Lecture 1 & 2 Flashcards by Riley Hrasky

term for when the immune system loses the ability to discriminate b/w self and non-self

autoimmunity

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‘self’

normal body constituents expressed by healthy cells

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non-self

cells/molecules that the immune system doesn’t have exposure to during its maturation or doesn’t normally encounter on healthy cells

foreign cells/substances
damaged, transformed or senescent

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pathogen

causes disease
evades innate immunity

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opportunistic pathogens

typically don’t cause disease but under the right conditions they can

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innate immunity

components of the immune system that rapidly respond to non-self invaders in a non-specific way

protects us from non-pathogens

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adaptive immunity (‘third line of defense’)

= acquired immunity; can be cell-mediated or humoral

antigen-specific responses that are highly adapted to specific pathogens
composed of lymphocytes
regulated by communication b/w innate and adaptive immune cells

at rest until a specific antigen interacts w/ their antigen receptor

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what type of immunity develops immunological memory

adaptive
- memory causes improved immune response over time

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how does innate immunity prevent microbes from establishing infection?

by blocking the entry of microbes by physical, mechanical, microbial or chemical methods = barrier defenses

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barrier defenses

skin, chemicals on skin like oil, mucous membranes

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skin as barrier

dry, acidic environment prevents growth of many bacteria, keratins discourages colonization, sloughing of skin cells removes bacteria that adheres to skin cell.

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mucosal epithelium

tears, the stomach is acidic, mucous traps things in airway entrance, colon has resident microbiota, bladder sphincter keeps bacteria out of urethra, etc.

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what prevents bacteria from accessing subcellular surfaces in mucosal epithelium

tight junctions

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importance of goblet cells

make and secrete mucus
- mixture of glycoproteins
- prevents bacteria from reaching epithelial cell surfaces

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mucociliary escalator

in respiratory track
- ciliated epithelial cells that line airways
- coated w/ mucus that traps pathogens
- cilia move mucus up and out of lungs

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what are the cells of innate immunity

WBCs (phagocytic and natural killer cells)
Complement (serum proteins that trigger inflammatory response and initiate phagocytosis of bacterial cells)
Cytokines (proteins made by immune cells to coordinate attack on invading pathogens)

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how do microorganisms gain access to cells or tissues

by colonizing or breaching the epithelial barrier

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colonization of the surface can lead to…

infection of epithelial cells, epithelial damage allowing microbe to cross into underlying tissue

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PAMP (pathogen-associated molecular pattern)

repeating patterns of molecular structures on surface of pathogens

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cells express ________ that recognize common microbial structures (PAMPs)

pattern recognition receptors (PRR)

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what are examples of PAMPs

LPS (lipopolysaccharides)
peptidoglycan
LTA (Lipotechoic acid)
Flagellin (major component of bacterial flagella)
viral RNA (dsRNA)
unmethylated CpG DNA

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what is CpG DNA?

CpG = cytosine phosphate guanine

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what is an example of pattern recognition receptors?

Toll-like receptors (TLRs)
**TLR4 binds to LPS
- LPS is released during bacterial cell lysis

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Imiquimoid (Aldara TM) does what

enhances immune response against equine sarcoids and aural plaques by binding TLR 7/8

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what does lysozyme break down

peptidoglycan

NADPH oxidase generates what

superoxide

what complement proteins induce pro-inflammatory cytokines

C3a and C5a activated macrophages and dendritic cells TNF, Interleukin 1 & 6 and others

what is the main function of cytokines

recruit immune cells and increase lymph flow - lymph returns antigens and microbes to lymphoid tissues to generate adaptive immune response

physical signs of the inflammatory response are caused by ....

increased blood flow and leakage of fluid and blood proteins into tissues

what causes septic shock

bacterial infections Septicemia = bacteria in blood stream, causes inflammatory response throughout the body

how does septic shock lead to death

septicemia leads to drop in BP, lower blood flow to vital organs and organs begin to fail

function of natural killer cells

induce apoptosis in infected host cells - they store toxic granules

a collection of soluble proteins present in blood and other body fluids, activated in response to pathogens or antibodies bound to pathogens

complement - made in liver - 'complement' to antibody activity

what is an antigen

Antibody Generator * foreign substances that bind B cell receptors, T cell receptors or antibodies

when are antibodies raised for attack

only when specific molecules are found

what is an epitope

4-16 amino acids that are recognized by the antigen binding site of an antibody

why are adaptive immune responses specific?

