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Unit 1: Basic Concepts in Immunology > Section 4: Adaptive Immunity > Flashcards

Section 4: Adaptive Immunity Flashcards

1
Q

What are the three main advantages of adaptive immunity?

A
  1. A strong and specific immune
  2. an immunological memory is created
  3. provides a protection system by which slow evolving vertebrates can keep up with the multiplicity of rapidly evolving microorganisms
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2
Q

What does adaptive immunity consist of?

A

-consist of two cell types
1. B cells (B- lymphocytes)
2. T cells (T- lymphocytes)

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3
Q

Innate Immune receptor

A

-the innate immune system uses a fixed repertoire of receptors
-evolve over time and are passed down generation to generation in a stable form

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4
Q

B-cell receptors (Immunoglobulins)

A

-are expressed on the surface of B-cells and act as their pathogen recognition receptor
-maturated effector B-cells (plasma cells) secrete soluble forms of B-cell receptors called antibodies
-they are just antibodies that are membrane-bound

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5
Q

T-Cell receptors

A

-expressed on the surface of T-cells and act as their pathogen recognition receptors
-are less diverse in their ability to bind different antigens (Ag), that is they recognize a more limited range of Ags
-B cell and T cell receptors are structurally related molecules with a shared ancestry

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6
Q

B-cell receptors contain two different polypeptide chains called?

A
  1. Heavy chain (blue)
  2. light chain (red)
    * each B-cell receptor has two light and heavy chains (adds variability)
    *each heavy chain is anchored by a transmembrane region
    * secreted B-cell receptors (antibodies) lack the heavy chain transmembrane region
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7
Q

Variable region in b-cell receptor

A

-found in a b-cell receptor, is an amino acid sequence region that differs from one b-cell to another
-where they bind

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8
Q

constant region in b-cell receptor

A
  • found in a b-cell receptor, is an amino acid sequence region that is very similar between each immunoglobulin
    -constant and crucial to the function of being an adapter to other cells that are binding with this antibody
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9
Q

T-cell receptors contain two polypeptide chains called?

A
  1. a chain (TCRa)
  2. b chain (TCRb)
    *each polypeptide chain is anchored in the t-cell membrane
    * they also have a constant and variable region
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10
Q

T-cell: antigen binding site

A

-each receptor’s variable regions form this and denote the specificity of the receptor (pathogen)

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11
Q

T:cell: constant region

A

-serves as binding sites to membranes or other proteins (ex: antibodies)
- the constant region of secreted antibodies confer different effector functions and directs Abs to specific sites in the body

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12
Q

receptor diversity

A

-the diversity of antigens that can be bound by the B- and T- cell receptors is determined by genes that encode these receptors
-the diversity is increased because these genes undergo rearrangement

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13
Q

somatic recombination

A

-is the process of gene rearrangement in B- and T- cell receptors (occurs in somatic not germ cells)
-multiple segments of genes (VDJ or VJ) have to be brought together to form functional forms of the receptor
-this increases diversity of the receptors because there are multiple V-, D-, and J- genes that can be combined

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14
Q

What else increases diversity in receptors?

A
  1. imprecision in rearrangement machinery
  2. combination of variable regions (ex: light and heavy chain)
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15
Q

Receptor diversity: somatic recombination

A

-when you are born you have areas of genes that will code for these receptors
-v = variable, c = constant, j = joining
-this germline is brought together and nicked to form this combination which is excised and you end up with two genes with a V and J. This is joined with the constant region – then produces a functional receptor

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16
Q

Consequences of somatic recombination

A
  • each lymphocyte expresses receptors of a SINGLE specificity
    -the total population of lymphocytes makes millions of different receptors
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17
Q

Clonal selection and expansion

A

-during an infection very few lymphocytes will have receptors that bind to pathogen-specific epitopes
-the few lymphocytes with receptors that do recognize the pathogen-specific epitopes will be activated (Selection) to differentiate and proliferate (Expansion)
-this is the guiding principle of the adaptive immune system

