Final Exam

INNATE

Innate - non specific initial response 

  1. Barriers (physical - skin, ear wax, eye lashes, etc. / chemical - lysozyme, sweating, sebum, gastric juice / mechanical - sneezing, coughing, shredding skin) *skin can be all 3

    1. Chemical is plasmalysis for skin, also barrier, and we shed skin 

  2. Cellular defense is activated when foreign invader is recognized. It can activate adaptive immune response *normal microbiome harms pathogens and takes up space 


Primary response: primary exposure is first exposure to an antigen. Works slow (days to weeks), weaker, less antibodies. Memory cells are not present initially (ex: first time getting chicken pox)

Secondary response: repeat exposure to the same antigen. Rapid (within hours to days). Stronger, higher antibody levels. Activated from memory B and T cells. (ex: getting exposed again or receiving booter shot)


Innate also has phagocytosis 

  1. Adhesion

  2. Ingestion

  3. Digestion

  4. Excretion 


Cells:

Cytokines are released by innate cells, indicated infection and recruit others and signal more immune cells to be released (messenger)

Chemokines are at exact location to draw in immune cells 


Mechanisms of innate immunity (5)

  1. Phagocyctosis: recruitment of phagocytes. Cells are ingested and destroyed by neutrophils, macrophages, and dendritic cells

  2. Fever: systemic rise in body temperature. Good because they increase speed of reaction, enforce rest, and increase uptake of iron. Bad bc proteins denature, inhibits CNS, causes dehydration 

  3. Inflammation: causes vasodilation, attracts phagocytes, increases blood which makes it red and warm, produces acute phase proteins which trigger the complement system, helps isolate pathogens, and gets cells to point of infection faster with increase of blood flow

  4. Complement: cause cell lysis, has opsonization proteins (handles to grab on to), inflammation, and MAC

  5. Interferons: paul revere infected cells release interferon which warns neighboring cells to be ready for attack and they make antiviral proteins which take over viral cells and turn them against themselves (AVP are like booby traps from home alone)


Toll like receptors (TLR): receptors that recognize antigens from pathogens and are nonspecific. Double stranded RNA and single stranded RNA + LPS and flagella are not in humans (if they have any of these the TLR will know that this is not the bodies cells)


Membranes role in cytolysis (cell death)

  • Cell membrane is a direct target during cytolysis. MAC forms pores in the membrane compromising its integrity. Loss of membrane function = cell death due to osmotic lysis 


Types of cells:

  • Neutrophils: phagocytic cells that guard skin and mucus membranes, make up 55-70% of WBCs. use toll like receptors, live hours to days, and undergo apoptosis (programmed cell death)

  • Monocytes: differentiates into macrophages and dendritic cells in response to inflammation 

  • Macrophage: destroy pathogens by phagocytosis

  • Dendritic cells: present antigens on surface trigger adaptive immunity 

  • Basophil: release histamine which leads to inflammation which leads to allergic reactions 

  • Eosinophil: defends against parasites

  • Mast cell: produces chemical mediators and recruits inflammation 

  • NK cells: cause programmed death if receptors don't line up with NK cell receptors (ex: kill cancer cells)


Opsonization: created handles for phagocytosis. bc there are no receptors for the phagocyte to grab it or it has a capsule to get away so the complement proteins as as little handles (handle-opsoms) so the phagocyte can grab it 



ADAPTIVE

Adaptive immunity responds to specific antigens


Humoral adaptive immunity - B cell mediated 

Cellular adaptive immunity - T cell mediated 


2 categories of cells 

Antigen presenting cells: macrophase, Bcell, dendritic cell

Phagocytic cells: macrophages, neutrophils, and dendritic cells 


Immunoglobulins: antibodies produced by plasma cells

Igg: used for compliment system, opsonization. Can cross the placenta from mother to fetus 

Iga: in colostrum. Protects against new bacteria and helps neutralize 

Igm: first antibody produced in response to infection 

Ige: activated mast cell and basophils, to release histamines which leads to allergic response and inflammation 

Igd: b-cell receptor 


Clonal selection: immune system process where a specific lymphocyte like b or t cell is selected when its unique receptor binds to a matching antigen. This cell rapidly clones itself and makes a bunch of the same cells that can fight that specific pathogen (find correct key to unlock door)

