Chapter 21: The Immune System Flashcards
Immunity
- > Body’s defense against invaders
- > Resistance to disease
- > Immune system has 2 intrinsic systems:
- Innate (nonspecific) defense system- you are born with it
*Adaptive (specific) defense system: active.
Innate defenses
1st line of defense: surface barriers (skin, mucous membranes)
2nd line of defense: Internal defenses (phagocytes, Natural Killer cells , inflammation, antimicrobial proteins, fevers)
Adaptive defenses
3rd line of defense:
- Humoral immunity (B cells)
- Cellular immunity (T cells-involved with cellular immunity)
***Must go through first and second lines of defenses and if it makes it past them then it reaches the 3rd line of defense
Innate Defenses
- Surface barriers (1st line of defense):
- skin (keratin)-physical barrier to most microorganisms
- Mucosae provide similar mechanical barriers
- hair
- > Protective chemicals inhibit or destroy microorganisms:
- skin acidity
- lipids in sebum and dermcidin in sweat-toxic
- stomach acids
- lysozyme of saliva and lacrimal fluid
- mucus- traps microorganisms
Internal defenses (2nd line of defense): cells and chemicals
- Necessary if microorganisms invade deeper tissues
1. phagocytes
2. Natural Killer cells (NK) cells
3. Inflammatory response(macrophages, mast cells, WBCs, and inflammtory chemicals)
4. Antimicrobial proteins (interferons and complement proteins)
5. Fever
- Phagocytes: Neutrophils and macrophages (and eosinophil)
- Neutrophils: most common
- Macrophages develop from monocytes to become the chief phagocytic cells
- Phagocyte mobilization:
1. Leukocytosis: Neutrophils enter blood from bone marrow.
2. Margination: Neutrophils cling to capillary wall
3. Diapedesis: neutrophils flatten and squeeze out of capillaries
4. chemotaxis: neutrophils follow chemical trail
Mechanism of phagocytosis
Step 1: Adherence of phagocyte to pathogen
-> facilitated by opsonization (“to make tasty” or yummy or taste good–dog story)-coating of pathogen by complement proteins or antibodies
- > Destruction of pathogens:
- acidification and digestion by lysosomal enzymes
- respiratory burst: release of cell-killing free radicals
- Natural Killer (NK) cells
- > Large granular lymphocytes
- > target cells that lack “self” cell-surface receptors, looks for abnormal cells
- > induce apoptosis (suicide) in cancer cells and virus- infected cells before immune system is activated
- > secrete potent chemicals that enhance the inflammatory response
Inflammatory response
- > Triggered whenever body tissues are injured or infected
- > prevents the spread of damaging agents
- > cardinal signs of acute inflammation:
1. redness
2. heat
3. swelling
4. pain
(5. and sometimes impairment of function)
Benefits of inflammation:
dilutes harmful substances, brings in useful substances, disposes of debris, pain immobilizes, prevents spread of damaging agents
- Antimicrobial proteins
Interferons (IFNs) and complement proteins
- > attack microorganisms directly
- > hinder microorganisms ability to reproduce
Interferons- “interfere”
* Viral-infected cells are activated to secrete IFNs
- IFNs enter neighboring cells
- Neighboring cells produce antiviral proteins that block viral reproduction
- Activate macrophages & mobilize NK cells
Interferons
interfere
- Viral-infected cells are activated to secrete IFNs
- IFNs enter neighboring cells
- Neighboring cells produce antiviral proteins that block viral reproduction
- Activate macrophages & mobilize NK cells
picture on slide 16
Complement activation
Activated complement:
-> 1. Enhances inflammation
-> 2. Promotes phagocytosis through opsonization
- >
- Causes cell lysis:
- formation of a membrane attack complex (MAC)
- MAC causes cell lysis by inducing a massive influx of water
“Complement” enhances the effectiveness of both the innate and adaptive defenses. complement system is major mechanism for destroying foreign substances
- Fever
- > Systemic response to invading microorganisms
- > leukocytes and macrophages secrete pyrogens (heat)
- > pyrogens reset the bodys thermostat upward (hypothalamus)
- > high fevers are dangerous because heat denatures enzymes
->benefits of moderate fever
(increases metabolic rate, which speeds up repair)
Adaptive defenses
- The adaptive immune (specific defense) system- immunity to one disease dosent protect you against a different disease
- > protects against infectious agents and abnormal body cells
- > amplifies the inflamatory response
- > activates complement
Adaptive defenses
adaptive immune response:
- is specific
- is systemic
- has memory
- 2 separate overlapping arms:
1. Humoral (antibody-mediated) immunity (“humors” are fluids)- B cells