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18
Q

primary immune response

A

-takes time because very few cells need to differentiate into effector cells and proliferate into a population large enough to combat infection

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19
Q

Clonal selection and expansion steps

A
  1. during development, progenitor cells give rise to large members of circulating lymphocytes, each having a different form of cell-surface receptor
  2. The receptors of only a few circulating lymphocytes interact with any given pathogen
  3. pathogen reactive lymphocytes are triggered to divide and proliferate (assisted by a dendritic cell or follicular dendritic cell)
  4. pathogen activated lymphocytes differentiate into effector cells that eliminate the pathogen
    *dendritic cell responsible for grabbing and taking up and processing that antigen and showing it to the B-cells and T-cells to be selected and expanded
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20
Q

What initiates the adaptive immune response?

A

-is initiated by antigen-bearing dendritic cells (DCs) and T-cells in secondary lymphoid tissue (lymph node, spleen (white pulp), and peyer’s patches)
-these tissues have the microanatomy that facilitates the interaction of antigen-presenting cells and the very few lymphocytes with receptors that will recognize the antigen

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21
Q

Native T-cells

A

are circulating T-cells that have not recognized a specific antigen

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22
Q

effector T-cells

A

-are T-cells that recognize antigens and become activated, resulting in differentiation and proliferation

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23
Q

antigen processing

A

-unlike receptors of the innate immune response, the adaptive immune receptors recognize degraded fragments (peptides) of pathogen-associated proteins
-the degradation is called antigen processing

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24
Q

Antigen processing steps

A
  1. dendritic cells take up pathogens for degradation
  2. pathogen is taken apart inside the dendritic cell
  3. pathogen proteins are unfolded and cut into small pieces
  4. peptides bind to MHC molecules and the complexes go to the cell surface
  5. T-cell receptors bind to peptides; MHC complexes on the dendritic cell surface
    *The processed antigenic peptides are presented to T-cell receptors by human cell-surface molecules
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25
Q

Major histocompatibility complex (MHC)

A

-are glycoproteins that bind antigenic peptides and present them on the surface of the cell (this, antigen-presenting cells (APC) like DCs)
-each MHC molecule is specific for one peptide
- the genes encoding MHC molecules are highly polymorphic giving MHC a wide range of possible peptide binding capabilities
-most people (vertebrates) are heterozygotes for the MHC genes (different combination of genes from parents)
-MHC also is the basis of tissue typing
-there are two classes of MHC molecules specialized to present antigens from different cellular spaces
-each class of MHC molecule is recognized (or are specific) to a single kind of effector T-cell

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26
Q

MHC Class I

A

present antigen from intracellular pathogens
-expressed by all cells (nucleated) b/c they are involved in different types of antigens

27
Q

MHC Class II

A

present antigen from extracellular pathogens
-only need for phagocytic cells
-expressed by only antigen-presenting cells (dendritic, macrophages, monocytes)

28
Q

cytotoxic T cells

A

-are defenders against intracellular pathogens and express the co-receptor CD8 which allows for the binding of MHC class I
-responsible for viral infections

29
Q

Helper T-cells

A

-are defenders against extracellular pathogens and express the co-receptor CD4 which allows for the binding of MHC Class II
-mobilize the whole adaptive immune response

30
Q

Receptor-mediated endocytosis

A

Type of pathogen presented: extracellular bacteria
MHC molecules loaded: MHC Class II
Type of naive T cell activated: CD4T cells

31
Q

Macropinocytosis

A

Type of pathogen presented: extracellular bacteria, soluble antigens, virus particles
MHC molecules loaded: MHC Class II
Type of naive T cell activated: CD4T cells

32
Q

viral infections

A

Type of pathogen presented: viruses
MHC molecules loaded: MHC Class I
Type of naive T cell activated: CD8T cells

