Exam 2- Lecture 1: Antigen Presentation

What type of immunity occurs in response to infection as immune system must adapt itself to previously unseen molecules?

Adaptive immunity

What happens following recovery from certain infections w/ a particular micro-organism?

Individuals will never again develop infection w/ the same organism, but can w/ other micro-organisms

• Protected against one micro-organism

What type of protection is it called when one is protected against one micro-organsim?

Immunity

• Individual is said to be immunized against that organism

What are the 2 arms of adaptive immunity?

• Humoral immunity (refers to blood)

• Cell-mediated immunity

What does humoral immunity contain?

B cells & permanent antibodies

What does cell-mediated immunity contain?

T cells & cytotoxicity

What but the T & B cells must first be before responding?

Selected since they can inflict harm to body’s own tissues

What is innate immunity?

Inbuilt immunity to resist infection

What are aspects of innate immunity?

• Not pathogen-specific

• Present from birth

• No obvious enhancement by subsequent exposure

• No specific memory

• Is poorly effective w/o adaptive immunity

What is adaptive immunity?

Immunity established to adapt to infection

What are the aspects of adaptive immunity?

• Confers pathogen-specific immunity

• Continues to mature after birth; influenced by environment

• Enchanted by subsequent exposure

• Develop long-term, specific memory

• Is poorly effective w/o innate immunity

What causes “inflammation”?

TRLs, cytokines, & chemokines

What do both adaptive & innate immunity depend upon?

White blood cells or leukocytes

What is innate immunity mediated largely by?

PMNs & monocyte-derived cells (monocytes & dendritic cells)

What is adaptive immunity mediated primarily by?

Lymphocytes & monocyte-derived cells (monocytes & dendritic cells)

What are activities of all leukocytes?

Interconnected & often co-operative

What may both innate & adaptive immunity trigger?

Inflammatory response & tissue damage

What does protective immunity require both?

Innate & adaptive immunity

What is lag time in developing adaptive immune responses due to?

Dendritic cells select lymphocytes to activate & proliferate

What is the immune system?

A body wide network of cells & organs for defending the body against attacks by “foreign” invaders

What does the danger model suggest?

Immune responses depend on context of how antigen is presented

• Inflammation (innate response)

What are the proper targets of the immune defenses?

Any signals that may cause damage to the host

• Self-replicating microorganisms, tumors

What is an antigen?

Any molecular entities capable of triggering adaptive immune responses

What are antigens most often?

Proteins, secreted toxins or on viruses

What else can antigens be besides proteins?

Carbohydrates, nucleic acids, or phospholipids

What is immunological specificity?

Cells of the immune system respond to molecular structure of an antigen

What is an epitope?

A sub-structure of an antigen to which lymphocytes respond & remember

What can an antigen have many?

Epitopes

What is immunological versatility?

In course of a normal lifetime, individual encounters 10s of 1000s of antigens. Immune system can differentiate among them, producing specific & appropriate responses to each of them

What are there billions of in the body b/c of immunological versatility?

Distinct T & B cells

What is immunological memory?

Immune system remembers all antigens that it encounters. Response after a 2nd exposure to same antigen (epitope) is faster & stronger than response to initial exposure

What are aspects to immunological memory?

• Memory T & B cells

• Alive but dormant up to decades

• High degree of uncertainty in population

What is immunological tolerance?

Ability of immune system to respond to foreign cells & compounds, but to generally ignore normal tissues & cells

• Don’t do harm to body

• Continuously maintained

• Cultural & peripheral tolerance

What is the lymphatic system?

Cells in lymph nodes, spleen, bone marrow (1st lymphoid organ), lymphatic vessels, & tissues

What are HSCs?

Uncommitted stem cells that give rise to committed cells

What are leukocytes continuously populated by?

HSCs

What do white cells, or leukocytes, exist in?

Variable numbers & types but make up a very small part of blood’s volume

What do white cells have unlike red cells?

Nuclei

What happens as a result of some white cells provide a physiological defense against infection?

Their numbers increase when body is under attack by bacteria & viruses

What do other types of white cells have the function of?

Getting rid of old, unneeded blood cells (MPS)

• Monocytic-phagocytic system (sewage of body)

What is the typical concentration of leukocytes?

5,000-9,000 per cubic millimeter of human blood (“White cell count”)

What do some important characteristics of WBCs include?

• Phagocytic (internalize & digest (killing))

• Diapedesis (escape, extravasation (squeeze through blood vessel))

• Migration (move)

• Chemotactic (smell (sense sources of inflammatory rxn- gravitate toward site))

How many types of leukocytes, or WBCs, are there & what are the all involved in?

5 types & all involved in body’s defense systems

What are the 5 types of leukocytes grouped into?

2 classes according to nuclear morphology

• “polymorphs” or “PMNs”

What do polymorphonuclear granulocytes have?

Segmented nuclei & cell-specific cytoplasmic granules

What are the types of polymorphonuclear granulocytes?

(innate)

• Neutrophils- number in blood inc. during infection → bacteria

• Eosinophils- allergic rxns (asthma) → parasites

• Basophils- allergic rxns (histamine, heparin) → parasites

What do mononuclear agranulocytes have?

Nonsegmented nuclei (1 nuclei) & no specific cytoplasmic granules

What are the types of mononuclear agranulocytes?