Consequences:

  • Each receptor is specific and there is a limited number of segments 

  • Irreversible generation arrangement 


All the different types of t-cells:

  • Cytotoxic cd8 cell: kills infected host cell with mhc1 presentation 

  • Helper cd4 cells: differentiates into other immune cells

    • TH1: activated macrohpage and turns it into super macrophage 

    • TH2: activates b cell via mh2 receptor, b cell matures into plasma cell and antibodies, causes mast cell inflammation. More specifically it makes IGE which fights of allergy and parasites 

    • Th17: recruits neutrophils to the scene 

    • Tfh: also activates b cell via mh2 receptor, b cell matures into plasma cell and antibodies 

  • Regulatory t cell: suppressed immune responses when done/everything fought off, inhibited dendritic cells


B cells

  • Mature in bone marrow 

  • Live for hours to days

  • When activated it turns into plasma cell which then produces antibodies

  • Always a supply 

  • Activation > neutralization, opsonization, and compliment 

T cells

  • Mature in thymus

  • Live for years

  • Cd4 and cd8 are regularly going around t cells

  • Once activated it triggers helper t cells (cd4 which then differentiate), cytotoxic (cd8) cells, regulatory t cells

  • Must divide bc thymus ATV?


Compliment triggers

  • Antibodies

  • Endotoxins

  • LPS

Compliment outcomes

  • Opsonization 

  • Inflammation 

  • Cytolysis 


Receptors: 

  • MHC1: presented by infected cells, binds to cytotoxic t cells (cd8) and leads to death of infected host cell 

  • MHC2: presented by APC cells and binds to helper t cells (cd4)


ANTIVIRALS

Could target reverse transcriptase and integrase processes. 

Using protease, people have been successful with stopping budding.


Problem: reverse transcriptase makes a lot of mistakes (evolution = resistance)


Solution: a lot of times more than 1 drug is presented at a time. Unlikely to get mutations at once. Important to not miss a close bc every time you miss a close you allow the virus to replicate in the presence of the drug at an ion close which promotes the chance for mutations to happen.


HIV

Retrovius: has RNA genome, uses reverse transcriptase to turn its RNA into DNA (latent)

  • Reverse transcriptase: is included inside the capsid of the virus since humans don’t have this

Structure of HIV: contains glycoproteins, gp120 + gp41


Infection of CD4 + T cells: gp120 and gp41 attach to receptor on the CD4+ cell (co-receptors CCR5 and CXCR4 help). Membrane fusion allows virus to enter cells. Receptor and corrector bind (attachment phase) to HIV glycoprotein = membrane fusion (penetration phase) 


HIV becomes AIDS when: CD4 levels drop below 200. The immune system weakens and the body becomes vulnerable to opportunistic infections


HIV/AID wont kill you, a bioinfection will!


Why no vaccine?

  • Mutation rates of RT are too high 

  • Integrate into T cells is too dangerous 


Antivirals:

  • Could target attachment, reverse transcriptase, 

budding (HIV drugs)

  • ^prevent growth, keep viral load down, and so 

you can’t pass it on 





PICTURE


  1. The virus infects the healthy human cell and becomes a sick human cell.

  2. A natural killer may come in and kill the infected cell. A nearby mast cell can also arrive and release chemicals that cause inflammation. A macrophage can also come to engulf the virus.

  3. The dendritic cell displays antigens to naive CD4 T-cells via MHC 2.

  4. Activated CD4 cells differentiate into helper T-cells

    1. Th1 helper cells activate macrophage, making it an activated macrophage (super macrophage)

    2. Th2 presents antigen via MHC 2 to the B-cell, changing it to a plasma cell. Plasma cell makes antibodies. 

  • This either triggers neutralization, opsonization, or the complement system. Within the complement system the mast cells arrive, cytolysis can occur, or opsonization can happen. 

  1. T17 helper cells recruits neutrophils to the scene, enhancing phagocytosis 

  1. The CD8 cell recognizes the antigen on the MHC 1 of the sick human cell, and destroys it.

  2. After infection is gone, some B and T cells stay behind as memory cells.