33
Q

cross-presentation after phagocytotic or macropinocytotic uptake

A

Type of pathogen presented: viruses
MHC molecules loaded: MHC Class I
Type of naive T cell activated: CD8T cells

34
Q

transfer from incoming dendritic cell to resident dendritic cell

A

Type of pathogen presented: viruses
MHC molecules loaded: MHC Class I
Type of naive T cell activated: CD8T cells

35
Q

Phagocytosis

A

internalization of matter by means of endocytosis, usually involving a specific receptor (receptor-mediated endocytosis)

36
Q

macropinocytosis

A

nonspecific uptake of extracellular fluid by endocytosis, characteristic of DCs

37
Q

clusters of differentiation (CD)

A

-is a classification system of cell surface proteins that help distinguish different lineages, developmental stages, and types of cells (cell phenotype)
-all circulating T-cells express CD3 and either CD4 or CD8 but not both
-the binding specificity results in T-cells interacting with other specific lymphocytes
-ex: helper-T cells will only recognize antigens from macrophages, B-cells, and dendritic cells because they are the only cells that express MHC Class II molecules
-MHC Class I can be expressed by almost all cells in the body

38
Q

Antigen Processing and Presentation : T-cells

A

MHC class I
1. Virus infects cell
2. Viral protein synthesized in the cytoplasm
3. peptide fragments of viral proteins bound by MHC class I in ER
4. Bound peptides transported by MHC class I to the cell surface
5. Cytotoxic T cell recognizes complex of viral peptide with MHC class I and kills infected cell

MHC class II
6. Macrophage engulfs and degrades bacterium-producing peptides
7. Bacterial peptides bound by MHC class II vesicles
8. Bound peptides transported by MHC class II to the cell surface
9. Helper T cells recognize complex of peptide antigen with MHC class II and activate macrophage

39
Q

Antigen processing and presentation: B-cells

A

-during infection, bacterial and viral particles are brought to the lymph node where naive B cells are waiting to encounter the antigen
-unlike T-cell receptors (that recognize processed pathogen peptides), B-cell receptors can recognize native pathogen macromolecules
-helper (CD4) T-cells help B-cells become antibody-producing plasma cells
** maturation of a B-cell requires a helper T-cell and modulation

40
Q

Humoral Immunity

A

-the immune response governed by antibodies

41
Q

isotypes

A

-immunoglobulins produced by B-cells and plasma cells are divided into 5 classes
- IgA, IgG, IgE, IgM, IgD
-IgM, IgA, and IgG is the main antibodies present in the body
-secreted antibodies combat pathogens in two specific ways
(neutralization and opsonization)

42
Q

IgM

A

-membrane-bound or secreted form
-acts as a receptor on naive B cells
-first antibody secreted during infection
-this is actually the B-cell receptor, a membrane-bound form of the naive B cell

43
Q

IgD

A

-membrane-bound
-acts as a receptor on naive B-cells

44
Q

neutralization

A

antibodies bind tightly to a pathogen or pathogen-associated molecules inhibiting growth, function, and replication

45
Q

opsonization

A

antibodies bound to pathogens enhance phagocytosis and complement activation

46
Q

Antibody effector functions

A
47
Q

adaptor molecules

A

-antibodies are adaptor molecules that bring together pathogens and their means of destruction
-during infection the quality of antibody improves by two mutational mechanisms ( somatic hypermutation) and (type switching)

48
Q

somatic hypermutation

A

the process of nucleotide substitution in the variable regions of Ab heavy and light chains which lead to antibodies that will bind tighter to pathogen molecules

49
Q

type switching (class switch recombination)

A

-the second mechanism affects the constant region of the antibody, by altering gene transcription in different constant regions can be made which results in class switching of the antibody
ex: plasma cells secreting first IgM will switch after to secreting other Ab isotypes depending on the infection

50
Q

Memory cells

A

-clonal selection and expansion during the adaptive immune response not only produces effector cells but also results in long-lived clones of memory cells

