Lecture Final: Chapter 25

Question 1

Innate vs Adaptive Immunity

+ Types of Response for each

Answer 1

INNATE: all animals – in place before the infection

• • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors (germline encoded)
• • Rapid response, basically immediate

Types of defense:

1. Barrier: physical barriers; first line of defense – eg. skin, mucous membranes, secretions
2. Internal: mobile; second line when your barrier is overcome – eg. phagocytic cells, natural killer cells, antimicrobial proteins, inflammatory response

ADAPTIVE: vertebrates only! Usually for pathogens that have evolved to overcome the innate immunity – so we evolved with them → responds when the innate cannot immediately kill the foreign
– Slower response; responds after the infection has started

Types of Response

1. Humoral response: antibodies defend against infection in body fluids (navy team) → ie. viruses, secretions
   - - B cell: activated, co stimulated, release antibodies that can tag foreign bodies for destruction
2. Cell mediated response: cytotoxic T cells that defend against infection in body cells

Question 2

Leukocytes to Know pt 1

• Define
• Neutrophils
• Macrophages
• Dendritic Cells

Answer 2

Leukocytes = white / warrior blood cells formed in bone marrow

Neutrophils: phagocytic, will eat the enemy → first responders at the site of infection; most numerous of circulating leukocytes (looking for trouble); also secrete h2O2 and HCIO (bleach) to destroy bacteria; can also explode as a last resort to destroy foreign invaders

Macrophages: aka mature monocytes; also phagocytic → follow neutrophils; mostly in lymph nodes and spleen; major role in removing bacteria and cellular debris at the site of infection; shoot first, aim later, TAKE NO PRISONERS

• • also function as antigen presenting cell (APC), which means they will take the antigen they consume and display it on themselves as they travel to the lymph node to present it to the adaptive system to trigger a higher level of response
• • Co stimulation (the chain of command)

Dendritic cells: also phagocytic; present in tissues exposed to environment (mucosal, intestinal); professional APC (digest, expose, alert)
– Alarm the adaptive system to go to war (the big trigger)

Question 3

Leukocytes to Know pt 2

• Granulocytes (2)
• Natural Killer Cells
• Mast Cells
• B and T Cells

Cytokines
+ Functions (3)

Answer 3

Granulocytes:

• • Eosinophils: release granules to target parasites (worms)
• • Basophils: trigger allergic reactions by releasing histimines

Natural Killer cells: patrol blood and lymph; touch kill (DEATH TOUCH YOOOOO) viral infected cells and cancerous cells which often fail to display antigens on MHC

Mast cells: similar to basophils bc release granules that trigger hypersensitivity (allergic) response

B cells and T cells: lymphocytes of adaptive response; covered in depth later

CYTOKINES:
have receptors for chemical signals that coordinate innate and adaptive systems; usually local (autocrine, paracrine)

Functions

1. Growth and Differentiation of lymphocytes
2. Stimulate effector function: eg formation of cytotoxic cell
3. Produce CHEMOKINES: subset that are used to attract a leukocyte to the site of need
4. Produce ENDOTHELIAL ADHESION MOLECULES: adhere to leukocytes and slowly have them migrate to the site of need

Question 4

Innate cell receptors: pattern recognition receptors (PRR)
+ examples (5)
+ where occur
+ recognition leads to what

Answer 4

All animals use TOLL LIKE RECEPTORS (TLR), a type of PRR that are EVOLUTIONARILY conserved that can recognize STRUCTURALLY conserved molecules of microbes (PAMPs) that are common amongst different types of bacteria
– germ line encoded and expressed by bound ribosomes

Examples of PAMPs (pathogen associated molecular patterns)

1. Bacterial cell wall in lipids
2. Fungal polysaccharides
3. Microbial and viral DNA / RNA
4. Bacterial flagellin
5. Bacterial peptidoglycan

TLR occur on surfaces, where they are likely to encounter pathogen == OR ENDOSOMAL MEMBRANES, incase something has compromised the cell internally
– more examples: macrophages, epithelial cells of resp/GI tract, B cells

TLR recognition of microbial ligands results in activation of signalling pathways, which lead to gene expression of proteins involved in INFLAMMATION (manual) and ANTIVIRAL RESPONSES (type 1 interferons)

Question 5

Phagocytosis

Answer 5

exhibited by innate immune cells

Pathogens engulfed inside a PHAGOSOME, which fuses with a lysosome to form a PHAGOLYSOSOME → pathogens will be destroyed by lysosomal enzymes OR ROS (Reactive oxygen species; free radical) or NO (nitric oxide)
– Once digested, debris released from cell or displayed on surface of phagocytes that function as ANTIGEN PRESENTING CELLS (APC)

Question 6

Complement Proteins

• Functions (3)
• Pathways (3)

Answer 6

1. Opsonization: coating pathogens in order to make them more obvious to phagocytes; can adhere to antibodies too
2. Trigger inflammation by recruiting phagocytes to the site of infection
3. If no phagocytes, then will form ATTACK COMPLEX: formation of tube that will allow water to flow into pathogen and swell until explosion

PATHWAYS:

1. Classical: complement proteins will attach to antibodies (AB) that are already attached to the pathogen → goal: make antibodies-attached microbes must more recognizable to the macrophage (macrophage has receptors to the complement protein)
2. Alternative: no antibodies! complement will bind directly to the surface of the pathogen (ie no antibodies) → goal: again, makes pathogens more obvious to the macrophage
3. Lectin (proteins that bind sugars; C3B would bind to sugars on the surface of the microbe) → complement again makes this more visible to the macrophage

Question 7

Inflammation pt 1

- Pathway (LMDC)

