Intro Immunology - Sant'Angelo 3.31.16 Flashcards Preview

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Flashcards in Intro Immunology - Sant'Angelo 3.31.16 Deck (24):
1

what is immunity?

protection that one organism has in place against another organism

  • elimination/control of offending org
  • est of conditions to prevent organism causing problems down the road 

2

what is the immune system?

what does the immune system seek to target?

 

what are major challenges in achieving this goal?

network of many diff proteins, cells, tissues, organs

  • highly regulated interations between all of them in order to...

1. target pathogens (disease-causing organisms: bacteria, viruses, fungi, parasites, prions)

2. target cancers (abberrant, uncontrolled cell growth due to gene mutations, oncogenes)

goal: coordinated attack against offending org

challenge: tricky to target pathogens and cancers bc they are numerous and largely made of the same stuff as us

3

what is autoimmunity?

what is tolerance?

immune system is constantly parsing out which cells are self and non-self

if it mistakes self cells as non-self, it can trigger an immune response against normal cells of the body via autoimmunity

 

tolerance: ability of the immune system to recognize and tolerate self cells

  • loss of tolerance → autoimmunity!
  • ex. Type 1 diabetes (immune system targets beta cells of Islets of Langerhaans)

4

antigens

  • definition
  • epitopes
  • non-pathogen antigens

antibody generator

aka immunogen

  • substance that elicits an immune response
  • most are proteins or polysacchs; often components of invading microbe (capsule, flagella, cell wall, toxin)

the reactive (structurally conserved) portion of the antigen (epitope) interacts with antibodies → antigen-antibody complex or immune complex

 

antigens can also be overexpressed, misexpressed, mutated proteins (i.e. cancer!)

5

antigen receptor diversity

diff antibodies can have diff antigen receptors for the same antigen (bind to diff epitopes)

6

antibody structure

secreted version of B cell antigen receptors!

bivalent: two heads (identical on a given ab)

comprised of 2 heavy chains, 2 light chains with variable and constant regions

  • antigen binds to region of ab formed by association of variable light/variable heavy chains

 

variable regions : diff for every ab

  • FR 1-4 : framework regions, imp for protein folding (without which, ab won't fold right, won't work)
  • HV 1-3 : hypervariable regions, 

constant region: similar for every ab

 

7

antibodies and relation to B cells and T cells

B cells: antibodies are secreted version of B cell receptors

  • B cells will differentiate into plasma cells, which make antibodies

T cells: similar structure to antibodies and BCRs except 

  • always membrane-bound
  • not bivalent (single head; alpha/beta instead of light/heavy)

8

how does tremendous antibody diversity come about?

 

V(D)J recombination

generation of TCR and BCR genes via V to J somatic recombination

instead of typical exon/intron setup, TCR and BCR genes are present as gene fragments in the germline

  • V alpha fragments - variable - approx 60
  • J alpha fragments - junctional - approx 50
  • C alpha fragments - constant - 1

as T cells and B cells mature, V to J somatic recombo occurs...

1. double stranded break in V section and in J section, intervening DNA discarded

2. fusion of gene segments : "messy", involves random addition/deletion of random nucleotides (diversity!!!)

9

types of tolerance

1. central tolerance

  • removal of self-reactive clones
  • occurs in thymus (T cells) and bone marrow (B cells)

2. peripheral tolerance

  • ignorance : hiding self antigens from immune system to shut down autoimmune response
  • anergy : shut down self-reactive clones
  • suppression : use of other molecules/proteins/cells to keep self-reactive clones in check

10

immune system "memory"

antibodies and effector T cells persist for weeks after an infection to confer "protective immunity"

 

another exposure to the same antigen will produce a much faster, bigger, better response via "immunological memory"

11

lymphatic system

part of circ system comprising lymphatic vessels that carry clear lymph

  • contains immune cells (T cells, B cells, dendritic cells)
  • filtered by lymph nodes before returning to circ

tissues and organs of lymphatic system are designed to bring antigen into contact with lymphocytes

  • lymph nodes and spleen are key sites for immune system activation

 

