Bio 204 Immune System

2 step process of activation of T cells

1. Antigen binding 2. Co-stimulation

How do antimicrobial proteins enhance innate defense?

1. Attacking microorganisms directly 2. Hindering microorganisms' ability to reproduce

Class II MHC proteins

- Bind with longer fragments (14-17 amino acids) of exogenous (extracellular) antigens that have been engulfed and broken down in a phagolysosome by antigen-presenting cell - Class II MHC proteins recognized by helper T cells • Signal CD4 cells that help is required

Innate (non-specific) defense system

-First and second lines of defense

Dendritic Cells

-Found in connective tissues and epidermis and act as mobile sentinels of boundary tissues. Also phagocytize pathogens that enter tissues Most effective antigen presenter known

Adaptive defenses examples

-Humoral immunity (B cells) -Cellular immunity (T cells)

Benefits of edema

-Surge of fluid in tissue sweeps foreign material into lymphatic vessels for processing in lymph nodes -Delivers clotting proteins and complement to area

Step 1: Antigen Binding

-T cell antigen receptors (TCRs) bind to antigen-MHC complex on APC surface -TCR must perform double recognition by recognizing both MHC and foreign antigen it displays -Binding of TCR to complex triggers multiple intracellular signaling pathways that start T cell activation -Other T cell surface proteins are involved in T cell activation (e.g., CD4 and CD8 help maintain coupling during antigen recognition)

Vasodilation and increased vascular permeability

-Vasodilation causes hyperemia—congestion with blood—which leads to redness and heat -Increased capillary permeability causes exudate—fluid containing clotting factors and antibodies—to leak into tissue -Results in local swelling (edema)

Humoral immunity

-antibodies, produced by lymphocytes, circulate freely in body fluids -Bind temporarily to target cell -TEMPORAILY INACTIVE & MARK FOR DESTRUCTION BY PHAGOCYTES OR COMPLEMENT Humoral immunity has EXTRACELLULAR TARGETS

Memory cells function

-provide immunological memory -mount an immediate response to future exposures to the same antigen

5 major antibody classes

IgM, IgA, IgD, IgG, IgE

Where do T cells mature?

In the thymus under negative and positive selection pressures ("tests")

Characteristics of adaptive immunity

It is specific: recognizes and targets specific antigens It is systemic: not restricted to initial site It has memory: mounts an even stronger attack to "known" antigens (second and subsequent exposures)

Cellular immunity

Lymphocytes act against target cell Directly - by killing infected cells Indirectly - by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages Cellular immunity has cellular targets.

2 classes of MHC proteins

MHC I and MHC II both are synthesized in the endoplasmic reticulum

Set of important-self proteins are a group of glycoproteins called...

MHC proteins

complement fixation and activation

Main antibody defense against cellular antigens, several antibodies bind close together on a cellular antigen, their complement-binding sites trigger complement fixation into the cell's surface, complement triggers cell lysis, activated complement functions, amplifies the inflammatory response, opsonization, and enlists more and more defensive elements.

Is there a cure for AIDS?

No

Free Macrophages

wander through tissue spaces (alveolar macrophages)

Basic antibody structure

Overall T- or Y-shaped antibody monomer consists of four looping polypeptide chains linked by disulfide bonds 4 chains consist of 2 identical heavy (H) chains and 2 identical light (L) chains Stems make up constant (C) regions - area determines antibody class

What do most clone cells become?

Plasma cells

Immune system

Provides resistance to disease

Secondary immune response

Re-exposure to same antigen gives faster, more prolonged, more effective response

Precipitation

Soluble molecules (instead of cells) are cross-linked into complexes. Complexes precipitate out of solution

Where is rate of HIV diagnosis the highest in the world?

South Africa or Africa

Where is HIV located most frequently in US?

Southeast region (Florida, Georgia, Texas, California, etc..)

