Immunology Exam 1 Important Info

Red stars from notes, things to memorize

4 antigen-presenting cells

• dendritic cells

• macrophages

• B-cells

• follicular dendritic cells

CD4+

• helper T-lymphocytes

• B cell activation (humoral immunity)

• macrophage activation (cell-mediated immunity)

• stimulation of inflammation

• MHC II

CD8+

• cytotoxic/killer T-lymphocytes

• killing of cells infected w/ intracellular microbes, tumor cells

• MHC I

B cell lineage

• formed in bone marrow

• mature in bone marrow

T cell lineage

• formed in bone marrow

• mature in thymus

generative/primary lymphoid organs

• bone marrow

• thymus

peripheral/secondary lymphoid organs

• lymph nodes

• spleen

• mucosal and cutaneous lymphoid tissues

• B & T cells circulate these “meeting places” until they find their antigen

• swelling lymph node = B or T cell has met its antigen

Naive B & T cells enter lymph node at…

HEV (High endothelial venule)

Antigens enter lymph node at…

Afferent lymphatic vessel

Follicular zone

B cell zone

Parafollicular zone

T cell zone

Where is the B-cell zone?

follicles

Where is the T-cell zone?

PALS: periarteriolar lymphoid sheath

B & T cells exit lymph node at…

efferent lymphatic vessel

GALTs

gut associated lymphoid tissues

• more distinct part: Peyer’s patch

MALTs

mucosal associated lymphoid tisssues

CXCR5

• receptors on B cells that sense CXCL13, showing them where to go (follicular zone)

CXCL13

• chemokines (ligands) produced in follicular zone, causing, B-cells to gravitate toward B-cell zone

CXCR7

• receptor on T cells that sense CXCL19/21, showing them where to go (parafollicular zone)

CXCL19/21

• chemokines (ligands) produced in parafollicular zone, causing T-cells to gravitate toward T-cell zone

where do naive T cells go?

peripheral/secondary lymph nodes

where do activated/effector T cells go?

inflamed tissue/site of infection

pro-inflammatory cytokines

IL-1, IL-6, TNF alpha, IL-12

IL = inter-leukocyte

TNF = tumor necrosis factor

innate immune receptors are…

germ-line encoded/hard-wired receptors

→ less diversity than B & T cell receptors

cytoplasm/cytosolic PRRs

• NLR (NOD-like receptor)

• RLR (RIG-like receptor)

• CDS (Cytosolic DNA sensor)

Endosomal PRRs

• TLR-3

• TLR-7

• TLR-8

• TLR-9

TLR-3 recognizes

dsRNA

TLR-7 recognizes

ssRNA

TLR-8 recognizes

ssRNA

TLR-9 recognizes

CpG DNA

extracellular/surface PRRs

• TLR-4

• TLR-5

TLR-4 recognizes

LPS (which is a PAMP)

TLR-5 recognizes

Bacterial flagellin

Inflammasome

• senses bacteria & extracellular ATP (mitochondrial damage)

• activates Casapase-1

• Casapase-1 cleaves pro-IL-1B into active IL-1B

• IL-1B causes inflammation

functions of epithelia in innate immunity

• physical barrier to infection

• killing of microbes by locally produced antibiotics

• killing of microbes and infected cells by intraepithelial lymphocytes

NK cells (natural killer cells)

• lymphocytes

• solely for fighting viruses & tumors very fast, with limited receptors (not very specific)

• like B & T cells, but in innate immunity instead of adaptive

antigen-presenting cells

present to T cells:

• dendritic cells

• macrophages

• B cells

present to B cells:

• follicular dendritic cells

macrophages that come from fetal yolk sac/organs

• brain: microgial cells

• liver: kupffer cells

• lung: alveolar macrophages

• spleen: sinusoidal macrophages

IFN-gamma

• macrophages have special receptors for it

• produced by helper T cells

• when this binds to receptor, macrophage becomes dramatic in function, & more microbicidal (incr. killing & production of nitric oxide + ROS to kill)

M1 (classically activated macrophage)

produce ROS, NO, & proteases to phagocytose/kill bacteria and cause inflammation

M2 (alternatively activated macrophage)

