Lecture 3 Outline: Immunity Part 1 Flashcards
(42 cards)
1
Q
Innate Immunity
A
- nonspecific and non-adaptive, natural immunity
- first line of defense: skin and external body membranes
- second line of defense: internal defenses (inflammatory response)
2
Q
Acquired (Adaptive) Immunity
A
- specific
- overview (3rd line of defense)
- has specific memory of antigens (adaptive)
- results in specific responses to specific antigen (Ag)
- result of active or passive processes
- 2 components: humoral (B-cells) and cell-mediated (T-cells)
- can be broken down into active and passive immunity as well
3
Q
Active Immunity
A
- protection acquired by introduction of an Ag into a responsive host which activates Ab’s or T-cells
- expected to be permanent
- vaccination is an example
4
Q
Passive Immunity
A
- Abs or sensitized lymphocytes transferred from one person to another
- preformed Ab’s or T-cells are transferred from a donor to a recipient
- transplacental or via breast milk from mother to child
- does not result from formation of memory cells, only temporary immunity until antibodies are degraded
5
Q
The Immune Response: Innate Immunity
A
- exterior defenses: (1st line of defense) mechanical and chemical protection (ex: skin and mucosal membranes, lysozyme in tears, saliva, waxy secretions in ear canal, nasal hair, stomach acid, low pH vaginal secretions, acidic urine)
- internal non-specific defenses (2nd line of defense)
- internal can be inflammatory response, phagocytes, inflammatory mediators, natural killer cells, fever
6
Q
Internal Non-Specific Defenses: Phagocytes
A
- neutrophils (also called polymorphonuclear cells-PMN’s): fast, come right to scene, die after phagocytosis and often part of pus that drains
- dendritic cells: best activators of immune system
- monocytes: mature into macrophages once move from blood into tissue; macrophage phagocytosis is first step leading to a specific immune response; following phagocytosis expresses epitope of foreign Ag on surface which is recognized by helper T-cells–APCs, MHCII complex
7
Q
Different Names for Helper T-Cells
A
- helper/inducer lymphocyte
- T4 lymphocyte
- CD4 lymphocyte
8
Q
Internal-Non Specific Defenses: Inflammatory Mediators
A
- complement system
- interferons: (IFNs, type of cytokine) diffuse into uninfected cells and bind to surfaces–stimulate macrophages and NK cells, stimulate production of antiviral proteins which block viral replication, suppress growth of tumor cells
9
Q
Internal Non-Specific Defenses: Natural Killer Cells (NK)
A
- large granular lymphocytes
- await activation in thymus
- recognize infected cells (d/t virus, bacteria or tumor) and directly attack and kill them (not by phagocytosis)
- act before Ag specific immune system is activated
- secrete potent chemical signals that enhance inflammatory response
10
Q
Internal Non-Specific Defenses: Fever
A
- pyrogens reset temperature set point in hypothalamus
- increases effects of antimicrobial substances produced by immune system (stimulates immune reactions)
11
Q
The Immune Response: Acquired (Adaptive) Immunity
A
- overview
- acts to immobilize, neutralize, or destroy foreign substances and cells; acquired with exposure to foreign substances
- amplifies inflammatory response and activates complement
- is Ag-specific* system and has memory (*recognizes specific foreign molecules)
- 2 types of responses to most pathogens: humoral or AMI (B-cells)-involved in producing Abs against epitopes, B-cell receptors bind free Ags or
- Cellular or CMI (T-cells)-provide resistance through lysis of infected or abnormal cells, T-cell receptors bind processed Ag’s
12
Q
Immunity Definition
A
-ability of body to defend itself against specific foreign invaders (molecules or cells)
13
Q
Immunogenicity Definition
A
-ability to stimulate proliferation of specific lymphocytes and specific Ab production
14
Q
Specificity Defintion
A
-Ag triggers focused immune defenses (from particular lymphocyte lineages) that respond only to Ag’s of this foreign substance/cell
15
Q
Memory Definition
A
-immune system produces clones of specific memory lymphocytes (B and T) which react rapidly when the particular foreign substance/cell is encountered again
16
Q
Antigens
A
- any foreign substance that provokes specific immune responsess
- antigenic determinants: parts of Ag’s that trigger specific immune response=Epitopes (small molecular group recognized by Ab’s, B and T cells)
- epitopes protrude from surface, the more epitopes, the greater the antigenicity and the greater the immune response
- ag receptor diversity: more than a billion different antigenic determinants are recognized by the body; need to be exact fit to trigger effects
17
Q
Requirements for Antigenicity
A
- foreignness (recognition of non-self)
- large size
- complexity
- first two are most antigenic
18
Q
Major Histocompatibility Complex (MHC) Ag’s
A
- proteins expressed on surface of all cells that allow self-recognition
- unique to each individual’s cells: help in identifying self vs. foreign
- 2 classes: Class I MHC and Class II MHC
19
Q
Class I MHC
A
- found on all body cells except RBC’s
- recognized by T cells and APC
20
Q
Class II MHC
A
- only on Ag presenting cells (APCs), thymus cells, and B-cells
- synthesized in ER
- phagosome containing pathogen (with exogenous Ag’s) merges with lysosome
- MHC Class II proteins migrate into phagosome
- Ag–MHC Class II complex migrates to cell membrane and displays antigenic peptide for recognition by CD4 helper T cells
21
Q
APC’s
A
- phagocytose, process, and present Ag’s to lymphocytes
- do not respond to specific Ags
- actively migrate to lymph nodes and secondary lymphoid organs and present Ags to T and B cells
- a T cell can only see anAg that has been processed (if not presented on cell surface it cannot be seen)
- contribute to coordinating specific immunity: macrophages, dendritic (Langerhans) cells, B-cells
22
Q
Where are lymphocytes produced and developed?
