Patho 3PA2: Adaptive Immunity (part 1)

primary goal of the adaptive immune system

to maintain homeostasis by protecting the body from pathogens, foreign molecules, and toxins

body's first line of defence

intrinsic barriers

intrinsic barriers

- physical barriers of the skin and mucus membranes

- other mechanical, chemical, or microbiological mechanisms

mechanical barriers

explusive forces

chemical barriers

pH and enzymes

microbiological barriers

commensal flora

body's second line of defence

innate immunity

innate immunity:

protects against a broad spectrum of pathogens through surface receptors on phagocytic cells that respond to PAMPs like LPS (found on outer wall of G- bacteria)

innate system is made up of many components:

phagocytes, NK cells, the inflammatory response, antimicrobial proteins like interferons and complement, and fever

phagocytes

- wandering macrophages

- tissue resident cells

NK cells produce:

cytotoxic chemicals to destroy other cells

Inflammatory process

localized response to inflammation

Interferons

released by infected cells, induce nearby cells to produce antiviral proteins

Complement

increase inflammation, inc. phagocytosis, inc. cell lysis (end goal MAC)

Fever

systemic response to widespread infection

these activate fever

pyrogens

Body's third line of defence

adaptive immunity

purpose of adaptive immunity:

to eliminate pathogens that may have circumvented or overwhelmed the first 2 lines of defence and confer protection from new and emergent strains of pathogens

two arms of the adaptive system:

1. cellular

2. humoral

cellular immunity

involves targeted killing of infected or abnormal cells

humoral immunity

involves the production of soluble immunoglobulins that confer protection from specific pathogens through a variety of effector functions

two key characteristics of adaptive immunity

specificity (self vs non-self)

memory

Specificity

the ability to mount a response to a particular pathogen or foreign substance while being able to discriminate between self and non-self antigens

consequence of specificity

B cells may only be able to mount a response to one particular strain of a pathogen without recognizing any of a number of closely related pathogens

memory

the ability to recall past exposures to specific pathogens, giving the adaptive system the ability to mount stronger repeat responses to the same pathogen

principle behind vaccination

immunologic memory

immune response in a vaccinated person

may be so quick and robust that they never even show s/s of an illness when they are infected

primary response to exposure/vaccination is ___________ than the secondary response/first 'real exposure' to the pathogen

smaller, takes a little while longer --> secondary response is big and fast

specificity of the innate response

broad

what does broad specificity mean?

that the innate response broadly recognizes PAMPs

what are PAMPs and how are they presented?

- pathogen associated molecular patterns

- often found on essential parts of the pathogen needed for survival

- accessible to host pattern-recognition receptors like TLRs on phagocytes

TLRs and PAMPs

TLRs recognize PAMPs common to broad classes of organisms --> TLR-4 recognizes LPS, a component of the outer cell wall of all G- bacteria

Repertoire scope of innate response

limited

Pathogen r

- receptors encoded in the host germ line DNA

- limits the absolute number of PAMPs for which PRRs are produced

if pathogens modify their PAMPs, this is the consequence:

PRRs will not mount a response

time to innate response

immediate

immediate response of the innate system is due to

pre-formed components of the response, ready to respond to pathogens immediately on binding PRRs

innate response may include these components

- inc. phagocytosis

- complement activation

- inflammation

Innate memory

- lacks memory

- the innate response is the same every damn time

- same same same, nothing gets better about the response with re-infection

Specificity of adaptive response

- narrow

- TCRs and BCRs recognize very particular things (like 8-10 amino acids)

- may be specific to only one strain of a pathogen

antigenic determinants that set off adaptive response:

very specific things, may not be essential to pathogenic survival like the ones that trigger innate response are

Adaptive repertoire

vast

vast adaptive repertoire comes from this process:

somatic recombination of host gene segments --> makes T and B cell receptors that can detect almost any antigenic determinant

Timeline to adaptive response

3-5 days to activate, many steps in the process

how is the adaptive response triggered:

APCs from the site of infection go to a lymph node nearby where immune cells of the adaptive system reside

process of activation of adaptive response (very simplified)

- antigen presentation

- differentiation

- clonal expansion of T and/or B cells

Adaptive memory

- hallmark of adaptive response

- conferred by a subset of memory cells produced in each adaptive response

memory cells ensure that there is a large reservoir of these:

differentiated cells ready to respond to infections mediated by previously-encountered germs

where does the initiation of the adaptive response occur:

in the secondary lymphoid tissues

secondary lymphoid tissues:

spleen

MALT

lymph nodes

the spleen

acts to filter the blood of pathogens

MALT

loose aggregation of lymphoid tissue that is a in a unique position to eliminate pathogens @ mucosal surfaces before they spread to underlying tissues

MALT:

adenoids, tonsils, payer's patches in the gut

--> may even be found in the resp and GU system, even the appendix

Lymph nodes:

immune surveillance of lymphatic fluid returning from the tissues

how many lymph nodes are there in the body

> 1000

during infection, lymph nodes:

may become swollen and can be seen/felt

lymph nodes are very important in ________ and _______ the adaptive response. Why?

initiating and co-ordinating the response

they facilitate rapid interaction among immune cells + b/w immune cells and pathogens

rapid interaction among immune cells + b/w immune cells and pathogens facilitated by lymph nodes is like this

'tinder on steroids' (lol thank you Dr. Helli)

structure of lymph nodes

- many aff. vessels, fewer eff ones

- germinal center, cortex, medulla

- resident T and B cells

- macrophages and dendritic cells from the infected tissues

innate and adaptive crossover episode:

the macrophages and dendritic cells that come from the infected tissues are the point of intersection for the innate and adaptive responses

during active infection, lymph nodes may contain these cells:

actively proliferating B cells

where are proliferating B cells found within the lymph nodes

in the germinal centers of the cortex

the proliferating B cells will differentiate into these and migrate to this location to carry out their immunologic function

diff into antibody secreting plasma cells

migrate to the medulla or enter the body tissues where they carry our their immunologic functions

the adaptive response is mediated by 2 cell types:

T and B cells

the activation of either B or T cells during an adaptive response can lead to this:

damage to host tissues

because of the potential for tissue damage, T and B cell activity is:

tightly regulated

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