Innate defenses examples

Surface barriers: skin and mucous membranes Internal defenses: Phagocytes, NK cells, Inflammation, antimicrobial proteins, Fever

B cells may be activated without helper t cells by binding to...

T cell- independent antigens

What causes delayed hypersensitivities?

T cells

Which are more complex? T cells or B cells?

T cells in both classification and function

clonal selection

The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen. The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen.

Adaptive (specific) defense system

Third line of defense

Phagocytes

WBCs that ingest and digest (eat) foreign invaders

What triggers a humoral immune response?

When B cell encounters target antigen

What activates B cell?

When antigens bind to surface receptors, cross linking them.

What is inflammation triggered by?

Whenever the body is injured. Injuries can be due to trauma, heat, irritating chemicals, or infections by microorganisms.

Macrophages

Widely distributed in connective tissues and lymphoid organs. Present antigens to T cells, which not only activates T cell, but also further activates macrophage.

immunogenicity

ability to stimulate proliferation of specific lymphocytes and antibodies

Reactivity

ability to with activated lymphocytes and antibodies released REACT by immunogenic reactions

Self anitgens

all cells are covered with variety of proteins located on surface that are not antigenic to self, but may be antigenic to others in transfusions or implants

What is the most common type of organ transplant?

allograft: transplant from same species success depends on similarity of tissues. ABO, other blood antigens, and MHC antigens are matched as closely as possible

Antibodies

also called immunoglobulins (Igs) are proteins secreted by plasma cells make up gamma globulin portion of blood

Hodgkin's Disease

an acquired immunodeficiency that causes cancer of B cells, which depresses lymph node cells and thus leads to immunodeficiency

What does an activated macrophage become?

an uncontrollable phagocytic killer

Naturally acquired passive humoral immunity

antibodies delivered to fetus via placenta or to infant through milk

What are plasma cells?

antibody-secreting effector cells

T cells can be activated only when..

antigen is presented to them

Defensins

antimicrobial peptides that inhibit microbial growth

Second line of defense

antimicrobial proteins, phagocytes, and other cells (inhibit spread of invaders; inflammation most important mechanism)

Lectins

are produced by innate system to recognize foreign invaders

Granulomas

area of infected macrophages surrounded by uninfected macrophages and outer capsule

Third line of defense

attacks particular foreign substances (takes longer to react than innate)

Primary immune response

cell proliferation and differentiation upon exposure to antigen for the first time lag period= 3-6 days

Cytokines

chemical messengers of the immune system Mediate cell development, differentiation, and responses in immune system include interferons and interleukins

monoclonal antibodies

commercially prepared pure antibodies that are specific for a single antigenic determinant produced by hybridomas

Antigens can be either....

complete or incomplete

immunodeficiency

congenital or acquired conditions that impair function or production of immune cells or molecules

Pus

creamy yellow mixture of dead neutrophils, tissue/cells, and living/dead pathogens

human immunodeficiency virus (HIV)

cripples immune system by interfering with activity of helper T cells

Regulatory T cells (TReg)

dampen the immune response by direct contact or by inhibitory cytokines

Pathogen definition

disease causing organism

Adaptive Immune System main function is:

eliminates almost any pathogen or abnormal cell in the body. Activities of adaptive immune system include: 1. amplifies inflammatory response 2. activates complement

T cells that are activated...

enlarge and proliferate in response to cytokines

Interferons (IFN)

family of immune modulating proteins

Naturally acquired humoral immunity

formed in response to actual bacterial or viral infection

Artificially acquired humoral immunity

formed in response to vaccine of dead or attenuated pathogens

Severe Combined Immunodeficiency (SCID)

genetic defect with marked deficit in B and T cells

What are hypersensitivities?

immune responses to perceived (otherwise harmless) threat that cause tissue damage

What do sensitized memory cells provide?

immunological memory

artificially acquired passive humoral immunity

injection of serum, such as gamma globulin Protection immediate but ends when antibodies naturally degrade in body

