CH 15 Host Defense II

How many categories of defense are there

2. Innate and Acquired

How many lines of defense are there

How many lines of defense is included in innate defense?

2. First and Second

Describe the first line of defense

• includes physical and chemical barriers

• apart of innate (nonspecific) defense

Describe the second line of defense

• includes cellular and chemical protection

• phagocytosis, inflammation, fever, and antimicrobial proteins

• apart of innate (nonspecific) defense

Describe the third line of defense

• includes specific host defenses that must be uniquely developed for each microbe using specialized white blood cells

• B cells, T cells

• apart of acquired (specific) defense

Acquired specific immunity

• refers to antigen-specific immune response

• produce of B and T lymphocytes

• lymphocytes react to only one specific antigen or immunogen

Immunocompetence

the ability of the body to react with countless foreign substances

Antigens

• aka immunogens

• are chemical subatnces that stimulte a response by T and B cells

• are proteins/polysaccharides

Characteristics of antigens

must be perceived as foreign

Chemical categories of antigens

• proteins and polypeptides

• lipoproteins

• glycoproteins

• nucleoproteins

• polysaccharides and lipopolysaccharides

Effects of Molecular Size

Molecules with a molecular of 100,000 are the most immunogenic

Characteristics of specific immunity

• specificity

• diversity

• inducibility

• clonality

• tolerance

• memory

Specificity

response focused on a single antigen

Diversity

always at least one cell that can react against any antigen

Inducitbility

only turned on when triggered

Clonanlity

generates millions of cells with teh same specificity

Tolerance

Does not react with self antigens

Memory

rapid mobilization of lymphocytes preprogrammed to recall their first engagement with specific antigen

What are the principal stages of immunologic development and interaction

1. lymphocyte development

2. presentation of antigens

3. antigen challenge of B and T lymphocytes

   1. B - antibody production and response

   2. T - cell-mediated immunity

1. Lymphocyte development

B cells mature in bone marrow. T cells mature in thymus. Both are located in lymphoid organs (lymph node and spleen).

2. Presentation of antigens

• antigen makes contact with MHC markers

• antigen is processed by a phagocytic cell

• phagocytic cell displays antigen and presents it to T helper cell

• B cells are stimulated by helper T cells activated by antigen

3. Antigen challenge of B and T lymphocytes

• Activated T helper cells can: become a specialized effector cell, an activated cytotoxic T cell, and memory T cell

• Activated B cell leads to: memory B cells and plasma cells that secrete antibodies

4. B and T-lymphocyte responses

• Leads to the production of T helper cells, T regulatory cells, (specialized effector cells) and T cytotoxic cells (memory T cells)

• Leads to antibody immunity

Major functions of immune system markers

• Attachment to nonself or foreign antigens

• Binding to cell surface receptors that indicates self

  • MHC (major histocompatibility Complex) molecules, clonal deletion

• Receiving and transmitting chemical messages to coordinate the response

• Aiding in cellular development

How many classes of MHC Genes

3

Class 1 MHC Genes

• Markers appear on all nucleated cells except red blood cells

• Display unique characteristics of self

• Allow for recognition of self and the regulation of immune reactions

• Each human inherits a particular combination of class I MHC genes

Class 2 MHC Genes

• Code for immune regulatory markers found on macrophages, dendritic cells, and B cells

• Involved in presenting antigens to T cells during cooperative immune reactions

Class 3 MHC Genes

encode proteins involved with the complement system

Markers found on T cells

• antigen-specific T-cell receptor

• CD3 markers

• CD4 coreceptor

• CD8 coreceptor

CD3 markers

surround the T-cell receptor and assist in binding

CD4 coreceptor

binds to MHC class 2 molecules

CD8 coreceptor

• on cytotoxic T cells

• binds to MHC class 2 molecules

Contrasting properties of B cells and T cells

Specific surface markers

• B - immunoglobin

• T - T-cell receptor

Concentration in blood

• B - low

• T - high

Receptors for antigen

• B - B-cell receptor

• T - T-cell receptor

Location

• B - cortex

• T - paracortical sites

Require antigen presented with MHC

• B - no

• T - yes

Product of antigenic stimulation

• B- plasma and memory cells

• T - activated T cells and memory cells

General functions

• B - produces antibodies to handle antigens

• T - aids other immune cells and makes cytokines

Immunoglobin

• B-cell receptor

• composed of 2 heavy chains, 2 light chains, 1 variable region, 1 constant region

T-cell receptors

• Formed by genetic modification

• Has variable and constant regions

• Inserted into the membrane

• Has antigen binding site formed from two parallel polypeptide chains

  Unlike the immunoglobulins:

  • Relatively small

  • Never secreted

Epitope

• A portion of the antigen molecule recognized and responded to by a lymphocyte

• The primary signal that a molecule is foreign

Haptens

• Consist only of a determinant group

• Too small by themselves to elicit an immune response

• If linked to a carrier group, the combined molecule develops immunogenicity

Hapten-Carrier Phenomenon

When a hapten infects a molecule, no antibody is formed. When a hapten bound to carrier molecule infects, an antibody is formed in response to hapten.

