ch. 1 - cells + tissues of the immune system

protein structure determines what 4 things

sasa!

stability, affinity, specificity and activity

4 types of pathogens

virus, bacteria, fungus and parasite

pathogen associated molecular pattern (PAMP)

shapes associated with pathogens

• individual AA sequences that fold into a shape

pattern recognition receptors (PRR)

host proteins for pathogens

• can distinguish different PAMPs (self vs. nonself)

• good for immune responses

autoimmunity

immune response that accidentally recognizes self molecules as foreign, attacking them

antigen

piece of protein taken from a pathogen that is used to stimulate pathogen-specific adaptive immunity

antibody

protein produced by B cells that specifically binds to a specific antigen and helps eliminate its associated pathogen

antigen vs. PAMP

we adapt to antigens, we are born being able to recognize PAMPs

innate immunity characteristics:

• response time

• specificity

• response to repeat

• major components

• minutes to hours

• limited + fixed

• same each time

• barriers + phagocytes

adaptive immunity characteristics

• response time

• specificity

• response to repeat

• major components

• days

• diverse + dynamic

• progressively better

• T and B cells; antibodies

genetics of innate immunity

relies on PRR recognizing PAMPs

• PRRs are encoded into the gene

• results in all nucleated cells

genetics of adaptive immunity

antigen receptors come from recombined genes

• recognizes Many more antigens

• B and T cells

major functions of innate immunity

• detect infection w PRRs

• phagocytose pathogens

• secrete soluble mediators (cytokines/chemokines, cytotoxic effectors)

• present antigen to T cells

major functions of adaptive immunity

• B cells produce antibodies

• T helper cells support

• Cytotoxic T cells kill infected cellla

• Both B and T cells product long-lived memory cells

can T cells recognize antigens on their own?

no

antigen presenting cells (APCs)

instruct T cells when antigen is present

APC phagocytosis steps

1. APC detects pathogen via PRR

2. APC phagocytizes pathogen

3. APC digests pathogen into peptides that can serve as antigens

4. APC presents antigen to T cell for activation

major histocompatibility complex (MHC) proteins

present antigen to T cells

MHC-1

all nucleated cells express

• allows infected cells to alert nearby T cells

• present to only Tc cells when infected

MHC-2

only professional APCs express

• usually present phagocytosis-derived antigens

• present to both Tc and Th

professional APCs

express both MHC-1 and MHC-2

Tc cell TCR + coreceptor

CD8 receptor + TCR → MHC-1

Th cell TCR + coreceptor

CD4 receptor + TCR → MHC-2

• NEEDS CD4 to interact with MHC-2

Tc effector functions

• recognizes infected cell

• induced apoptosis in target

• neighboring uninfected cells are not killed

Th effector function

secrete cytokines to modulate immune response

hematopoiesis

development and differentiation of immune cells

myeloid cells

• 2 categories

granulocytes and mononuclear phagocytes

myeloid: granulocytes

eosinophil, mast cell, basophil and neutrophil

myeloid: mononuclear phagocytes

monocyte → denritic cell + macrophage

neutrophils

• most abundant leukocyte

• aka polymorphonuclear leukocytes (PMNs)

• short-lived 1st responders

• specialized phagocytosis + killing bacteria/ fungi

• excude neutrophil extracellular traps (NETs)

eosinophils

• bilobed nuclei; bright red/orange

• defend against parasites (helminths)

• major effector in allergic inflammation + asthma

basophils + mast cells shared features

• both contain large granules rich in histamine, heparin, and proteases

• mediate allergic and anti-parasite responses

basophils

• rare, short-lived circulating granulocytes (<1% of WBCs)

  • develop in bone marrow and circulate in blood

mast cells

• long-lived, tissue-resident cells

• derived from bone marrow precursors but mature in tissue

monoculear phagocytes features

• single and non-segmented nucleus

• high phagocytic capacity

• professional APCs (express MHC-I and MHC-II)

monocytes

• circulating precursors; short-lived in blood

• rapidly recruited to sites of infection/injury

• can differentiate into macrophages or DCs in tissues

macrophages

• long-lived, tissue-resident phagocytes

• specialized forms in different organs

  • key roles in inflammation and resolution/healing

dendritic cells

• most potent antigen-presenting cells (APCs)

• can migrate from tissues to secondary lymphoid tissues

lymphocytes

T cells

B cells → plasma cell

NK cell

NK cells

• granular lymphocytes of innate immune system

• do NOT recognize antigen

• can detect absence of MHC-I on infected/cancerous cells

B cells

• detect antigens using B cell receptor (BCR)

• produce antibodies

• are professional APCs (express MHC-II)

• develop in bone marrow

• DO NOT REQUIRE PRESENTATION

plasma cells

• differentiate from activated B cells

• produce large quantities of antibody

• long-lived residence in bone marrow

T cells

• detect antigens using T cell receptor (TCR)

• require antigen presentation via MHC molecules

• CD8 T cells are directly cytotoxic

• CD4 T cells modulate the activity of other immune cells

• develop in thymus

primary lymphoid organs

thymus + bone marrowse

• immune cell development

secondary lymphoid organs

spleen, lymph nodes and MALT

• immune cell activation

lymphatic system

1. capillary bed

2. drianing lymph node

3. thoracic duct

4. lymph returns to circulation via subclavian veins

interstitial fluid

lost plasma from capillaries

lymph → cardiovascular circulation

1. interstitual fluid

2. draining lymph nodes → lymph

3. thoracic duct

4. subclavian veins return lymph to heart to be used as blood

how do Ags and APCs traffic to secondary lymphoid organs

1. innate immune cells eat any loose molecules from bacteria → loaded with Ags

2. immune cells travel to the draining lymph node

3. present Ags to T cells inside lymph node

afferent lymphatics

APCs and soluble antigens enter lymph node

efferent lymphatics

activated lymphocytes exit

high endothelial venule (HEV)

naive lymphocytes enter

naive lymphocyte

never seen Ag before

• B and T cells

naive B cells

enriched in primary follicles

naive T cells

enriched in paracortex

• capture soluble antigen

• also proliferate in paracortex

germinal center

where activated B cells bring a soluble Ag and proliferate

red pulp contains ______ that recycle erythrocytes

macrophages

white pulp is site of ____ _______ and lymphocyte _______

antigen presentation, activation

Leukocytes and soluble antigen enter through splenic _________

arterioles

periarteriolar lymphoid sheath (PALS)

enriched in naive T cells

marginal zone

enriched in APCs

mucosal associated lympoid tissues (MALT)

• respiratory tract

• digestive system

• urinary tract

• salivary glands

• lactating breast

• lachrymal glands

• tonsils + adenoids

• appendix