2 most important antimicrobial proteins:

interferons and complement proteins

What do T cells provide defense against?

intracellular antigens

incomplete antigens (haptens)

involve molecules too small to be seen so are not immunogenic by themselves

Clone cells that do not become plasma cells become...

memory cells

Neutrophils

most abundant phagocytes, but die fighting; become phagocytic on exposure to infectious material

Active humoral immunity

occurs when B cells encounter antigens and produce specific antibodies against them

Passive humoral immunity

occurs when ready-made antibodies are introduced into body

Antigenic determinants

parts of antigen that antibodies or lymphocyte receptors bind to

Fixed macrophages

permanent residents of some organs; examples: stellate macrophages (liver) and microglia (brain)

Helper T Cells

play central role in adaptive immune response activate both humoral and cellular arms without no helper T cells there is no immune response

What is autoimmunity?

production of autoantibodies and sensitized TC cells that destroys body tissues

What do skin and mucous membranes produce?

protective chemicals that inhibit or destroy microorganisms

Interleukin 1 (IL-1)

released by macrophages, stimulates T cells to release interleukin 2 (IL-2) and to synthesize more IL-2 receptors

2 types of lymphocytes

1. B lymphocytes (B cells) - Humoral Immunity 2. T lymphocytes (T cells) - Cellular immunity

What 3 pathways can complement system be activated?

1. Classical Pathway 2.Lectin Pathway 3. Alternative Pathway

3 major types of Antigen-Presenting Cells (APCs)

1. Dendritic cells 2. Macrophages 3. B cells

2 main branches of adaptive system:

1. Humoral (antibody-mediated) immunity 2. Cellular (cell-mediated) immunity

What is an autoimmune disease?

results when immune system loses ability to distinguish self from foreign

2 reasons lymphocytes are educated:

1. Immunocompetence 2. Self-tolerance

Weakened, failed, or dysfunctional immune system can be in the form of...

1. Immunodeficiencies 2. Autoimmune diseases 3.Hypersensitivities

stages of inflammation

1. Inflammatory chemical release 2. Vasodilation and increased vascular permeability 3. Phagocyte mobilization

2 intrinsic systems that make up immune system:

1. Innate (non-specific) defense system 2. Adaptive (specific) defense sytsem

Steps for phagocyte mobilization

1. Leukocytosis 2. Margination 3. Diapedesis 4. Chemotaxis

2 types of humoral immunity

1. Naturally acquired 2. Artificially acquired

2 types of passive humoral immunity

1. Naturally acquired 2. Artificially acquired

Defensive mechanisms used by antibodies

1. Neutralization 2. Agglutination 3. Precipitation 4. Complement fixation

Natural killer (NK) cells

1. Nonphagocytic, large granular lymphocytes that police blood and lymph 2. Can kill cancer and virus-infected cells before adaptive immune system is activated. 3. Kill by inducing apoptosis in cancer cells and virus infected cells.

5 steps of Lymphocyte Development

1. Origin- Both lymphocytes originate in red bone marrow 2. Maturation- lymphocytes are educated by 2-3 day process and mature in primary lymphoid organs. 3. Seeding secondary lymphoid organs and circulation- immunocompetent B and T cells not yet exposed to antigen are called naive. 4. Antigen encounter and activation- Naive lymphocytes first encounter with antigen triggers lymphocyte to develop further. 5. Proliferation and differentiation- once selected and activated, lymphocyte proliferates.

Phagocytosis Process

1. Phagocyte sticks to pathogens or debris using receptors 2. Phagocyte forms pseudopods that engulf particles forming a phagosome 3.Lysosome fuses with the phagocytic vesicle, forming a phagolysosome 4. Toxic compounds and lysosomal enzymes destroy pathogens 5. Sometimes exocytosis of the vesicle removes indegestible and residual material.