Alloantigens

• Proteins and other molecules of one person that are antigenic to another

• Cell surface markers that occur in some members of the same species but not in others

• The basis for an individual’s blood group and major histocompatibility profile

  • Responsible for incompatibilities that occur in blood transfusion or organ grafting

Superantigens

• Bacterial toxins

• Potent stimuli for T cells

  • Activate T cells at a rate 100 times greater than ordinary antigens

  • Can result in an overwhelming release of cytokines and cell death

• Toxic shock syndrome and certain autoimmune diseases are associated with these antigens

Dendritic cells, macrophages, and B cells are serve as ______

antigen-presenting cells

Describe the various ways to encounter antigens

• Between WBC and Ags

• Most via respiratory or GI mucosa

• Less via skin or placenta or other mucosa

• Bloodstream via intravenous –liver, spleen, BM, K and lung

• Drained into LN, in contact with LCs

B-Cell Activation Steps

1. Binding of antigen

2. Antigen processing and presentation

3. B cell/ T helper cell cooperation and recognition

4. B-cell activation

5. Differentiation (plasma cells, memory cells, and regulatory cells)

6. Clonal expansion

Cytotoxic T Cell Secretions After Activation

• Perforins

• Granzymes

Perforins

• Proteins that punch holes in the membranes of target cells

• Causes ions to leak out of target cells

• Creates a passageway for granzymes to enter

Granzymes

enzymes that attack proteins of target cells

Target cells that cytotoxic t cells can destroy

• virally infected cells

• cancer cells

• cells from other animals and humans

Products of B and T lymphocytes

undergo a selective process to specifically respond to only one antigen

Immunocompetence

the ability of the body to react with countless foreign substances

Specificity

highly specific to the antigen against which the third line of defense is directed

memory

the rapid mobilization of lymphocytes that have been programmed to recall their first engagement with the invader and rush to the attack again

B cells are formed in

bone marrow

T cells are formed in

thymus

plasma cells secrete

antibodies

MHC molecules

indicate self

Class 1 MHC

-appears on all nucleated cells
-displays unique characteristics of self
-each human inherits a particular combination of class I MHC genes.

Class II MHC genes:

-codes for immune regulatory markers found on macrophages, dendritic cells, and B cells.
-involved in presenting antigens to T cells during cooperative immune reactions.

Cluster of Differentiation (CD)

-Markers important in immunity
-Found on the membranes of a variety of different cells involved in the immune response
-Over 300 have been described

Tissue dendritic cells

-Ingest the antigen
-Migrate to the nearest lymphoid organ
-Process and present antigen to T-lymphocytes

antigen presenting cells

dendritic cells, macrophages, B cells

B cells and T cells proliferate and differentiate when

they are challenged by antigen

clone

-proliferation of a particular lymphocyte.
-genetically identical cells, some of which are memory cells.

Helper T cells

activate macrophages, assist B-cell processes, and help activate cytotoxic T cells

Regulatory T cells

control the T-cell response

Cytotoxic T cells

A type of lymphocyte that kills infected body cells and cancer cells

when activated by an antigen, B cells

divide and give rise to plasma cells

Plasma cell function

produce antibodies

markers are found on all cells except

Reb blood cells

stem cells become granulocytes, monocytes, or lymphocytes in the

bone marrow

Lymphocytes

can either become B or T cells

B and T cells are each equipped to

respond to a single unique antigen

immunoglobulins

bind with specific antigens in the antigen-antibody response

immunoglobulins are composed of

-two heavy (H) chains
-two light (L) chains
-one light chain is bonded to one heavy chain
-the two heavy chains are bonded to each other with disulfide bonds
-creates a symmetrical Y-shaped arrangement

antigen binding site

pockets on an antibody
that bind specific antigens

variable regions

-found in antigen binding sites
-amino acid position is highly varied from one clone of B lymphocytes to another as the result of genetic reassortment

constant regions

amino content does not vary greatly from one antibody to another

T cell receptor

similar to be cell receptor; different because it is small and never secreted

clonal selection theory

States that the antigen selects which lymphocyte will undergo clonal expansion and produce more lymphocytes bearing the same type of receptor.

immune tolerance

-removal of any potentially harmful clones through clonal deletion
-autoimmune diseases arise from loss of immune tolerance

the B-cell receptor is

immunoglobulin

T cell display CD3 marker and either the

CD4 or CD8 coreceptor

Antigen

A protein that, when introduced in the blood, triggers an immune response in specific lymphocytes

Immunogenicity

Ability of pathogens to induce an immune response

epitope

Small, accessible portion of an antigen that can be recognized.

Haptens

antigens too small to provoke immune responses; attach to carrier molecules and can develop immunogenicity.

molecules with molecular weight between 1000-10,000 are

weak antigens

molecules with molecular weight of

100,000 are most immunogenic

Alloantigens

cell surface markers and molecules that occur in some members of the same species but not in others; responsible for incompatibilities that occur in blood transfusions or organ grafting

three molecules that serve as antigens

-lipoproteins
-glycoproteins
-polysaccharides

role of antigen processing and presentation

-in order for the T cells to recognize antigens, an antigen must be further acted upon and formally presented to lymphocytes by cells called antigen-presenting cells (APC's)

common lymphoid progenitor

Stem cell that gives rise to all lymphocytes and is derived from a pluripotent hematopoietic stem cell.

CD4+ and CD8+ cells

are fully developed but not yet activated

Primary signal

-the recognition of a peptide-MHC complex by TCR
-interaction is stabilized by either CD4 or CD8 binding to MHC
-APC has taken up and process the antigen

secondary signal

- co-stimulation is mediated by CD28-CD80 interaction.
-several adhesion molecules help stabilize interaction between T cell and APC.

CD80

Activated B cells, macrophages and dendritic cells

third signal

-cytokins produced by APC during activation tell the T cells how to differentiate

after activation, T cells undergo differentiation to become

effector T cells or memory T cells

Helper T cells

help other cells to proliferate and become activated

Regulatory T cells

help regulate immune responses so the immune system isn't overreactive