b/c each B and T cell expresses a unique receptor on the cell surface - every B and T cell has surface receptors (BCR and TCR) that have an antigen-binding site specific for one epitope

how do BCR and TCR differ

BCR - binds antigens of varying shapes and sizes TCR - binds linear peptides displayed by MHC (HLA) molecules

what T cells are responsible for expressing different versions of TCR

CD8 and CD4 T cells

antibody-based immunity produced by effector B cells (plasma cells)

Humoral immunity - important in defense against extracellular pathogens

Cell-mediated immunity is mediated by ______ cells that produce their effect by _______ contact w/ target cells

effector T cells direct contact

what cells are involved in cell-mediated immunity

Helper T cells Cytotoxic T cells

what causes the activation of B and T cells

upon antigen recognition

how do effector cells participate in the elimination of antigens ?

secretion of antibodies or through cell-mediated killing

adaptive immunity includes what two types of immunity and what cells make them up

cell-mediated - T cell defense humoral - antibody defense (B cells)

Proteins made by immune cells to co-ordinate attack on invading pathogens

cytokines

Serum proteins that trigger inflammatory response and initiate phagocytosis of bacterial cells

complement

what are the 2 types of WBCs involved in the innate immune response

Phagocytes (neutrophils, macrophages, dendritic) Natural Killers

* Frequent sites of methylation in Mammals * Unmethylated in bacteria * Aberrant DNA methylation involved in many cancers

CpG

when are lipopolysaccharides released

during bacterial cell lysis

LPS binding protein (LBP) binds what

CD14 and ultimately TLR4

3 pathways of complement

classical alternative lectin **all converge at the generation of C3b from C3

C3 convertase does what

it is a protease that cleaves C3 --> C3a and C3b

C3b directly binds to pathogens leading to what

opsonization = tag foreign pathogens for elimination by phagocytes

what are antibodies made by?

B cells * they bind epitopes on antigens

# has to do with epitopes types of antigens

* monovalent: antigen w/ one epitope * multivalent: antigen w/ multiple of the SAME epitope * polyvalent: antigen w/ several different epitopes

what are haptens

antigens that bind to antigen receptor but can't initiate an immune response alone * can become immunogenic if conjugated to a carrier | conjugated vaccines!

membrane bound antibody on B cell surface | binds antigens of various shapes and sizes

BCR | B cell receptor

what type of cells are effector B cells

plasma cells

The first exposure to an antigen leads to development of a ________

primary immune response * Results in clonal proliferation and differentiation of activated B and/or T cells into populations of effector and memory B and/or T cells * Activation of these memory cells by the original antigen results in generation of a secondary immune response

# has to do w/ repeated exposure... why do we vaccinate?

Repeated exposure to the same antigen induces a heightened state of reactivity higher antibody titers)

MHC Class 1 (major histocompatability complex)

* made by all nucleated cells * presents antigens to **CD8 or cytotoxic T cells** * displays antigens from INTRACELLULAR bacteria * results in apoptosis of antigen presenting cells

MHC Class II

* made by APCs (antigen presenting cells) only * presents antigens to CD4 or helper T cells * displays antigens from EXTRACELLULAR sources * Leads to activation of macrophages, stimulation of B cells to produce antibodies

APCs use _____ to display antigens

MHC molecules

CD8 T cells AKA...

Cytotoxic T cells * similar to NK cells but w/ specificity

What do CD8 T cells do

* Deliver toxic granules to infected cells * Can target all cells with MHC Class I molecules (All nucleated cells)

Helper T cells AKA...

CD4 T cells * help other cells activate

function of Th1

activates macrophges

function of Th2

* responds to extracellular bacteria and fungi generating inflammatory response

function of Th17

stimulate neutrophil response to extracellular bacteria and fungi

function of Tfh

stimulate antibody production from B cells; including class switching and affinity maturation

function of Treg

regulates immune response

cytokines

* intercellular regulatory proteins produced by a variety of cells in response to microbes and other antigens. * Primarily act as autocrines or paracrines, but some have endocrine action.

which class of MHC results in the apoptosis of the presenting cell

Class I