A
- mature and develop immunocompetence (ability to recognize specific Ag) in different locations
- lymphoid organs: central and peripheral
- central: thymus, bone marrow (B and T lymphocytes develop here)
- peripheral: tonsils, lymph nodes, spleen
- lymphocyte=small leukocyte found in lymph (ex: NK cells, T and B cells)
- T cells mature in thymus and provide cell-mediated immunity
- B cells mature in bone marrow and provide Ab mediated immunity
23
Q
Humoral Immunity (AMI)
A
- antibody mediated immunity
- circulating Ab’s present in humors of body (saliva, blood)
- key player is B lymphocyte: surface receptor for specific Ag (membrane bound Ab’s), b-cells can only detect 1 Ag out of millions available
- becomes activated when binding to Ag (along with helper T cell, which is needed to destroy the Ag): begins cloning itself into two types of B cells–memory B cells and plasma B cells which bind to Ag and tag it (opsonization) for phagocytosis (produces more Abs specific to that Ag)
- Abs can activate complement system
- more rapid than cell mediated response
- can be transmitted to another person
- B cells recognize Ag bound to surface –> B cells change into plasma cell/memory cell which makes Abs specific to that Ag
24
Q
Basic Ab Structure and Info
A
- 4 polypeptide chains linked with disulfide bonds
- 4 chains bound together form Ab monomer
- each chain has a variable (V) region at one end and a constant region at other
- variable regions of the heavy and light chains form Ag binding site (each B cell has different variable regions)
- Abs are unique soluble proteins secreted by activated B cells and plasma cells in response to Ag
- capable of binding specifically with that Ag
- constitute much of the gamma globulin fraction of plasma proteins
- also called immunoglobulins
25
5 Classes of Ab's (Immunoglobulins)
- IgD: attached to surface of B cells, important in B cell activation
- IgM: released by plasma cells during primary immune response
- IgG: most abundant and diverse Ab in primary and secondary responses, crosses placenta and confers passive immunity
- IgA: helps prevent attachment of pathogens to mucosal surfaces
- IgE: binds to mast cells and basophils causing histamine release when activated
26
Ab Mechanisms of Action
- neutralization: Abs bind to and block specific sites on viruses or exotoxins thus preventing these Ags from binding to receptors on tissue cells
- agglutination: Ab aggregation; cross-linking cells or particles into large clumps
- opsonization: process of coating microorganisms or other particles with specific Abs (more readily recognized by phagocytes)
- complement fixation: IgM and IgG Ab's bound to cellular Ag's bind complement via classical pathway (complement cascade causes chemotaxis, opsonization, phagocytosis and cell lysis; complement activation enhances inflammatory response)
27
Ab Functions
- all Abs form Ag-Ab complex
- do not directly destroy Ag, though they may immobilize or inactivate Ag
- act as opsonins and tag Ag for immune attack and destruction
- defensive mechanism triggered by Abs include neutralization, agglutination, precipitation, opsonization, and complement fixation
28
Cell-Mediated Immunity
- T cell differentiation: CMI involved in most aspects of specific immune defense
- different types of T-cells regulate specific immunity: helper T cells which carry CD4+ markers, suppressor T cells, memory T cells
- following interaction with specific Ag, will produce additional lymphocytes: helper T cells or cytotoxic T cells
- capable of turning the entire immune system on or off
- cannot be transferred passively to another person
29
Helper T Cells
- 75% of all T cells
- has T cell receptors on surface to bind to MHC II complex (dendritic cells best at activating it); activated by IL-1 from macrophages, when activated (non-naive) produce IL-2 interferon and other chemicals
- these chemicals activate B cells to produce Abs
- activate macrophages
- help other T cells recognize and destroy virally infected cells
- help NK cells kill infected cells
- basic steps: 1. recognition by T cells of Ag presented by APC with matching MHC Class II markers 2. proliferation and differentiation of T cells once activated 3. production of clones of identical effector T cells capable of recognizing specific Ag 4. appropriate action (help, attack, memory, suppression) from T-cell subclones
30
Cytotoxic T Cells
- carry CD8+ markers destroy tumor cells and virus infected cells; also attack transplanted cells and tissues
- attack infiltrated or abnormal cells (Abs of no use inside cell)
- bind to MHC I complex and forces cell to kill itself
31
How are the cells of the immune response different from cells of inflammatory response?
