Immunology memorization

MIMG 185A midterm memorization

innate immune cells

• macrophages

• DCs

• neutrophils

• NK cells

• granule cells

branches of adaptive immunity

humoral (Abs and B cells), Cell mediated (T cells)

innate response time

hours

innate specificity

highly specific but limited number of innate receptors that specifically look for patterns only found in pathogens

adaptive specificity

hiughly diverse and robust with very specific receptors

how do the innate and adaptive immunity differ in responding to repeat infection?

innate - all responses are identical

adaptive - much more rapid than primary response

major components of innate immunity

barriers (skin), phagocytes, PRRs

major components of adaptive immunity

lymphocytes (B and T cells), antigen specific receptors, antibodies

anatomic barriers in innate immunity

skin (epidermal layer) mucosal membranes

innate immunity physiologic barriers

temp, pH, oxygen tension, soluble factors (lysozyme, interferons, complement system)

neutrophils

phagocytic, short lives and have FcR (FC gamma receptor recognizes constant region of IGg)

mast cells/basophils/eosinophils

highly granular, granules contain mediators (pre packed poisons that create killing or inflammation responses)

FCR usually binds IgE

monocytes/macrophages

phagocytic, FcR binding allows Ag:Ab complexes, Ag presentation, can initiate T cell response

DC

found all over the body, trap Ag on surface and traffic to lymph nodes, role in T cell activation

endocytosis

delivers macromolecules to endosomes

phagocytosis

(monocytes, macrophages, neutrophils) engulfs particles and organisms via receptor binding and degrades them in lysozymes. peptides left in lysozymes can be presented via MHC

are any immune cell receptors germline encoded?

yes - receptors in innate immunity

PRRs

pattern recognition receptors in innate immune system recognize PAMPS (dsRNA, LPS in gram neg bacteria, etc)

why does blood go slower in vasodilation

larger vessel volume but same amount of pressure

why is inflammation important

alert system, tells cells in the neighborhood about an issue

margination

adherence of immune cell to capillary wall

extravasation

exit of immune cell from capillary

chemotaxis

in immunology, migration towards area of inflammation

soluble mediators involved in inflammation

• inflammatory cytokines

• chemokines

• acute phase proteins (released by liver, bind bacterial polysaccharides, initiate complement sys)

• kinins (released following injury, stimulate vasodilation and pain receptors in skin)

what isotypes are naive B cells

IgM+ and possibly IgD+

what isotypes can memory B cells be?

IgM+, IgG+, IgA+, or IgE+

what markers do T cells express

CD3, and either CD4 or CD8

what type of macromolecule (lipid, nucleic acid, protein, carbohydrate) is Abs

proteins

are antibodies and TCRs germ line?

no

why is T cell activation highly regulated

innate immune sys is able to handle most pathogens, T cells are also very powerful and activating them results in killing of bystander cells in the microenvironment

what is needed for B cell activation (think upstream)

CD4 T cell activation is needed for full force B cell activation and memory

what types of B cells do naive B cells polarize into when activated by CD4

memory B cell or plasma cell (depending on cytokines present)

how are antigens presented on APCs

via MHC

effector cells

B cells (make + secrete Ab) T cells (kill infected cells and help other cells by cytokine release in response to Ag)

antibody roles

bind and remove (neutralize) antigen, opsonization (to improve phagocytic activitiy), Ab binding can activate complement

primary immune organs

thymus, bone marrow

secondary immune organs

lymph nodes, spleen, gut (where immune cells live and become activated)

lymphatic system

recovers fluid in blood that leaks from capillaries, and returns to subclavian vein. lymph nodes screen for pathogens and are packed with leukocytes (lymphoctes, apcs)

lymph node

packed with B and T cells, can more easily pick up complementary Ag and recognize epitope. APCs that bind antigen will migrate to lymph node

spleen

filters blood, white pulp acts like lymph node

GALT

gut associated lymphoid tissue

why does the gut relate to imunity

largest immune organ with lots of bacteria

two dysfunctions of immunity

autoimmunity and immunodeficiency (loss of immune function/response)

paracrine

cytokines being released to other cells inclose proximity

are cytokines reusable?

prob not because they bind to cell and sometimes are endocytosed

endocrine

cytokine moves via circulatory sys to reach distant cell

pleiotropic

cell makes cytokine that can affect diff target cells, and same cytokine has different effects depending on target cell

cytokine redundancy

multiple cytokines have the same effect on same target cell

synergy

multiple cytokines synergize/work together to create more pronounced effects

antagonistic cytokines

one cytokine blocks pathways induced by other cytokines (inhibiting outcome)

