Antigen
binds to antibodies or TCRs
Immunogen
Capable of binding with antibodies or TCRs AND stimulating an immune response; used interchangeably with antigen in common usage
Epitope
antigenic determinant site of an antigen; determines antibodies to be produced
Constitutive Response
nonspecific, general response including inflammatory response; not directly a part of the immune system
Constitutive Response?
*vasodilation; increased permeability of capillaries; "leaky"
*"call" phagocytes to site
*phagocytosis occurs, producing pus and swelling
Phagocytosis
antigenic substance is engulfed and digested by phagocytic cells (macrophages & nuetrophils)
Chemotaxis
called" to site of inflammation or intrusion via cellular products or complement components
Step 1 of Phagocytosis
Adherence
Step 2 of Phagocytosis
Ingestion
*psuedopod ---> phagosome
Step 3 of Phagosytosis
Digestion
*lysosome + phagosome = phagolysosome
*waste discharged
Induced Response
*specific response to foreign material by pre-committed lymphocytes in the lymph nodes and spleen
*"remembers"; primed for future response
*two types: cell mediated & humoral
Cell Mediated Response
defense activities based on pre-committed T-cells to kill invaders
Humoral Response
*defense activities based on the role of antigen specific Ig
*B-cells ---> plasma cells ---> Ig produced
*Ig binds to respective antigen; enhances phagocytosis; Ig remains in circulating serum for months to years
Immunoglobulins (Ig)
*anitgen specific proteins which bind to epitopes of antigen and assist in inactivating the microbe
*produced by plasma cells
Ig Classes
*IgM - initial Ig (5-10)
*IgG - long term Ig (primary response: produced after 10 days, secondary response: 1-3 days)
*IgA - in breast milk, mucous, secretions
*IgE - involved in allergic response
*IgD - helps initiate immune response
*Account for 20% of
Ig Structure
* "Y" shaped
*Fab site on arms of "Y", Fc on bottom portion
*Fab site binds with antigen; Fc site binds with phagocyte
*comprised of two heavy chains and two light chains
Ig Heavy Chains
*Constant Region (C^H "subscript H")
-consist of 3-4 (C^H1, C^H2, C^H3, C^H4); five amino acid sequence determines class of Ig
-IgM & IgG have complement binding sites
*Variable Regions (V^H)
-amino acid sequence and 3D structure account for ability to re
Ig Light Chains
*one pair; identical to each other
*short chain of amino acids
*Constant Region (C^L)
-two types: Kappa & Lambda
*Variable Region (V^L)
-amino acid sequences vary from one Ig to another
-match with variable region of heavy chain
Complete Ig Molecule
*chains held together by DISULFIDE bonds
*pair of heavy chains flexible; "Y" or "T" conformation
*Fab site combinations are sufficient to deal the number of different types of antigens
Phagocytic cells
*Macrophages
*Nuetrophils
Nuetrophils
*primary phagocytic cells
*most abundant
*circulate for 6.5 hours and then adhere to endothelium of blood vessels and wait to respond
Macrophages
*MATURE form of monocytes
*large phagocytic cells
*not as abundant
*broad specificity
*major line of defense via phagocytosis & APC role
T-Lymphocytes
*mature in Thymus, then concentrate in lymph nodes
*T-cell surface markers
-CD3
-CD28
-CD40
*antigen specific T-cell receptors (TCR)
CD3
identifies mature T-cell
"Toddlers MATURE at 3 years old"
^^^that's a lie but it helps me remember
CD28
receives activation co-signal from CD80/86 molecule on APC
CD40
Helper T-cell CD40 receptor binds with CD-40 molecule on B-cell
B-Lymphocytes
*mature in bone marrow, then concentrate in peripheral lymphoid tissue
*B-cell surface markers
-CD40
-CD19, CD20, CD21
-CD80/86 (when the B-cell is acting as an APC to bind with T-cells
*upon activation B-cells differentiate into Plasma Cells to manufactu
Antigen Presenting Cell
*possess MHC-II
*bind antigen to specific receptors --->place some on MHC-II to present to the Helper T-cell
*PRODUCE Interleukin-1 to assist activating lymphocytes
*assisted by cytokines produced by lymphocytes (ie interferon to activate macrophages
Examples of APCs
*macrophages
*B-lymphocytes
*dendritic cells
-spidery shape
-little to NO phagocytic capacity
-possess numerous MHC-II
-initiate primary response
-located in specific tissues
Cytokine Products of Cells
small proteins produced by specific human cells that act as chemical mediators to enhance certain immunity actions (ie interleukins, tumor necrosis factor, inteferon)
Lymph Nodes
lymphatic fluid containing antigens and APCs flows through the lymph nodes where antigens encounter and activate pre-committed lymphocytes; responds to LOCAL or REGIONAL infections
Spleen
filters blood and traps blood-borne antigens; responds to SYSTEMIC infections
Cell Mediated Response - Major Cells Involved
*APCs
*T-Lymphocytes
*Natural Killer Cells ((NK)
Functional Aspects of Cell Mediated Immunity
*Helper T-cells