Answer 7

hallmark of innate response

Involves PHAGOCYTE MOBILIZATION: here’s the pathway

1. Leukocytosis: production of more white blood cells, in particular neutrophils, in response to the cytokines secreted by circulating cells (ie macrophages)
   - - Exits bone marrow to approach the site of tissue damage
2. Margination: getting the white blood cells to slow down their transit through a venule in a capillary bed so that they are aware – allows for insertion of selectins and integrins (stabilizes position of cell?) – also inserts chemokines that attract white blood cells – inner lining is kind of sticky now
3. Diapedesis: Once attached by the surface receptors bound to the inner lining, will slowly crawl through the cleft, attracted by the gradient of chemokines
4. Chemotaxis: movement towards increasing gradient of chemokines; will eventually reach site of need and then remove the enemy

Question 8

Inflammation pt 2

• Features / Presentation (4)
• Purpose (4)

Answer 8

1. Redness: some of the substances secreted by the damaged tissue will release HISTAMINES, triggering vasodilation / bringing blood into the region = increased blood flow, makes it red
2. Warmth: more blood means more plasma, which has a high specific heat
3. Swelling: due to increased blood flow
4. Pain: swelling will trigger nerves in the (something) and send signals to the brain about pAIN
5. Prevent spread of microorganism and toxins
6. Disposal of microorganisms and cell debris
7. Set stage for tissue repair – ie blood clots will be accompanied by growth factors to promote cell division
8. Alert adaptive immune system

Question 9

Adaptive Immunity, revisited (2)

+ features (3)

Answer 9

Recognition of traits specific to particular pathogens, using a vast array of receptors (not from germ line; unique and derived from antigen) via recombination to produce a unique protein that can respond to a specific antigen, therefore can counter a bunch of different enemies

Can respond to pathogens that are circulating in the body fluids (freely expose) via HUMORAL RESPONSE or even those in infected cells (not as freely exposed until host cell is lysed) via CELL MEDIATED RESPONSE

Cardinal features of adaptive immune response

1. Specificity and diversity: potential
   - - clonally selected for by antigen; will be unique and allowed to proliferate in response to exposure
2. Memory : will remember the pathogen by the memory cells (throwback to PRR) → foundation for recognition
3. Nonreactive to self

Question 10

Humoral Response of Adaptive Immunity

• B cell, defined
• Activation of T cell (4)
• Activation of B cell (4)

Answer 10

B cell lymphocytes : produced by red marrow in bones; maturation involves recognizing non self from self; when mature, they exit bone marrow and move into secondary lymphoid organs where they will encounter ANTIGENS

ACTIVATION OF T CELL

1. An APC (usually dendritic cell) engulfs and digests a microbe in phagolysosome; cell will then migrate to a lymph node and displays antigen with MHC2 for display to naive CD4+ T cells (signal 1)
2. Naive CS4+ T cell will recognize display using self non self receptors and become activated CD4+ Helper T cell
   - - Innate production of cytokines stimulates APC to sprout co-stimulatory molecules that bind to receptor on CD4+ T cell (signal 2)
   - - B7 SPIKE! Protrudes from APC, comes out as a result of the cytokine productions; acts as a bridge to reach the T cell
3. Activated CD4+ Helper T cell stimulated to divide into effector and memory cells
   - - Clonally selected by the antigen

ACTIVATION OF B CELL (end goal)

1. Naive B cell captures antigen with receptor (signal 1) and the antigen is endocytosed and digested
2. Antigen displayed with MHC 2 on surface of B cell (signal 1)
3. Activated CD4+ Helper T cell binds to B cell displaying cognate antigen on MHC 2 and secretes cytokines (Signal 2) to stimulate cloning of B cell into effector plasma cells and memory cells
4. B cell differentiates into:
   - - Memory cells: wait for the next encounter
   - - Plasma: secrete Ig antibodies that circulate in blood and lymph to tag microbe for destruction

Question 11

Cell Mediated Response of Adaptive Immune System (6)

Answer 11

T Cell Receptors: heterodimer of two transmembrane polypeptides – each peptide with a constant region, variable region, and a antigen-binding sit that consists of three hypervariable regions

1. Dendritic cells engulfs and digests microbe inside phagolysome; antigen displayed on surface with MHC1 via CROSS PRESENTATION
2. Dendritic cells will then migrate to lymph nodes and encounters naive CD8+ T cell
3. Antigen displayed along with MHC1 by dendritic cell (signal 1) and co stimulatory molecule from B7 spikes (signal 2) activates naive CD8+ T cell into CD8+ Cytotoxic T Cell
4. CD8+ T cell divides repeatedly forming clones of effector CD8+ CTL and memory cells
5. CD8+ CTL will exit from lymph nodes and migrate to the site of infection
6. CD8+ CTL initiate killing of infected cells that display antigen with MHC1

Methods of Touch Kill:

1. Insertion of protein PERFORIN which will create pores for water to flow in until swell / pop
2. Secretion of GRANZYMES, which will stimulate apoptosis in infected cell

Question 12

Antibodies

• Functions
• Types

Answer 12

1. Neutralization: coating pathogens in order to cover the host receptor area
2. Opsonization
3. Activation of complementation

Antibodies referred to by “Ig”
— SECRETED:
G) main antibody; activates complementation, neutralizes toxins, protects fetus via milk
A) dimeric and from exocrine; interferes with binding of pathogens to body cells
— MEMBRANE BOUND:
E) anchored to surface of basophils / mast cells / eosinophils / some dendritic; binding to antigen will induce release of histamines and cytokines; factor in allergies and asthma + parasites
D and M) receptors on naive B cells; will become IgG when stimulated