IL-1

• interleukin 1, lymphocyte activation

• mainly produced by APCs and DCs

• endogenous pyrogen (causes fever in brain cells)

• works on T, B, and other cells

• promoted differentiation and clonal expansion

• increases expression of adhesion molecules on endothelial cells (helps cells get out of blood to site of infection)

IL-2

• helpful for T cell response

• causes proliferaton + growth of T and NK cells

• can be autocrine

Tfh cells

T follicular helper cells

• regulate B cell immunity

• located in lymphoid follicles

• help B cells form memory and plasma cells

• regulate antibody isotypes

Th17 cells

CD4 subset, produce IL-17

• promote inflammatory responses

• found under mucosal surfaces (inside gut, mouth, intestinal tract)

• fight extracellular pathogens

• depleted by HIV infection

main thing: combats extracellular pathogens in barrier tissues

Treg cells

• make immunosuppressive cytokines

• use cell surface contact to surpress immune responses

• may prevent autoimmunity

• express foxp3 transcription factor

what cytokines help differentiate naive Th to Th1

IL-12, IFN-γ

what cytokines help naive Th differentiate into Th2

IL-2, IL-4, IL-33

what cytokines help differentiate into Tfh

IL-6, IL-21

what cytokines help differentiate into Th17

IL-6, TGFβ, IL-23

what cytokines help differentiate into Treg

TGFβ, IL-2

what pathogens are are cytokines more helpful against compared to antibodies?

cytokines are more helpful within the cell because Ab can only act extracellularly/on cell surface

What three main signals are needed for T cell activation?

1. MHC T cell binding

2. cofactor binding: CD28 on naive T cell binding to CD80/CD86 on DC

3. cytokine polarizing factors that tell what subset to mature into

Th1 cells

• inflammatory cells, activate macrophages and stimulate cellular response

• better for intracellular responses than Th2

• secrete IL2, IFN-gamma, TNF-beta

• IFN-gamma inhibits Th2 proliferation

Th2

• helps with B cell response and good for extracellular pathogens

• stimulate humoral response (Ab production)

• secrete IL-4, IL-10 (both of which inhibit IFN-gamma synthesis — a key factor for Th1)

• IL-5 also secreted. and helps with B cell, eosinophil growth + differentiation

think allergy

FoxP3

master transcriptional regulator for Treg cells

inflammatory cytokines

TNF-alpha, IL-8

TNF-alpha

inflammatory cytokine that increases vascular permeability + expression of adhesion molecules which recruits cells to site of inflammation

• also a pyrogen (helps reduce fever)

• harmful if produced systemically (sepsis)

IL-8

• inflammatory cytokine (but also a chemokine)

• helps recruitment of monocytes to infection, and alters conformation of adhesion molecules on monocytes to encourage high affinity binding

• increases affinity for ICAM-1 (adhesion molecule) + guides migration through tissues

type I interferons

IFN-alpha, IFN-beta

• lead to production of certain molecules that prevent virus replication, produced by cells in response to infection

• double stranded RNA causes expression of IFNs

type II interferon

IFN-gamma

• produced by activated T, NK cells, and NK T cells

• increases expression of MHC I and II, inhibits virus rep

• Th1 cytokine

what is hematopoiesis

• process of bone marrow progenitors differentiating

chemokines

• small peptides (smaller than normal cytokines) released by many cells in response to injury

• acts as a chemoattractant to guide cell migration

• chemokines bind to extracellular matrix bc of charge difference

MCAF chemokine (C-C chemokine)

chemotactic activating factor (attacts monocytes) and activates them

C-C chemokine

chemokine that has two cysteine (C) residues next to each other

C-X-C chemokine

have cysteine -AA - cysteine structure

RANTES (C-C)

chemokine made by activated T cells to attract memory cells

MIP-1 alpha and beta

chemokines that attract T cells

what are types of C-X-C chemokines

IL-8, SDF-1

common gamma chain receptor

found in receptors IL-2, 4, 7, 9, 15, 21

• same gamma chain used — mutation in gene means there would be an inability to respond to any of these cytokines, called X-SCID

  • with SCID, you are unable to make B, T, or NK cells

why might high stress affect the immune system?

high stress leads to neuroendocrine peptide release (specifcally ACTH) which leads to immune supression

what types of innate immune cells travel exclusively in blood?

granulocytes and monocytes

how do naive lymphocytes from blood enter the spleen or lymph node?

adhesion molecules bind naive lymphocytes to lymphoid tissues, and they are able to squeeze out