• Monocytes: dendritic cells & macrophages → antigen presentation

• Lymphocytes: respond to antigens

What are the organs of the immune system that are stationed throughout the body?

Thymus (1*), spleen (2*), bone marrow (1*), & lymph vessels & nodes (2*)

• A body-wide network that extends to skin & mucosal tissue

What are lymphoid organs concerned w/?

Growth, development, & development of lymphocytes- WBCs that are key operatives of immune system

What are the organs of the immune system connected w?

One another & w/ other organs of body by a network of lymphatic vessels similar to blood vessels

What are immune cells & foreign particles conveyed through?

Lymphatics in lymph, a clear fluid that bathes the body’s tissues (draining lymph nodes)

What is the difference b/w 1* & 2* lymphoid organs?

Primary are places where T & B cells are linked to function

Where does B cell maturation occur?

Bone marrow

Where does T cell maturation occur?

Thymus

What do the libraries of T & B cells have?

Potential to respond to antigen

What happens to stem cells in the red bone marrow?

Differentiate into pre-B cells & pre-T cells

• Pre-B cells differentiate into B cells then circulate to lymph nodes

• Pre-T cells differentiate into T cells in thymus then circulate to lymph nodes

What is the thymus located b/w?

Sternum & aortic arch

What does the thymus prevent? (Central tolerance)

Autoimmunity by inducing apoptosis of auto-reactive T cells

• Immune T cells must pass through thymus before homing to lymph nodes

• Important in 1st couple years of life

What is thymic selection?

• Immature T cells (>10^8 unique specificities) generated in bone marrow through random recombination of genes

• Only T cells do not react strongly w/ body’s own antigens would survive

• Mature T cells exit thymus to populate rest of lymphatic system

What

Where are T & B lymphocytes located?

B/w sternum & aortic arch

What do B cells produce?

Antigen (epitope)- specific antibodies when activated

• If epitope doesn’t come → no engagement

What do T cells do?

Regulate, help & kill in antigen (epitope)- specific manner

What is each B & T cell defined by?

Its epitope-specific receptor

What are B cell receptors (BCR)?

• Surface immunoglobulins

• 2 identical antigen recognition sites

What are T-cell receptors (TCR)?

• One antigen recognition site

What does each T & B cell “clone” express?

A unique receptor that defines the cell’s antigen specificity

What are select T & B cells activated?

Antigen presentation

What do monocytes eventually do?

Leave bloodstream & become tissue macrophages or dendritic cells, the professional antigen presenting cells (APCs) (exclusivity talks only listen to), which are responsible for removal of debris & defense against pathogens that cannot be dealt w/ effectively by neutrophils

What do APCs reside in?

Tissues & migrate to lymph nodes to present antigens to lymphocytes

• Constantly sampling particulates in their environment

What are the type of T lymphocytes?

• Cytotoxic T cells (CTL)

• Helper T cells (Th)

• Regulatory T cells (Tregs)

  • Peripheral tolerance

What is the type of B lymphocytes?

• Plasma cells (→ antibodies)

  • Cannot convert back to B cells

What are the cells involved in adaptive response?

• Lymphocytes

  • T lymphocytes

  • B lymphocytes

  • Natural killer (NK) cells

• Antigen presenting cells (APCs)

What are the types of APCs?

• Dendritic cells

• Macrophages

• B lymphocytes

What is the precursor of a B cell?

Lymphoid

What is the precursor for macrophages?

Myeloid

What do APCs select?

Relevant T cell clones & tailor response

• By signal 1 & signal 2

What is signal 1?

MHC-TCR (antigen recognition)

• Defines specificity of immune response

What is signal 2?

Costimulation (inflammation)

• Dictates intensity of immune response

What is activation of T cells by APC?

Contact dependent (both are in lymph nodes)

What is an MHC-bound peptide?

An epitope if it is recognized by T cells

What is MHC?

Major histocompatibility complex

• Human leukocyte antigens (HLA)

What is MHC class I?

• HLA-A, HLA-B, HLA-C

  • Many subtypes (HLA-A2, HLA-A3, HLA-B53)

• Engage cytotoxic T cells

• Expressed in all nucleated cells

What is MHC class II?

• HLA-D

  • Many subtypes (HLA-DQ1, HLA-R4)

  • Each bind to a distinct set of peptides

• Engage helper T cells

• Expressed mostly by APCs

What are the amino acids of MHC class I?

8-11

• Derived primarily from endogenous proteins

• Floating in binding groove/pocket

What are the amino acids of MHC class II?

13-25

• Derived primarily from exogenous proteins

What are MHC genes highly?

Polymorphic: genetic variations in populations

• Several hundred alleles have been identified in humans

What can each person express up to?

12 different HLA alleles

What is the probability of 2 individuals expressing the same set of MHC molecules?

Extremely low

What may different MHC alleles select?

Different peptides from antigens to present

What do T cells recognize antigens in the context of?

MHC molecules

• MHC-TCR

What are antigens displayed to T cells by?

2 classes of MHC molecules: I & II

What are MHC I found in all?

Nucleated cells

What aer MHC II found MOSTLY in?

APCs

What do both MHC I & II bind?

Peptides

What do MHC I present peptides to?

CTL

What do MHC II present peptides to?

Th

What are peptides presented by MHC I derived from?

Mostly proteins synthesized w/in cells

What are peptides presented by MHC II derived from?

Mostly proteins internalized through phagocytosis