• repair tissues/wound repair

• IL-10 & TGF-B have anti-inflammatory effects

2 anti-inflammatory cytokines

• IL-10

• TGF-B

prototypical antigen presenting cell

dendritic cells (called Langerhaans cells in the skin)

• process & present antigens to helper T cells

• follicular dendritic cells present antigens to B cells

NK cell effect on macrophage w/ phagocytosed microbe

• macrophage released IL-12 to NK cell → activates NK cells which produce IFN-gamma → IFN-gamma activates macrophage killing → phagocytosed microbe is killed

• positive feedback loop

• secretion of IFN-gamma from NK cells is important for M1 macrophages

job of complement

help w/ killing of a pathogen better

• lysis of bacteria, cells, & viruses

• promotion of phagocytosis (opsonization) through C3b

• trigger inflammation & secretion of immunoregulatory molecules

• clearance of immune complexes from circulation

pathway of complement

• initiation of complement activation w/ antibody, microbe, or lectin

• C3a: causes inflammation

• C3b deposited on microbe: opsonization and phagocytosis

• C4a: inflammation

• C5a: inflammation

• C6-9: lysis of microbe

  • complement proteins form membrane attack complex (MAC) that forms hole on surface of bacteria so it lysis

IFN’s are mainly produced by, and they cause

• plasmacytoid dendritic cells

• antiviral state

ways pathogens can evade immunity

• resistance to phagocytosis (inhibitions of phagocytosis)

• resistance to reactive oxygen intermediates in phagocytes (production of catalase, which breaks down reactive oxygen intermediates)

• resistance to complement activation (blocking of C3 binding to organism, and C3b binding to complement receptors)

• resistance to antimicrobial peptide antibiotics

class-I MHC

• expressed in all nucleated cells in man

• only present proteins: T cells only recognize proteins

• presents to CD8+/killer T cells

class-II MHC

• expressed primarily on antigen presenting cells (dendritic cells, macrophages, B cells)

  • these cells also have class-I MHC bc they’re nucleated

• presents to CD4+/helper T cells

MHC is the most __ locust

polymorphic (many forms)

• allows us to fight viruses/microbes as a population

Structure of MHC 1

• 1 long alpha chain and 1 external protein chain

• antigen binds btwn alpha 1 and alpha 2

Structure of MHC 2

• 1 alpha chain & 1 beta chain

• antigen binds btwn alpha 1 and beta 1

cross presentation

• exogenous antigen: DC phagocytoses entire cell that has an endosome w/ antigen

• DC does not get infected by virus

• lysosome fuses & breaks down external cell and leaves virus inside endolysosome

• DC breaks down virus in the endosome & transports viral proteins into the cytoplasm

• proteins are ubiquitinated → goes through proteasome → peptides loaded onto MHC 1

• peptides are shown to CD8+ T cells on MHC 1

signal transduction units for B cells

• Iga

• IgB

signal transduction units for T cells

• CD3

• zeta

where do antigen receptors bind the antigen?

epitopes

T cells bind to __ epitopes, and B cells binds to __ epitopes

• linear

• conformational & linear

Effector functions of B and T cell receptors are mediated by:

B cell:

• constant C (Fc) regions of secreted Ig: because this region binds to the phagocyte

T cell

• TCR does not perform effector functions bc they are always attached to surface & are never secreted

**where does antigen bind on antibody?

between variable regions of heavy & light chains

what is the FAB region made of?

• 2 heavy & 2 light chains

• it is the arms, and they bind to antigen

• FAB = fragment for antigen binding

Fc region

• crystallizable fragment

• made up of 2 heavy chains

• binds to receptor on the phagocytes

what determines the isotype/type of antibody?

Fc region/constant heavy region

which chain is formed first in B cell antibodies?

heavy chain

How many antigens does secreted IgA bind?

4

because it is a dimer

How many antigens does secreted IgM bind?

10

because it is a pentamer

where does antigen bind on T cell antigen receptor (TCR)?

between variable regions of alpha & beta chains

which chain is formed first in TCRs?

beta chain

which chains only have D region?

heavy chains in BCRs; beta chains in TCRs

immature B cells have only 1 receptor __, then get __ when mature

IgM; IgD