- specificity
- lasting "memory"
- Ag induces an immune response
32
T-Cell Activation Step 1
-Ag binding and Ag presentation
33
T-Cell Activation Step 2: Co-Stimulation
- T cells must bind to MHC Class II surface receptors on APC
- after co-stimulation with cytokines, T-cells enlarge, proliferate and form clones
- activated T-cells differentiate and perform functions according to T-cell class
34
T-Cell Activity
- primary T-cell response usually peaks within a week
- T-cells then undergo apoptosis within a month
- reduced activity parallels elimination of Ag
- negative feedback control
- few memory T-cells remain to respond to any future exposure to same Ag
35
Helper T-Cells Pt 2
- regulatory cells that play central management role in immune response
- once primed by APC Ag presentation, helper T cells: stimulate proliferation of other T-cell classes, and stimulate B-cells that have already been bound to Ag
- no coordinated immune response without helper T cell function
- helper T cells interact directly with B cells that have Ag fragments on surfaces bound to MHC Class II receptors
- helper T cells express CD4+ cell identify markers
- helper T cells stimulate B cells to divide more rapidly and begin Ab formation
- B cells may be active without helper T cell help by binding to T-cell-independent Ag's
- most Ag's require helper T cell co-stimulation to activate B cells
- cytokines released by helper T cells amplify nonspecific defenses
36
Suppressor T Cells
- immune regulatory cells which release cytokines that suppress activity of both T-cells and B-cells
- generated with other specific T cell clones are generated
- negative feedback control to bring the body back to normal after the battle has been won
37
Cytotoxic T Cells Pt 2
- express CD8+ identity markers
- aka killer T cells are only T cells that can directly attack and kill other cells
- circulate throughout body in search of body cells that display Ag to which they have been sensitized
- targets include: virus-infected cells, cells with intracellular bacteria or parasites, cancer cells, foreign cells from blood transfusions or tissue and organ transplants
- bind to self/anti-self complexes on any body cell
- infected or abnormal cells can be destroyed as long as appropriate Ag and co-stimulatory regulators are present
- in contrasts NK cells activate their killing machinery when they bind to a different MHC-related cell surface marker on cancer cells, virus-infected cells and transplant cells
38
Cytotoxic T Lymphocyte Actions
- secret perforins which cause cell lysis by creating transmembrane pores
- secrete lymphotoxin which fragments the target cell's DNA
- secrete gamma interferon which stimulates macrophage attack
39
Putting it All Together: Ab-Mediated Immunity
- Ag challenge: first encounter between Ag and naive B cell
- Ag presentation usually occurs in spleen or lymph node but can occur in any lymphoid tissue
- Ag presentation usually made by macrophage, but some B-cells can react directly against certain bacterial Ag's
- binding of Ag to B cell specific Ag receptor activates B cell
40
Putting it All Together: Primary Response
- activated B cells grow and divide forming clones bearing same Ag-specific receptors and secreting same Ag-specific Ab
- initial B cell differentiation, proliferation, and AB synthesis requires time after first Ag exposure
- lag period 3-6 days after Ag challenge
- peak plasma levels of Ab achieved in ~10 days
- Ab molecules also reach interstitial fluids, especially where inflammation exists
- Ab levels then decline gradually if there is no additional Ag exposure
41
Putting it All Together: Secondary Response
- Any subsequent exposure to same Ag
- sensitized memory cells (B and T) respond within hours
- Ab levels peak in 2-3 days at higher plasma levels than in primary response
- activated B subclones generate Abs that bind with greater affinity
- plasma Ab levels can remain high for weeks to months
42
Putting it All Together: Immunological Memory
- with any subsequent exposure, the immune system responds more quickly, forcefully
- secondary response: Ab's produced during subsequent exposures are produced in greater quantities and have greater attraction for Ag