51
Q

secondary immune response

A

-upon repeat exposure to the same pathogen these cells produce a stronger more rapid response known as…
-memory B-cells make better antibodies
-memory T-cells can patrol non-lymphoid tissues, thus detecting pathogens at an earlier stage

52
Q

consequences of an adaptive immune response

A
  • the variability of the adaptive immune response allows us protection against almost an infinite number of antigens
    -some of this variability can lead to receptors that recognize self-antigens
    -this leads to the potential of the adaptive immune system attacking and damaging human tissues
53
Q

immunological tolerance

A

-mechanisms that have evolved to prevent recognition of self
ex: positive selection, negative selection

54
Q

Immunological tolerance steps

A
  1. In the thymus, T-cell progenitors give rise to billions of thymocytes each with a different T-cell receptor
  2. Thermocytes are positively selected by epithelial cells in the cortex of the thymus
  3. Positively selected thymocytes survive and divide
  4. positively selected thymocytes clones are negatively selected in the thymic medulla
  5. clones surviving negative selection leave the thymus for the circulation
    ** pathogens select upon less than 1% of T cells originating in the thymus
55
Q

positive selection

A

ex: T cell development in the thymus
1. T-cells need to recognize some self-antigens (MHC molecules)
2. T-cells that can bind effectively to MHC are given positive signals to continue to mature
3. T-cells that bind poorly are triggered to die (apoptosis)

56
Q

Negative selection

A

ex: T cell development in the thymus
1. following positive selection some T-cell receptors that bind to MHC too strongly are triggered to die (apoptosis)
2. less than 1% of thymocytes mature to become circulating naive T-cells

57
Q

Regulatory T-cells (Treg)

A

-a second important mechanism of effector cells
-these cells function to suppress self-reactive T-cells and out-of-control/harmful immune responses

58
Q

autoimmune diseases

A

-despite these mechanisms, a wide range of diseases are caused by the adaptive immune system
-can be caused by a failure in the innate mechanisms of immune tolerance OR by exposure to pathogens that result in an adaptive response that also reacts to self-antigens
ex: type 1 diabetes mellitus

59
Q

Type I diabetes mellitus

A
  • type 1 diabetes results from the destruction of insulin-producing B cells of the pancreas
    -there appears to be a correlation between a history of viral infections by Coxsackie viruses and the development of type 1 diabetes
    1. a childhood infection of the upper respiratory tract is terminated by the adaptive immune response
    2. by chance, one clone of virus-specific T cells also reacts with MHC: peptide complex on the surface of healthy B cells in the pancreas
    3. activated T cells attack and kill pancreatic B cells
60
Q

Allergy Hypersensitivity

A

-arises when an adaptive immune response is elicited against innocuous substances (allergens)
-most commonly attributed to IgE
-IgE recognizes an allergen and binds to Mast cells through their constant region
-upon repeat exposure to an allergen the mast cells release inflammatory substances which can lead to violet and sometimes life-threatening reactions

61
Q

Hygiene hypothesis

A

-hypersensitivities and autoimmune diseases are rising in developed countries
-some believe this is attributed to hygiene practices, vaccinations, and or antibiotic therapies used in these countries
-growing up in this overly immune sterile environment results in immune systems that are overly sensitive or are less able to regulate their responses

62
Q

Inflammatory bowel disease (IBS)

A

-rates of IBS are fast rising in developed countries although almost non-existent in underdeveloped/ developing countries
-scientist hypothesized this could be explained by the relative lack of exposure to helminths in developed countries
-the authors proceeded to use helminths antigens to treat IBS and saw improvement

63
Q

dendritic cell in adaptive immunity

A
  • dendritic cells in peripheral tissue take survey and sample the environment by nibbling off membranes (macropinocytosis) to see what is going on
    *when it finds something it circulates to the lymphatic but changes shape (maturation)
  • in the lymphatic it sets up shops and starts to raise and allow T cells to proliferate and grow around the dendritic cell

Unit 1: Basic Concepts in Immunology (6 decks)

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