- Cellular (cell-mediated) immunity- T cells
Antigens- “antibody generator”
- > antigens are the targets of immune response
- >most are large, complex molecules not normally found in the body (nonself, foreign)
Complete Antigens (large molecules)
- > immunogenicity: can stimulate specific lymphocytes to multiply
- > reactivity: ability to react with these lymphocytes and antibodies
Incomplete antigens- Haptens (small molecules)
- > are not immunogenic
- > combine with bodys own proteins and casue an attack that is harmful not protective (animal hair, detergents, peanut butter)
antigenic determinants
- > certain parts of an entire antigen that are immunogenic
- > antibodies and lymphocyte receptors bind to them
- > large, chemically simple molecules (e.g plastics) have little or no immunogenicity
Self-antigens: MHC proteins
- > Protein molecules (self-antigens) on the surface of all your cells. self antigens are not foreign to you
- > antigenic to others in transfusions or grafts
- > MHC (major histocompatibility complex) proteins
- presence of this protein allows immune system to differentiate btwn our cells and foreigners
**MHC are cells’ identity markers
Cells of the adaptive immune system
2 types of lymphocytes:
-> B lymphocytes (B cells)- humoral immunity
->T lymphocytes (T cells)- cell mediated immunity
Antigen-presenting cells (APCs):
- > do not respond to specific antigens
- > play essential auxiliary roles in immunity
- > Dendritic cells, macrophages and B lymphocytes
Antigen-presenting cells (APCs)
- > engulf antigens
- > present fragments of antigens to be recognized by T cells- like signal flags on their surface
Major types:
-> dendritic cells capture antigens and enters lymph system to node, most important APC
- > Macrophages present antigens to T cells which activates them into voracious phagocytes
- > B cells- presents antigens to T cell which assist in own activation
Humoral immunity response
Antigen challenge:
- > first encounter between an antigen and a naive immunocompetent lymphocyte
- > usually occurs in the spleen or a lymph node
If the lymphocyte is a B cell:
-> the antigen provokes a humoral immune response
->antibodies are produced
Clonal selection
- B cell is activated when antigens bind to its surface receptors
- stimulated B cells grows to form a clone of identical cells bearing the same antigen-specific receptors
Fate of the clones
-> Most clone cells become plasma cells: secrete antibodies at the rate of 2000 molecules per second for 4 to 5 days
Fate of the clones
Secreted antibodies:
- Circulate in blood or lymph
- Bind to free antigens
- Mark the antigens for destruction
- Antibodies do not kill antigens
- ***Clone cells that do not become plasma cells become memory cells!
- > Provide immunological memory
- > Mount an immediate response to future exposures of the same antigen
Immunological memory
Primary immune response:
- Occurs on the first exposure to a specific antigen
- Lag period: three to six days
- Peak levels of plasma antibody are reached in 10 days
- Antibody levels then decline
Immunological memory
Secondary immune response:
-Occurs on re-exposure to the same antigen
- Sensitized memory cells respond within hours
- Antibody levels peak in two to three days at much higher levels
- Antibodies bind with greater affinity
- Antibody level can remain high for weeks to months
Active humoral immunity
-> Occurs when B cells encounter antigens and produce specific antibodies against them
- > 2 types:
- Naturally acquired: response to a bacterial or viral infection
*Artificially acquired: response to a vaccine of dead or attenuated pathogens
Active humoral immunity
Vaccines:
-Spare us the symptoms of the primary response
-provide antigenic determinants that are immunogenic and reactive
- vaccines have wiped out smallpox and have significantly reduced measles, polio, and whopping cough
- edward jenner- first person to develop vaccines
- cowpox and milkmaids
- “vacca”= cow
Passive humoral immunity
- B cells are not challenged by antigens
- antibodies “borrowed” from another source and lasts for a short period
- Drawbacks:
- short-lived
- does not trigger memory
- antibodies eventually are degraded
Passive humoral immunity
2 types:
- Naturally acquired: antibodies delivered to a fetus via the placenta or to infant through breast milk
- Artificially acquired: injection of serum, such as gamma globulin (IVIG treatments)
* protection is immediate but ends when antibodies naturally degrade in the body
* ex: antivenom for treatment of poisonous snake bites
review slide 49. goes over both passive and active humoral immunity.