*Cytotoxic T-cells
*Memory T-cells
*Natural Killer Cells
Helper T-cell
*possesses CD4 & CD3
*recognize antigens bound to MHC-II of APC
Helper T-cell Activation Events
*contact of TCR with antigen bound to MHC-II on APC
*binding of CD28 with CD80/86 on APC; stimulatory CO-SIGNAL
*Interleukin-1; activation CO-SIGNAL
-ALL THREE EVENTS REQUIRED FOR ACTIVATION TO OCCUR
Helper T-cell Activation
*leads to differentiation into T^H1 & T^H2 cells
*stimulates proliferation of activaed T-cells (multiplies the effects of activating the first T-cell)
Initial Activated Helper T-cell
T^H0 or T-helper Zero
T^H1
*antigen specific local inflammatory response
-amplifies cytotoxic T-cell response
-promotes phagocytosis
-down regulates production of T^H2
T^H2
*antigen specific Ig response
-helps recruit & activate B-cells
-enhances roles of Mast Cells, Basophils, and Eosonophils to attack large, multicellular microbes too large for phagocytosis
-down regulates production of T^H1
Cytotoxic T-Lymphocytes (CTL)
*possess CD8
*recognize antigenic determinants of MHC-I
- contact required between MHC-I & TCR
-requires IL-2 co-signal from Hlper T-cell for CD28 - CD80/86 interaction
*destroys cells via cytotoxic granules: perforin & granzymes
*suppresses immune respon
Perforin
pore forming protein creating entrance into cell
"Hole Punch
Granzymes
toxic molecule inserted in target cell cytoplasm via perforin created opening
"Poison
Memory T-Lymphocytes
long lived, self renewing cells which "remember" the antigen and remain primed to initiate a secondary response for future encounters in a significantly shorter period of time
Natural Killer Cells (NK)
*possess CD16 & CD56
*binding to target cell
-does NOT possess antigen specific TCR
-does not require presentation from MHC-I or II
-binds to surface proteins and carbohydrates on target cells
-binds to Fc of Ig already attached to target cell; Antibody D
Roles of NKs
*major role in early recognition of and killing of VIRUS infected host cells and TUMOR cells
*amplifies inflammatory response after bacterial infection
*activity occasionally enhanced by IL-2 and Interferon; referred to as Lymphokine-Activated Killer acti
Humoral Response - Major Cells Involved
*APCs
*Activated Helper T-cells
*B-cells activated to plasma cells
Activation of B-cells
*antigen binds to antigen B-cell receptor
*B-cell internalizes the receptor, processes, presents on MHC-II
*B-cells & T-cells interact
*activated helper T-cell produces cytokines to enhance/activate B-cells
Interactions between B-cells & T-cells
*activation of Helper T-cell
*activation of B-cell
*produces linked reactions between Helper T-cell & B-cell generating heightened amplification of B-cell production & differentiation
*direct contact of B-cell MHC-II and TCR of Helper T-cell
*IL-1 from B-
Helper T-cell Cytokines Produced
*IL-2
*IL-4
*IL -6
IL-2
T-cell proliferation inducer
IL-4
B-cell activation & proliferation
IL-6
*promotes B-cell growth & Ig production
*B-cells may also secrete this
B-cells differentiate into...
*Plasma Cells
-secrete Ig
-initially IgM, but switches to IgG, IgA, and/or IgE
Class Switching
gene rearrangement leading to expression of a new heavy chain class without altering specificity (Fab)
Memory B-cells
remembers the antigen it was committed to responding to
Primary Response
events which occur in the host's immune system following FIRST TIME exposure to a specific foreign substance
Events of Primary Response
*constitutive response
*APC presentation to lymphocytes & memory cells
*Ag not recognized by any memory cells
*pre-committed Ag-specific T-cells activated
*Activated Helper T-cells begin producing lymphokines
*activated CTLs inhibit or kill invaders
*acti
Secondary Response
rapid & highly specific response by host's immune system against a specific foreign substance which HAS BEEN PREVIOUSLY encountered
Events of Secondary Response
*Ig's may attach to Ag and either neutralize or opsinize the Ag
*constitutive defenses work to eradicate invader
*APCs encounter foreign antigen and present it to T&B-cells & memory cells
*presented Ag "remembered" by memory cells
*memory T & B-cells diff
Rapid Memory T-cell Differentiation
*Helper T-cells activate B-cells
*CTL inhibit invaders
*memory T-cells continue to "remember" Ag
Rapid Memory B-cell Differentiation
*serve as APC to activate Helper T-cell, which in turn activate other B-cells
*proliferate & differentiate into a large number of plasma cells
*form memory cells for future use
Active Immunity
*results from direct stimulation of host immune system
*duration of effects: LONG LASTING
*primed to give secondary response
Passive Immunity
*results from transfer of preformed Ig's and/or cells from a donor to host
-host immune system DOES NOT participate
*duration of effects: TRANSIENT; SHORT LIVED
*NOT primed for secondary response