12

common progenitor of immune system cells

hematopoeitic stem cells

→ lymphoid precursors (T cells - thymus, B cells - bone marrow, NK cells)

  • helper T cell
  • suppressor T cells
  • cytotoxic T cell
  • B cell → plasma cell

→ myeloid precursor

  • monocyte
  • neutrophil
  • eosinophil
  • platelets
  • basophil
  • mast cell → macrophage

13

CD#

cluster of differentiation #

  • cell membrane molecules are used to classify leukocytes into subsets
  • CD# is defined or classified by reference monoclonal antibodies to which they bind

ex. helper T cells (CD4 T cells), killer T cells (CD8 T cells), Tregs (CD25)

14

T lymphocytes

once mature, T cells migrate to lymphoid organs and wait to make contact with antigens

  • once contact is made, they can kill infected cells and help activate other cells (B cells, macrophages)

form basis of cell-mediated immunity

15

B lymphocytes

antibody-producing cells that account for humoral immunity

  • abs can provide protective immunity for decades

16

myeloid cells:

macrophages

dendritic cells

develop in bone marrow, often acquire specific functions later in the tissues

myeloid cells lumped together as mononuclear phagocytic system

  • phagocytosis
  • secretion of cytokines
  • antigen presentation

17

how is the adaptive immune response triggered?

cells have to be tagged to get the adaptive immune response rolling → antigen presentation

tags in mice: MHC (major histocompatibility complexes)

tags in humans: HLA (human leukocyte antigens)

  • pathogens are ingested and "tags" are displayed on membranes of macrophages or dendritic cells
  • helper (CD4) and cytotoxic (CD8) recognize, proliferate, launch adaptive response

18

MHC/HLA Class I antigen processing pathway

 

general overview

virus enters a cell, duplicates

  • viral protein is chopped up via proteasome → shuttled into ER, where it combines with Class I MHC/HLA → shuttled to Golgi and out to cell membrane
  • CD8 killer T cells can recognize, prolif, destroy these cells

***MHC/HLA I mols are loaded with peptide made inside the cell → killing of infected target cells, activation of macrophages

MHC/HLA Class I molecules have a groove (peptide-binding cleft)

19

MHC/HLA Class II antigen processing pathway

 

general overview

bacteria enters a cell, shuttled to endosome

  • bacterial protein is chopped up via enzymes in endosome, combines with Class II MHC/HLA → shuttled out to cell membrane
  • CD4 helper T cells can recognize, prolif, assist in destruction of these cells

MHC/HLA II mols are loaded with peptides taken up by phagocytosis → activates macrophages, B cells, others; inflammatory response

20

NK cells

capable of destroying other cells, esp virus-infected cells and tumor cells; also parasites

do not express TCRs or BCRs

 

important application: some pathogens downregulate MHC; NK cells can get these cells that T cells can't

 

21

"specific" defenses vs. "nonspecific" defenses

 

nonspecific

macrophages

inflammatory response

specific

B cells defend against antigens/pathogens in body fluids : humoral immunity

T cells defend against abnormal cells, pathogens inside living cells : cell-mediated immunity

22

immunologist's dirty little secret

Janeway

"clean" antigens will not activate immune system particularly well

  • must be mixed with another substance that is not antigenic in and of itself, but which will potentiate the immune response: adjuvant

ex. mycobacterium in mice

why???

components of pathogens are recog'd by "pattern recognition receptors" (germline-encoded receptors that bind path-specific mols like LPS)

  • these receptors have to be activated before adaptive response can occur!

23

FACS

fluorescence activated cell sorting via flow cytometry

  • can measure granularity and cell size → indicative of amount and type of cells present
  • can use fluorescent tags to mark diff cell types and then quantify them using FACS

24

generation of monoclonal antibodies

inject antigen+adjuvant into an organism, wait for the immune response to occur, then isolate the spleen

fuse B cells with immortalized myeloma cell line (to keep them alive) and put in an HAT medium

  • HAT will kill unfused myeloma cells; unfused B cells will die off by themselves after a few days

screen to see which B cells actually make the antibody of interest and now you have a hybridoma producing a monoclonal antibody!!!