Antibodies
- > Immunoglobulins—gamma globulin portion of blood (Ig)
- > Proteins secreted by plasma cells (from B cells)
- > Capable of binding specifically with antigen detected by B cells
- > All antibodies can be grouped into one of five classes (IgM, IgA, IgD, IgG, IgE) “MADGE”
Basic antibody structure
- > Two identical heavy (H) chains (long) and two identical light chains (short)
- > Variable (V) regions of each arm combine to form two identical antigen-binding sites
- > Constant (C) region determines antibody class (IgM, IgA, IgD, IgG, IgE)
Classes of antibodies
IgM:
- a pentamer (large); first antibody released
- potent agglutinating agent, in blood plasma
- readily fixes and activates complement
IgA (secretory):
- Monomer or dimer; in mucus and other secretions
- found in body secretions: saliva, sweat, milk
IgD:
*functions as a B cell receptor
IgG:
- from secondary and late primary responses
- crosses the placental barrier, most abundant
IgE:
- monomer active in some allergies and parasitic infections
- causes mast cells and basophils to release histamine; inflammation
Antibody targets
- > Antibodies inactivate and tag antigens (antibodies cannot destroy antigens)
- Form antigen-antibody (immune) complexes
- > Defensive mechanisms used by antibodies:
1. Neutralization
2. Agglutination
3. Precipitation
4. Lysis. complement fixation
“PLAN”
- Neutralization- surrounds
- > antibodies block specific sites on viruses or bacterial exotoxins
- > prevent these antigens from binding to receptors on tissue cells
- > antigen-antibody complexes undergo phagocytosis
- Agglutination- “clumps”
- Cross-linked antigen-antibody complexes agglutinate. ex: clumping of mismatched blood cells
- these clumps are easily destroyed by phagocytosis
- Precipitation
- soluble small molecules are cross-linked and fall out of solution
- complexes precipitate and are subjected to phagocytosis
- Lysis: complement fixation and activation
- main antibody defense against cellular antigens
- their complement-binding sites trigger complement fixation into the cells surface
- complement triggers cell lysis
cell mediated immune response
-> T cells provide defense against intracellular antigens
- > T cells:
- cause inflammation
- activate macrophages
- get other T cells fired up
- regulate much of the immune system
Cell mediated immune responses
Types of T cells:
-Helper T cells (TH)
- Cytotoxic T cells (TC) that destroy cells harboring foreign antigens
- Regulatory T cells (TREG)
- Memory T cells
Comparison of humoral (B cell) and cell-mediated response
Antibodies of the humoral response
*the simplest ammunition of the immune response
Targets:
*bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph- “humors”)
Comparison of humoral and cell mediated response (T cell)
T cells of the cell mediated response
*recognize and respond only to processed fragments of antigen displayed on the surface of body cells
Targets:
- body cells infected by viruses or bacteria
- abnormal or cancerous cells
- cells of infused or transplanted foreign tissue
Antigen recognition
-Immunocompetent T cells are activated when their surface receptors bind to a recognized antigen (nonself)
- T cells must simultaneously recognize:
- Nonself (the antigen)
- Self (an MHC protein of a body cell)
T cells cannot see free antigens, can only recognize fragments of antigens displayed on surface of cell
T cell activation
- > Primary T cell response peaks within a week
- > T cell apoptosis occurs between days 7 and 30
- > Effector activity wanes as the amount of antigen declines
- > Benefit of apoptosis: activated T cells are a hazard
- > Memory T cells remain and mediate secondary responses
activated T cells become either effector or memory T cells
True
Roles of Helper T cells
-Play a central role in the adaptive immune response
- Once primed by APC presentation of antigen, they:
- Help activate T cells – Activates CD8 into cytotoxic T cells
- Help activate B cells
- Induce T and B cell proliferation
- Activate macrophages and recruit other immune cells
***Without TH (helper T cells), there is no immune response
Roles of cytotoxic T cells
- > Only T cells that can directly attack and kill other cells
- > Activated cytotoxic T cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize
Targets:
- Virus-infected cells
- Cells with intracellular bacteria or parasites
- Cancer cells
- Foreign cells (transfusions or transplants)
Regulatory T cells
- > Dampen the immune response by direct contact or by inhibitory cytokines
- > Important in preventing autoimmune reactions
- > Also called suppressor T cells
understand slide 75
yes
Antibodies typically act extracellularly in body fluids and are therefore considered part of the humoral branch of adaptive immunity.
true
How is the cytotoxic T cell mechanism of action similar to that of complement?
Cytotoxic T cells induce cell lysis with perforin,a protein similar to complement’s MAC
Disorders of immune system
Immunodeficiencies:
- Congenital and acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally
- SCID, lymphoma, HIV/AIDS
- > Autoimmune diseases
- > Hypersensitivities: immediate, subacute, delayed
SCID
- > severe combined immunodeficiency syndrome
- > Congenital immunodeficiency, deficit of B & T cells
Hodgkin’s disease
- An acquired immunodeficiency
- Cancer of the B cells
- Leads to immunodeficiency by depressing lymph node cells
Acquired immune deficiency syndrome (AIDS)
cripples the immune system by interfering with the activity of helper T cells
Autoimmune disease
- Immune system loses the ability to distinguish self from foreign
- production of autoantibodies and sensitized TC cells that destroy body tissues
Exmaples include:
- multiple sclerosis (myelin),
- myasthenia gravis (nerves & MM),
- Graves’ disease (thyroid),
- type I diabetes mellitus (pancreas),
- systemic lupus erythematous (SLE) (systemic),
- glomerulonephritis (kidneys),
- rheumatoid arthritis (joints)
Hypersensitivities
- > Immune responses to a perceived (otherwise harmless) threat
- > causes tissue damage
- > different types are distinguished by:
- their time course
- whether antibodies or T cells are involved
- > antibodies cause immediate and sub acute hypersensitivities
- > T cells cause delayed hypersensitivity
Hypersensitivities- types
Immediate- local or systemic (IgE)
*allergies, begins in seconds after contact
- > Subacute-slow onset (IgM, IgG)
- ex: mismatched blood
- > delayed- onset 1-3 days
- cytotoxic T cells. ex: poison ivy
