate if the antigen appears again
Activation and clonal selection of cytotoxic t cells
- most taht display CD8 develop into cytotoxic T cells (CD8 T cells)
- recognize antigens combined with MHC-I
- Maximal activation also requires presentation of antigen with MHC-II to cause helper T cells to make IL-2
- Undergoes clonal selection
- Active cytotoxic T cells attack body cells
- Memory cytotoxic T cells don’t attack, but wait for an antigen to appear again
Elimination of invaders
- cytotoxic T cells migrate to seek out and destroy infected target cells
- kill like NK cells
- major difference is T cells have specific receptor for particular microbe, but NK cells eat a ton of stuff
2 ways to kill: granzyes cause apoptosis; perforin and/or granulysin causes cytolysis
immunological surveillance
tumor antigens displayed on cancerous cells targeted by cytotoxic T cells, macrophages, and NK cells
Roles of helper T cells
- central role in adaptive immunne response
- activate both humoral and cellular arms
- once primed by APC presentation of antigen they help activate T and B cells, induce T and B cell proliferation, and their cytokines recruit other immune cells
Without helper T cells, there’s no immune response
Helper T cells’ activation of B cells
- interact directly with B cells displaying antigen fragments bound to MHC II receptors
- release cytokines to stimulate B cells to divide more rapidly and begin atibody formation
- B cells may be activated without helper t cells by binding to T cell-independent intigens (response is weak and short, though)
- Most antigens require helper T cell co-stimulation to activate B cells: T cell-dependent antigens
Helper T cell activation of CD8 cells
- CD8 cells require hleper T cell activation into destructive cytotoxic T cells
- cause dendritic cells to express co-stimulatory molecules required for CD8 cell activation
Helper T cells amplification of innate defenses
- amplify responses of innate immune system
- activate macrophages –> more potent killers
- mobilize lymphocytes and macrophages and attract other types of WBCs
Hypersensitivities
- immune responses to perceived threat cause tissue damage
- different types distinguished by their time course and whether antibodies or T cells involved
- Antibodies cause immediate and subacute hypersensitivities
- T cells cause delayed hypersensitivity
Subacute Hypersensitivities
- caused by IgM and IgG transferred via blood plasma or serum
- slow onset (1-3 hours) and long duration (10-15 hours)
Cytotoxic (type II) reactions
- antibodies bind to antigens on specific body cells, stimulate phagocytosis and complement-mediated lysis of cellular antigens
- example: mismatched blood transfusion
Delayed hypersensitivities (type IV)
- slow onset (1-3 days)
- mechanism depends on helper T cells
- cytokine-activated macrophages and cytotoxic T cells cause damage
- example: allergic contact dermatitis (e.g. poison ivy)
- agents act as haptens
- TB skin test depends on this reaction
Acquired immue deficiency syndrome (AIDs)
- Cripples immune system by interfering with activity of helper T cells
- characterized by severe weight loss, night sweats, and swollen lymph nodes
- opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma
AIDs and HIV
- caused by human immunodeficiency virus (HIV) transmitted via body fluids (blood, semen, and vaginal secretions)
- HIV enters blood via blood transfusions, blood contaminated needles, sexual intercourse and oral sex, mother to fetus
- HIV destroys hleper T cells and depresses cellular immunity
autoimmune diseases
- immune system loses ability to distinguish self from foreign
- production of autoantibodies and sensitized Tc cells taht destroy body tissues