Benefits of inflammation

1. Prevents spread of damaging agents 2. Disposes of cell debris and pathogens 3. Alerts adaptive immune system 4. Sets the stage for repair

Cytotoxic T cells deliver lethal hit by using two mechanisms:

1. Release perforins and granzymes by exocytosis 2. Cytotoxic T cell binds specific membrane receptor on target cell and stimulates apoptosis.

4 cardinal signs of inflammation

1. redness 2. heat 3. swelling 4. pain

Second line of defense cells & chemicals

1.Phagocytes 2. Natural killer (NK) cells 3. Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals 4. Antimicrobial Proteins (Interferons and complement proteins) 5. Fever

Neutralization

simplest, but one of the most important defensive mechanism.

Fever

Abnormally high body temperature that is systemic response to invading microorganisms

Acid function

Acidity of skin and some mucous secretions inhibits growth; called acid mantle

Agglutination

Antibodies can bind same determinant on two different antigens at the same time Allows for antigen-antibody complexes to become cross-linked into large lattice-like clumps

Antibody targets and functions

Antibodies do not destroy antigens; they inactivate and tag them Form antigen-antibody (immune) complexes

Summary of antibody actions

Antigen-antibody complexes do not destroy antigens; prepare them for destruction by innate defenses Antibodies do not invade solid tissue unless lesion present Can act intracellularly if attached to virus before it enters cell Activate mechanisms that destroy virus

Mucin

sticky mucus that lines digestive and respiratory tract traps microorganisms

Helper T cells function

stimulate activation of B cells, cytotoxic T cells, macrophages and suppressor T cells ( all thru interleukins)

Antigens

substances that can mobilize adaptive defenses and provoke an immune response Targets of all adaptive immune responses Most antigens are large, complex molecules not normally found in the body.

What are pyrogens?

substances that cause fever. Pyrogens act on body's thermostat in hypothalamus, raising the body temperature

Class I MHC proteins

Bind with short fragment (8-9 amino acids) of endogenous antigen, protein synthesized inside cell

How is HIV transmitted?

Bodily fluids -Blood -Semen -Vaginal fluid -Breast milk

What causes opsonization?

C3b

Cell lysis begins when...

C3b binds to target cell, triggering insertion of complement proteins called membrane attack complex (MAC) into cell's membrane

Naive cells are simply termed ....

CD4 or CD8 cells

Characteristics of antigens

Can be a complete antigen or hapten (incomplete) Contain antigentic determinants Can be a self-antigen

What do complete antigens and haptens cause the immune system to do?

Causes the immune system to mount attack that is harmful to person because it attacks self-proteins as well as hapten examples: poison ivy or detergents

Step 2: co-stimulation

Complete T cell activation requires T cell to also bind to one or more co-stimulatory signals on surface of APC

Macrophages

Develop from monocytes and are chief phagocytic cells; most robust phagocytic cell.

Cytotoxic T cells

Directly attack and kill other cells Activated cytotoxic cells target virus infected cells, cancer cells, foreign cells

Acquired Immune Deficiency Syndrome (AIDS)

Disease which causes ineffectiveness of your immune system. Caused by HIV

B lymphocytes

Do not activate naive T cells Present antigens to helper T cell to assist their own activation.

What is Complement Fixation

Double binding

Antigen Presenting Cells (APCs)

Engulf antigens and present fragments of antigens to T cells for recognition.

Enzymes of surface barriers

Enzymes including saliva, respiratory mucous, and lacrimal fluids kill many microorganisms.

First Line of Defense

External body membranes (skin & mucosa)

What determines which foreign substances the immune system will recognize?

Genes

IL-2 is a key....

Growth factor Encourages activated T cells to divide rapidly Ex: gamma interferon- enhances killing power of macrophages

Complete antigens

Have two important functional properties: immunogenicity and reactivity

Complement proteins

•The complement system consists of about 30 proteins found in the serum •Designated by the letter "C" •Act in a cascade (one reaction triggers another) •Complement activation occurs in 3 pathways -Classical -Lectin -Alternative